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.

Modelling impacts of climate change and socio-economic change on the Ganga, Brahmaputra, Meghna, Hooghly and Mahanadi river systems in India and Bangladesh.

The Ganga-Brahmaputra-Meghna (GBM) River System, the associated Hooghly River and the Mahanadi River System represent the largest river basins in the world serving a population of over 780 million. The rivers are of vital concern to India and Bangladesh as they provide fresh water for people, agriculture, industry, conservation and support the Delta System in the Bay of Bengal. Future changes in both climate and socio-economics have been investigated to assess whether these will alter river flows and water quality. Climate datasets downscaled from three different Global Climate Models have been used to drive a daily process based flow and water quality model. The results suggest that due to climate change the flows will increase in the monsoon period and also be enhanced in the dry season. However, once socio-economic changes are also considered, increased population, irrigation, water use and industrial development reduce water availability in drought conditions, threatening water supplies and posing a threat to river and coastal ecosystems. This study, as part of the DECCMA (Deltas, vulnerability and Climate Change: Migration and Adaptation) project, also addresses water quality issues, particularly nutrients (N and P) and their transport along the rivers and discharge into the Delta System. Climate will alter flows, increasing flood flows and changing pollution dilution factors in the rivers, as well as other key processes controlling water quality. Socio-economic change will affect water quality, as water diversion strategies, increased population and industrial development alter the water balance and enhance fluxes of nutrients from agriculture, urban centers and atmospheric deposition.

Modeling future flows of the Volta River system: Impacts of climate change and socio-economic changes.

As the scientific consensus concerning global climate change has increased in recent decades, research on potential impacts of climate change on water resources has been given high importance. However in Sub-Saharan Africa, few studies have fully evaluated the potential implications of climate change to their water resource systems. The Volta River is one of the major rivers in Africa covering six riparian countries (mainly Ghana and Burkina Faso). It is a principal water source for approximately 24 million people in the region. The catchment is primarily agricultural providing food supplies to rural areas, demonstrating the classic water, food, energy nexus. In this study an Integrated Catchment Model (INCA) was applied to the whole Volta River system to simulate flow in the rivers and at the outlet of the artificial Lake Volta. High-resolution climate scenarios downscaled from three different Global Climate Models (CNRM-CM5, HadGEM2-ES and CanESM2), have been used to drive the INCA model and to assess changes in flow by 2050s and 2090s under the high climate forcing scenario RCP8.5. Results show that peak flows during the monsoon months could increase into the future. The duration of high flow could become longer compared to the recent condition. In addition, we considered three different socio-economic scenarios. As an example, under the combined impact from climate change from downscaling CNRM-CM5 and medium+ (high economic growth) socio-economic changes, the extreme high flows (Q5) of the Black Volta River are projected to increase 11% and 36% at 2050s and 2090s, respectively. Lake Volta outflow would increase +1% and +5% at 2050s and 2090s, respectively, under the same scenario. The effects of changing socio-economic conditions on flow are minor compared to the climate change impact. These results will provide valuable information assisting future water resource development and adaptive strategies in the Volta Basin.

Clinical classification and staging for primary malignancies of the maxillary antrum.

A study of 51 patients with primary malignant maxillary sinus neoplasms was conducted. None of the patients had neck nodes and/or metastases, and each had 5-year follow-up. The tumors were staged according to the 1983 and 1988 American Joint Committee on Cancer staging systems for maxillary sinus cancers. There were 13 early stage (T1, T2) and 38 advanced (T3, T4) tumors in both systems. Cox regression analyses of survival curves showed increasingly worse prognoses for advanced tumors in both T-staging systems. Further analyses showed a significant difference in survival between T3 and T4 in the 1988, but not in the 1983 system. There were no significant differences in survival according to treatment modality or histological type of malignancy. We conclude that the 1988 system prognosticates successfully for T-stage (1 to 4) and demonstrates significant improvement in detecting T3 versus T4 differences compared to the 1983 system. The 1988 system applies equally for epidermoid cancer and other malignancies of the antrum.

Surgical pathology of cancer of the oral cavity and oropharynx.

A study was designed to determine the influence of certain surgical pathologic findings on tumor spread and survival in patients with cancer of the oral cavity and oropharynx. All patients with the histopathological diagnosis of carcinoma of the oral cavity or oropharynx from 1955 to 1983 were included in the study. Using the Head and Neck Tumor Registry of the department of otolaryngology of the Washington University School of Medicine, information was obtained regarding preoperative evaluation, staging, classification, diagnosis, treatment, surgical pathology parameters, and outcome results. The patient populations consisted of 545 patients with oral cavity cancer and 224 patients with oropharynx cancer, all of whom were eligible for 3-year follow-up. Information from a retrospective analysis of the pretreatment examination records regarding site and size of the primary tumor and neck dissection, and specific treatment, and from surgical pathology reports regarding site, size, tumor spread and resection margins, was correlated with treatment outcome. The database file was analyzed using dbase III and its companion program Framework, and SAS PC (Statistical Analysis Systems for personal computers).

Clinical staging for primary malignancies of the supraglottic larynx.

A study of 520 patients with primary supraglottic cancer was conducted. The tumors were staged according to the 1983 and 1988 American Joint Committee on Cancer (AJCC) T- and N-stage definitions. There were 293 patients with early stage (T1, T2) tumors, 227 with advanced stage (T3, T4) tumors and 428 with early nodal disease (N0, N1) in both systems. In the 1983 N-staging, there were 44 N2 and 48 N3 lesions; in the 1988 N-staging, there were 62 N2 and 30 N3 lesions. Cox regression analysis showed that the 1983 and 1988 T-stage (T1 through T4) definitions successfully prognosticate for survival when patients were without neck node involvement. In contrast, when neck nodes were present, the N-stage (N0 through N3) of the disease prognosticated survival better than T-stage. Further analyses showed that the 1988 N-stage definition provided a better separation between N2 and N3 lesions compared to the 1983 version. Combined-modality treatment (surgery and radiation) significantly improved survival compared to single-modality treatment (surgery or radiation alone) when patients were staged T4 and N0 through N3 neck disease, but not when patients advanced from T1 to T3. Comparison of treatment efficacy over the last four decades for single- and combined-modality treatment did not reveal statistically significant differences in survival rates in our patient population. This was consistent with cumulative results of various institutions over the last four decades. We conclude that the 1988 AJCC T- and N-stage definitions successfully prognosticate for T-stage (T1 through T4) and N-stage (N0 through N3) with better separation of N2 and N3 lesions compared to the 1983 version.

Prediction of occult neck disease in laryngeal cancer by means of a logistic regression statistical model.

The ability to accurately predict the presence of subclinical metastatic neck disease in clinically N0 patients with primary epidermoid cancer of the larynx would be of great value in determining whether to perform an elective neck dissection. We describe a statistical approach to estimating the probability of occult neck disease given pretreatment clinical parameters. A retrospective study was performed involving 736 clinically N0 patients with primary laryngeal cancer who were treated surgically with primary resection and ipsilateral neck dissection. Nodal involvement was determined histologically after surgical lymphadenectomy. A logistic regression model was used to derive an equation that calculated the probability of occult neck metastasis based on pretreatment T stage, tumor location, and histologic grade. The model has a sensitivity of 74%, a specificity of 87%, and can be entered into a programmable calculator.

Comparison of clinical evaluation and computed tomographic diagnostic accuracy for tumors of the larynx and hypopharynx.

Ninety-five patients with laryngeal and hypopharyngeal cancer were examined and staged preoperatively by clinical evaluation (CE) and computed tomography (CT). The CE and CT staging were compared to each other and to the pathologic (PT) staging of the tumors. The CT staging showed high accuracy in staging transglottic (88%), supraglottic (68%), and oropharyngeal tumors invading the larynx (68%) when compared to the PT findings. The CT staging was less effective in evaluating glottic tumors (46%), both overstaging (12%) and understaging (20%) cases. Combined CE-CT evaluation showed higher accuracy in staging all tumors (84%) compared to CE alone (52%) or CT alone (68%). The findings suggest that combined CE-CT should be used to evaluate laryngeal and hypopharyngeal tumors.

Epidermoid carcinoma of the oral cavity and oropharynx: validity of the current AJCC staging system and new statistical tools for the prediction of subclinical neck disease.

The 1983 and 1988 AJCC T- and N-staging systems were compared using the case records of 531 patients with primary epidermoid malignancies of the oral cavity. All patients had a minimum followup of 5 years. There were 390 patients with early stage (T1, T2) disease and 141 with advanced stage (T3, T4) lesions according to both the 1983 and 1988 T-definitions: 342 patients manifested no clinical nodes (NO), 189 had clinically evident nodes (N1-N3), and none had metastatic disease. Cox regression analysis demonstrated that the 1983/1988 T-stage definitions differentiated survival successfully (p < 0.001). The 1988 staging system for nodal disease showed a highly significant separation of N2 and N3 when compared with the 1983 system (p < 0.001). Of the 342 patients who were staged N0, 154 had primary neck dissection. Logistic regression predicted the incidence of subclinical disease according to the site and the T-stage of the primary tumor with a sensitivity of 78% and a specificity of 95%. We conclude that the 1988 N-stage definition is a better prognosticator of survival than the 1983 definition. Furthermore, a logistic regression model can be used to predict the probability of subclinical disease in primary oral cavity cancers.

Natural history of treated T1N0 squamous carcinoma of the glottis.

The records of 373 patients with T1N0 squamous carcinoma of the glottis were examined. Of these, 271 underwent initial hemilaryngectomy; 102 had full-course irradiation for cure. While the overall survival rates of the two initial therapies were similar, failure of the initial treatment modality was approximately twice as frequent in the irradiated patients (34.4%) as in the patients undergoing hemilaryngectomy (16.9%). The effect of this difference in initial failure rate on quality of life and on cost of overall therapy will be discussed.

Guidelines for the management of spontaneous pneumothorax. Standards of Care Committee, British Thoracic Society.

Simple flow diagrams, with explanatory notes, have been devised to assist in the immediate and subsequent management of patients presenting to casualty departments with spontaneous pneumothorax. They cover decision making about which patients require admission; whether a drainage procedure is necessary; if so, the appropriate method, including technical details; inpatient treatment; referral of inpatients to a respiratory specialist; and follow up arrangements. The guidelines, designed for incorporation into casualty and ward handbooks, have already proved valuable in several district general hospitals, and can be used as a basis for audit.