Search

Malignant pleural mesothelioma is an uncommon thoracic cancer with a relatively poor outcome, which has only seen modest improvements when compared to non-small cell lung cancer. The mainstays of treatment have been surgery and systemic therapy, with radiation reserved for palliation or as an adjunct. However, there is re-emergent interest in the use of radiotherapy in the treatment of mesothelioma, given recent technical advances in radiotherapy delivery which permit increased treatment accuracy. This overview article reviews the radiobiology of the mesothelioma and whether or not mesothelioma is an inherently radioresistant cancer and the potential impact that hypofractionation may have on different histological subtypes in mesothelioma. This overview also considers the role of radiation in palliation, as adjunct to surgical resection and as adjunct to pleural tract procedures. In particular we review the growing evidence that pleural tract or port site adjuvant radiotherapy provides no clinical benefit. This overview will also consider potential emerging therapeutic strategies such as pre-operative short course hypofractionated radiotherapy. The role of novel radiotherapy techniques such as stereotactic ablative radiotherapy, image guided radiotherapy, proton therapy and the potential role of radiotherapy as an immune stimulating agent in combination of immunotherapy, will also be discussed. Finally, given the many unanswered questions, this review discusses some of the emerging and ongoing clinical trials of radiotherapy in the treatment of mesothelioma.

Purpose: Not all patients with stage III non-small cell lung cancer (NSCLC) are suitable for concurrent chemoradiation therapy (CRT). Local failure rate is high for sequential concurrent CRT. As such, there is a rationale for treatment intensification. Methods and Materials: Isotoxic intensity modulated radiation therapy (IMRT) is a multicenter feasibility study that combines different intensification strategies including hyperfractionation, acceleration, and dose escalation facilitated by IMRT. Patients with unresectable stage III NSCLC, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2, and unsuitable for concurrent CRT were recruited. A minimum of 2 cycles of platinum-based chemotherapy was compulsory before starting radiation therapy (RT). Radiation dose was increased until a maximum dose of 79.2 Gy was reached or 1 or more of the organs at risk met predefined constraints. RT was delivered in 1.8-Gy fractions twice daily, and an RT quality assurance program was implemented. The primary objective was the delivery of isotoxic IMRT to a dose >60 Gy equivalent dose in 2-Gy fractions (EQD2 assuming an α/β ratio of 10 Gy for acute reacting tissues). Results: Thirty-seven patients were recruited from 7 UK centers. Median age was 69.9 years (range, 46-86 years). The male-to-female ratio was 17:18. ECOG PS was 0 to 5 in 14.2% of patients; PS was 1 to 27 in 77.1% of patients; PS was 2 to 3 in 8.6% of patients. Stage IIIA:IIIB ratio was 22:13 (62.9%:37.1%). Of 37 patients, 2 (5.4%) failed to achieve EQD2 > 60 Gy. Median prescribed tumor dose was 77.4 Gy (range, 61.2-79.2 Gy). A maximum dose of 79.2Gy was achieved in 14 patients (37.8%). Grade 3 esophagitis was reported in 2 patients, and no patients developed grade 3 to 4 pneumonitis. There were 3 grade 5 events: acute radiation pneumonitis, bronchopulmonary hemorrhage, and acute lung infection. Median follow-up at time of analysis was 25.4 months (range, 8.0-44.2) months for 11 of 35 survivors. The median survival was 18.1 months (95% confidence interval [CI], 13.9-30.6), 2-year overall survival was 33.6% (95% CI, 17.9-50.1), and progression-free survival was 23.9% (95% CI, 11.3-39.1). Conclusions: Isotoxic IMRT is a well-tolerated and feasible approach to treatment intensification.

Aims Specialty trainees in clinical oncology must be competent in the coordination of both radiotherapy and systemic therapy at the completion of their training. Radiotherapy technology and postgraduate medical education have evolved significantly over the last two decades, but little is known of the educational impact of those changes within the dual training of the clinical oncology programme. A qualitative assessment of the radiotherapy component of training was undertaken at a single regional cancer centre in order to identify potential areas for improvement. Materials and methods Consultants and trainees (n = 10) at a regional cancer centre underwent semi-structured interviews regarding their lived experience of learning radiotherapy skills and knowledge. As consultants and trainees can be considered equal co-investors in the process of radiotherapy learning, the same question stems were used for both groups. An interpretative phenomenological analysis was undertaken by the investigators to elicit the perception of both groups. Results Consultant and trainee assessments of current radiotherapy learning standards differ for several aspects of training, as do their expectations of the other in learning processes. A lack of time is a major barrier in modern practice, and both groups can propose novel measures to improve learning locally. Conclusions Arrangements for learning radiotherapy have not kept pace with the rate of change in the clinical oncology discipline. Trainees and consultants have contrasting views on the state of training, its strengths and weaknesses, and pathways to improvement, which should be reconciled by programme coordinators charged with upgrading the training system.

PURPOSE: Fewer attendances for radiation therapy results in increased efficiency and less foot traffic within a radiation therapy department. We investigated outcomes after single-fraction (SF) stereotactic body radiation therapy (SBRT) in patients with oligometastatic disease. METHODS AND MATERIALS: Between February 2010 and June 2019, patients who received SF SBRT to 1 to 5 sites of oligometastatic disease were included in this retrospective study. The primary objective was to describe patterns of first failure after SBRT. Secondary objectives included overall survival (OS), progression-free survival (PFS), high-grade treatment-related toxicity (Common Terminology Criteria for Adverse Events grade ≥3), and freedom from systemic therapy (FFST). RESULTS: In total, 371 patients with 494 extracranial oligometastases received SF SBRT ranging from 16 Gy to 28 Gy. The most common primary malignancies were prostate (n = 107), lung (n = 63), kidney (n = 52), gastrointestinal (n = 51), and breast cancers (n = 42). The median follow-up was 3.1 years. The 1-, 3-, and 5-year OS was 93%, 69%, and 55%, respectively; PFS was 48%, 19%, and 14%, respectively; and FFST was 70%, 43%, and 35%, respectively. Twelve patients (3%) developed grade 3 to 4 treatment-related toxicity, with no grade 5 toxicity. As the first site of failure, the cumulative incidence of local failure (irrespective of other failures) at 1, 3 and 5 years was 4%, 8%, and 8%, respectively; locoregional relapse at the primary was 10%, 18%, and 18%, respectively; and distant failure was 45%, 66%, and 70%, respectively. CONCLUSIONS: SF SBRT is safe and effective, and a significant proportion of patients remain FFST for several years after therapy. This approach could be considered in resource-constrained or bundled-payment environments. Locoregional failure of the primary site is the second most common pattern of failure, suggesting a role for optimization of primary control during metastasis-directed therapy.

Introduction Limb injury is a major health concern that imposes a direct danger to both life and limb viability. At Kandou Hospital Manado, hyperbaric oxygen (HBO) therapy has been performed as an adjunctive treatment for crush injury although no study has yet directly compared outcomes of HBO versus conventional therapy. Documentation of the association between HBO therapy and the healing process of crush injury is necessary to reduce the gaps in the literature and to establish an evidence-based clinical use of HBO therapy. Methods In this study, we assessed the changes in the vascular endothelial growth factor (VEGF) serum levels and VEGF mRNA expression as biomarkers of wound healing using ELISA and qRT-PC at four different measurement times: at baseline, after receiving initial treatment (debridement and limb-salvage surgeries), 2 h after the first session HBOT, and after a full 10 HBOT sessions. A randomized controlled trial (RCT) was used to enroll patients subjected to crush injury who were admitted to the Surgical Emergency Department (ER) of Kandou Hospital Manado, Indonesia. Results VEGF serum levels increased significantly in patients suffering from crush injury who received HBO therapy versus the control group. The increased VEGF serum is expected to result in an acceleration time of wound healing and a reduction in amputation rate. Conclusion There was a significant difference between crush injury patients who received conservative therapy versus those receiving HBO therapies; thus, there was an increased likelihood of an accelerated wound healing and a reduction in the risk of amputation.

Organ motion as a result of respiratory and cardiac motion poses significant challenges for the accurate delivery of radiotherapy to both the thorax and the upper abdomen. Modern imaging techniques during radiotherapy simulation and delivery now permit better quantification of organ motion, which in turn reduces tumour and organ at risk position uncertainty. These imaging advances, coupled with respiratory correlated radiotherapy delivery techniques, have led to the development of a range of approaches to manage respiratory motion. This review summarises the key strategies of image-guided respiratory motion management with a focus on lung and liver radiotherapy.

The type of patients with stage III non-small-cell lung cancer (NSCLC) selected for concurrent chemoradiotherapy (cCRT) varies between and within countries, with higher-volume centres treating patients with more co-morbidities and higher-stage disease. However, in spite of these disease characteristics, these patients have improved overall survival, suggesting that there are additional approaches that should be optimised and potentially standardised. This paper aims to review the current knowledge and best practices surrounding treatment for patients eligible for cCRT. Initially, this includes timely acquisition of the full diagnostic workup for the multidisciplinary team to comprehensively assess a patient for treatment, as well as imaging scans, patient history, lung function and genetic tests. Such information can provide prognostic information on how a patient will tolerate their cCRT regimen, and to perhaps limit the use of additional supportive care, such as steroids, which could impact on further treatments, such as immunotherapy. Furthermore, knowledge of the safety profile of individual double-platinum chemotherapy regimens and the technological advances in radiotherapy could aid in optimising patients for cCRT treatment, improving its efficacy whilst minimising its toxicities. Finally, providing patients with preparatory and ongoing support with input from dieticians, palliative care professionals, respiratory and care-of-the-elderly physicians during treatment may also help in more effective treatment delivery, allowing patients to achieve the maximum potential from their treatments.

Cardiovascular diseases (CVDs) and diabetes are the primary causes of death in the Philippines. This manuscript reviewed previous studies on the use of predictive analytics for CVD and diabetes risk scoring. This paper also discussed barriers and strategies on how to access/generate available data sets for CVDs and diabetes in the country. CVD and diabetes risk scoring requires the availability of data sets related to such diseases. Although the Philippines has taken strides to implement the Philippine National eHealth solution, such a program does not include strategies toward the use of predictive analytics for CVD and diabetes risk scoring. CVD and diabetes risk scoring research is particularly limited in the Philippines due to challenges related to costs, gaps in policies, and stakeholder involvement. A possible theoretical framework for the analysis and utilization of data sets as well as recommendations and research directions were discussed in this manuscript.

A method using Fourier transform infrared with attenuated total reflectance spectroscopy and partial least squares (PLS) chemometric analysis to simultaneously quantify the mass percent concentrati...

Key points During development the giant, auditory calyx of Held forms a one‐to‐one connection with a principal neuron of the medial nucleus of the trapezoid body.While anatomical studies described that most of the target cells are temporarily contacted by multiple calyces, multi‐calyceal innervation was only sporadically observed in in vivo recordings, suggesting a structure–function discrepancy.We correlated synaptic strength of inputs, identified in in vivo recordings, with post hoc labelling of the recorded neuron and synaptic terminals containing vesicular glutamate transporters (VGluT).During development only one input increased to the level of the calyx of Held synapse, and its strength correlated with the large VGluT cluster contacting the postsynaptic soma.As neither competing strong inputs nor multiple large VGluT clusters on a single cell were observed, our findings did not indicate a structure–function discrepancy. Abstract In adult rodents, a principal neuron in the medial nucleus of the trapezoid (MNTB) is generally contacted by a single, giant axosomatic terminal called the calyx of Held. How this one‐on‐one relation is established is still unknown, but anatomical evidence suggests that during development principal neurons are innervated by multiple calyces, which may indicate calyceal competition. However, in vivo electrophysiological recordings from principal neurons indicated that only a single strong synaptic connection forms per cell. To test whether a mismatch exists between synaptic strength and terminal size, we compared the strength of synaptic inputs with the morphology of the synaptic terminals. In vivo whole‐cell recordings of the MNTB neurons from newborn Wistar rats of either sex were made while stimulating their afferent axons, allowing us to identify multiple inputs. The strength of the strongest input increased to calyceal levels in a few days across cells, while the strength of the second strongest input was stable. The recorded cells were subsequently immunolabelled for vesicular glutamate transporters (VGluT) to reveal axosomatic terminals with structured‐illumination microscopy. Synaptic strength of the strongest input was correlated with the contact area of the largest VGluT cluster at the soma (r = 0.8), and no indication of a mismatch between structure and strength was observed. Together, our data agree with a developmental scheme in which one input strengthens and becomes the calyx of Held, but not with multi‐calyceal competition., Key points During development the giant, auditory calyx of Held forms a one‐to‐one connection with a principal neuron of the medial nucleus of the trapezoid body.While anatomical studies described that most of the target cells are temporarily contacted by multiple calyces, multi‐calyceal innervation was only sporadically observed in in vivo recordings, suggesting a structure–function discrepancy.We correlated synaptic strength of inputs, identified in in vivo recordings, with post hoc labelling of the recorded neuron and synaptic terminals containing vesicular glutamate transporters (VGluT).During development only one input increased to the level of the calyx of Held synapse, and its strength correlated with the large VGluT cluster contacting the postsynaptic soma.As neither competing strong inputs nor multiple large VGluT clusters on a single cell were observed, our findings did not indicate a structure–function discrepancy.

Phenome-wide association studies (PheWASs), a powerful approach that examines phenotypes associated with a genetic marker, have been used extensively in highly developed countries. Although there may be a clear need for PheWAS in a developing country such as the Philippines, limitations related to resources and practicality would make conducting them a challenge.

To evaluate the proportion of cancer patients who received radiation therapy (RT) within 12 months of cancer diagnosis (RTU12) and identify factors associated with RTU12.This is a population-based cohort of individuals with incident cancer, diagnosed between 2013 and 2017 in Victoria. Data linkages were performed between the Victorian Cancer Registry and Victorian Radiotherapy Minimum Dataset. The primary outcome was the proportion of patients who had RTU12. For the three most common cancers (i.e., prostate, breast and lung cancer), the time trend in RTU12 and factors associated with RTU12 were evaluated.The overall RTU12 in our study cohort was 26-20% radical RT and 6% palliative RT. Of the 21,735 men with prostate cancer, RTU12 was 17%, with no significant change over time (P-trend = 0.53). In multivariate analyses, increasing age and lower socioeconomic status were independently associated with higher RTU12 for prostate cancer. Of the 20,883 women with breast cancer, RTU12 was 64%, which increased from 62% in 2013 to 65% in 2017 (P-trend 0.05). In multivariate analyses, age, socioeconomic status and area of residency were independently associated with RTU12 for breast cancer. Of the 13,093 patients with lung cancer, RTU12 was 42%, with no significant change over time (P-trend = 0.16). In multivariate analyses, younger age, male and lower socioeconomic status were independently associated with higher RTU12.In this large population-based state-wide cohort of cancer patients, only 1 in 4 had RT within 12 months of diagnosis. There were marked sociodemographic disparities in RTU12 for prostate, breast and lung cancer patients.

Facile, robust, and accurate analyses of honey adulterants are required in the honey industry to assess its purity for commercialization purposes. A stacked regression ensemble approach using Fourier transform infrared spectroscopic method was developed for the quantitative determination of corn, cane, beet, and rice syrup adulterants in honey. A training set (n=81) was used to predict the percent adulterant composition of the aforementioned constituents in an independent test set (n=32). A comprehensive comparison of the performance of various machine learning techniques including support vector regression using linear function, least absolute shrinkage and selection operator, ride regression, elastic net, partial least squares, random forests, recursive partitioning and regression trees, gradient boosting, and gaussian process regression was assessed. The predictive performance of the aforementioned machine learning approaches was then compared with stacked regression, an ensemble learning technique which collates the performance of the various abovementioned techniques. Results show that stacked regression did not primarily outperform other techniques across all four syrup adulterant constituents in the testing set data. Further, elastic net generalized linear model generated the optimum results (Rootmeansquareerrorofprediction(RMSEP)

Quantification of sugars is considered to be a key factor in the assessment of honey quality. Standard chromatographic methods for sugar quantification in honey may be unsuitable for routine analysis due to the associated time, cost, and complexity. Herein, a comparison between non-genetic and genetic algorithm���partial least squares (GA-PLS) chemometric and infrared spectroscopic approaches is reported for the direct quantification of glucose, fructose, and sucrose in Philippine honeys. A full factorial set (n = 61) was designed to predict Box-Behnken test set (n = 16) sugar concentrations. First derivative (FD) signal processing followed by PLS of the 1500���800 cm���1 spectral region harboring the analytes provided optimum results with R2average = 0.943 in the training set and a mean root mean square error of prediction (RMSEPaverage) of 0.049 across fructose, glucose, and sucrose. Applying GA-PLS after FD processing across the spectral region from 3700 to 700 cm���1 did not further improve the results (R2average = 0.926, RMSEPaverage = 0.077). FD followed by PLS (1500���800 cm���1) provided minimal differences between the actual and predicted sugar content in training and testing values, implying that the probe produced developmental avenues to directly quantify these sugars. When applied to real samples (n = 26), the method potentially differentiated real honey from non-honey and adulterated samples.