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.

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.

Apolipoprotein E polymorphism and vitamin K status in cystic fibrosis patients not supplemented with vitamin K.

OBJECTIVE: ApoE alleles have been shown to significantly correlate with vitamin K status, however, data concerning this phenomenon in cystic fibrosis (CF) are scarce. This study aimed to investigate the effect of ApoE polymorphism on vitamin K status in a unique group of CF patients who had never received vitamin K supplementation. PATIENTS AND METHODS: The study group consisted of 93 CF patients aged from 3 months to 32 years. Vitamin K status was assessed by the concentration of prothrombin induced by vitamin K absence (PIVKA-II) and the percentage of undercarboxylated osteocalcin (u-OC). The clinical status was evaluated in all patients. RESULTS: Fifty-four (65.1%) out of 83 patients had a pathological PIVKA-II concentration (≥2 ng/ml) and an abnormal percentage of u-OC (≥20%). There were no differences in the clinical parameters, including PIVKA-II concentration (p=0.7752) and u-OC percentage (p=0.8395), between patients with genotypes ApoE2/3, ApoE3/3 and ApoE3/4. Moreover, the frequency of vitamin K deficiency did not significantly differ in CF patients with ApoE2/3, ApoE3/3 and ApoE3/4 genotypes (66.7 vs. 69.9 vs. 80%, p=0.8411; 87.5 vs. 89.6 vs. 100%, p=1.000, respectively). CONCLUSIONS: The presence of the ApoE4 allele does not influence the vitamin K status in CF patients who have never received vitamin K supplementation.

Molecular biology for the radiation oncologist: the 5Rs of radiobiology meet the hallmarks of cancer.

Recent advances in our understanding of the biology of cancer have provided enormous opportunities for the development of novel therapies against specific molecular targets. It is likely that most of these targeted therapies will have only modest single agent activities but may have the potential to accentuate the therapeutic effects of ionising radiation. In this introductory review, the 5Rs of classical radiobiology are interpreted in terms of their relationship to the hallmarks of cancer. Future articles will focus on the specific hallmarks of cancer and will highlight the opportunities that exist for designing new combination treatment regimens.

Investigation and management of the unknown primary with metastatic neck disease: United Kingdom National Multidisciplinary Guidelines.

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. It discusses the evidence base pertaining to the management of metastatic neck disease in the setting of an unknown primary and provides recommendations on the work up and management for this group of patients receiving cancer care. Recommendations • All patients presenting with confirmed cervical lymph node metastatic squamous cell carcinoma and no apparent primary site should undergo: ○ Positron emission tomography-computed tomography whole-body scan. (R) ○ Panendoscopy and directed biopsies. (R) ○ Bilateral tonsillectomy. (R) • Tongue base mucosectomy can be offered if facilities and expertise exists. (G) • Concomitant chemotherapy with radiation should be considered in patients with an unknown primary. (R) • Concomitant chemotherapy with radiation should be offered to suitable patients in the post-operative setting, where indicated. (R) • Neo-adjuvant chemotherapy can be used in gross 'unresectable' disease. (R) • Patients should be followed up at least two months in the first two years and three to six months in the subsequent years. (G) • Patients should be followed up to a minimum of five years with a prolonged follow up for selected patients. (G) • Positron emission tomography-computed tomography scan at three to four months after treatment is a useful follow-up strategy for patients treated by chemoradiation therapy. (R).

Using a commercial software package to support treatment planning peer review activities in small radiotherapy departments.

OBJECTIVE: To implement peer review of radiotherapy treatment planning processes between two geographically separated hospitals with different treatment planning systems. METHODS: The feasibility of using Microsoft(®) Lync 2013™, available in one of the hospitals, was investigated to determine its utility in sharing radiotherapy treatment planning information between hospitals with small numbers of clinical oncologists available to participate in peer review of treatment plans. RESULTS: Microsoft Lync 2013 has been successfully used to implement remote, real-time review of all aspects of treatment planning, including contours, beam arrangements, isodose distributions and dose-volume histograms. CONCLUSION: A reliable system for remote, real-time peer review of radiotherapy treatment plans has been implemented between two geographically distant hospitals using Microsoft Lync 2013. Interest in use of the system is developing regionally. ADVANCES IN KNOWLEDGE: This work appears to be the first to describe the use of Microsoft Lync 2013 in this area and demonstrates that smaller radiotherapy centres separated by distance can share clinical and scientific resources to participate in improved peer review processes, in line with recent UK national guidance.

Case report. Isolated intrathyroid metastasis from undifferentiated and squamous carcinoma of the head and neck: the case for surgery and re-irradiation.

Metastasis to the thyroid gland is rare, with fewer than 450 cases reported in the literature. Furthermore, intrathyroid metastasis from head and neck squamous cell carcinoma (HNSCC) is even more unusual, with only nine previously documented cases. This study details the cases of three patients (from one centre) who presented with intrathyroid metastasis from HNSCC and who were treated with a combination of surgery and radiotherapy. Although previous reports have suggested that this pattern of spread is associated with a poor outcome, we are able to show that appropriately selected patients benefit from a combination of both radical surgery and adjuvant radiation therapy, even when this entails some areas of re-irradiation.