Sam Guglani

Extended survival in women with brain metastases from HER2 overexpressing breast cancer.

Objectives:Brain metastases (BM) are a significant complication of metastatic breast cancer (MBC). The high incidence of BM in HER2 overexpressing MBC is now well recognized, however, the optimal management of such patients is not yet clearly defined. We aimed to analyze factors affecting survival after diagnosis of BM in patients treated in our center. Materials and Methods:Retrospective analysis of survival in all patients treated with antineoplastic therapy for BM from MBC in our institution between May 1st 2002 and April 30th 2005, according to HER2 expression and use of trastuzumab after diagnosis of BM. Results:The median survival of the 26 patients with HER2 overexpressing disease after diagnosis of BM was significantly longer than that of the 60 patients with HER2 nonoverexpressing disease (6.2 vs. 3.8 months, P = 0.027). Further analysis revealed that this seems to be due to the favorable outcome of the 70% (n = 18) of HER2 overexpressing patients who received trastuzumab after BM were diagnosed. Median survival of this group was 11.9 months, compared with 3.8 months (HER2 nonoverexpressing disease, P = 0.002) and 3.0 months (HER2 overexpressing disease not treated with trastuzumab after development of BM, P = 0.05). Conclusion:Patients with HER2 overexpressing MBC who received trastuzumab after diagnosis of BM survived longer than expected. This finding justifies an active therapeutic approach: disease progression within central nervous system does not preclude benefit from trastuzumab treatment.

The South West Area Mesothelioma and Pemetrexed trial: a multicentre prospective observational study evaluating novel markers of chemotherapy response and prognostication

Background:Robust markers that predict prognosis and detect early treatment response in malignant pleural mesothelioma (MPM) would enhance patient care.Methods:Consecutive patients with MPM who were considered fit for first-line chemotherapy were prospectively recruited. Patients of similar performance status opting for best supportive care were included as a comparator group. Baseline and interval CT, PET-CT and serum markers (mesothelin, fibulin-3 and neutrophil–lymphocyte ratio (NLR)) were obtained, and patients followed up for a minimum 12 months.Findings:Seventy-three patients were recruited (58 chemotherapy/15 comparator arm). Baseline TGV (total glycolytic volume on PET-CT) was an independent predictor of worse overall survival (OS) (P=0.001). Change in interval TGV(baseline/after two cycles of chemotherapy) did not predict OS or chemotherapy response on CT. Baseline NLR<4 was an independent predictor of better OS (median survival 453 (IQR 272–576) days vs NLR⩾4, 257 (IQR 147–490), P=0.002). Although baseline serum mesothelin did not predict OS, a falling level at 8 weeks significantly predicted longer time to progression (TTP) (P<0.001).Interpretation:Neutrophil–lymphocyte ratio and baseline TGV predict prognosis in malignant pleural mesothelioma (MPM), but PET-CT is unhelpful in monitoring chemotherapy response. Serum mesothelin is a useful early treatment response marker when measured serially during chemotherapy and may have a role in evaluating patients’ treatment response.

The effect of chemotherapy on health-related quality of life in mesothelioma: results from the SWAMP trial.

Background:The effect of chemotherapy on health-related quality of life (HRQoL) in malignant pleural mesothelioma (MPM) is poorly understood. Patient-individualised prognostication and prediction of treatment response from chemotherapy is useful but little evidence exists to guide practice.Method:Consecutive patients with MPM who were fit for first-line chemotherapy with pemetrexed and cisplatin\carboplatin were recruited and followed up for a minimum of 12 months. This study focussed on the HRQoL outcomes of these patients using the EQ-5D, EORTC QLQ-C30 and LC13.Results:Seventy-three patients were recruited of which 58 received chemotherapy and 15 opted for best supportive care (BSC). Compliance with HRQoL questionnaires was 98% at baseline. The chemotherapy group maintained HRQoL compared with the BSC group whose overall HRQoL fell (P=0.006) with worsening dyspnoea and pain. The impact of chemotherapy was irrespective of histological subtype although those with non-epithelioid disease had worse HRQoL at later time points (P=0.012). Additionally, those with a falling mesothelin or improvement on modified-RECIST CT at early follow-up had a better HRQoL at 16 weeks.Conclusions:HRQoL was maintained following chemotherapy compared with a self-selected BSC group. Once chemotherapy is initiated, a falling mesothelin or improved RECIST CT findings infer a quality-of-life advantage.

Target localisation for tumour bed radiotherapy in early breast cancer

Introduction: To compare clinical and CT techniques in localisation of the tumour bed in patients undergoing adjuvant breast radiotherapy for breast cancer.

Return of the postcode lottery

Many of the issues arising from changes to NHS drug pricing in 2014 already apply to the Interim Cancer Drugs Fund.1 The government’s initial pledge of £50m up to April 2011 has been followed by a proposal for …

Bilateral patellar metastases from non-small cell lung cancer.

Patellar metastases are rare. A literature review revealed only approximately seven reported cases of patellar metastases from lung cancer, many of which were adenocarcinomas, with one epidermoid carcinoma and one small cell carcinoma. Other reported cases originated from the salivary gland, floor of the mouth, breast, bladder, colon, and renal cell carcinoma. Bilateral patellar metastases are even less common. There is only one other reported case of bilateral patellar metastases originating from the lung, a bronchogenic adenocarcinoma.1 In this article, we present another such a case.

The Notes: encounters with medicine

www.thelancet.com Vol 387 April 9, 2016 1497 Some instances from the day persist. Seen directly they go unnoticed, but brighten, almost like stars, in the margins of our sight. Medicine is extraordinary in this way, in what it reveals. Like art, it shows us the world, all humanity, the tragic and the beautiful, the wondrous. How might we contend with it all? Arthur Miller, in Death of a Salesman, demands that “attention must be paid”, and this feels right. And of course, the humanity is ours as much our patients’. Belief, anger, fear, hope: this and more moves in doctors, crystallising in language, in the words we arrive at in consultations. So much of medicine is more than the requisite reason and evidence, more than the nuts and bolts of what’s measured, measurable, remunerated, perfected through study or found in trials. This is hard to locate but we all know it: we recognise it as fundamentally important and also elusive. Strange then for a poet to point to it so clearly. Seamus Heaney distinguishes between craft and technique in poetry, and so speaks to us in medicine. He suggests that craft is just a “skill of making...deployed without reference to the feelings or the self”. But technique is much greater: it is a defi nition of the poet’s “stance towards life”. In medicine, in the throes of all our encounters, what is our stance towards life, and indeed towards death? In this new Lancet column, The Notes, the hope is to wonder about this, to look obliquely again at events that hold meaning for us and for the persons we meet as patients, who are of course all of us.

The South West Area Mesothelioma and Pemetrexed trial; a multicentre prospective observational study evaluating novel markers of chemotherapy response and prognostication: The South West Area Mesothelioma and Pemetrexed trial

Background:Robust markers that predict prognosis and detect early treatment response in malignant pleural mesothelioma (MPM) would enhance patient care.Methods:Consecutive patients with MPM who were considered fit for first-line chemotherapy were prospectively recruited. Patients of similar performance status opting for best supportive care were included as a comparator group. Baseline and interval CT, PET-CT and serum markers (mesothelin, fibulin-3 and neutrophil–lymphocyte ratio (NLR)) were obtained, and patients followed up for a minimum 12 months.Findings:Seventy-three patients were recruited (58 chemotherapy/15 comparator arm). Baseline TGV (total glycolytic volume on PET-CT) was an independent predictor of worse overall survival (OS) (P=0.001). Change in interval TGV(baseline/after two cycles of chemotherapy) did not predict OS or chemotherapy response on CT. Baseline NLR<4 was an independent predictor of better OS (median survival 453 (IQR 272–576) days vs NLR⩾4, 257 (IQR 147–490), P=0.002). Although baseline serum mesothelin did not predict OS, a falling level at 8 weeks significantly predicted longer time to progression (TTP) (P<0.001).Interpretation:Neutrophil–lymphocyte ratio and baseline TGV predict prognosis in malignant pleural mesothelioma (MPM), but PET-CT is unhelpful in monitoring chemotherapy response. Serum mesothelin is a useful early treatment response marker when measured serially during chemotherapy and may have a role in evaluating patients’ treatment response.

The South West Area Mesothelioma and Pemetrexed trial; a multicentre prospective observational study evaluating novel markers of chemotherapy response and prognostication

Background:Robust markers that predict prognosis and detect early treatment response in malignant pleural mesothelioma (MPM) would enhance patient care.Methods:Consecutive patients with MPM who were considered fit for first-line chemotherapy were prospectively recruited. Patients of similar performance status opting for best supportive care were included as a comparator group. Baseline and interval CT, PET-CT and serum markers (mesothelin, fibulin-3 and neutrophil–lymphocyte ratio (NLR)) were obtained, and patients followed up for a minimum 12 months.Findings:Seventy-three patients were recruited (58 chemotherapy/15 comparator arm). Baseline TGV (total glycolytic volume on PET-CT) was an independent predictor of worse overall survival (OS) (P=0.001). Change in interval TGV(baseline/after two cycles of chemotherapy) did not predict OS or chemotherapy response on CT. Baseline NLR<4 was an independent predictor of better OS (median survival 453 (IQR 272–576) days vs NLR⩾4, 257 (IQR 147–490), P=0.002). Although baseline serum mesothelin did not predict OS, a falling level at 8 weeks significantly predicted longer time to progression (TTP) (P<0.001).Interpretation:Neutrophil–lymphocyte ratio and baseline TGV predict prognosis in malignant pleural mesothelioma (MPM), but PET-CT is unhelpful in monitoring chemotherapy response. Serum mesothelin is a useful early treatment response marker when measured serially during chemotherapy and may have a role in evaluating patients’ treatment response.