A randomised phase II study of extended pleurectomy/decortication (e-PD) preceded or followed by chemotherapy in patients (pts) with early-stage pleural mesothelioma (PM): EORTC 1205.

BACKGROUND: The role of surgery in pleural mesothelioma remains controversial. It may be appropriate in highly selected patients as part of a multimodality treatment including chemotherapy. Recent years have seen a shift from extrapleural pleuropneumonectomy toward extended pleurectomy/decortication. The most optimal sequence of surgery and chemotherapy remains unknown. METHODS: EORTC-1205-LCG was a multi-centric, non-comparative phase 2 trial, 1:1 randomising between immediate (arm A) and deferred surgery (arm B), followed or preceded by chemotherapy. Eligible patients (ECOG 0-1) had treatment-naïve, borderline resectable T1-3 N0-1 M0 mesothelioma of any histology. Primary outcome was rate of success at 20 weeks, a composite endpoint containing (1) successfully completing both treatments within 20 weeks; (2) being alive with no signs of progressive disease; and (3) no residual grade 3-4 toxicity. Secondary endpoints were toxicity, OS, PFS, and process indicators of surgical quality. FINDINGS: 69 patients were included in this trial. 56 patients (81%) completed 3 cycles of chemotherapy and 58 patients (84%) underwent surgery. Of the 64 patients in the primary analysis, 21/30 patients in arm A (70.0%; 80% CI: 56.8-81.0) and 17/34 patients (50.0%; 80% CI: 37.8-62.2) in arm B reached the statistical endpoint for rate of success. Median progression-free survival and overall survival were 10.8 [95% CI 8.5-17.2] and 27.1 months [95% CI 22.6-64.3] in arm A, and 8.0 [95% CI 7.2-21.9] and 33.8 months [95% CI 23.8-44.6] in arm B. Macroscopic complete resection was obtained in 82.8% of patients. 30- and 90-day mortality were both 1.7%. No new safety signals were found, but treatment-related morbidity was high. INTERPRETATION: EORTC 1205 did not succeed in selecting a preferred sequence of pre- or postoperative chemotherapy. Either procedure is feasible with a low mortality, albeit consistent morbidity. A shared informed decision between surgeon and patient remains essential.

Resource Oriented Decision Making for Treatment of Metastatic Colorectal Cancer (mCRC) in a Lower-Middle Income Country: Egyptian Foundation of Medical Sciences (EFMS) Consensus Recommendations 2020.

PURPOSE: Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide and the second cause of cancer related mortality. Treatment options for patients with metastatic CRC (mCRC) expanded during the last two decades, with introduction of new chemotherapeutic and targeted agents. Egypt is a lower middle-income country; Egyptian health care system is fragmented with wide diversity in drug availability and reimbursement policies across different health care providing facilities. We report the results of consensus recommendations for treatment of patients with metastatic colorectal cancer developed by Egyptian Foundation of Medical Sciences (EFMS), aiming to harmonize clinical practice through structured expert consensus-based recommendations consistent with the national status. EFMS recommendations could be utilized in other countries with similar economic status. METHODS: EFMS recommendations were developed using a modified Delphi process, with three rounds of voting till the final recommendations were approved. A non-systematic review of literature was conducted before generating the provisional statements. Content experts were asked to vote on some recommendations in two different resource groups (restricted resources and non-restricted resources). External review board of experts from a low income and lower-middle countries voted on the applicability of EFMS recommendations in their countries. RESULTS: The current recommendations highlighted the discrepancy in health care between restricted and non-restricted resources with expected survival loss and quality of life deterioration. Access to targeted agents in first line is very limited in governmental institutions, and no access to agents approved for third line in patients who failed oxaliplatin and irinotecan containing regimens for patients treated in restricted resource settings. CONCLUSION: Management of mCRC in developing countries is a challenge. The currently available resource-stratified guidelines developed by international cancer societies represent a valuable decision-making tool, adaptation to national status in each country based on healthcare system status is required.

Micro RNA-148a Targets Bcl-2 in Patients with Non-Small Cell Lung Cancer.

OBJECTIVE: Lung cancer is one of the most prevalent cancers and the leading cause of cancer-related deaths worldwide. MicroRNAs regulate more than 60% of human genes, including tumor suppressor genes and oncogenes. Accordingly, they can affect cancer risk. This study aimed to evaluate the role of serum miR-148a as a non-invasive biomarker in non-small cell lung cancer (NSCLC) patients and to assess the correlation between miR-148a and Bcl-2, as one of its target proteins. MATERIALS AND METHODS: A total of 50 newly diagnosed NSCLC cases and 30 apparently healthy controls were recruited in this study. MiR-148a level was measured by TaqMan- Real time RT-PCR assay and Bcl-2 level was measured by ELISA. RESULTS: Significant lower expression of serum miR-148a and higher serum Bcl-2 levels were observed in NSCLC patients as compared to the control group (p.

Cardiotoxicity with immune system targeting drugs: a meta-analysis of anti-PD/PD-L1 immunotherapy randomized clinical trials.

Background: With antiprogrammed death receptor-1 (anti-PD-L1) therapy, a recent meta-analysis reported higher incidence of cutaneous, endocrine and gastrointestinal complications especially with dual anti-PD-L1 immunotherapy (IMM). Methods: Our primary outcome was assessment of all cardiotoxicity grades in IMM compared with different treatments, thus a systemic review and a meta-analysis on randomized clinical trials (RCTs) were done. Results: We included 11 RCTs with 6574 patients (3234 patients in IMM arm vs 3340 patients in the other arm). Three non-small-cell lung cancer RCTs, seven melanoma RCTs and only one prostatic cancer RCT met the inclusion criteria. There were five RCTs that compared monoimmunotherapy to chemotherapy "(n = 2631 patients)". No difference exists in all cardiotoxicity grades or high-grade cardiotoxicity (p > 0.05). Lung cancer exhibited a higher response rate and lower mortality in IMM. Conclusion: There was no reported statistically significant cardiotoxicity associated with anti-PD/PD-L1 use. Lung cancer subgroups showed better response and survival rates.

Pneumonitis as a complication of immune system targeting drugs?-a meta-analysis of anti-PD/PD-L1 immunotherapy randomized clinical trials.

BACKGROUND: Anti-PD/PD-L1-targeted immunotherapy is associated with remarkably high rates of durable clinical responses in patients across a range of tumor types, although their high incidence of skin, gastrointestinal, and endocrine side effects with their use. The risk of pneumonitis associated with checkpoint inhibition therapy is not well described. METHODS: A systematic review of the literature was conducted on randomized clinical trials (RCTs) comparing anti-PD/PD-L1 mono-immunotherapy (IMM) to chemotherapy (CTH) protocols in cancer patients. The primary endpoint was the pneumonitis rate in IMM compared to CTH. Secondary endpoints were (I) high-grade pneumonitis rate in IMM compared to CTH and (II) tumor response rate, progression-free survival (PFS), and overall survival (OS) between IMM and CTH. Random model and leave-one-out-analysis were performed. RESULTS: Thirteen RCTs studying 7,246 patients were included; 3,704 (51.12%) patients in the IMM arm and 3,542 (48.88%) patients in the chemotherapy arm. Seven non-small cell lung cancer (NSCLC) RCTs were included with 4,164 patients; 2,101 in the IMM arm and 2,063 patients in the CTH arm. Three RCTs were on melanoma patients (n=1,390). Nine RCTs compared mono-immunotherapy to CTH [docetaxel in 5 studies (38.5%), platinum-based in 2 studies (15.4%), dacarbazine in 1 study (7.7%) and everolimus in 1 study]. Both high-grade and all-grade pneumonitis were higher among patients in the IMM arm when compared to the CTH arm (OR =4.39, 95% CI: 1.65-11.69, P=0.003 and OR =2.46, 95% CI: 1.29-4.6, P=0.007). Tumor response rate was significantly better in the immunotherapy arm (OR =2.31, 95% CI: 1.62-3.29, P<0.001). PFS and OS were longer in patients who received IMM compared to patients in the CTH arm (HR =0.75, 95% CI: 0.65-0.85, P<0.001, and HR =0.71, 95% CI: 0.66-0.77, P<0.001). CONCLUSIONS: The incidence of high-grade and all-grade pneumonitis is higher in anti-PD-1 therapy but not in anti-PD-L1 therapy when compared to traditional CTH regimens for NSCLC and melanoma. High-grade adverse events were otherwise more common in the CTH arm. Tumor response rate, PFS, and OS are all substantially improved with IMM over CTH. These results can be used to guide therapy selection and set expectations for treatment effect in these patients.

Contributing factors to the outcome of primary malignant chest wall tumors.

BACKGROUND: Primary malignant chest-wall tumors (PMCWTs) are a heterogeneous group of tumors. They require a special experience in designing resection and reconstruction. They account for less than 1% of all primary malignant tumors. This study is designed to clarify different factors contributing to the outcome of patients with PMCWTs in our institution. METHODS: A retrospective study included 98 patients with pathology proven PMCWTs, treated at the National Cancer Institute (NCI), Cairo University, Egypt, during the past 10 years. Used variables were: age, sex, forced expiratory volume in the 1st second (FEV1), site, size, multiplicity, pathologic subtype, tumor grade, safety margin (SM), excised ribs, complications, estimated blood loss (EBL), neo-adjuvant and adjuvant treatments, Overall and disease free survival (DFS) were obtained using Kaplan-Meier method and compared using Log rank test. Cox regression was used to identify DFS predictors. RESULTS: PMCWTs represented 10.5% of all thoracic malignancies in our institution. There were 51 females (52%). The median age was 39 years [interquartile range (IQR) =25-52.3)] years. Chondrosarcoma was the commonest tumor histology (20.4%). The median tumor size was 8 cm (IQR =5-14). Tumor multiplicity was found in 18.4% of patients. Bone resection was performed in 76 patients (78.3%), ribs resection was performed in 59 patients and the median number of resected ribs per patient was 3 (IQR =1-3) ribs. Sternal resection was done in 7 (7.1%) cases. R0 resection was achieved in 62.2% of patients. There was one operative related mortality (1.02%) and 17.3% patients suffered procedure related complications. Local recurrence developed in 35 (35.7%) patients. The overall survival (OS) at 1, 3 and 5 years was 73.9%, 45.6% and 34.6% respectively and the median OS was 33 months (95% CI, 21.8-44.2), while median DFS was 24 months (95% CI, 19.6-28.4). Predictors of better DFS were -ve SM (P<0.001), tumors <5 cm (P=0.039), low grade (P=0.033), lower EBL (P=0.003) and absence of adjuvant therapy (P=0.007); however, on multivariate analysis, only -ve SM was the only predictor (HR =0.54; 95% CI, 0.29-0.97, P=0.041). CONCLUSIONS: In primary malignant CWTs (PMCWTs) achievement of wide resection margins is of great importance to minimize the local tumor recurrence that will have an adverse impact on long-term survival.