Search

The majority of new nasopharyngeal cancer (NPC) cases occur in LMICs, but these patients experience poorer overall survival than patients in high income countries. The goal of this study was to determine whether the introduction of a radiotherapy quality assurance (RT QA) program can improve NPC patient outcomes in LMICs. Phase 1 was composed of a survey of RT resources, patient characteristics and treatment, and results of RT QA performed post treatment by the expert panel for 134 patients treated at 10 participating centers. Each center received a detailed RT QA report for every patient they treated. An educational workshop, which included review of all RT QA details for every patient treated during Phase 1, was conducted prior to centers accruing patients for Phase 2. In Phase 2, the feedback from the RT QA performed by the expert panel was given prior to patients commencing treatment to allow for pre-treatment implementation of RT QA feedback. The primary endpoints of the study are: 1) Difference in major protocol deviations (defined as major deviations in contour and/or dosimetry of GTVs, high dose PTV and critical organs at risk (OARs), and 2) comparison of 3-year progression free survival (PFS), between Phase 1 and 2 patient cohorts. The results of the first phase of this study showing 60.4% cases with major protocol deviations have been reported previously. We now report the RT QA findings in the second phase of this study. 154 patients were accrued from 9 centers. 106 (69%) cases were reviewed pre-treatment and 48 (31%) post-treatment. In the pre-treatment group there were 32/106 (30.2%) with major protocol deviations. Among them, one case was not resubmitted, while 31 cases were corrected and resubmitted with 20 assessed as acceptable and 11 remaining unacceptable. In the post-treatment reviews, 6/48 (12.5%) had major protocol deviations. Overall, there were 18/154 (11.7%) cases with major protocol deviations. Introduction of a RTQA program for NPC resulted in a significant reduction in major protocol deviations in Phase 2 compared to the baseline previously documented in Phase 1 (60.4% to 11.7%, p<0.001). At this time there is insufficient follow-up time for comparison of the 3-year PFS in each group, but we are hopeful the major improvement in RT planning quality will translate to future improvement in PFS. [ABSTRACT FROM AUTHOR]

This study investigates the integration of a cloud-native Radiation Oncology Clinical Decision Support (RO-CDS) system, Horizon, and an Automated Treatment Planning Framework in Australian Radiation Oncology centers. The aim is to evaluate the impact on standardization, consistent quality, and decreased variability, focusing on enhancing quality and efficiency within a standardized framework. Horizon involves more than 178 radiation oncologists at 43 centers in Australia, utilizing evidence-based Care Pathways (CPs) developed collaboratively with references like NCCN, EVIQ, and NICE. In the Automated Treatment Planning Framework, in 44 centers in Australia (urban and rural), utilizes Eclipse and Monaco systems. The study assesses compliance to CPs across 60% of the most common cancers prescribed with integrated automated planning, usability (System Usability Scale), and clinical workflow efficiency. It also looks at examining how the framework impacts on planning time, clinician approval rates, and dosimetry-related errors, with a focus on quality and efficiency improvement. Since 2018, Horizon has generated over 190,000 prescriptions, achieving 97% compliance and an SUS score of 84.2, indicating excellent usability. Implementation led to a 20-minute decrease in documentation time and prescription times averaged 3 minutes per patient, highlighting efficiency and consistent quality. The Automated Treatment Planning Framework, initiated in August 2021, processed >40,000 plans with a >50% clinician approval rate for >66.6% average automation utilization across >19 common tumor streams covering VMAT, IMRT, 3D CRT, and SBRT/SRS techniques. It reduced the average time between target volume delineation and plan approval by 25%, from 1.6 to 1.2 days. Dosimetrist productivity increased by 40%, with an 85-minute time saving per plan. A 72% reduction in dosimetry-related errors contributed to enhanced quality and efficiency. Integration of Horizon RO-CDS and the Automated Treatment Planning Framework successfully advances standardization, consistent quality, and efficiency in radiation oncology. Emphasizing adherence to evidence-based CPs, excellent usability, reduced planning time, and a significant decrease in dosimetry-related errors, this study aligns with physicians' perspectives on quality improvement in radiation oncology practices. It offers valuable insights for ongoing excellence in patient care and treatment planning within and beyond Australian Radiation Oncology centers. [ABSTRACT FROM AUTHOR]

As part of a program to reduce numbers of the human pathogen Campylobacter on retail chickens, 22 broiler processing lines, representing more than 90% of UK production, were characterized by enumerating Campylobacter on pooled neck skins after exsanguination, scalding, defeathering, evisceration, crop removal, inside-outside washing, and air-chilling stages of processing. Sixteen of the processing lines investigated showed significant (P < 0.05) reductions in Campylobacter numbers because of carcass scalding. However, in all of these lines, the following defeathering stage caused a significant increase in Campylobacter contamination that effectively negated the reductions caused by scalding. On four processing lines, primary chilling also caused a significant reduction in numbers of Campylobacter. On three lines, there was a significant microbiological benefit from inside-outside washing. The stages where Campylobacter numbers were reduced require further investigation to determine the specific mechanisms responsible so that the observed pathogen reductions can be optimized and then more widely implemented. The transfer of up to 4 log CFU Campylobacter per g of neck skin from a colonized flock to a following uncolonized flock was observed. Cross-contamination was substantial and still detectable after 5,000 carcasses from an uncolonized flock had been processed. Numbers of Campylobacter recovered from the uncolonized flocks were highest on the first of the uncolonized birds to pass along the line, and in general, the numbers declined as more uncolonized birds were processed. Air sampling recovered low numbers at the processing stages monitored, indicating that airborne transmission was unlikely to be the primary transfer mechanism operating for cross-contamination between flocks. Campylobacter spp. were enumerated at seven key stages on 22 chicken processing lines. Scalding, inside-outside washing, and chilling reduced Campylobacter numbers on some lines. Defeathering negated Campylobacter reductions caused by scalding. Campylobacter-positive birds cross-contaminated immediately following birds. Airborne transmission was unlikely to be the primary mechanism of between-flock transfer. [ABSTRACT FROM AUTHOR]

Because of concerns regarding the prevalence of Campylobacter in chicken meat, member countries in the European Union (EU) undertook a surveillance program to determine Campylobacter levels on chicken carcasses. A sample mass of 25 g principally composed of neck skin was used, although breast skin could also be used if there were insufficient neck skin to meet the required sample mass. The aim was to establish a baseline for Campylobacter contamination of carcasses against which future interventions could be assessed. However, in the United Kingdom researchers wanted to explore whether different ratios of neck to breast skin in samples could affect the results obtained. A comparison of the Campylobacter levels on neck and breast skin samples obtained from the same chilled chicken carcasses was undertaken at four chicken slaughterhouses. The neck skins were significantly more heavily contaminated (P < 0.05) with Campylobacter than was breast skin. Statistical analyses revealed no relationship that would allow a conversion between levels obtained on the two skin types. Ongoing surveillance of Campylobacter for 6 years was funded by United Kingdom poultry processors using samples consisting solely of neck skin, and the results of this surveillance (2011 to 2016) are reported here. Given the higher Campylobacter levels on a sample exclusively consisting of neck skin, this protocol could yield results with which the poultry industry would find it more difficult to achieve the contamination reduction target. The contamination reduction target for the United Kingdom (≤10% of chicken carcasses exceeding neck skin Campylobacter levels of 1,000 CFU/g) was not met by the end of 2015, the date stipulated by the United Kingdom government. Campylobacter levels on chicken neck and breast skin were compared. Neck skin was significantly more contaminated (P < 0.05) than breast skin. No relationship between the two skin types was found for Campylobacter levels. A UK government reduction target for highly contaminated chicken was not achieved. [ABSTRACT FROM AUTHOR]

Forward genetic screens using novel assays of nematode chemotaxis to soluble compounds identified three independent transposon-insertion mutations in the gene encoding the Caenorhabditis elegans dynein heavy chain (DHC) 1b isoform. These disruptions were mapped and cloned using a newly developed PCR-based transposon display. The mutations were demonstrated to be allelic to the che-3 genetic locus. This isoform of dynein shows temporally and spatially restricted expression in ciliated sensory neurons, and mutants show progressive developmental defects of the chemosensory cilia. These results are consistent with a role for this motor protein in the process of intraflagellar transport; DHC 1b acts in concert with a number of other proteins to establish and maintain the structural integrity of the ciliated sensory endings in C. elegans. Key Words: chemotaxis; cilium; flagella; nonmotile; dynein; IFT; DHC1b; taste.

Abstract: Direct crystallization is a convenient and generally efficient method to increase the optical purity of partially resolved enantiomers. The design of chiral purification processes based on crystallization requires measurement of solubility of all stable phases, i.e. enantiomers and racemic mixtures, in the process solvent. Enantiomeric systems have been classified by the nature of the solid phases formed as racemic compounds, conglomerates or solid solutions. In rare cases, however, enantiomers form crystalline addition compounds with a stoichiometry other than 1(S):1(R). These structures are generally known as “anomalous racemates”. The solubility and melting point diagrams of each type of enantiomeric system exhibit characteristic features which have significant implications on the efficiency of the crystallization to enhance optical purity. In this study, we report the formation of a non-equimolar 3:1 addition compound in the R/S 3-hydroxy-4-(2,4,5-trifluorophenyl) butanoic acid. [Copyright &y& Elsevier]

This study constitutes a planned secondary endpoint analysis of oncological and functional-related treatment outcome priorities of patients with HPVOPC before and after primary CRT/RT. Patients diagnosed with HPVOPC who were suitable for curative-intent primary CRT/RT were eligible to participate. Patient-reported outcome measures included a modified version of the Chicago Priorities Scale (CPS-modified), which incorporated a 'keeping my sexual function' item. The 13-item CPS-modified was administered before and 12 months after CRT/RT. Patients first classified items as top, middle and low priorities (≤6 items/group) and then ranked items within each priority group, resulting in a possible rank of 1 to 13 for each item. Only patients with valid item responses at both assessments were included in the analysis. Paired responses (top priority before and after CRT/RT) were compared with the exact McNemar test. From October 2020 to November 2021, 100 eligible patients were enrolled: median age 61 years (range 44-79), 87% male, 52% stage I and 97% receiving concurrent CRT. Of enrolled patients, 99/100 and 90/98 completed the CPS-modified before and after CRT/RT, respectively. Based on items classified as a top priority, the top five priorities were consistent over time (before/after CRT/RT): 'being cured of my cancer' (93%/91%), 'living as long as possible' (69%/66%), 'being able to swallow all foods and drinks' (56%/56%), 'having a normal amount of energy' (51%/48%) and 'having no pain' (51%/48%). Compared with before CRT/RT, more patients classified 'keeping my normal sense of taste and smell' and 'having a comfortably moist mouth' as a top priority 12 months after CRT/RT (26%/44%, p = 0.002; and 19%/39%, p = 0.003, respectively). After CRT/RT, 'being cured of my cancer' and 'living as long as possible' were ranked '1' (of all 13 items) by 73% and 12% of patients, respectively. The frequency with which patients ranked the swallowing item above other highly prioritized items after CRT/RT were: 'being cured of my cancer (14%), 'living as long as possible' (36%), 'having no pain' (47%), 'having a normal amount of energy' (54%), 'keeping my normal sense of taste and smell' (54%) and 'having a comfortably moist mouth' (66%). For HPVOPC patients, the most important oncological and functional-related treatment priorities remain stable before and after treatment. While HPVOPC survivors in this study frequently ranked swallowing within their top survivorship priorities, nearly half (44%) did not, and only 14% ranked it higher than being cured of their cancer. Patient priorities should be considered when designing aggressive de-escalation treatment strategies. [ABSTRACT FROM AUTHOR]

This study constitutes the final analysis of self-reported sexual health, facial appearance, and appearance distress outcomes in HPVOPC patients treated with primary CRT/RT from before to 24 months after CRT/RT. Eligible patients had HPVOPC and were planned for curative CRT/RT. Patients were assessed before treatment (BL), week 7 of treatment (W7), and 3, 12 and 24 months after CRT/RT (3m, 12m and 24m). Study outcomes were assessed with the EORTC SHQ22 and relevant FACE-Q modules (Appearance and Appearance distress). Linear mixed models (LMM) were used to analyze outcome data. 100 eligible patients were enrolled: median age 61y (range 44-79), 87% male, 77% partnered, 95% heterosexual, stage I disease (52%) and treated with CRT (97%). At 12m and 24m, 91% and 77% completed the SHQ22, and 93% and 74% completed the FACE-Q modules. Analysis of BL SHQ22 scores through 12m (primary analysis) indicated that sexual satisfaction, libido, sex life affected by fatigue, sexual activity affected by treatment, confidence in an erection, and feeling less masculine were significantly impacted at W7 and 3m after CRT/RT (>10-point difference, all p<0.001). Sexual satisfaction, libido, and sex affected by fatigue all returned to near-BL levels at 12m (<5-point difference, all p>0.10). Score differences on the remaining items were still significant at 12m (all p<0.05). Score differences between BL and 24m, and 12m and 24m (secondary analysis) indicated minimal differences between both sets of scores on most SHQ22 scales/items. However, at 24m, men were still feeling less masculine compared with BL (-9, 95% CI = -15, -2, p = 0.001), with little change between 12m and 24m (0, 95% CI = -6, 7, p = 0.89). Conversely, on average, the impact of treatment on sexual activity decreased between 12m and 24m, and the difference between scores at BL and 24m was not significant (-5, 95% CI = -14, 4, p = 0.26). Similarly, on average, differences in erection confidence at BL and 24m was not significant (0, 95% CI = -10, 9, p = 0.92). Score differences on sexual pain and insecurity with partner were minimal at all follow-up assessments through to 24m (<5-point difference, all p>0.10). LMM results for FACE-Q module scores BL through 24m indicated worse appearance distress at W7 (-10, 95% CI = -16, -4, p<0.001), but not 3m (-5, 95% CI = -11, 0), 12m (-2, 95% CI = -8, 4) or 24m (-3, 95% CI = -10, 3) compared to BL. In contrast, appearance scores were relatively stable from BL to 24m (global p = 0.12). By 24m after RT/CRT, treatment affecting sexual activity and erection confidence items had shown ongoing improvement from 12m to 24m to recover to BL scores. Appearance distress, but not facial appearance, was worse in the last week of treatment but showed improvement by 3m. [ABSTRACT FROM AUTHOR]

High CD103+ intratumoral immune cell (ITIC) abundance is associated with better prognosis in unselected patients with human papilloma virus-associated oropharyngeal squamous cell carcinoma (HPV-associated OPSCC) treated with cisplatin and radiotherapy (CIS/RT). Substituting cetuximab (CETUX) for CIS with RT in HPV-associated OPSCC resulted in inferior efficacy. Our aim was to determine whether quantification of CD103 ITIC could be used to identify a population of HPV-associated OPSCC with superior prognosis. We pooled data from the TROG 12.01 and De-ESCALaTE randomized trials that compared CETUX/70GyRT with CIS/70GyRT in low-risk HPV-associated OPSCC: American Joint Committee on Cancer 7 stage III (excluding T1-2N1) or stage IV (excluding N2b-c if smoking history >10 pack-years and/or distant metastases), including all patients with available tumor samples. The primary endpoint was failure-free survival (FFS) in patients receiving CETUX/RT comparing CD103+ ITIC high (≥30%) versus low (<30%). High and low CD103 were compared using Cox regression adjusting for age, stage and trial. Tumor samples were available in 159/182 patients on TROG 12.01 and 145/334 on De-ESCALaTE. CD103+ ITIC abundance was high in 27% of patients. The median follow-up was 3.2 years. The 3-year FFS in patients treated with CETUX/RT was 93% [95% confidence interval (CI) 79% to 98%] in high CD103 and 74% (95% CI 63% to 81%) in low CD103 [adjusted hazard ratio = 0.22 (95% CI 0.12-0.41), P < 0.001]. The 3-year overall survival in patients treated with CETUX/RT was 100% in high CD103 and 86% (95% CI 76% to 92%) in low CD103, P < 0.001. In patients treated with CIS/RT, there was no significant difference in FFS. CD103+ ITIC expression separates CETUX/RT-treated low-risk HPV-associated OPSCC into excellent and poor prognosis subgroups. The high CD103 population is a rational target for de-intensification trials. • ITIC CD103 expression separates CETUX/RT-treated low-risk HPV-OPSCC into good and poor prognosis groups. • There was an increase in distant and locoregional failures in the low CD103 population treated with CETUX/RT. • In a low-risk HPV-OPSCC population, weekly CIS/RT achieves excellent outcomes in both high and low CD103 groups. • In the high CD103 population, CIS/RT and CETUX/RT achieve similar excellent outcomes. • CD103 expression stratifies CETUX/RT-treated patients with abundant CD8 tumor-infiltrating lymphocytes into distinct prognostic groups. [ABSTRACT FROM AUTHOR]

This study constitutes a planned secondary endpoint analysis from a longitudinal unmet needs study. The aim was to: (1) describe FCR outcomes 12m after RT/CRT; (2) examine associations between FCR severity scores 12m after RT/CRT and patient and disease characteristics and other patient-reported outcomes (PROs); and (3) to evaluate preferred FCR referral pathways. Eligible HPVOPC patients scheduled for curative RT/CRT were approached for enrolment. FCR was assessed with the 42-item Fear of Cancer Recurrence Inventory (FCRI) 12m after RT/CRT, as were patients' preferences for FCR referral pathways, using customized questions. Optimism (LOT-R) and resilience (Connor-Davidson Resilience Scale) were assessed at enrolment. Health-related quality of life (HRQL, EORTC QLQ-C30), disease-specific symptom severity and interference (MDASI-HN) and emotional distress (PROMIS Anxiety 7a, Depression 8a) were assessed 12m after RT/CRT. A total of 100/129 eligible patients were enrolled between October 2020 and November 2021. 85/93 (91%) alive patients without recurrence completed the FCRI; patients were mostly men (n = 73, 86%), with a median age of 60 years (range 44-77). A majority had stage I disease (n = 46, 54%) and received CRT (n = 82, 96%). The mean FCRI total score was 45.4 (SD = 26.3, range 0-102, possible range 0-168). The mean FCRI severity score was 12.1 (SD = 7.4, median = 11.0, range 0-29); 13%, 31% and 56% of respondents scored in the severe (≥22), moderate (>12-22) and low (≤12) range, respectively. Univariable regression analysis indicated that lower resilience, lower HRQL (global health status, all functional domains), higher emotional distress (anxiety, depression), and higher symptom severity and interference were associated with higher FCR severity scores 12m after RT/CRT. Apart from lower levels of education, associations between FCRI severity scores and other patient and disease factors were not statistically significant. If FCR had been a problem (n = 66), 86%, 44%, 14% and 5% of patients indicated they would like to discuss it with their oncologist, primary care physician, a psychologist or nurse, respectively (multiple responses allowed). If specific FCR interventions were available, 70/85 indicated their preferred sources for delivery (ordered by median rank) were oncologist, primary care physician, psychologist or nurse (tied), self-management or group sessions (tied). Almost half of HPVOPC patients reported moderate-to-severe FCR 12m after RT/CRT. Increased FCR severity was associated with education and self-reported resilience at baseline and with other measures of HRQL, toxicity and emotional distress at 12m. While patients view oncologists as central in FCR management, education about the benefits of other FCR-reducing approaches may be necessary. [ABSTRACT FROM AUTHOR]

This secondary analysis aimed to identify HNSS and HRQL trajectories during and following CRT for HPVOPC. All 182 evaluable TROG 12.01 patients were included. HNSS was assessed with the MDASI-HN (range 0-10) at baseline (BL), weekly during CRT (weeks (w) 1-7) and then 1, 3, 5, 9 and 13w and 6, 12 and 24 months (m) post CRT. HRQL was assessed using the FACT-G (range 0-108) at BL, and 7w, 6m, 12m and 24m post CRT. Latent class growth mixture modelling (LCMM) was performed to identify trajectories. Mean estimates and 95% confidence intervals (CI) were calculated at each time point. The HNSS model identified 4 trajectory classes (HNSS1-4) distinguished by differences in HNSS at BL, during the peak of treatment symptoms (w7 CRT/1w post CRT) and during early (1w to 9w post CRT) and intermediate recovery (9w to 12m post CRT). The trajectories of all 4 classes were stable beyond 12m. The reference trajectory (HNSS4, n=74) score was 0.1 (CI 0.1-0.2) at BL, peaking at 4.6 (CI 4.2-5.0), with rapid early recovery (1.1, CI 0.8-2.2) and gradual improvement to 12m (0.6, CI 0.5-0.8). HNSS2 ("high BL", n=30) reported higher BL scores (1.4, CI 0.8-2.0) but was otherwise similar, HNSS3 ("low acute", n=53) reported reduced acute symptoms (2.5, CI 2.2-2.9) with stable scores beyond 9w post CRT (1.1, CI 0.9-1.4). HNSS1 ("slow recovery", n=25) had slower recovery from an acute peak of 4.9 (CI 4.3-5.6) to 0.9 (CI 0.6-1.3) at 12m. Compared to HNSS4, the high BL group were younger (mean 53.6 vs 57.4), with fewer ECOG0 (87 vs 99%) or with higher degree (38 vs 69%), and higher baseline anxiety (HADS, mean 6.8 vs 4.4). The low acute group were older (mean 60.1), had fewer ECOG0 patients (87%) and were more likely to have received cetuximab (68% vs 43%). The slow recovery group had fewer with a higher degree (52%). The HRQL model included 2 trajectory classes. The reference trajectory (HRQL2, n=156) scores were 90 (CI 88-92) at BL, similar 7w post CRT (88, CI 85-90) with slow but clinically meaningful improvement to 12m (98, CI 96-100). HRQL1 (n=26) had lower BL mean scores (80, CI 74-86), with a significant decline at 7w post CRT (57, CI 50-63) and a slower recovery to BL scores over 12m (83, CI 72-94). Both trajectories were flat beyond 12m. The slow recovery group were older (mean 61.1 vs 56.8), with worse BL anxiety (mean 6.5 vs 4.4) and depression (mean 4.5 vs 2.1). In addition, LCMM identified 4 trajectories for head and neck symptom interference, 3 for anxiety and 4 for depression, which will be presented. LCMM identified distinct trajectories of HNSS and HRQL during and after CRT. These and their associations with variations in HPVOPC patients' characteristics and treatment factors provide clinically relevant insights into identifying patients who may require increased support during and after CRT. [ABSTRACT FROM AUTHOR]

Background Despite the association with more advanced nodal stage, patients with human papillomavirus (HPV) positive oropharyngeal cancers have better outcomes. We examined whether the HPV can modify the effect of known prognostic factors in tonsillar cancer. Patients and methods A total of 489 patients from 10 centres were followed up for recurrence or death for a median of 3.2 years. Determinants of the rate of locoregional recurrence, death from tonsillar cancer and overall survival were modelled using Cox regression. Results The prognostic value of T and N stages were modified by HPV as indicated by statistically significant interaction terms. After adjusting for age, gender and treatment, T stage appeared relevant only for HPV-positive cancers (where a higher T stage was associated with worse outcomes). There was some evidence that N stage was a more relevant prognostic factor for HPV-negative than -positive cancers. There was no evidence that the HPV modifies the effect of age, gender or grade on outcomes. Conclusions This study suggests that the prognostic significance of the conventional staging system in tonsillar cancer is modified by HPV. [ABSTRACT FROM PUBLISHER]

Abstract: Aims: Parotid-sparing radiotherapy (PSRT) was introduced for patients with selected head and neck cancer requiring bilateral upper-neck irradiation at our centre in 2000. The aim of this study was to compare the subjective degree of xerostomia in patients treated with PSRT between January 2000 and June 2003 with patients treated using conventional techniques (radiotherapy) over the same period. Materials and methods: Eligible patients were required to have completed treatment 6 months previously and be recurrence-free at the time of interview. PSRT was defined as conformal radiotherapy, in which the mean dose to at least one parotid gland was 33Gy or less, as determined by the dose–volume histogram. Patients receiving radiotherapy were treated with standard parallel-opposed fields, such that both parotids received a minimum of 40Gy. Xerostomia was assessed using a validated questionnaire containing six questions with a rating between 0 and 10. Lower scores indicated less difficulty with xerostomia. Results: Thirty-eight eligible patients treated with PSRT were identified: 25 with oropharyngeal cancer and 13 with nasopharyngeal cancer (NPC). The mean overall questionnaire score (Q1–5) for this group was 4.20 (standard error=0.33). Forty-four patients (24 oropharyngeal, 21 NPC) treated with radiotherapy over the same period were eligible. The mean overall questionnaire score (Q1–5) for this group was 5.86 (standard error=0.35). The difference in mean overall scores between the two groups of patients was statistically significant (P <0.001), as were the scores for four of the six individual questions. Conclusion: These results suggest that PSRT offers improved long-term xerostomia-related quality of life compared with conventional radiotherapy. [Copyright &y& Elsevier]