Colorectal cancer survivorship: A systematic review and thematic synthesis of qualitative research.

INTRODUCTION: With rapid changes in treatments for colorectal cancer (CRC), qualitative research into CRC survivorship requires greater synthesis. This paper aims to fill this gap through a systematic review (PROSPERO CRD42019131576) and thematic synthesis of the qualitative literature on survivorship experiences across early-stage and advanced CRC survivors. METHODS: CINAHL, Embase, MEDLINE, PsycINFO and PubMed were searched for qualitative CRC survivorship papers. Titles, abstracts and full texts were screened. Included articles (n = 81) underwent data extraction, CASP qualitative bias ratings and thematic synthesis. RESULTS: Bowel dysfunction caused functional limitations and negative quality of life (QoL), while stomas posed threats to body image and confidence. Physical symptoms hindered return to work, increasing financial burdens. Survivors' unmet needs included information regarding symptom expectations and management, and ongoing support throughout recovery. Advanced and early-stage survivors shared similar experiences. Advanced survivors struggled with fear of cancer recurrence/progression and feelings of powerlessness. Functional limitations, financial impacts and sexuality in advanced survivors were underexplored areas. CONCLUSION: CRC and its treatments impact survivors' QoL in all areas. A coordinated supportive care response is required to address survivors' unmet needs. Future qualitative studies should explore advanced CRC subpopulations, treatment-specific impacts on QoL and long-term (>5 years) impacts on CRC survivors.

Estimation of an optimal chemotherapy utilization rate for malignant pleural mesothelioma: an evidence-based benchmark for cancer care.

AIMS: Chemotherapy with cisplatin and pemetrexed has been shown to provide a survival benefit and improvement in quality of life in patients with malignant pleural mesothelioma (MPM). The reported chemotherapy utilization rates range from 18% to 61%. This study aimed to estimate the proportion of MPM patients that should receive chemotherapy based on best available evidence. METHODS: An optimal chemotherapy utilization model for MPM was constructed using indications for chemotherapy identified from evidence-based MPM treatment guidelines. Epidemiological data on the proportion of patients and their tumor-related attributes were combined with the chemotherapy indications to estimate the optimal chemotherapy utilization rate using decision analysis software (TreeAge Pro 2007). Sensitivity analyses were performed to assess the impact of major variations in the epidemiological data on the optimal chemotherapy utilization rate. The optimal rate was compared with the actual rate reported in the literature. RESULTS: Chemotherapy is recommended at least once during the disease trajectory in 65% of MPM patients. Sensitivity analyses indicate an optimal utilization rate ranging from 50% to 65%. This optimal rate is relatively comparable to the rates mentioned in contemporary reports from Canada (61% between 2003 and 2005) and Australia (54% between 2007 and 2009) and high when compared with data from the Netherlands (36% during 2005-2006). CONCLUSION: An evidence-based model provided an optimal chemotherapy utilization rate of 65% for patients with MPM. Chemotherapy for MPM may be underutilized and barriers are likely multifactorial.

The predictive role of serum VEGF in an advanced malignant mesothelioma patient cohort treated with thalidomide alone or combined with cisplatin/gemcitabine.

There is a need for new treatment strategies and prognostic markers for the management of malignant mesothelioma (MM). The activity of thalidomide/cisplatin/gemcitabine (arm A) or thalidomide alone (arm B) was investigated in two parallel phase II studies in patients with advanced MM, using 6 month progression free survival (PFS) as the principal end-point. The predictive role of pre-treatment and 8 week follow-up serum C-reactive protein (CRP), interlukin-6 (IL-6), interlukin-6 soluble receptor (sIL-6R), mesothelin (SMRP) and vascular endothelial growth factor (VEGF) was also assessed. The proportion of patients with stable disease for >6 months was similar in both studies (arm A 35%, arm B 29%) and toxicity was mainly grade I/II. In univariate analyses only pre-treatment VEGF and CRP were correlated with survival. At 8 weeks post treatment, increased survival was found with low (median) VEGF and CRP (P<0.05). Change in VEGF over the first 8 weeks of treatment was also predictive for survival (P<0.05). When pre-treatment VEGF was >median, decreasing VEGF was associated with increased survival (P<0.05). In conclusion, thalidomide alone, or in combination with cisplatin/gemcitabine, controlled disease for >6 months in ∼30% of patients. Patients with decreasing VEGF during treatment had longest survival. Pre-treatment VEGF or CRP and early change in VEGF on treatment may predict treatment benefit and should be examined in future studies.

Aquaporin 1 is an independent prognostic factor in pleural malignant mesothelioma.

BACKGROUND: Malignant mesothelioma (MM) is an aggressive cancer of serosal membranes, mostly pleura. It is related to asbestos exposure and its incidence in most industrialized countries is projected to remain stable or to increase until 2020. Prognosis remains poor. Clinical prognostic scoring systems lack precision. No prognostic tissue markers are available. Aquaporin 1 (AQP1) is a cell membrane channel involved in water transport, cell motility, and proliferation. A blocker and an agonist are available. METHODS: Two independent cohorts of MM were studied. Cohort 1 consisted of 80 consecutive patients who underwent radical surgery (extrapleural pneumonectomy [EPP]). Cohort 2 included 56 conservatively managed patients from another institution. Clinical information was obtained from files. Diagnoses were histologically verified. Immunohistochemical labeling for AQP1 was performed on tumor tissue and the percentage of positive cells was scored. RESULTS: We demonstrated expression of AQP1 in normal and neoplastic mesothelium at the apical aspect of the cell, in keeping with a role in water transport. For both cohorts, expression of AQP1 by ≥50% of tumor cells was associated with significantly enhanced survival (9.4 months vs 30.4 months in EPP patients and 5 months vs 15 months in conservatively treated patients). This was independent of established prognostic factors, including histologic subtype, pathologic stage, sex, and age at time of diagnosis. CONCLUSION: Expression of AQP1 correlated significantly with prognosis in MM, irrespective of treatment or established prognostic factors. Immunohistochemical labeling for AQP1 should be included in the routine histopathologic workup. An agonist or blocker may become useful for treatment.

Low calretinin expression and high neutrophil-to-lymphocyte ratio are poor prognostic factors in patients with malignant mesothelioma undergoing extrapleural pneumonectomy.

INTRODUCTION: Survival after extrapleural pneumonectomy (EPP) is variable in patients with malignant pleural mesothelioma (MPM), and there are no validated prognostic factors that could be used preoperatively. We investigated the calretinin and D2-40 expression and the neutrophil-to-lymphocyte ratio (NLR), an index of systemic inflammation as potential preoperative prognostic factors. METHODS: Consecutive patients who underwent EPP were included in this retrospective study. Potential prognostic factors such as age, gender, histological subtype, baseline laboratory parameters including NLR, and immunohistochemical staining for calretinin and D2-40 were evaluated. Overall survival (OS) from the date of surgery was determined by the Kaplan-Meier method. The prognostic value of the variables was examined using Cox regression, and significant factors (p < 0.05) were entered into a multivariate model to determine their independent effect. RESULTS: A total of 85 patients were included: median age 58 years; 80% men; 77% epithelial and 23% biphasic MPM. The median OS was 19.7 months. The following variables were predictive of longer OS: female gender (p = 0.02), epithelial subtype (p = 0.04), low NLR (p < 0.01), and high calretinin score (p < 0.001). In a multivariate analysis, only NLR ≥3 (hazard ratio 1.79; 95% confidence interval: 1.04-3.07; p = 0.04) and calretinin score ≤33 versus more than 67% (hazard ratio 4.72; 95% confidence interval: 1.97-11.32; p < 0.01) remained independent predictors. The addition of calretinin score increased the explained variation by 10.1%. CONCLUSIONS: Both low calretinin expression and high NLR were independently associated with poor prognosis in patients with MPM undergoing EPP, and the calretinin score seemed to improve the accuracy of the prognostic model.

Validation of a minimal panel of antibodies for the diagnosis of malignant pleural mesothelioma.

AIMS: We previously established the use of a minimal panel of antibodies as sufficient to diagnose most epithelial malignant mesothelioma (MPM). We aimed to validate this approach and investigate the utility of a D2-40 antibody. METHODS: A series of 80 MPM patients selected for surgery and 21 consecutive patients with pleural metastatic carcinoma were included. A minimal panel of antibodies, consisting of calretinin, BG8 and CD15, and D2-40 was investigated. RESULTS: There were 61 epithelial and 19 biphasic MPM as well as 12 metastatic lung, six breast (5 ductal adenocarcinomas, 1 mixed ductal/lobular adenocarcinoma), two serous papillary ovarian carcinomas and one moderately differentiated colorectal adenocarcinoma. The sensitivity of positive calretinin labelling to confirm the diagnosis of MPM was 97.5%, while the 'diagnostic sensitivities' of lack of labelling for BG8 and CD15 were 91.3% and 97.5%, respectively. The use of calretinin, BG8 and CD15 resulted in correct classification in 97.5% of all MPMs. All MPM cases investigated showed at least focal positive D2-40 labelling. CONCLUSIONS: We have validated the usefulness of a minimal panel of antibodies with calretinin, BG8 and CD15 as the initial step to the diagnosis of MPM. D2-40 emerged as a helpful diagnostic tool for cases where our initial approach failed to conclusively diagnose MPM.

Molecular biomarkers in malignant mesothelioma: state of the art.

Malignant mesothelioma (MM) is an aggressive tumour affecting the mesothelial surfaces of the pleural and peritoneal cavities and, rarely, the pericardium and the tunica vaginalis testis. Despite a ban of asbestos in many industrialised nations, the present high incidence of MM is expected to continue, due to the long latency period between first asbestos exposure and occurrence of disease, making it an important health issue for the future. The diagnosis of MM can be difficult, both from a clinical and pathological perspective. It is not unusual for patients to undergo several medical investigations without definitive diagnosis early in their course of illness. Understandably, there is intense interest in the discovery of markers that can be assessed in pleural effusions, histological specimens, and serum to assist with the difficult early diagnosis of MM. Considering the primary aetiological role of asbestos, there is theoretically an easily identifiable target population for screening with a biomarker with adequate sensitivity and specificity or with a combination of biomarkers. In this review we focus on biomarkers that have been examined in the setting of either early diagnosis of MM in symptomatic patients or screening of asbestos-exposed individuals.

Accuracy of diagnostic biopsy for the histological subtype of malignant pleural mesothelioma.

INTRODUCTION: Histological subtype is an established prognostic factor in malignant pleural mesothelioma (MPM). We retrospectively investigated the accuracy of classifying histological subtype on diagnostic biopsies and examined the impact of different diagnostic procedures on the outcome. METHODS: Consecutive patients with histologically confirmed MPM who underwent extrapleural pneumonectomy (EPP) from 1994 to 2009 were included. Patient records were reviewed, and the initial diagnoses of histological subtype were obtained. The archival EPP specimens were reviewed by a panel of pathologists. The histological subtype obtained at review was compared with the initial diagnosis. RESULTS: Eighty-five patients underwent EPP. Two patients achieved a pathological complete response after neoadjuvant chemotherapy, leaving 83 patients to be included in this review. Different diagnostic methods were used before EPP: 81% thoracoscopy; 7% thoracotomy; 11% computed tomography-guided procedure; and 1% other. Patients determined to have an epithelial subtype (n = 64) at EPP were diagnosed correctly at initial diagnostic biopsy in 84% of cases, whereas patients considered to have a biphasic subtype (n = 19) at EPP were diagnosed correctly at diagnostic biopsy in 26% of cases. The sensitivity and specificity of diagnostic biopsy for epithelial MPM was 93% and 31%, respectively. The overall subtype misclassification rate was 20%. Biopsy by thoracotomy was most accurate in subtype classification (83%) compared with thoracoscopy (74%) and computed tomography-guided procedure (44%). CONCLUSIONS: The determination of histological subtype from a diagnostic biopsy is difficult due to sampling error, but an adequate specimen obtained from surgical biopsy increases the accuracy of subtype classification compared with radiological-guided biopsies.