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Sophie Papa,
Sanjay Popat,
Riyaz Shah,
A Toby Prevost,
Rohit Lal,
Blair McLennan,
Paul Cane, Loic Lang-Lazdunski,
Zaid Viney,
Joel T Dunn,
Sally Barrington,
David Landau,
James Spicer
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ABSTRACT: INTRODUCTION:: The incidence of mesothelioma is rising. First-line cisplatin and pemetrexed confers a survival benefit, with a median progression-free survival (PFS) of 5.7 months. Sorafenib inhibits tyrosine kinases, including receptors for vascular endothelial growth factor, which are implicated in mesothelioma pathogenesis by preclinical and clinical data. METHODS:: Sorafenib, at 400 mg twice daily, was assessed in a single-arm multicenter phase 2 study, using Simon's two-stage design. Eligible patients had received platinum combination chemotherapy earlier. The primary endpoint was PFS at 6 months, with secondary endpoints, including response rate and metabolic response, assessed using fluorodeoxyglucose positron emission tomography. Published reference values for PFS in mesothelioma provide a benchmark for the null hypothesis of 28% progression-free at 6 months, and for moderate or significant clinical activity of 35% or 43% progression-free at 6 months, respectively. RESULTS:: Fifty-three patients (72%) were treated. Most had epithelioid histology. Ninety-three percent of patients had a performance status 0 or 1. Treatment was well tolerated with few grade 3 or 4 toxicities. Median PFS was 5.1 months, with 36% of patients being progression-free at 6 months. Nine percent of patients remained on study beyond 1 year. Changes in fluorodeoxyglucose positron emission tomography parameters did not predict clinical outcome. CONCLUSIONS:: Sorafenib is well tolerated in patients with mesothelioma after completion of platinum-containing chemotherapy. PFS of sorafenib compares favorably with that reported for other targeted agents, and suggests moderate activity in this disease.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 04/2013; · 4.55 Impact Factor
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Judith M Bliss,
Gill Coombes,
Liz Darlison,
John Edwards,
James Entwisle,
Lucy S Kilburn,
David Landau, Loic Lang-Lazdunski,
Mary O'Brien,
Ken O'Byrne,
Julian Peto,
Suresh Senan,
Michael Snee,
James Spicer,
Carol Tan,
Gill Thomas,
Tom Treasure,
David Waller
The lancet oncology 11/2011; 12(12):1094-5. · 14.47 Impact Factor
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The Journal of thoracic and cardiovascular surgery 07/2011; 142(1):e2-3. · 3.41 Impact Factor
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Tom Treasure, Loic Lang-Lazdunski,
David Waller,
Judith M Bliss,
Carol Tan,
James Entwisle,
Michael Snee,
Mary O'Brien,
Gill Thomas,
Suresh Senan,
Ken O'Byrne,
Lucy S Kilburn,
James Spicer,
David Landau,
John Edwards,
Gill Coombes,
Liz Darlison,
Julian Peto
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ABSTRACT: The effects of extra-pleural pneumonectomy (EPP) on survival and quality of life in patients with malignant pleural mesothelioma have, to our knowledge, not been assessed in a randomised trial. We aimed to assess the clinical outcomes of patients who were randomly assigned to EPP or no EPP in the context of trimodal therapy in the Mesothelioma and Radical Surgery (MARS) feasibility study.
MARS was a multicentre randomised controlled trial in 12 UK hospitals. Patients aged 18 years or older who had pathologically confirmed mesothelioma and were deemed fit enough to undergo trimodal therapy were included. In a prerandomisation registration phase, all patients underwent induction platinum-based chemotherapy followed by clinical review. After further consent, patients were randomly assigned (1:1) to EPP followed by postoperative hemithorax irradiation or to no EPP. Randomisation was done centrally with computer-generated permuted blocks stratified by surgical centre. The main endpoints were feasibility of randomly assigning 50 patients in 1 year (results detailed in another report), proportion randomised who received treatment, proportion eligible (registered) who proceeded to randomisation, perioperative mortality, and quality of life. Patients and investigators were not masked to treatment allocation. This is the principal report of the MARS study; all patients have been recruited. Analyses were by intention to treat. This trial is registered, number ISRCTN95583524.
Between Oct 1, 2005, and Nov 3, 2008, 112 patients were registered and 50 were subsequently randomly assigned: 24 to EPP and 26 to no EPP. The main reasons for not proceeding to randomisation were disease progression (33 patients), inoperability (five patients), and patient choice (19 patients). EPP was completed satisfactorily in 16 of 24 patients assigned to EPP; in five patients EPP was not started and in three patients it was abandoned. Two patients in the EPP group died within 30 days and a further patient died without leaving hospital. One patient in the no EPP group died perioperatively after receiving EPP off trial in a non-MARS centre. The hazard ratio [HR] for overall survival between the EPP and no EPP groups was 1·90 (95% CI 0·92-3·93; exact p=0·082), and after adjustment for sex, histological subtype, stage, and age at randomisation the HR was 2·75 (1·21-6·26; p=0·016). Median survival was 14·4 months (5·3-18·7) for the EPP group and 19·5 months (13·4 to time not yet reached) for the no EPP group. Of the 49 randomly assigned patients who consented to quality of life assessment (EPP n=23; no EPP n=26), 12 patients in the EPP group and 19 in the no EPP group completed the quality of life questionnaires. Although median quality of life scores were lower in the EPP group than the no EPP group, no significant differences between groups were reported in the quality of life analyses. There were ten serious adverse events reported in the EPP group and two in the no EPP group.
In view of the high morbidity associated with EPP in this trial and in other non-randomised studies a larger study is not feasible. These data, although limited, suggest that radical surgery in the form of EPP within trimodal therapy offers no benefit and possibly harms patients.
Cancer Research UK (CRUK/04/003), the June Hancock Mesothelioma Research Fund, and Guy's and St Thomas' NHS Foundation Trust.
The lancet oncology 06/2011; 12(8):763-72. · 14.47 Impact Factor
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ABSTRACT: We report the case of a 69-year-old man presenting with a primary right lung cancer and a complete double aortic arch. An extended right pneumonectomy was successfully performed and the patient remained well at the one-year follow-up. We discuss the surgical approach and the technical considerations imposed by this rare vascular abnormality.
Interactive cardiovascular and thoracic surgery 12/2010; 11(6):862-3.
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ABSTRACT: The optimal treatment for Masaoka stage IVA thymoma remains controversial. Whilst extrapleural pneumonectomy (EPP) has been proposed, we sought to examine the results of our institutional preference for induction chemotherapy, cytoreductive surgery and intraoperative hyperthermic pleural irrigation. We undertook a retrospective study of patients undergoing surgery for Masaoka stage IVA thymoma following induction chemotherapy over a three-year period at our institution. Between February 2007 and February 2010, 42 patients underwent surgery for thymoma. Six patients underwent surgery with intent to perform cytoreductive surgery and intraoperative hyperthermic pleural irrigation. Complete cytoreductive surgery was not feasible in one patient and thymectomy only was performed. One patient had re-operation for recurrent disease 24 months after the first operation and there were therefore seven procedures undertaken in six patients during the study period. There were no in-hospital deaths. Median follow-up was 18.8 months (range 1.5-31.9 months). One patient died 14 months postoperatively from an acute cardiovascular event. The four remaining patients are alive and well with no evidence of disease recurrence. Multimodality therapy consisting of induction chemotherapy and cytoreductive surgery is a safe, feasible treatment for stage IVA thymoma. Our experience suggest that full pleurectomy is an alternative to EPP.
Interactive cardiovascular and thoracic surgery 12/2010; 12(5):744-7.
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Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 06/2010; 5(6):921-3. · 4.55 Impact Factor
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ABSTRACT: A 59-year-old woman presented with a large mediastinal mass. At thoracotomy, the mass was found tightly adherent to the esophageal wall and right lower lobe of the lung. Histological examination showed a solid tumor composed of closely packed nests of cells with clear and eosinophilic cytoplasm, which were strongly and diffusely positive for S100 protein but negative for HMB45 and Melan-A. The diagnosis of clear cell sarcoma was supported by demonstrating the presence of an EWS gene rearrangement by fluorescence in situ hybridization. There was no evidence that this lesion represented metastatic disease. To the best of our knowledge, primary mediastinal clear cell sarcoma has not been previously reported in the literature. We present the case and discuss the differential diagnosis.
Annals of diagnostic pathology 07/2009; 13(3):197-200.
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The Journal of thoracic and cardiovascular surgery 08/2007; 134(1):235-6. · 3.41 Impact Factor
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ABSTRACT: We report the devastating complication of constrictive pericarditis after multimodality therapy including left extrapleural pneumonectomy for malignant pleural mesothelioma. The patient presented with progressive dyspnea, ascites, and peripheral edema 6 months after receiving adjuvant radiotherapy. A diagnosis of constrictive pericarditis was made late in the clinical course after exhaustive investigation to exclude primary disease recurrence. Pericardial decortication was subsequently undertaken 12 months after the initial surgery, but the patient died of multi-organ failure. Our experience, combined with a review of the available literature, leads us to advise a low level of suspicion and early operation to relieve cardiac constriction. Furthermore, these complications emphasize the importance of trials such as the Mesothelioma and Radical Surgery (MARS) study.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 08/2007; 2(7):673-5. · 4.55 Impact Factor
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ABSTRACT: We report a 65-year-old man presenting with recurrent pulmonary metastases 20 years after an appendectomy for mucinous cystadenocarcinoma with pseudomyxomatous peritonei. He underwent bilateral staged metastatectomies for metastases 7 years after the diagnosis and further metastasectomy after a recent recurrence. This is a rare case of recurrent pulmonary metastatic mucinous cystadenocarcinoma, and despite poor prognosis and nondefinitive initial treatment, this patient remains alive and well 20 years later.
The Annals of thoracic surgery 06/2007; 83(5):1893-4. · 3.74 Impact Factor
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ABSTRACT: We set out to find a policy for the management of the pneumonectomy space which would minimise risk and be acceptable to all the surgeons. We believe this will reduce opportunities for error, be welcomed by nursing staff, and improve adherence to protocols.
We sought evidence in the scientific and educational literature. Finding no sure guidance, we audited our own experience of two policies, with the emphasis on minimising risk.
There was no evidence from randomised trials. There was no cohesive advice in the text books. Our data indicated that it was improbable that randomised controlled trial (RCT) would have the power to find the evidence. Unable to establish the best strategy, we chose what appeared to be the lowest risk management policy.
It is instructive that such a fundamental question should be unanswered. We have adopted a low risk and well established strategy--an unclamped underwater seal drain--but have no evidence base other than clinical experience. This is illustrative of much of what we do in clinical surgical practice. Avoiding major risk is often more important than proving small differences in benefit.
Heart Lung & Circulation 05/2007; 16(2):103-6. · 1.20 Impact Factor
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The Annals of thoracic surgery 09/2006; 82(2):767; author reply 767. · 3.74 Impact Factor
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ABSTRACT: Surgery may offer a long-term survival benefit to a small proportion of patients with operable non-small cell lung cancer (NSCLC) and solitary adrenal metastasis. Several approaches to lung resection with a separate open or laparoscopic adrenalectomy have been advocated. We describe a technique that allows a single incision, single operation through a transdiaphragmatic approach to the ipsilateral adrenal gland following a standard lung resection through a postero-lateral thoracotomy. By using this approach, along with the harmonic scalpel to aid adrenal dissection, both lobectomy and adrenalectomy can be carried out safely and effectively with minimal perioperative and postoperative morbidity.
European Journal of Cardio-Thoracic Surgery 08/2006; 30(1):194-5. · 2.55 Impact Factor
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Journal of the Royal Society of Medicine 02/2005; 98(1):26-8. · 1.41 Impact Factor
