The Clinical Desire for Pressurized Intraperitoneal Aerosol Chemotherapy in South Korea: An Electronic Survey-based Study.

BACKGROUND/AIM: To evaluate the clinical desire for pressurized intraperitoneal aerosol chemotherapy (PIPAC) in South Korea. PATIENTS AND METHODS: We performed an online survey on surgical oncologists between November and December 2019 using a questionnaire consisting of 20 questions. RESULTS: A total of 164 respondents answered the questionnaire. Among those specialized in ovarian cancer, pseudomyxoma peritonei, and malignant mesothelioma 41.7-50% preferred PIPAC for the curative treatment of primary diseases, whereas 32.7-33.3% majoring in colorectal and hepatobiliary cancers chose it for the palliative treatment of recurrent diseases. Furthermore, 66.7-95.2% considered PIPAC appropriate for the cancers they specialized in, and 76-78.7% expected a treatment response of more than 50% and considered grade 1 or 2 complications acceptable. Most respondents answered the reasonable costs to purchase and implement PIPAC once at between 1,000,000-5,000,000 South Korean Won (KRW). CONCLUSION: Most Korean surgical oncologists expected relatively high tumor response rates with minor toxicities through the repeated implementation of PIPAC.

Assessment of interferon-γ in pleural fluid as a prognostic factor of survival in malignant pleural mesothelioma.

BACKGOUND: Literature reports suggest that the host immune system may control Malignant Pleural Mesothelioma (MPM) growth, although its activity is limited by regulatory mechanisms. In this retrospective study, we analyzed the levels of pro-inflammatory (IL-1, IL-6, TNF), immune-regulatory (IL-10) and Th1/CTL-related cytokines (IL-12p70, IFN-γ) in the pleural exudate and their relationship with overall survival (OS) in MPM. METHODS: Cytokines were quantified by multiplexed immunoassay. Concentrations were dichotomized with respect to the median value. Correlation between cytokine level and OS was assessed using univariate (Kaplan-Meier curves) and multivariate (Cox regression) analyses. RESULTS: Regarding outcome, tumor histology, therapies undergone and IFN-γ were independent prognostic factors of OS in a 72 MPM training cohort. Notably, high concentrations of IFN-γ halved death probability (HR of high vs low IFN-γ concentration = 0.491, 95%CI 0.3-0.8, p = 0.007). Also in patients with epithelioid histology and those receiving at least one line of therapy, high IFN-γ level was an independent factor predictive of OS (HR of high vs low IFN-γ concentration were 0.497, p = 0.007 and 0.324, p = 0.006, respectively). However, these data were not confirmed in a 77 MPM validation cohort, possibly due to the low IFN-γ levels encountered in this population, and the heterogeneous distribution of disease stages between the training and the validation cohorts. None of the other cytokines showed any effect on survival. CONCLUSIONS: High level of IFN-γ in pleural effusion may be associated with better survival in MPM patients and potentially serve as a prognostic biomarker. Larger prospective studies are needed to ascertain this hypothesis.

The role of volumetric method in the assessment of chemotherapy response and predicting survival in malignant pleural mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a pleural tumor with high mortality rate and short-term survival expectancy after diagnosis. Assessment of the response to chemotherapy, which is the first choice in treatment of MPM, is important for the transition to alternative chemotherapy protocols and immunotherapy. There is no clarity in the response to chemotherapy treatment. OBJECTIVE: Our study aims to compare the assessment of chemotherapy response using the Modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria and volumetric measurements and to correlate with median survival. MATERIALS AND METHODS: Thirty-two patients (16 females and 16 males) were included in the study, and their ages ranged from 28 to 78 years. Chemotherapy response was determined by both mRECIST and volumetric approach. Tumor volume was measured by linear interpolation and semi-automatic segmentation. Log-rank multiple cutoff analysis was used to determine appropriate cutoff values of volumetric response criteria. RESULTS: According to both mRECIST and volumetric approach, median survival times in partial response, stable disease, and progressive disease groups were 24, 15, and 9 months, respectively. The survival times of the three groups were different (logrank: 17.76; P < 0.001) by mRECIST. The survival of the progressive disease group was shorter than that of the other groups (logrank: 18.91; P < 0.001) by volumetric approach. CONCLUSIONS: In the assessment of chemotherapy response, even though classifications obtained according to the mRECIST criteria and volumetric measurements are statistically compatible, we think that the measurement of the volumetric values will increase the standardization. In our study, threshold values for volumetric measurements were determined; however, these values should be supported by large-scale multicenter studies.

Gender-based Disparities in Receipt of Care and Survival in Malignant Pleural Mesothelioma.

BACKGROUND: Despite accounting for a minority of malignant pleural mesothelioma (MPM) diagnoses, females may experience differential survival relative to males. It is unclear if there are gender-based differences in receipt of treatment or disease-related outcomes for patients with MPM. We therefore utilized the National Cancer Database (NCDB) to assess patterns-of-care and overall survival (OS) among patients with MPM by gender. MATERIALS AND METHODS: Patients with histologically confirmed MPM treated from 2004 to 2013 were identified from the NCDB. The association between female gender and OS was assessed using multivariable Cox proportional hazards models with propensity score matching. Patterns-of-care were assessed using multivariable logistic regression. The overall treatment effect was tested in subsets of patients by treatment strategy, histology, and clinical stage. RESULTS: A total of 18,799 patients were identified, of whom 14,728 (78%) were male and 4071 (22%) were female. Females were statistically more likely to present at a younger age, with fewer comorbidities, and with epithelioid histology. Despite these favorable prognostic features, women were less likely to receive surgery (P ≤ .001) or chemotherapy (P ≤ .001) compared with males. On multivariable analysis, female gender was associated with improved OS (hazard ratio, 0.83; 95% confidence interval, 0.80-0.86; P ≤ .001). Gender-based survival differences were seen across all stages, but only among patients with epithelioid (P ≤ .001) and not biphasic (P = .17) or sarcomatoid (P = 1.00) histology. CONCLUSIONS: Surgery and chemotherapy are disproportionately underutilized in female patients with MPM. Despite this concerning disparity, female gender is independently associated with improved survival relative to males. Further research to understand factors that lead to gender disparities in MPM is warranted.

18F-FDG PET Assessment of Malignant Pleural Mesothelioma: Total Lesion Volume and Total Lesion Glycolysis-The Central Role of Volume.

Cancer survival is related to tumor volume. 18F-FDG PET measurement of tumor volume holds promise but is not yet a clinical tool. Measurements come in 2 forms: the first is total lesion volume (TLV) based on the number of voxels in the tumor, and the second is total lesion glycolysis (TLG), which is the TLV multiplied by the average SUL (i.e., SUV normalized for lean mass) of the tumor (SULaverage). In this study, we measured tumor volume in patients with malignant pleural mesothelioma (MPM). Methods: A threshold-based program in Interactive Data Language was developed to measure tumor volume in 18F-FDG PET images. Nineteen patients with MPM were studied before and after 2 cycles (6 wk) of chemoimmunotherapy. Measurements included TLV, TLG, the sum of the SULs in the tumor (SULtotal, a measure of total 18F-FDG uptake), and SULaverageResults: Baseline TLV ranged from 11 to 2,610 cm3 TLG ranged from 32 to 8,552 cm3 g/mL and correlated strongly with TLV. Although tumor volumes ranged over 3 orders of magnitude, SULaverage stayed within a narrow range of 2.4-5.3 units. Thus, TLV was the major component of TLG, whereas SULaverage was a minor component and was essentially constant. Further evaluation of SULaverage showed that in this cohort its 2 components, SULtotal and TLV, changed in parallel and were strongly correlated (r = 0.99, P < 0.01). Thus, whether the tumors were large or small, 18F-FDG uptake as measured by SULtotal was proportional to the TLV. Conclusion: TLG equals TLV multiplied by SULaverage, essentially TLV multiplied by a constant. Thus TLG, commonly considered a measure of metabolic activity in tumors, is also in this cohort a measure of tumor volume. The constancy of SULaverage is due to the fact that 18F-FDG uptake is proportional to tumor volume. Thus, in this study, 18F-FDG uptake was also a measure of volume.

Interobserver variation in the assessment of the sarcomatoid and transitional components in biphasic mesotheliomas.

The percentage of sarcomatoid component has an impact on prognosis in patients with biphasic malignant pleural mesothelioma. Recent study showed that the transitional pattern similar to sarcomatoid component of malignant mesothelioma has negative prognostic significance. Practice guidelines recommend quantification of sarcomatoid component despite poor diagnostic reproducibility of biphasic mesothelioma among thoracic pathologists. The aim of this study was to determine the interobserver agreement in the quantification of sarcomatoid component, and in the diagnosis of a transitional component in the biphasic malignant mesothelioma. Thirteen experts in thoracic pathology reviewed the representative H&E and cytokeratin whole-slide images of the 54 biphasic mesotheliomas, without knowledge of BAP1 or p16 deletion status, and completed the survey of 25 questions. The overall interobserver agreement in the assessment of the percentage of the sarcomatoid component in 25% increments was good (wK = 0.62). Excellent agreement was present in 14 of 54 cases (26%), and 3 cases were unanimously scored. Excellent agreement was reached for the cases with 0-24% and > 75% of the sarcomatoid component.The most commonly used criteria for the diagnosis of sarcomatoid component were malignant spindle cells, frank sarcomatoid features and high N/C ratio. The overall interobserver agreement for transitional pattern was fair (wK = 0.40). Unanimous opinion about the absence of transitional pattern was observed in only one case. At least 70% agreement regarding the presence of transitional pattern was observed in 12 cases, with the rest of the cases showing a wide range of disagreement. Morphologic characteristics that favor transitional pattern over non-transitional include sheet-like growth of cohesive, plump, elongated epithelioid cells with well-defined cell borders and a tendency to transition into spindle cells. Our study defined precise morphologic criteria that may be used in the differential diagnosis between transitional pattern and other mesothelioma subtypes including sarcomatoid and epithelioid.