Juliet King

Intracavitary ‘T4 immunotherapy’ of malignant mesothelioma using pan-ErbB re-targeted CAR T-cells

Malignant mesothelioma remains an incurable cancer. We demonstrated that mesotheliomas expressed EGFR (79.2%), ErbB4 (49.0%) and HER2 (6.3%), but lacked ErbB3. At least one ErbB family member was expressed in 88% of tumors. To exploit ErbB dysregulation in this disease, patient T-cells were engineered by retroviral transduction to express a panErbB-targeted chimeric antigen receptor (CAR), co-expressed with a chimeric cytokine receptor that allows interleukin (IL)-4 mediated CAR T-cell proliferation. This combination is referred to as T4 immunotherapy. T-cells from mesothelioma patients were uniformly amenable to T4 genetic modification and expansion/enrichment thereafter using IL-4. Patient-derived T4+ T-cells were activated upon contact with a panel of four mesothelioma cell lines, leading to cytotoxicity and cytokine release in all cases. Adoptive transfer of T4 immunotherapy to SCID Beige mice with an established bioluminescent LO68 mesothelioma xenograft was followed by regression or eradication of disease in all animals. Despite the established ability of T4 immunotherapy to elicit cytokine release syndrome in SCID Beige mice, therapy was very well tolerated. These findings provide a strong rationale for the clinical evaluation of intracavitary T4 immunotherapy to treat mesothelioma.

Tracheobronchial stenting for malignant airway disease: long-term outcomes from a single-center study.

The aim of this retrospective study is to investigate the immediate and long-term outcomes following the insertion of covered and uncovered self-expandable metallic stent (SEMS) for the management of malignant tracheobronchial disease. A total of 49 patients (27 male, mean age 60.9 ± 15 years) underwent 77 SEMS insertions (57 uncovered). The procedure was performed in theater using combined bronchoscopic and fluoroscopic guidance. The study’s primary end points included technical success (97.9%), clinical success (91.8%), and symptom recurrence (14.2%). The mean follow-up time was 5.5 ± 5.9 months. We concluded that tracheobronchial SEMSs provide safe and effective minimally invasive long-term management of patients with symptomatic malignant airway disease.

New-onset atrial fibrillation after anatomic lung resection: predictive factors, treatment and follow-up in a UK thoracic centre

ObjectivesnPostoperative atrial fibrillation (POAF) increases morbidity, hospital stay and healthcare expenditure. This study aims to determine the perioperative factors correlating with POAF as well as to evaluate both treatment strategies and AF persistence beyond discharge.nnnMethodsnThe records of all patients undergoing anatomical lung resection over a 1-year period were retrospectively reviewed. Patients with a history of arrhythmia were excluded. POAF was defined by clinical diagnosis and electrocardiography. Pre- and postoperative demographic and clinical data were collected, and uni- and multivariable regression were performed to determine the factors associated with POAF.nnnResultsnPOAF occurred in 11.4% (43/377) of patients with a mean of 3.55 days postoperatively and significantly increased hospital stay (6.78 ± 4.42 vs 10.8 ± 5.8 days (P = 0.0014)). No correlation was found with gender, hypertension, ischaemic heart disease, beta-blocker use, alcohol consumption or thyroid dysfunction. However, older age (P = 0.001) and postoperative infection (P < 0.0001; χ2 = 26.03) were found to be significant uni- and multivariable predictors of POAF. Open surgery rather than video assisted thoracoscopic surgery (VATS) (open 26/189 (13.8%); VATS 17/188 (9.0%); P = 0.150) demonstrated a tendency towards increased postoperative AF; however, this was not statistically significant. Four (9.3%) patients remained in AF on discharge, and three required long-term anticoagulation. Three (7%) patients were found to have ongoing AF at 1-month follow-up.nnnConclusionsnIncreasing age and postoperative infection are most strongly associated with POAF. Adoption of enhanced recovery protocols, along with more rigorous monitoring and early treatment of postoperative infection may help reduce POAF and its associated morbidity. Rhythm assessment is crucial to identify persistent AF after discharge, and clinicians should be vigilant for recurrence of AF at follow-up.

Sorafenib for the Treatment of Advanced Hepatocellular Cancer – a UK Audit

AIMSnSorafenib is the current standard treatment for advanced hepatocellular carcinoma. We carried out a national audit of UK patients treated with sorafenib as standard-of-care and those treated with systemic therapy in first-line trials.nnnMATERIALS AND METHODSnSorafenib-treated and trial-treated patients were identified via the Cancer Drugs Fund and local databases. Data were collected retrospectively from medical records according to a standard case report form. The primary outcome measure was overall survival, estimated by the Kaplan-Meier method.nnnRESULTSnData were obtained for 448 sorafenib-treated patients from 15 hospitals. The median age was 68 years (range 17-89) and 75% had performance status ≤ 1. At baseline, 77% were Child-Pugh A and 16.1% Child-Pugh B; 38% were albumin-bilirubin grade 1 (ALBI-1) and 48% ALBI-2; 23% were Barcelona Clinic Liver Classification B (BCLC-B) and 72% BCLC-C. The median time on sorafenib was 3.6 months, with a mean daily dose of 590xa0mg. The median overall survival for 448 evaluable sorafenib-treated patients was 8.5 months. There were significant differences in overall survival comparing Child-Pugh A versus Child-Pugh B (9.5 versus 4.6 months), ALBI-1 versus ALBI-2 (12.9 versus 5.9 months) and BCLC-B versus BCLC-C (13.0 versus 8.3 months). For trial-treated patients (n=109), the median overall survival was 8.1 months and this was not significantly different from the sorafenib-treated patients.nnnCONCLUSIONnFor Child-Pugh A patients with good performance status, survival outcomes were similar to those reported in global randomised controlled trials. Patients with ALBI grade > 1, Child-Pugh B or poor performance status seem to derive limited benefit from sorafenib treatment.

Thoracotomy and decortication: impact of culture-positive empyema on the outcome of surgery

OBJECTIVESnThis study aimed to assess the efficacy of thoracotomy and decortication (T/D) in achieving lung re-expansion in patients with Stage III empyema and assess the impact of culture-positive empyema on the outcome of decortication.nnnMETHODSnThis is a retrospective observational study of consecutive patients treated with T/D over a 6-year period.nnnRESULTSnA total of 107 consecutive patients were identified. The median age was 55 (range 16-86) years; of which, 86% were male. The median length of hospital stay was 9 (range 2-45) days. Full lung re-expansion was achieved in 86% of cases. There were no postoperative deaths. Pleural cultures were positive in 56 (52%) cases. Patients with culture-positive empyema had a longer duration of pleural drainage (median of 11 days, range 3-112 versus median of 5 days, range 3-29 days for negative culture; P = 0.0004), longer length of hospital stay (median of 11 days, range 4-45 versus median of 7 days, range 2-34 days; P = 0.0002) and more complications (P = 0.0008), respectively. There was no statistically significant difference in the outcome of surgery, i.e. lung re-expansion versus trapped lung (P = 0.08) between the two groups.nnnCONCLUSIONSnT/D is safe and achieved lung re-expansion in the majority of patients. Culture-positive empyema was associated with worse outcomes.

A rare case of high-grade serous ovarian epithelial carcinoma presenting as an isolated cystic mediastinal mass: a case report and brief review of the literature

A 70-year-old woman presented with a 2-year history of increasing breathlessness. Computed tomography (CT) of the chest confirmed a well-defined cystic lesion abutting the mediastinum in the right hemi thorax measuring 8 x 6 cm. She underwent a right thoracotomy to excise the cystic lesion. Biopsies for histology demonstrated metastatic serous ovarian epithelial carcinoma. We report a very unusual primary presentation of ovarian epithelial carcinoma as a single cystic mediastinal mass. We also include a brief review of the literature.

Prognostic factors including lymphovascular invasion on survival for resected non–small cell lung cancer

Objectives The aim of this study was to report on the influence of tumor lymphovascular invasion on overall survival and in patients with resected non–small cell lung cancer and identify prognostic factors for survival. Methods This is a retrospective observational study of a consecutive series of patients who had surgical resection of non–small cell lung cancer in a single institution. The study covers a 3‐year period. Overall survival was estimated by Kaplan‐Meier method and multivariate Cox regression analysis was used to evaluate the relationship of lymphovascular invasion and other clinicopathologic variables. A multivariate regression was used to assess the relationship between tumor lymphovascular invasion and other clinical and pathologic characteristics. Results A total of 524 patients were identified and included in the study. Two hundred twenty‐five patients (43%) had tumors with lymphovascular invasion. Patients with tumor lymphovascular invasion had a lower overall survival (P < .0001). Tumor lymphovascular invasion was independently associated with visceral pleural involvement (P < .0001). In a multivariable model, lymphovascular invasion (hazard ratio [HR], 2.58; 95% confidence interval [CI], 1.63‐4.09; P < .0001), parietal pleural invasion (HR, 45.4; 95% CI, 2.08‐990; P = .015), advanced age (HR, 1.028; 95% CI, 1.009‐1.048; P = .004), and N2 lymph node involvement (HR, 1.837; 95% CI, 1.257‐2.690; P = .002) were independent prognostic factors for lower overall survival. Conclusions Lymphovascular invasion is associated with a worse overall survival in patients with resected non–small cell lung cancer regardless of tumor stage. Parietal pleural involvement, N2 nodal disease, and advanced age independently predict poor overall survival.

Interrupted inferior vena cava: high-risk anatomy for right thoracotomy

Interrupted inferior vena cava (IVC) is a rare developmental defect characterised by azygos continuation following failure of fusion of one or more of the component parts of the embryological IVC and occurring in approximately one in 5000 of the general population. It is usually an isolated finding and generally asymptomatic. We present a case of non-small cell lung cancer requiring right pneumonectomy in a patient with an interrupted IVC with azygos continuation.