Emerging biological therapies for the treatment of malignant pleural mesothelioma.

Introduction: Malignant pleural mesothelioma (MPM) has limited treatment options with minimal new therapy approvals for unresectable disease in the past 15 years. However, considerable work has occurred to develop immunotherapies and biomarker driven therapy to improve patient outcomes over this period.Areas covered: This review examines current standard of care systemic therapy in the first- and second line setting. The last 12 months has seen 2 significant trials (Checkmate 743 and CONFIRM) which provide evidence supporting the role of immunotherapy in the management of MPM. Further trials are underway to assess the role of combination chemoimmunotherapy and personalized therapy. Additionally, a large number of clinical trials are ongoing to assess the efficacy of oncoviral, dendritic cell, anti-mesothelin and chimeric antigen receptor T cell therapy in the treatment of MPM.Expert opinion: Recent Phase III trial results have established a role for immunotherapy in the management of MPM. The optimal sequencing and combination of chemotherapy and immunotherapy remains to be determined. Novel therapies for MPM are promising however efficacy remains to be determined and issues remain regarding access to and delivery of these therapies.

Near Infrared Photoimmunotherapy for Mouse Models of Pleural Dissemination.

The efficacy of photoimmunotherapy can be evaluated more accurately with an orthotopic mouse model than with a subcutaneous one. A pleural dissemination model can be used for the evaluation of treatment methods for intrathoracic diseases such as lung cancer or malignant pleural mesothelioma. Near-infrared photoimmunotherapy (NIR-PIT) is a recently developed cancer treatment strategy that combines the specificity of tumor-targeting antibodies with toxicity caused by a photoabsorber (IR700Dye) after exposure to NIR light. The efficacy of NIR-PIT has been reported using various antibodies; however, only a few reports have shown the therapeutic effect of this strategy in an orthotopic model. In the present study, we demonstrate an example of efficacy evaluation of the pleural disseminated lung cancer model, which was treated using NIR-PIT.

Hyperthermic intrathoracic chemotherapy combined to iterative cytoreductive surgery to treat a pleural carcinosis from psudomixoma peritonei. A case report.

Pseudomyxoma peritonei (PMP) is an uncommon disease with locally-invasive attitude. Intrathoracic spread is rarely reported and its management extremely challenging. A 51-year-old Caucasian female presented with left pleural carcinosis 9-months after two sequential abdominal surgical procedures combined with HIPEC for low-grade PMP. Cytoreductive surgery (pleurectomy/decortication) was followed by 60-minutes hyperthermic intrathoracic chemotherapy mitomycin-C (215 mg/m2) infusing at same temperature (42°C) and intrapleural pression (2-4 mmH2O). No intra-operative complication occurred, the post-op stay was uneventful and no sign of recurrence was observed 9-months after surgery. Cytoreductive thoracic surgery and hyperthermic chemotherapy (HITHOC) could be a feasible therapeutic option in very selected cases.

Surgical Cytoreduction and HITOC for Thymic Malignancies with Pleural Dissemination.

BACKGROUND: Objective of this study was to assess postoperative morbidity and mortality as well as recurrence-free and overall survival in patients with thymic malignancies and pleural dissemination undergoing surgical cytoreduction and hyperthermic intrathoracic chemotherapy (HITOC). METHODS: Retrospective study between September 2008 and December 2017 with follow-up analysis in May 2018. RESULTS: A total of 29 patients (male: n = 17) with thymic malignancies and pleural spread (primary stage IVa: n = 11; pleural recurrence: n = 18) were included. Surgical cytoreduction was performed via pleurectomy/decortication (P/D; n = 11), extended P/D (n = 15), and extrapleural pneumonectomy (EPP; n = 3). These procedures resulted in 25 (86%) patients with macroscopically complete (R0/R1) resection. Intraoperative HITOC was performed for 60 minutes at 42°C either with cisplatin (100 mg/m2 body surface area [BSA] n = 8; 150 mg/m2 BSA n = 6; 175 mg/m2 BSA n = 1) or with a combination of cisplatin (175 mg/m2 BSA)/doxorubicin (65 mg; n = 14). Postoperative complications occurred in nine patients (31%). Cytoprotective therapy resulted in lower postoperative creatinine levels (p = 0.036), and there was no need for temporary dialysis in these patients. The 90-day mortality rate was 3.4%, as one patient developed multiple organ failure. While recurrence-free 5-year survival was 54%, an overall 5-year survival rate of 80.1% was observed. Survival depended on histological subtype (p = 0.01). CONCLUSION: Surgical cytoreduction with HITOC is feasible in selected patients and offers encouraging survival rates. The application of cytoprotective agents appears to be effective for the prevention of postoperative renal insufficiency.

Acute kidney injury after cytoreductive surgery and hyperthermic intraoperative cisplatin chemotherapy for malignant pleural mesothelioma.

OBJECTIVES: Cytoreductive surgery with hyperthermic intraoperative chemotherapy with cisplatin has been used successfully to treat malignant pleural mesothelioma, a highly aggressive malignancy that is rapidly fatal in most cases. We hypothesized that the combination of ischemic injury with nephrotoxic injury from cisplatin would result in high rates of acute kidney injury. METHODS: We conducted an observational study in 503 patients to study the risks and outcomes of acute kidney injury after surgical resection of malignant pleural mesothelioma. Eligible subjects underwent extrapleural pneumonectomy or pleurectomy/decortication with or without hyperthermic intraoperative chemotherapy. Acute kidney injury was defined as an increase in creatinine of 26.5 µmol/L or greater within 48 hours of surgery or a 50% or greater increase over 7 days. RESULTS: Acute kidney injury developed in 243 patients (48.3%). Severe acute kidney injury requiring renal replacement therapy developed in 16 patients (3.2%). Major significant predictors for acute kidney injury included male sex (odds ratio, 2.98; P < .001), intraoperative cisplatin administration (odds ratio, 3.12; P < .001), previous cisplatin exposure (odds ratio, 1.96; P = .02), hypertension (odds ratio, 1.57; P = .02), and longer surgical time (odds ratio, 1.15 per hour; P = .02). Compared with patients without acute kidney injury, those with severe acute kidney injury had longer length of stay (26 vs 13 days) and a 2.71-fold increased risk of death in multivariable-adjusted models. CONCLUSIONS: Acute kidney injury is common after cytoreductive surgery with hyperthermic intraoperative chemotherapy with cisplatin and is associated with poor long-term outcomes. Strategies to prevent postoperative acute kidney injury are needed to improve multimodal treatment of malignant pleural mesothelioma.

Surgical treatment of pleural recurrence of thymoma: is hyperthermic intrathoracic chemotherapy worthwhile?

OBJECTIVES: Recurrence of thymoma is described in 10-30% of cases after surgical resection. Iterative surgery for thymoma pleural relapses (TPRs) is often part of a multimodal treatment. Hyperthermic intrathoracic chemotherapy (HITHOC) following macroscopic radical surgery is an option that combines the effects of mild hyperthermia with those of chemotherapeutic agents. We evaluated the effectiveness of surgery + HITHOC, compared with surgery alone, in the treatment of TPR. METHODS: We retrospectively collected data of all patients who underwent surgery for TPR in our centre from 2005 to 2017. Relapses were treated by partial pleurectomy with radical intent, followed by HITHOC when not contraindicated. Patients were divided into 2 groups: surgery + HITHOC and surgery alone. We collected demographic and clinical data and analysed postoperative results together with oncological outcomes. RESULTS: Forty patients (27: surgery + HITHOC, 13: surgery alone), mean age 49.8 (±13.7) years, were included in this study. There were no perioperative deaths. We experienced 33.3% perioperative morbidity in the surgery + HITHOC group compared with 23.1% in the surgery alone group (P = 0.71). The overall survival rate was comparable between the 2 groups (P = 0.139), whereas the local disease-free interval was 88.0 ± 15 months in the surgery + HITHOC group and 57 ± 19.5 months in the surgery alone group (P = 0.046). The analysis of factors affecting the outcomes revealed that radical surgery is related with a better survival rate whereas the local disease-free interval was significantly influenced by HITHOC. CONCLUSIONS: The safety and feasibility of HITHOC in the treatment of TPR are already known, even if it should be reserved for selected patients. Surgery + HITHOC seems to be associated with a longer local disease-free time compared to surgery alone.

50 Patients with Malignant Mesothelioma of Both the Pleura and Peritoneum: A Single-Institution Experience.

BACKGROUND: The most common sites of malignant mesothelioma are the pleura and peritoneum, but little is known about the incidence, prognosis, or treatment of patients with disease in both cavities. Previous series suggest that multimodality treatment improves overall survival for pleural or peritoneal disease, but studies typically exclude patients with disease in both cavities. Despite limitations, this investigation is the only study to broadly examine outcomes for patients with malignant mesothelioma in both the pleural and peritoneal cavities. METHODS: This study retrospectively examined 50 patients with both pleural and peritoneal mesothelioma treated with the intent to prolong survival. The primary end point was overall survival from the initial operative intervention. RESULTS: The median overall survival was 33.9 months from the initial intervention. Female gender and intraperitoneal dwell chemotherapy were independent predictors of overall survival. Within 1 year after the initial diagnosis, second-cavity disease was diagnosed in 52% of the patients. The median time to the second-cavity diagnosis for those with a diagnosis 1 year after the initial diagnosis was 30 months. CONCLUSIONS: Well-selected patients with both pleural and peritoneal mesothelioma have a survival benefit over palliative treatment that is comparable with that seen in single-cavity disease. The presence of disease in both cavities is not a contraindication to multimodality treatment aimed at prolonging survival, whether the disease is diagnosed synchronously or metachronously. Patients with an initial diagnosis of single cavity disease are at the highest risk for identification of second-cavity disease within the first year after diagnosis.

The use of apatinib in treating primary pleural synovial sarcoma: A case report.

RATIONALE: Apatinib is an oral tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2. It has been shown that apatinib is effective and safe for treatment of multiple solid tumors, including gastric cancer, liver cancer, non-small-cell lung cancer, and breast cancer. However, there is currently no consensus as to using Apatinib for the treatment of pleural synovial sarcoma, due to the rarity of primary pleural synovial sarcoma and lack of clinical studies as a consequence. PATIENT CONCERNS AND DIAGNOSES: We reported here in the case of a 26-year-old Chinese woman diagnosed with pleural synovial sarcoma. She has undergone 2 surgeries, multiple regimens of chemotherapy and traditional Chinese medicine in other hospitals. Then the patient was admitted to our hospital with the compliant of chest pain and dyspnea. The medical history and available data supported the diagnosis of recurrence of pleural synovial sarcoma. INTERVENTIONS AND OUTCOMES: Due to the lack of efficacy of previous standard treatment, the patient was given apatinib and radiotherapy to relieve the symptoms. This patient achieved stable disease with apatinib at a dose of 500 mg/day. Her progression-free survival time was more than 7 months, and her overall survival was 8.5 months. Except for hand-foot syndrome, no grade 3 or 4 side effects were observed. CONCLUSIONS: Apatinib may thus be an option for treatment of advanced synovial sarcoma after failure of other treatments. However, further study is needed to determine the efficacy of apatinib in pleural synovial sarcoma.

Malignant Peritoneal Mesothelioma: Patterns of Care and Survival in the Netherlands: A Population-Based Study.

BACKGROUND: Malignant peritoneal mesothelioma (MPM) is a rare and aggressive disease. Recently, focus has shifted toward a more aggressive and multimodal treatment approach. This study aimed to assess the patterns of care and survival for MPM patients in the Netherlands on a nationwide basis. METHODS: The records of patients with a diagnosis of MPM from 1993 to 2016 were retrieved from the Dutch Cancer Registry. Data regarding diagnosis, staging, treatment, and survival were extracted. Cox regression analyses and Kaplan-Meier survival curves were used to study overall survival. RESULTS: Between 1993 and 2016, MPM was diagnosed for 566 patients. Overall, the prognosis was very poor (24% 1-year survival). The most common morphologic subtype was the epithelioid subtype (88%), followed by the biphasic (8%) and sarcomatoid (4%) subtypes. Surgical treatment has become more common in recent years, which most likely has resulted in improved survival rates. In this study, improved survival was independently associated with hyperthermic intraperitoneal chemotherapy (hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.21-0.55) and surgery with adjuvant systemic chemotherapy (HR, 0.33; 95% CI, 0.23-0.48). Nonetheless, most patients (67%) do not receive any form of anti-cancer treatment. CONCLUSION: This study indicated that MPM still is a rare and fatal disease. The survival rates in the Netherlands have improved slightly in the past decade, most likely due to more aggressive treatment approaches and increased use of surgery. However, most patients still do not receive cancer-directed treatment. To improve MPM management, and ultimately survival, care should be centralized in expert medical centers.

Adequate nephroprotection reduces renal complications after hyperthermic intrathoracic chemotherapy.

BACKGROUND AND OBJECTIVES: Hyperthermic intrathoracic chemotherapy (HITOC) is used for the treatment of malignant pleural tumors. Although HITOC proved to be safe, postoperative renal failure due to nephrotoxicity of intrapleural cisplatin remains a concern. METHODS: This single-center study was performed retrospectively in patients who underwent pleural tumor resection and HITOC between September 2008 and December 2018. RESULTS: A total of 84 patients (female n = 33; 39.3%) with malignant pleural tumors underwent surgical cytoreduction with subsequent HITOC (60 minutes; 42°C). During the study period, we gradually increased the dosage of cisplatin (100-150 mg/m2 BSA n = 36; 175 mg/m2 BSA n = 2) and finally added doxorubicin (cisplatin 175 mg/m2 BSA/doxorubicin 65 mg; n = 46). All patients had perioperative fluid balancing. The last 54 (64.3%) patients also received perioperative cytoprotection. Overall 29 patients (34.5%) experienced renal insufficiency. Despite higher cisplatin concentrations, patients with cytoprotection showed significantly lower postoperative serum creatinine levels after 1 week (P = .006) and at discharge (P = .020). Also, they showed less intermediate and severe renal insufficiencies (5.6% vs 13.3%). CONCLUSIONS: Adequate perioperative fluid management and cytoprotection seem to be effective in protecting renal function. This allows the administration of higher intracavitary cisplatin doses without raising the rate of renal insufficiencies.

[Hyperthermic intrathoracic chemotherapy in thoracic surgery]. / Hypertherme intrathorakale Chemotherapie in der Thoraxchirurgie.

In regional chemotherapy of the pleural space a differentiation is made between intrapleural hyperthermic perfusion (IHP) and hyperthermic intrathoracic chemotherapy (HITOC). The HITOC in particular is carried out as an additive procedure after surgical cytoreduction of the pleural tumor manifestation. The main indications are for malignant pleural mesothelioma and thymoma with pleural spread (stage IVa), whereas treatment of secondary pleural carcinomatosis is indicated only in selected patients suitable for resection followed by HITOC. Cisplatin is the standard chemotherapeutic agent and a concentration of 150-175 mg/m2 body surface area is recommended. Postoperative, HITOC-related complications (e.g. renal insufficiency) can be minimized by an adapted perioperative management. Safety measures should be accomplished adhered to for the protection of personnel. The aim of HITOC is to achieve a better local tumor control with a corresponding longer recurrence-free and overall survival.

Managing malignant pleural mesothelioma: experience and perceptions of health care professionals caring for people with mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) has a poor prognosis and heavy symptom burden. Here, we investigate health professionals' attitudes to management and decision-making in people with MPM. METHODS: Survey questions were based on previous interviews with health professionals, MPM patients, and caregivers. Surveys were sent to specialist doctors and nurses who treat MPM. RESULTS: Surveys were completed by 107 doctors and 19 nurses from January-September 2014. Most doctors were respiratory physicians (50%) or medical oncologists (35%). Overall, 90% of doctors estimated > 10% of eligible MPM patients did not receive chemotherapy; 43% estimated the rate was > 20%. Doctors believed clinical barriers to chemotherapy were clinician nihilism (70%); non-referral to medical oncology (49%); and lack of specialists in rural/regional areas (44%). Nurses perceived barriers as follows: delayed diagnosis (74%); non-referral to medical oncology (63%); lack of clinician knowledge (58%). Patient-related barriers were negative perception of chemotherapy (83%) and belief survival benefit not worthwhile (63%). Doctors' preference in decision-making was for the patient to make the decision while strongly considering the doctor's opinion (33%); equally with the doctor (29%); and using knowledge gained (23%). Nurses described their roles as providing patient support (100%); information (95%); intermediary (74%); and link to palliative care (74%). Overall, 95% believed they enabled better resource allocation and provided patients with holistic care (95%); clearer communication (89%); more time (89%); additional information (89%); timely referrals (89%). CONCLUSIONS: Caring for patients with MPM is challenging and complex. Health care professionals believe under-utilisation of chemotherapy is occurring, primarily due to clinician nihilism and lack of medical oncology referral.

Cytoreductive Pleurectomy and Intrathoracic Chemohyperthermia for Pleural Relapse of Thymomas.

Several surgical procedures, from debulking to extrapleural pneumonectomy, may be applied for stage IVa Masaoka thymomas, but their efficiency is still controversial. Case studies have favored R0 resection as the cornerstone of multimodal therapy for locoregional metastatic extension. This report describes a standardized procedure combining a cytoreductive surgical procedure and intrathoracic chemohyperthermia on a 46-year-old patient presenting with B2 thymoma and synchronous unilateral pleural metastasis.

Treatment of malignant pleural mesothelioma with chemotherapy preceding versus after surgical resection.

OBJECTIVES: There are 2 main treatment paradigms recognized by the National Comprehensive Cancer Network for resectable malignant pleural mesothelioma (MPM): induction chemotherapy followed by resection (IC/R), and up-front resection with postoperative chemotherapy (R/PC). These paradigms are being compared in an accruing randomized phase II trial. In the absence of such completed trials, in this study we evaluated overall survival (OS) and postoperative outcomes of IC/R and R/PC. METHODS: The National Cancer Database was queried for newly diagnosed epithelioid/biphasic MPM. Metastatic, node-positive, and/or cT4 disease was excluded, along with nondefinitive surgery and lack of chemotherapy. Multivariable logistic regression ascertained factors independently associated with induction chemotherapy delivery. Kaplan-Meier analysis was used to evaluate OS between cohorts; multivariable Cox proportional hazards modeling was used to assess factors associated with OS. Survival was also evaluated between propensity-matched populations. Last, postoperative outcomes were assessed between groups. RESULTS: Overall, 361 patients (182 IC/R, 179 R/PC) were analyzed. Temporal trends revealed that IC/R is decreasing over time. Survival of the IC/R cohort was similar to that of R/PC patients (20.9 vs 21.7 months; P = .500); this persisted after propensity matching (20.8 vs 22.0 months; P = .270). However, patients who underwent IC/R experienced longer postoperative hospitalization (median 7 days vs 6 days; P = .001) and higher 30-day mortality (3.3% vs 0%; P = .020). CONCLUSIONS: To our knowledge, this is the only comparative investigation of the 2 major management paradigms of operable MPM. IC/R regimens are decreasing over time in the United States. Although associated with survival similar to R/PC, IC/R might be associated with worse postoperative outcomes. Careful induction chemotherapy patient selection is thus highly recommended.

Abrupt hemodynamic changes accompanying intrapleural hyperthermic chemotherapy: Case series.

RATIONALE: Intrapleural hyperthermic chemotherapy (IPHC) is the preferred method to locally treat lung cancer with pleural seeding. Anesthetic management during IPHC is a very challenging task for the anesthesiologist because of the hemodynamic instability associated with the procedure; however, there is no report on anesthetic considerations during the IPHC procedure. PATIENT CONCERNS: Three patients who diagnosed lung cancer with pleural invasion scheduled for IPHC were reported in this case series. DIAGNOSIS: Case 1, a 48-year-old woman, suffered from lung cancer (adenocarcinoma, T2NxM1a) with diffuse pleural seeding. Case 2, a 58-year-old female, diagnosed with lung cancer (adenocarcinoma, T3N0M1a) with pleural dissemination. Case 3, a 47-year-old male, diagnosed as sarcoma on the left lung with right pericardial invasion and right hemidiaphragm invasion (stage, T3N0M1a). INTERVENTION: All three patients underwent IPHC with cisplatin diluted in normal saline (2000 ml) at a rate of 600 ml/min. Inflow temperature of 42°C was using a heart-lung machine over 90 minutes. Hemodynamic changes were monitored through the procedure. OUTCOMES: The patient did not require supplemental oxygenation anymore after he recovered from lung transplantation. LESSONS: There was sudden drop in the cardiac output and an increase in the pulmonary vascular resistance, which were caused by the volume and temperature of the hyperthermic chemotherapeutic drugs in the pleura during the early stage of IPHC; these changes can be a major problem during the procedure, and supportive hemodynamic management may be needed.

Establishment of a human intrapleural hyperthermic perfusion model and analysis of pleural malignancy treatment depth.

INTRODUCTION: Although human intrapleural hyperthermic perfusion (HIHP) has achieved excellent palliative effects in metastatic pleural malignancies, the optimum treatment conditions, including inlet temperature and treatment times based on tumor size, have yet to be determined. However, such information is recognized to be critical for treatment planning in clinics. Therefore, the current research aimed to solve these issues. METHODS: Using the finite-element method (FEM), a simplified three-dimensional HIHP model was established and verified according to the temperature data of specific measuring points based on a clinical therapeutic case. Ultimately, the treatment depth of pleural malignancies was obtained by employing an equivalent thermal dose of 80 min as the damage threshold. RESULTS: The treatment depth of parietal pleural malignancies (PPM) is much larger than that of visceral pleura malignancies (VPM), and can therefore be overlooked. In addition, the average treatment depth of the PPM increased by 1 mm as treatment time increased by 30 min during the 60-120 min time frame and as the inlet temperature increased by 1 °C, while there was no further increase when treatment time exceeded 120 min. CONCLUSIONS: HIHP can provide superior treatment for PPM and only provided faintly therapeutic effects on VPM, and may not be appropriate for the larger VPM. Although we only studied one example in this article, this is the beginning of an intensive study into the detailed thermal behavior of pleural tissues under HIHP, and further analysis on more realistic cases is currently underway.

A Phase I Trial of Surgical Resection and Intraoperative Hyperthermic Cisplatin and Gemcitabine for Pleural Mesothelioma.

INTRODUCTION: The primary objective of this single-institution phase I clinical trial was to establish the maximum tolerated dose of gemcitabine added to cisplatin and delivered as heated intraoperative chemotherapy after resection of malignant pleural mesothelioma. METHODS: The extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D) treatment arms were based on investigators' assessment of patient fitness and potential for macroscopic complete resection. Previously established intracavitary dosing of cisplatin (range 175-225 mg/m2) with systemic cytoprotection was used in combination with escalating doses of gemcitabine, following a 3-plus-3 design from 100 mg/m2 in 100-mg increments. RESULTS: From 2007 to 2011, 141 patients were enrolled and 104 completed treatment. The median age of those completing treatment was 65 years (range 43-85 years), and 22 (21%) were female. In the EPP arm (n = 59), 31 patients (53%) had the epithelioid histologic type and the median radiographic tumor volume was 236 cm3 (range 16-4285 cm3). In the P/D arm (n = 41), 29 patients (71%) had the epithelioid histologic type and the median tumor volume was 79 cm3 (range 6-1107 cm3). The operative mortality rate was 2%, and 35 and 22 serious adverse events were encountered among 27 patients (46%) and 16 patients (39%) in the EPP and P/D arms, respectively. Dose-limiting toxicity (grade 3 leukopenia) was observed in two patients who were receiving 1100 mg/m2 of gemcitabine, thus establishing the maximum tolerated dose at 1000 mg/m2, in combination with 175 mg/m2 of cisplatin. The median overall and recurrence-free survival times in treated patients were 20.3 and 10.7 months, respectively. CONCLUSIONS: Combination cisplatin and gemcitabine heated intraoperative chemotherapy can be administered safely and feasibly in the context of complete surgical resection of malignant pleural mesothelioma by EPP or P/D.

Management and Survival of Pleural Mesothelioma: A Record Linkage Study.

BACKGROUND: Pleural mesothelioma (PM) is a rare, highly lethal tumor. A definite consensus on its management has yet to be established. OBJECTIVES: To assess management, overall survival (OS), and their predictors in a cohort of patients from Lombardy, the largest Italian region (about 10 million inhabitants). METHODS: Through a record linkage between Lombardy health care administrative databases, we identified patients diagnosed with PM in 2006-2011 without history of cancer, evaluating their management. OS from PM diagnosis was estimated using the Kaplan-Meier method. Predictors of OS and of treatment were assessed using Cox regression models with time-dependent covariates when appropriate. RESULTS: Out of 1,326 patients, 754 (56.9%) received treatment for PM: 205 (15.5%) underwent surgery, and 696 (52.5%) used chemotherapy. Surgery was spread across several hospitals, and most patients diagnosed in nonspecialized centers (70%) underwent surgery in the same centers. Age at diagnosis was a strong inverse determinant of surgery. Determinants of receiving chemotherapy were younger age, a more recent first diagnosis, and first diagnosis in a specialized center. OS was 45.4% at 1 year, 24.8% at 2 years, and 9.6% at 5 years (median 11 months). OS decreased with age, and was higher for those who underwent surgery, but not for those treated with chemotherapy. CONCLUSIONS: Management of PM varied widely in clinical practice, and significant predictors of treatment were younger age and recent diagnosis, though a high proportion of patients were not treated. Patients were treated in various hospitals, indicating the importance of concentrating serious rare neoplasms in Comprehensive Cancer Centers (as recognized by the Italian Health Ministry).

Low-dose Pressurized Intrathoracic Aerosol Chemotherapy (PITAC) as an Alternative Therapy for Pleuropulmonary Involvement in Pseudomyxoma Peritonei.

BACKGROUND/AIM: Pseudomyxoma peritonei (PMP) is a rare disease characterized by mucinous ascites and widespread peritoneal implants. It usually originates from the rupture of an adenoma/adenocarcinoma of the appendix. Although this tumor is only superficially invasive and does not metastasize, it could be a fatal disease. Extra-abdominal spread of PMP is an unusual occurrence with few reports in medical literature. CASE REPORT: A 50-year-old man was diagnosed with PMP according to the findings of thorax and abdomen CT scan and cytologic and histological examinations. The radiological exam showed irregular thickening on the surface of left diaphragmatic and parietal pleura. RESULTS: First, cytoreductive surgery associated with hyperthermic intraperitoneal chemotherapy (HIPEC) for the abdominal disease was performed. Histopathological examination confirmed the diagnosis of low grade PMP. The radiological evaluation performed 5 months later showed a dimensional increase in pleural nodules. The treatment consisted of an extensive intrathoracic cytoreductive surgery in combination with pressurized intra-thoracic aerosol chemotherapy (PITAC). Postoperative course was uneventful. CONCLUSION: PMP with pleural extension is a rare phenomenon and carries an unfavourable prognosis. Due to the rarity of this presentation, its correct treatment is still unclear. We present a therapeutic approach to be applied in selected patients.

Management of Malignant Lung Entrapment, the Oncothorax.

Pleural metastasis is a common occurrence in up to 30% of patients with metastatic cancer. When lung entrapment and loculation of fluid occur, treatment is more difficult and we have named this condition "oncothorax." The malignant adhesions that entrap the lung in an oncothorax are not typically amenable to surgical decortication. The standard approach for managing these patients is to place an indwelling catheter. Other options may include pleurectomy and decortication, intrapleural hyperthermic chemoperfusion, and intrapleural photodynamic therapy. However, these procedures should be provided selectively depending on patient performance status, extent of metastatic disease, and level of experience.