A controlled evaluation of the effect of social prescribing programs on loneliness for adults in Queensland, Australia (protocol).

BACKGROUND: In social prescribing, link workers support individuals whose persistent health problems are exacerbated by loneliness by connecting them to community-based social activities. This approach is well established in the UK and is gaining attention in Australia. However, a major limitation of research to date has been a lack of theoretically informed and rigorous evaluations of social prescribing. We will address these points in this study, applying a social identity framework to examine the effects of group-based social prescribing (SP) activity compared to primary care treatment as usual (TAU). METHODS: Ninety participants experiencing loneliness recruited from primary care services and community centres across five sites in Southeast Queensland will be assigned to one of two conditions (SP, TAU) and assessed at two timepoints (baseline, + 8 weeks). Individuals will be aged 18 years and over, have sufficient English language skills to provide consent, and at the time of recruitment they will not be experiencing acute symptoms or social issues that require urgent intervention. Primary outcomes are loneliness, mental well-being, and health service use (total number of GP, hospital, and allied health visits in the past 3 months). Secondary outcomes will assess social group processes, including number of important social groups, new group identification, multiple identity compatibility, and group-based support and emotion regulation. DISCUSSION: This study will provide comprehensive data about the extent to which, and how, social prescribing to community-based group activities may help people to feel less lonely, more socially integrated, and healthy over the first 8 weeks. If effective, this social identity-informed model of social prescribing can be disseminated in communities across Australia. TRIAL REGISTRATION: ANZCTR, Registered 8 June 2022 - Retrospectively registered, https://www.anzctr.org.au/ACTRN12622000801718.aspx.

The modified 'Jo'burg' technique for securing intercostal chest drains.

Insertion of an intercostal chest drain (ICD) is a common intervention in the management of either blunt or penetrating thoracic trauma. It is frequently performed by junior medical personnel as an emergency procedure during the initial resuscitation period and often within a stressful environment. Approximately one-fifth of all ICD insertions are associated with complications. In a retrospective review of over 1000 ICD insertions, 7% of the complications observed were due to inadequate fixation, resulting in dislodgement. The risk of dislodgement is greatest during transit or transfer of a casualty. In a military setting, this may involve movement of a casualty in a non-permissive environment and includes transfer on and off rotary wing, fixed wing, road vehicle and maritime transport platforms as well as between stretchers and hospital beds. While ICD insertion follows a standard technique in accordance with the Advanced Trauma Life Support guidelines, the method of securing ICDs has not been standardised across the Defence Medical Services (DMS). The aim of this paper is to first propose a modified version of a tried and tested technique of securing ICDs with alternative steps described for medical staff unfamiliar with surgical knot tying by hand. Second, we present the results from a pilot validation study of this technique when introduced to candidates on a trauma surgical skills course. We describe and demonstrate a robust, easily teachable and reproducible technique for securing ICDs. We would advocate the use of this technique among both surgically and non-surgically trained medical personnel and suggest that this should become the standardised technique for securing ICDs across the DMS. This could be easily implemented by introducing this technique into the various military trauma courses, for example the Military Operational Surgical Training, Medical Emergency Response Team and Critical Care Air Support Team courses.

Parental use and acceptance of an accessible, commercially available intraoral camera for teledentistry in their children.

PURPOSE: The potential of combining teledentistry and engaging parents as underutilised resources to monitor paediatric dental health was emphasised during the COVID-19 pandemic and remains underexplored. This study aims to assess parental acceptance and use of a commercially available intraoral camera (IOC) for effective remote monitoring. METHODS: 47 child-parent dyads, where the parent was the main caregiver and the child was treated under general anaesthesia for early childhood caries, were recruited. Caregivers were trained to image their child's teeth on a commercially available IOC. Subsequently, submitted images were reviewed asynchronously by dentists for image quality, presence of dislodged fillings, abscesses, cavitation, and oral hygiene. Post-surgery monitoring was performed using teledentistry at 1 and 2 months and in-person at 4 months. A modified Telehealth Usability Questionnaire (TUQ) was used to record caregiver acceptance for study procedures. RESULTS: A mean TUQ of 6.09 out of 7 was scored by caregivers. Caregiver-reported issues were limited to problems with technique and child uncooperativeness. The number of clear images during the second teledentistry review was improved compared to the first (p = 0.007). 68% of children liked having images of their teeth taken. CONCLUSION: This study supports the feasibility of using an IOC as a clinically appropriate avenue for teledentistry with a high level of caregiver-child acceptance.

Can population differences in chemotherapy outcomes be inferred from differences in pharmacogenetic frequencies?

Inter-ethnic differences in drug handling and frequencies of pharmacogenetic variants are increasingly being characterized. In this study, we systematically assessed the feasibility of inferring ethnic trends in chemotherapy outcomes from inter-ethnic differences in pharmacogenetic variant frequencies. Frequencies of 51 variants and chemotherapy outcomes of East Asian and Caucasian colorectal cancer patients on standard chemotherapy regimens were summarized by meta-analyses, and variant frequencies were validated by MassARRAY analysis. Inferences of relative chemotherapy outcomes were made by considering minor allele function and population differences in their frequency. Significant population differences in genotype distributions were observed for 13/23 (60%) and 27/35 (77%) variants in the meta-analyses and validation series, respectively. Across chemotherapy regimens, East Asians had lower rates of grade 3/4 toxicity for diarrhea and stomatitis/mucositis than Caucasians, which was correctly inferred from 13/18 (72%, P=0.018) informative genetic variants. With appropriate variant selection, inferring relative population toxicity rates from population genotype differences may be relevant.

Quantum device designing (QDD) for future semiconductor engineering.

In semiconductor device history, a trend is observed where narrowing and increasing the number of material layers improve device functionality, with diodes, transistors, thyristors, and superlattices following this trend. While superlattices promise unique functionality, they are not widely adopted due to a technology barrier, requiring advanced fabrication, such as molecular beam epitaxy and lattice-matched materials. Here, a method to design quantum devices using amorphous materials and physical vapor deposition is presented. It is shown that the multiplication gain M depends on the number of layers of the superlattice, N, as M = kN, with k as a factor indicating the efficiency of multiplication. This M is, however, a trade-off with transit time, which also depends on N. To demonstrate, photodetector devices are fabricated on Si, with the superlattice of Se and As2Se3, and characterized using current-voltage (I-V) and current-time (I-T) measurements. For superlattices with the total layer thicknesses of 200 nm and 2 µm, the results show that k200nm = 0.916 and k2µm = 0.384, respectively. The results confirm that the multiplication factor is related to the number of superlattice layers, showing the effectiveness of the design approach.

Tea Consumption and Depression from Follow Up in the Singapore Longitudinal Ageing Study.

OBJECTIVES: Experimental evidence suggest that tea polyphenols have anti-depressant effect and tea consumption may reduce the risk and severity of depression. We investigated whether tea consumption was associated with changes in depressive symptoms over time among Asian older adults. DESIGN: Population-based prospective cohort study with mean 4 years of follow up. SETTING: Singapore Longitudinal Ageing Study (SLAS) of community-living older persons. PARTICIPANTS: 3177 participants overall (mean age 67 years) and 3004 participants who were depression-free at baseline. MEASUREMENTS: Baseline tea consumption which include Chinese (black, oolong or green) tea or Western (mixed with milk) tea and change in Geriatric Depression Scale (GDS) measure of depression. Incident depression was defined by GDS≥5, and GDS depression improvement or deterioration by GDS change of ≥4 points. Estimated odds ratio and 95% confidence intervals (OR, 95%CI) were adjusted for baseline age, sex, ethnicity, education, housing type, single/divorced/widowed, living alone, physical and social activity, smoking, alcohol, number of comorbidities, MMSE, and baseline GDS level. RESULTS: Compared to non-tea drinkers, participants who consumed ≥3 cups of tea of all kinds were significantly less likely to have worsened GDS symptoms: OR=0.32, 95% CI=0.12, 0.84. Among baseline depression-free participants, the risk of incident GDS (≥5) depression was significantly lower (OR=0.34, 95%CI=0.13, 0.90) for daily consumption of all types of tea, and Chinese (black, oolong or green) tea (OR=0.46, 95%CI=0.21,0.99). CONCLUSION: This study suggests that tea may prevent the worsening of existing depressive symptoms and the reduce the likelihood of developing threshold depression.

Nutritional Status and Risks of Cognitive Decline and Incident Neurocognitive Disorders: Singapore Longitudinal Ageing Studies.

BACKGROUND: Studies suggest that nutritional interventions using the whole diet approach such as the Mediterranean diet may delay cognitive decline and dementia onset. However, substantial numbers of older adults are non-adherent to any ideally healthy dietary pattern and are at risk of malnutrition. OBJECTIVE: The present study investigated the relationship between global malnutrition risk and onsets of cognitive decline and neurocognitive disorders (NCD), including mild cognitive impairment (MCI) or dementia in community-dwelling older adults. METHODS: Participants aged ≥ 55 years in the Singapore Longitudinal Ageing Studies (SLAS) were assessed at baseline using the Elderly Nutritional Indicators for Geriatric Malnutrition Assessment (ENIGMA) and followed up 3-5 years subsequently on cognitive decline (MMSE drop ≥ 2) among 3128 dementia-free individuals, and incident neurocognitive disorders (NCD) among 2640 cognitive normal individuals. RESULTS: Individuals at high nutritional risk score (≥ 3) were more likely to develop cognitive decline (OR=1.42, 95%CI=1.01-1.99) and incident MCI-or-dementia (OR=1.64, 95%CI=1.03-2.59), controlling for age, sex, ethnicity, low education, APOE-e4, hearing loss, physical, social, and mental activities, depressive symptoms, smoking, alcohol, central obesity, hypertension, diabetes, low HDL, high triglyceride, cardiac disease, and stroke. Among ENIGMA component indicators, low albumin at baseline was associated with cognitive decline and incident NCD, and 5 or more drugs used, few fruits/vegetables/milk products daily, and low total cholesterol were associated with incident NCD. CONCLUSION: The ENIGMA measure of global malnutrition risk predicts cognitive decline and incident neurocognitive disorders, suggesting the feasibility of identifying vulnerable subpopulations of older adults for correction of malnutrition risk to prevent neurocognitive disorders.

Functional polymorphisms in the BRCA1 promoter influence transcription and are associated with decreased risk for breast cancer in Chinese women.

BACKGROUND: The BRCA1 gene is an important breast-cancer susceptibility gene. Promoter polymorphisms can alter the binding affinity of transcription factors, changing transcriptional activity and may affect susceptibility to disease. METHODS AND RESULTS: Using direct sequencing of the BRCA1 promoter region, we identified four polymorphisms c.-2804T-->C (rs799908:T-->C), c.-2265C-->T (rs11655505:C-->T), c.-2004A-->G (rs799906:A-->G) and c.-1896(ACA)(1)-->(ACA)(2) (rs8176071:(ACA)(1)-->(ACA)(2)) present in Hong Kong Chinese. Each polymorphism was studied independently and in combination by functional assays. Although all four variants significantly altered promoter activity, the c.-2265T allele had stronger binding than the C allele, and the most common mutant haplotype, which contains the c.-2265T allele, increased promoter activity by 70%. Risk association first tested in Hong Kong Chinese women with breast cancer and age-matched controls and replicated in a large population-based study of Shanghai Chinese, together totalling >3000 participants, showed that carriers of the c.-2265T allele had a reduced risk for breast cancer (combined odd ratio (OR) = 0.80, 95% CI 0.69 to 0.93; p = 0.003) which was more evident among women aged >or=45 years at first diagnosis of breast cancer and without a family history of breast cancer (combined OR = 0.75, 95% CI 0.61 to 0.91; p = 0.004). The most common haplotype containing the c.-2265T allele also showed significant risk association for women aged >or=45 years without a family history of breast cancer (OR = 0.64, 95% CI 0.46 to 0.89; p = 0.008). CONCLUSION: This comprehensive study of BRCA1 promoter polymorphisms found four variants that altered promoter activity and with the most significant contribution from c.-2265C-->T, which could affect susceptibility to breast cancer in the Chinese population. Its significance in other populations remains to be investigated.

An insight into cathode options for microbial fuel cells.

Microbial fuel cell (MFC) is an emerging and promising technology, particularly in the field of wastewater treatment. The MFC capability of achieving organic removal and generating in situ electricity could make it an attractive alternative wastewater treatment technology over conventional treatment technologies. However, MFC is still far from being economically viable, especially because of the cost of the platinum (Pt) catalyst that makes possible the reaction at the cathode. In this study, we tested alternative cathode catalysts, namely sputter-deposited Cobalt (Co) and denitrifying bacteria (biocathode). The performance of these innovative cathodes was compared with that of classic Pt-cathodes. Co competed well with Pt, but further research is still required for biocathodes. However, biocathodes MFC have showed promise.

International consensus (ICON) on functional and aesthetic rhinoplasty.

During the 2017 IFOS international congress in Paris, a roundtable discussion on the topic of functional and aesthetic rhinoplasty was organised. Five experts, from the five continents and renown in the field of rhinoplasty, were brought together to discuss the issue from an international perspective and to put forward a consensus or on the contrary practical differences. Five questions were put to the experts beforehand to guarantee independent answers, which were then discussed during the roundtable. The questions were the following: - What are the age limits for achieving a rhinoplasty? - Do you use objective measurements before, during and after surgery? (facial landmarks, airflow, peroperative measurements) - How do you manage the preoperative general information and computer imaging of the patient? - What are the indications in your practice to perform a CT-scan or endoscopic examination before doing a rhinoplasty? - What kind of graft or prosthesis do you use for an augmentation rhinoplasty? This paper offers a synthesis of the roundtable based on the experts' answers to the different questions.

Induction of matrix metalloproteinases by Epstein-Barr virus latent membrane protein 1 isolated from nasopharyngeal carcinoma.

Epstein--Barr virus latent infection is associated with human malignancies including Burkitt's lymphoma, gastric carcinoma and the highly invasive nasopharyngeal carcinoma (NPC). Increased expression of EBV latent membrane protein 1, LMP1, is correlated with tumor progression and metastasis in NPC. LMP1 induces cellular proteins including cytokines and matrix metalloproteinases (e.g., MMP1, MMP2 and MMP9). MMPs are endopeptidases involved in the degradation of extracellular matrix proteins; and their upregulation in cancer implicates their potential role in tumor metastasis. In light of the role of LMP1 in cytokine dysregulation and the fact that MMPs are regulated by cytokines, we examined whether LMP1 promotes NPC metastasis via the induction of MMPs. To delineate the oncogenic role of LMP1 in NPC, we first investigated the induction of MMP1, MMP2, MMP3 and MMP9 in LMP1-positive NPC tumor samples (n=15) by quantitative RT-PCR. We showed a significant induction of MMP1 and MMP3 transcripts in the EBV LMP1-positive NPC tissues, compared with biopsies obtained from the adjacent non-tumor tissues. To investigate the role of LMP1 in MMP expression in NPC, we cloned the LMP1 gene from NPC samples and transiently expressed it in MRC5 cells (human lung fibroblasts). Following transfection, a time-dependent elevation of endogenous MMP3 expression was found in the LMP1-transfectants by quantitative RT-PCR and Western analysis. Taken together, we observed that MMP3 is upregulated in LMP1-positive NPC tumors and LMP1-expression in fibroblasts is associated with MMP3 and cytokine expression. Our results suggest that LMP1 may contribute to invasiveness of NPC cells via the expression of MMP3 in fibroblasts.

Marginal ulcer perforation: a single center experience.

PURPOSE: Marginal ulcer (MU) is defined as ulcer on the jejunal side of the gastrojejunostomy (GJ) anastomosis. Most MUs are managed medically but those with complications like bleeding or perforation require intervention. It is recommended that GJ anastomosis be revised in patients with MU perforation (MUP). The aim of this case series is to study the clinical presentation and management of MUP. METHODS: Three hundred and thirty-two patients who underwent emergency surgery for perforated peptic ulcer at a single center were studied over a period of 5 years. RESULTS: Nine patients (2.7 %) presented with MUP. GJ was previously done for either complicated peptic ulcer (n = 4) or for suspected gastric malignancy (n = 5). Two patients had previously completed H. pylori therapy. None of the patients presented with septic shock. MU was on the jejunal side of GJ in all patients. The median MUP size was 10 mm. Four patients (44.4 %) had omental patch repair, three (33.3 %) had primary closure, and one each had revision of GJ and jejunal serosal patch repair. There were no leaks, intra-abdominal abscess or reoperation and no malignancies. CONCLUSION: MUP patients do not present with septic shock. Omental patch repair or primary closure is sufficient enough. Revision of Billroth-II-GJ into Roux-en-Y-GJ is not mandatory.

Chemotherapy as an adjunct to radiotherapy in locally advanced nasopharyngeal carcinoma.

BACKGROUND: A previous meta-analysis investigated the role of chemotherapy in head and neck locally advanced carcinoma. This work had not been performed on nasopharyngeal carcinoma. OBJECTIVES: The aim of the project was to study the effect of adding chemotherapy to radiotherapy on overall survival (OS) and event-free survival (EFS) in patients with nasopharyngeal carcinoma. SEARCH STRATEGY: We searched MEDLINE (1966 to October 2003), EMBASE (1980 to October 2003) and the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 3, 2003) and trial registers. Handsearches of meeting abstracts, references in review articles and of the Chinese medical literature were carried out. Experts and pharmaceutical companies were asked to identify trials. SELECTION CRITERIA: Randomised trials comparing chemotherapy plus radiotherapy to radiotherapy alone in locally advanced nasopharyngeal carcinoma were included. DATA COLLECTION AND ANALYSIS: The meta-analysis was based on updated individual patient data. The log rank test, stratified by trial, was used for comparisons and the hazard ratios (HR) of death and failure (loco-regional/distant failure or death) were calculated. MAIN RESULTS: Eight trials with 1753 patients were included. One trial with a 2 x 2 design was counted twice in the analysis. The analysis was performed including 11 comparisons based on 1975 patients. The median follow up was six years. The pooled hazard ratio of death was 0.82 (95% confidence interval (CI) 0.71 to 0.95; P = 0.006) corresponding to an absolute survival benefit of 6% at five years from chemotherapy (from 56% to 62%). The pooled hazard ratio of tumour failure or death was 0.76 (95% CI 0.67 to 0.86; P < 0.00001) corresponding to an absolute event-free survival benefit of 10% at five years from chemotherapy (from 42% to 52%). A significant interaction was observed between chemotherapy timings and overall survival (P = 0.005), explaining the heterogeneity observed in the treatment effect (P = 0.03) with the highest benefit from concomitant chemotherapy. AUTHORS' CONCLUSIONS: Chemotherapy led to a small but significant benefit for overall survival and event-free survival. This benefit was essentially observed when chemotherapy was administered concomitantly with radiotherapy.

Five year experience in management of perforated peptic ulcer and validation of common mortality risk prediction models - are existing models sufficient? A retrospective cohort study.

BACKGROUND: Emergency surgery for perforated peptic ulcer (PPU) is associated with significant morbidity and mortality. Accurate and early risk stratification is important. The primary aim of this study is to validate the various existing MRPMs and secondary aim is to audit our experience of managing PPU. METHODS: 332 patients who underwent emergency surgery for PPU at a single intuition from January 2008 to December 2012 were studied. Clinical and operative details were collected. Four MRPMs: American Society of Anesthesiology (ASA) score, Boey's score, Mannheim peritonitis index (MPI) and Peptic ulcer perforation (PULP) score were validated. RESULTS: Median age was 54.7 years (range 17-109 years) with male predominance (82.5%). 61.7% presented within 24 h of onset of abdominal pain. Median length of stay was 7 days (range 2-137 days). Intra-abdominal collection, leakage, re-operation and 30-day mortality rates were 8.1%, 2.1%, 1.2% and 7.2% respectively. All the four MRPMs predicted intra-abdominal collection and mortality; however, only MPI predicted leak (p = 0.01) and re-operation (p = 0.02) rates. The area under curve for predicting mortality was 75%, 72%, 77.2% and 75% for ASA score, Boey's score, MPI and PULP score respectively. DISCUSSION AND CONCLUSION: Emergency surgery for PPU has low morbidity and mortality in our experience. MPI is the only scoring system which predicts all - intra-abdominal collection, leak, reoperation and mortality. All four MRPMs had a similar and fair accuracy to predict mortality, however due to geographic and demographic diversity and inherent weaknesses of exiting MRPMs, quest for development of an ideal model should continue.

SAA1 polymorphisms are associated with variation in antiangiogenic and tumor-suppressive activities in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a cancer that occurs in high frequency in Southern China. A previous functional complementation approach and the subsequent cDNA microarray analysis have identified that serum amyloid A1 (SAA1) is an NPC candidate tumor suppressor gene. SAA1 belongs to a family of acute-phase proteins that are encoded by five polymorphic coding alleles. The SAA1 genotyping results showed that only three SAA1 isoforms (SAA1.1, 1.3 and 1.5) were observed in both Hong Kong NPC patients and healthy individuals. This study aims to determine the functional role of SAA1 polymorphisms in tumor progression and to investigate the relationship between SAA1 polymorphisms and NPC risk. Indeed, we have shown that restoration of SAA1.1 and 1.3 in the SAA1-deficient NPC cell lines could suppress tumor formation and angiogenesis in vitro and in vivo. The secreted SAA1.1 and SAA1.3 proteins can block cell adhesion and induce apoptosis in the vascular endothelial cells. In contrast, the SAA1.5 cannot induce apoptosis or inhibit angiogenesis because of its weaker binding affinity to αVß3 integrin. This can explain why SAA1.5 has no tumor-suppressive effects. Furthermore, the NPC tumors with this particular SAA1.5/1.5 genotype showed higher levels of SAA1 gene expression, and SAA1.1 and 1.3 alleles were preferentially inactivated in tumor tissues that were examined. These findings further strengthen the conclusion for the defective function of SAA1.5 in suppression of tumor formation and angiogenesis. Interestingly, the frequency of the SAA1.5/1.5 genotype in NPC patients was ~2-fold higher than in the healthy individuals (P=0.00128, odds ratio=2.28), which indicates that this SAA1 genotype is significantly associated with a higher NPC risk. Collectively, this homozygous SAA1.5/1.5 genotype appears to be a recessive susceptibility gene, which has lost the antiangiogenic function, whereas SAA1.1 and SAA1.3 are the dominant alleles of the tumor suppressor phenotype.

A phase II study of ifosfamide, 5-fluorouracil and leucovorin in patients with recurrent nasopharyngeal carcinoma previously treated with platinum chemotherapy.

The aim of this study was to evaluate the efficacy and toxicity of ifosfamide, 5-fluorouracil (5-FU) and leucovorin (IFL) as a second-line chemotherapy regimen in patients with recurrent undifferentiated nasopharyngeal carcinoma (NPC) previously treated with platinum/5-FU. Between June 1997 and February 1999, 18 patients were entered into the study. 3 patients had loco-regional recurrence, 12 had distant metastases and 3 had both loco-regional recurrence and distant metastases. All patients had previously received platinum/5-FU as adjuvant or palliative treatments. The IFL regimen consisting of ifosfamide 1.2 g/m(2) (with mesna), 5-FU 375 mg/m(2) and leucovorin 20 mg/m(2) for 5 days and was repeated every 21 days. The dose of ifosfamide was escalated to 1.4 and 1.6 g/m(2) in subsequent cycles according to the bone marrow toxicity, and the dose of 5-FU to 450 and 525 mg/m(2) according to the severity of mucositis. Patients received a median of 3 cycles of IFL (range: 2-6), with a median total ifosfamide dose of 21 g/m(2) (range: 13-46) and a median total 5-FU dose of 6.75 g/m(2) (range: 4.1-14.7). The median follow-up was 10 months (range: 4-25). 9 patients (50%) achieved a partial response and 1 patient (6%) achieved a complete response, with an overall response rate of 56% (95% confidence interval (CI): 32-80%). For those patients who responded to IFL, 8 had subsequent disease progression on follow-up, with a median response duration of 7.1 months (95% CI: 5.3-8.9). The median time to progression for all patients was 6.5 months (95% CI: 4.2-8.7). 12 patients are still alive with an estimated 1-year survival probability rate of 51%. Treatments were well tolerated, only 1 patient had grade 3 emesis. None of the patients had grade 3/4 anaemia, leucopenia or thrombocytopenia, although IFL was discontinued in 1 patient because of persisting thrombocytopenia. IFL is an effective second-line regimen in patients with recurrent NPC and is well tolerated with mild toxicity. Combining platinum and IFL in chemonaïve patients may further improve the overall response rate and duration and is worth investigating in future trials.

A new tool for dose conformity evaluation of radiosurgery treatment plans.

PURPOSE: A novel method for dose conformity evaluation of treatment plans produced by the stereotactic radiosurgery treatment planning system is postulated. METHODS AND MATERIALS: By consolidating the information contained in the integral dose-volume histogram and the treatment volume ratio, a plot of treatment volume ratio versus percentage dose may be considered as a useful tool for plan evaluation. To validate the suggested argument, two simple experiments simulating the conformal and nonconformal cases were conducted on the geometric phantom that is commercially available from Radionics. An actual patient treatment plan is also included to explore the effectiveness of the proposed parameters. It is an attempt to establish the baseline of a conformal plan. RESULTS: A plot showed the ability to give the user an idea whether the size of the collimator was adequate to cover the delineated lesion when the user-defined criteria had been in place. Two parameters, namely take-off dose (TOD) and take-off volume (TOV) were defined. The former was defined as the maximum dose level found on the surface of the target volume. The TOD is also the maximum possible dose to be received by the adjacent normal tissue. The latter was defined as the percentage of the target volume that received the TOD. Another parameter, irradiated percentage volume (IPV), was defined here as the percentage of the target volume receiving at least the prescribed dose. When the prescribed dose is also the TOD, the IPV becomes the TOV. They were proved to be effective in evaluating the dose conformity. Another term known as equivalent fall-off distance (EFOD) was defined as the equivalent radial distance calculated between two isodose lines. In fact, the dose fall-off rate can also act as a measuring index for plan comparison, because a fast dose fall-off rate is often a requirement for radiosurgery in order to minimize the risk of radiation damage to the surrounding structures. The two phantom studies showed consistent results with the theoretical predictions. The ability of the plot was further explored in the patient treatment plan studies. It was demonstrated that the plot had a remarkable ability to check whether the hot spot is in the vicinity of the lesion. A baseline of a conformal plan was also established; for example, a plan is said to be conformal if its IPV has attained a value of not less than 95% and its associated TVR is not greater than 2. CONCLUSION: The proposed method has demonstrated the effectiveness in dose conformity evaluation. It supplements the integral dose-volume histogram to provide a complete information of a treatment plan in terms of dose uniformity and conformity.

Tumor control probability of nasopharyngeal carcinoma: a comparison of different mathematical models.

PURPOSE: Radiation dose and tumor volume are factors known to affect the local control of a given type of tumor. Local tumor control is a major factor to consider when a treatment plan is evaluated. This article reports the correlation between tumor control probability, dose, and volume in a retrospective study of 142 patients with nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS: The tumor volume was outlined and calculated from a computed tomographic scan. Patients were categorized according to tumor volume and radiation dose received in treatment. Local control rate was calculated for each category by the Kaplan-Meier method. Mathematical models were fitted to correlate the local control rate, dose, and volume. Both empirical and mechanistic approaches were attempted; the former included logistic models with two and three parameters, and the latter, the formulation from Brenner and Bentzen with a radiobiological basis. RESULTS: Brenner's model estimated alpha at 0.041 Gy(-1) with 95% confidence limits (-0.032, 0.113) Gy(-1). The volume dependent constant h was estimated at 0.160 cm(-3) with 95% confidence limits (-0.729, 1.048) cm(-3). The Pearson correlation coefficient was 0.64. The magnitude and sign of the fitted parameters were reasonable and consistent with reported clinical experience. The other models were fitted with slightly better goodness of fit (r = 0.65 - 0.68), but with less interpretable parameters. CONCLUSION: Brenner's model is considered appropriate for a description of the dose and volume effect on the local control of the NPC. It could be used in combination with normal tissue complication probability for treatment plan evaluation to optimize treatment results.

The effect of interruptions and prolonged treatment time in radiotherapy for nasopharyngeal carcinoma.

PURPOSE: The effect of interruptions and prolonged overall treatment time in radiotherapy for nasopharyngeal carcinoma and the significance of timing of interruption was investigated. METHODS AND MATERIALS: Treatment records of 229 patients treated with continuous course (CC) and 567 patients treated with split course (SC) radiotherapy for nonmetastatic NPC were reviewed. Overall treatment time without inclusion of time for boost was calculated. Treatment that extended 1 week beyond scheduled time was considered prolonged. Outcome in patients who completed treatment "per schedule" were compared with those who had "prolonged" treatment. Because of known patient selection bias between CC and SC, patients on the two schedules were analyzed separately. Multivariate analysis was performed for patients on SC. Total number of days of interruption, age, sex, T and N stage, and the use of boost were tested for the whole SC group. Analysis on the effect of timing of interruption was performed in a subgroup of 223 patients on SC who had a single unplanned interruption. Timing of interruption, either before or after the fourth week for the unplanned interruption, was tested in addition to the other variables in multivariate analysis for this subgroup of SC. RESULTS: Twenty-seven (11.8%) patients on CC and 96 (16.9%) patients on SC had prolonged treatment. Patients on SC who had prolonged treatment had significantly poorer loco-regional control rate and disease free survival when compared with those who completed radiotherapy per schedule (p = 0.0063 and 0.001, respectively, with adjustment for stage). For CC, the effect of prolonged treatment on outcome was not significant. The small number of events for patients on CC probably account for the insignificant finding. The number of days of interruption was confirmed as prognostic factor, independent of T and N stages, for loco-regional control and disease-free survival in multivariate analysis for SC. The hazard rate for loco-regional failure increased by 3.3% for each day of interruption. The timing of interruption, at the beginning or towards end of treatment, did not significantly alter outcome. CONCLUSION: Interruptions and prolonged treatment adversely affect outcome in radiotherapy for NPC and the effect of repopulation was confirmed. Every effort should be made to keep treatment on schedule and interruptions for whatever reasons should be minimized.