Oncotarget 2017 November 14 [Link]

Lapa C et. al.

Abstract

C-X-C motif chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. This study investigated the feasibility of CXCR4-directed imaging with positron emission tomography/computed tomography (PET/CT) using [68Ga]Pentixafor in malignant pleural mesothelioma. Six patients with pleural mesothelioma underwent [68Ga]Pentixafor-PET/CT. 2′-[18F]fluoro-2′-deoxy-D-glucose ([18F]FDG)-PET/CT (4/6 patients) and immunohistochemistry obtained from biopsy or surgery (all) served as standards of reference. Additionally, 9 surgical mesothelioma samples were available for histological work-up. Whereas [18F]FDG-PET depicted active lesions in all patients, [68Ga]Pentixafor-PET/CT recorded physiologic tracer distribution and none of the 6 patients presented [68Ga]Pentixafor-positive lesions. This finding paralleled results of immunohistochemistry which also could not identify relevant CXCR4 surface expression in the samples analyzed. In contrast to past reports, our data suggest widely absence of CXCR4 expression in pleural mesothelioma. Hence, robust cell surface expression should be confirmed prior to targeting this chemokine receptor for diagnosis and/or therapy.

The British Journal of Radiology 2018 March [Epub ahead of print] [Link]

H St. AE et.al.

Abstract

OBJECTIVE:
To compare the N and M staging accuracy of positron emission tomography (PET) versus CT, as per the American Joint Committee on Cancer (AJCC) 8th edition in patients with malignant pleural mesothelioma (MPM) being considered for multimodality therapy in a tertiary referral center. A secondary aim was to assess survival outcome of patients chosen for surgical management after PET.

METHODS:
A retrospective, single institution comparison of PET and CT was performed in patients with histologically proven MPM being considered for multimodality therapy. Performance of each modality in identifying nodal category and presence or absence of distant metastases was abstracted from electronic patient records. The standard of reference was surgical histopathology for nodal stage and histopathology or clinical and imaging follow-up of >3 months for distant metastases.

RESULTS:
There were 101 eligible patients with complete datasets; 82 males, 19 females with a mean age of 66.6 years (range: 39-85). Most patients (n = 68) had epithelioid histology. Surgery was performed in 61/101 patients (60.4%), most of whom had multimodality therapy. Nodal category was concordant to surgical histopathology in 38/60 patients (63.3%) on PET, compared to 27/60 (45%) on CT (p = 0.001). For detection of ≥N1 disease only, PET and CT correctly staged 15/37 patients (40.5%) and 8/37 (21.6%), respectively (p = 0.023). Distant metastases were identified uniquely on PET in 8 patients and on CT only in 1 patient. Overall, PET and CT correctly identified 11/12 (91.6%) and 4/12 (33.3%) patients with distant metastases, respectively (p = 0.0391).

CONCLUSION:
PET identifies significantly more patients with nodal or distant metastatic disease than CT and may contribute to more appropriate selection of patients with MPM for surgery or multimodality therapy. Advances in knowledge: In patients with MPM, FDG-PET/CT detects significantly more patients with distant metastases than CT. PET/CT can help in the selection of patients with MPM who would benefit from surgery or multimodality therapy.

Topics in Magnetic Resonance Imaging [2018 April] [Link]

Carter BW, Betancourt SL, Shroff GS, Lichtenberger JP 3rd

Abstract

The pleura may be affected by primary tumors or metastatic spread of intrathoracic or extrathoracic neoplasms. Primary pleural neoplasms represent ∼10% of all pleural tumors, and malignant lesions are more common than benign lesions. The most common primary tumors include malignant pleural mesothelioma and solitary fibrous tumor. Although pleural neoplasms may initially be evaluated with computed tomography (CT) and/or fluorodeoxyglucose positron emission tomography (PET)/CT, magnetic resonance (MR) imaging is complementary to these other imaging modalities for disease staging and evaluation of patients. In this article, we discuss the etiology, clinical presentation, and imaging of pleural neoplasms, with specific attention given to the role of MR imaging.

Clinical Lung Cancer 2018 September 3 [Link]

Fodor A1, Broggi S2, Incerti E3, Dell’Oca I4, Fiorino C2, Samanes Gajate AM3, Pasetti M4, Cattaneo MG2, Passoni P4, Gianolli L3, Calandrino R2, Picchio M, Di Mu

Abstract

INTRODUCTION:
The objective of this study was to present the outcomes of moderately hypofractionated helical intensity-modulated radiation therapy (HT) with/without simultaneous integrated boost (SIB) on fluorodeoxyglucose-positron emission tomography (FDG-PET) positive areas (gross tumor volume [GTV]-PET) for patients with progressive malignant pleural mesothelioma (MPM) after previous treatments.
METHODS AND MATERIALS:
From May 2006 to April 2014, 51 patients with a median age of 68.8 years (range, 38.6-82 years) were treated. There were 41 men and 10 women; 43 epithelioid MPM and 8 sarcomatoid, involving the left pleura in 25 patients and the right pleura in 26 patients. The initial stage was: I, 11 patients; II, 14 patients; III, 17 patients; and IV, 9 patients. Chemotherapy was prescribed for 46 patients, for 6 cycles (range, 0-18 cycles). Eighteen patients had pleurectomy/decortication, and 33 had talc pleurodesis. FDG-PET was used for target identification. A median dose of 56 Gy/25 fractions was prescribed to the involved pleura, and SIB to 62.5 Gy to GTV-PET was added in 38 patients.
RESULTS:
The median survival from diagnosis was 25.8 months (range, 8.4-99.0 months). One patient, treated with SIB, was alive at the October 2017 follow-up. Two cases of grade 5 radiation pneumonitis were registered. A GTV-PET ≤ 205 cc was predictive of late ≥ grade 2 lung toxicity, but also of better survival in stage III and IV disease: 5.9 versus 11.7 months (P = .04). A GTV-PET ≥ 473 cc was predictive of early death (P = .001).
CONCLUSIONS:
Moderately hypofractionated, FDG-PET guided salvage HT in patients with progressive MPM after previous treatments showed acceptable toxicity and outcome results similar to adjuvant radiotherapy after pleurectomy/decortication, suggesting that the delay of radiotherapy is not detrimental to survival, and has the associated benefit of postponing inherent toxicity.zio N

Clinical Lung Cancer 2018 September 3 [Link]

Fodor A, Broggi S, Incerti E, Dell’Oca I, Fiorino C, Samanes Gajate AM, Pasetti M, Cattaneo MG, Passoni P, Gianolli L, Calandrino R, Picchio M,

Abstract

Annals of Gastroenterology 2018 Nov-Dec [Link]

Boussios S, Moschetta M, Karathanasi A, Tsiouris AK, Kanellos FS, Tatsi K, Katsanos KH, Christodoulou DK

Abstract

Malignant peritoneal mesothelioma (MPM) is a rare disease with a wide clinical spectrum. It arises from the peritoneal lining and commonly presents with diffuse, extensive spread throughout the abdomen and, more rarely, metastatic spread beyond the abdominal cavity. Computed tomography, magnetic resonance imaging and positron-emission tomography are important diagnostic tools used for the preoperative staging of MPM. The definitive diagnosis is based on histopathological analysis, mainly via immunohistochemistry. In this regard, paired-box gene 8 negativity represents a useful diagnostic biomarker for differentiating MPM from ovarian carcinoma. In addition, BRCA1-associated protein-1 (BAP1) loss is specific to MPM and allows it to be distinguished from both benign mesothelial lesions and ovarian serous tumors. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has become an increasingly important therapeutic approach, while systemic therapies are still being developed. Histology, Ki-67, completeness of cytoreduction, age, sex, and baseline thrombocytosis are commonly used to optimize patient selection for CRS with HIPEC. Additionally, it is well recognized that, compared to other subtypes, an epithelial morphology is associated with a favorable prognosis, whereas baseline thrombocytosis predicts an aggressive biologicalbehavior. Platelets and other immunologic cytokines have been evaluated as potential novel therapeutic targets. Epigenetic modifiers, including BAP1, SETD2 and DDX3X, are crucial in mesothelial tumorigenesis and provide opportunities for targeted treatment. Overexpression of the closely interacting phosphoinositide 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR) pathways appears crucial in regulation of the malignant phenotype. The use of targeted therapies with PI3K-mTOR-based inhibitors requires further clinical assessment as a novel approach.

Medicine 2018 November [Link]

Du Z, Yu Y, Wu D, Zhang G, Wang Y, He L, Meng R

Abstract

RATIONALE:
Malignant Pleural Mesothelioma (MPM) is rare cancer and has a poor prognosis with resistance to chemotherapy or radiotherapy. Until now there is no standard third-line treatment for patients who have failed second-line therapy.
PATIENT CONCERNS:
A 58-year-old non-smoking female peasant of ethnic Han was admitted to the oncology department of the 363 Hospital with a primary complaint of chest tightness and breathlessness from 3 months ago.
DIAGNOSES:
Positron emission tomography-computed tomography (PET/CT) examination showed “dirty” pleural and parietal pleural involvement as well as mediastinal and pulmonary hilar lymph node enlargement. Finally, cancer cells were seen after repeated pleural effusion cell examination. Immunohistochemistry confirmed epithelioid of pleural mesothelioma.
INTERVENTIONS:
Apatinib as a third-line treatment after failure from pemetrexed/cisplatin (PC) as the first-line chemotherapy and gemcitabine/cisplatin (GP) as the second-line chemotherapy. At first, 250 mg/day was given and 1 week later, the dose was increased to 500 mg/day.
OUTCOMES:
A 5-month progression-free survival was achieved and toxicity included severe hand-foot syndrome, mild proteinuria, and hypertension.
LESSONS:
Apatinib may be a potential therapeutic drug for MPM, particularly as a third-line treatment in cases resistant to chemotherapeutic options.

BioMed Research International 2019 December 20 [Link]

Pehlivan B, Sengul K, Yesil A, Nalbant N, Ozturk O, Ozdemir Y, Topkan E

Abstract

OBJECTIVE:

To compare volumetric arc therapy (VMAT) and helical tomotherapy (HT) plans in terms of dosimetric parameters in positron emission tomography- (PET-) computerized tomography- (CT-) based radiation therapy planning in unresectable malignant pleural mesothelioma (MPM).

METHODS:

CT and coregistered PET-CT data from seven patients with histologically-proven MPM were utilized for VMAT and HT plans. Target volumes and organs at risk (OARs) were delineated. The prescription doses for planning target volume 1 (PTV₁) and PTV₂ were 45.0 Gy and 54 Gy in 1.8 Gy/fr, respectively. Each technique was evaluated in terms of target volume coverage and OAR doses.

FINDINGS:

Although the maximum (p=0.001) and mean (p < 0.001) doses of PTV₁, and PTV₂ (p < 0.001 for maximum and p=0.001 for mean doses) favored the HT technique over VMAT, both techniques efficiently covered the target volumes. Additionally, HT also provided more homogeneous dose distribution (p < 0.001) and numerically lower doses received by most OARs, but again both rotational techniques were successful in keeping the OAR doses below the universally accepted limits. The major disadvantage of the HT technique was the requirement for longer treatment times (7.4 versus 2.5 minutes/fr; p < 0.001) to accomplish the intended treatment.

CONCLUSION:

Results of this dosimetric comparison clearly demonstrated the possibility of safe hemithoracic irradiation of medically/technically unresectable MPM patients with either of the two rotational RT techniques, namely the VMAT and HT. Clinically, considering their poor prognosis, these promising findings may open a potential new window for curative treatment of unresectable MPM patients, if further confirmed by future clinical studies.

Interactive Cardiovascular and Thoracic Surgery 2020 January 31 [Link]

Lococo F, Rena O, Torricelli F, Filice A, Rapicetta C, Boldorini R, Paci M, Versari A

Abstract

Although 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) scan has been generally validated in the staging of malignant pleural mesothelioma (MPM), its diagnostic and prognostic performances are not clearly established. Aiming to identify possible factors causing 18F-fluorodeoxyglucose PET/CT false-negative results and influencing prognosis in MPM patients, we analysed clinical, radiometabolic and pathological features in 141 MPM patients who underwent diagnostic 18F-fluorodeoxyglucose PET/CT scan (January 2009-July 2018) at 2 high-volume institutions. The Fisher’s exact test and the Cox model were used in statistical analysis. Overall detection rate was 88.3% with 16 patients (11.6%) presenting with a standardized uptake value (SUV) max <2.5 (PET-negative). PET-negative cases were more frequently detected in older patients (P = 0.027) and early-stage tumours (33.3% false-negative in stage I and 40.0% false-negative in T1-tumours, with P = 0.014 both). Mean SUVmax value was higher in sarcomatoid (11.8 ± 4.6) and biphasic MPM (9.3 ± 7.0), rather than in epithelioid MPM (6.9 ± 3.8, P < 0.001). Concerning overall survival, SUVmax (both as continuous and as categorical variable) was found to be a prognostic factor, in addition to stage (P = 0.032) and histology (P = 0.014) as confirmed by multivariable analysis (hazard ratio 2.65, confidence interval 1.23-5.70; P < 0.001). In the light of such results, we highlight that a low fluorodeoxyglucose uptake might be observed in more than 10% MPMs, especially in early-stage tumours affecting elderly patients. Furthermore, high SUVmax values significantly correlated with a worse prognosis.

Medicine 2020 May 29 [Link]

Hiroaki Ikushima, Toshio Sakatani, Sayaka Ohara, Hideyuki Takeshima, Hajime Horiuchi, Teppei Morikawa, Kazuhiro Usui

Abstract

Rationale: Malignant peritoneal mesothelioma is a rare tumor with a poor prognosis and has no recommended therapy after first-line pemetrexed and platinum-based chemotherapy. Moreover, effects of immune checkpoint inhibitors on peritoneal mesothelioma remains to be elucidated. We herein report the case of a 75-year-old man with peritoneal mesothelioma treated with cisplatin plus pemetrexed and subsequent nivolumab.

Patient concerns: A 75-year-old man was referred to our hospital due to lower abdominal pain.

Diagnosis: Positron emission tomography-computed tomography (CT) showed the accumulation of fluorodeoxyglucose in an intraperitoneal mass. A histological examination of a laparoscopic biopsy specimen revealed malignant peritoneal mesothelioma.

Interventions: After 4 cycles of cisplatin plus pemetrexed and 13 subsequent cycles of pemetrexed maintenance therapy showed beneficial responses until CT revealed liver metastasis. Nivolumab was then administered as the second-line therapy.

Outcomes: After 3 cycles of biweekly nivolumab administration, he developed severe abdominal distention. CT revealed an intraperitoneal mass growing much more rapidly than ever, indicating hyperprogressive disease after nivolumab treatment. He ultimately died 51 days after the initial nivolumab administration.

Lessons: To our knowledge, this is the first report of hyperprogressive disease in a case of peritoneal mesothelioma after nivolumab treatment. While immune checkpoint inhibitors may be promising therapeutic strategies for treating malignant peritoneal mesothelioma, careful monitoring must be practiced with their application.