5-EPIFAT trial protocol: a multi-center, randomized, placebo-controlled trial of the efficacy of pharmacotherapy for fatigue using methylphenidate, bupropion, ginseng, and amantadine in advanced cancer patients on active treatment.

BACKGROUND: Cancer-related fatigue (CRF) is still undertreated in most patients, as evidence for pharmacological treatments is limited and conflicting. Also, the efficacy of the pharmacological agents relative to each other is still unclear. Therefore, medications that may potentially contribute to improving CRF will be investigated in this head-to-head trial. Our main objective is to compare the efficacy of methylphenidate vs. bupropion vs. ginseng vs. amantadine vs. placebo in patients with advanced cancer. METHODS: The 5-EPIFAT study is a 5-arm, randomized, multi-blind, placebo-controlled, multicenter trial that will use a parallel-group design with an equal allocation ratio comparing the efficacy and safety of four medications (Methylphenidate vs. Bupropion vs. Ginseng vs. Amantadine) versus placebo for management of CRF. We will recruit 255 adult patients with advanced cancer who experience fatigue intensity ≥ 4 based on a 0-10 scale. The study period includes a 4-week intervention and a 4-week follow-up with repeated measurements over time. The primary outcome is the cancer-related fatigue level over time, which will be measured by the functional assessment of chronic illness therapy-fatigue (FACIT-F) scale. To evaluate safety, the secondary outcome is the symptomatic adverse events, which will be assessed using the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events in cancer clinical trials (PRO-CTCAE). Also, a subgroup analysis based on a decision tree-based machine learning algorithm will be employed for the clinical prediction of different agents in homogeneous subgroups. DISCUSSION: The findings of the 5-EPIFAT trial could be helpful to guide clinical decision-making, personalization treatment approach, design of future trials, as well as the development of CRF management guidelines. TRIAL REGISTRATION: IRCT.ir IRCT20150302021307N6. Registered on 13 May 2023.

[89Zr]-Atezolizumab-PET Imaging Reveals Longitudinal Alterations in PDL1 during Therapy in TNBC Preclinical Models.

Triple-negative breast cancers (TNBCs) currently have limited treatment options; however, PD-L1 is an indicator of susceptibility to immunotherapy. Currently, assessment of PD-L1 is limited to biopsy samples. These limitations may be overcome with molecular imaging. In this work, we describe chemistry development and optimization, in vitro, in vivo, and dosimetry of [89Zr]-Atezolizumab for PD-L1 imaging. Atezolizumab was conjugated to DFO and radiolabeled with 89Zr. Tumor uptake and heterogeneity in TNBC xenograft and patient-derived xenograft (PDX) mouse models were quantified following [89Zr]-Atezolizumab-PET imaging. PD-L1 expression in TNBC PDX models undergoing therapy and immunohistochemistry (IHC) was used to validate imaging. SUV from PET imaging was quantified and used to identify heterogeneity. PET/CT imaging using [89Zr]-Atezolizumab identified a significant increase in tumor:muscle SUVmean 1 and 4 days after niraparib therapy and revealed an increased trend in PD-L1 expression following other cytotoxic therapies. A preliminary dosimetry study indicated the organs that will receive a higher dose are the spleen, adrenals, kidneys, and liver. [89Zr]-Atezolizumab PET/CT imaging reveals potential for the noninvasive detection of PD-L1-positive TNBC tumors and allows for quantitative and longitudinal assessment. This has potential significance for understanding tumor heterogeneity and monitoring early expression changes in PD-L1 induced by therapy.

Evaluating potential overuse of surveillance care in cancer survivors.

BACKGROUND: Survivorship care plans (SCPs) communicate cancer-related information from oncology providers to patients and primary care providers. SCPs may limit overuse testing by specifying necessary follow-up care. From a randomized, controlled trial of SCP delivery, we examined whether cancer-related tests not specified in SCPs, but conducted after SCP receipt, were appropriate or consistent with overuse. METHODS: Survivors of breast, colorectal, or prostate cancer treated at urban-academic or rural-community health systems were randomized to one of three SCP delivery arms. Tests during 18 months after SCP receipt were classified as consistent with overuse if they were (1) not included in SCPs and (2) on a guideline-based predetermined list of "not recommended surveillance." After chart abstraction, physicians performed review and adjudication of potential overuse. Descriptive analyses were conducted of tests consistent with overuse. Negative binomial regression models determined if testing consistent with overuse differed across study arms. RESULTS: Among 316 patients (137 breast, 67 colorectal, 112 prostate), 140 individual tests were identified as potential overuse. Upon review, 98 were deemed to be consistent with overuse: 78 tumor markers and 20 imaging tests. The majority of overuse testing was breast cancer-related (95%). Across sites, 27 patients (9%) received ≥1 test consistent with overuse; most were breast cancer patients (22/27). Exploratory analyses of overuse test frequency by study arm showed no significant difference. CONCLUSIONS: This analysis identified practice patterns consistent with overuse of surveillance testing and can inform efforts to improve guideline-concordant care. Future interventions may include individual practice patterns and provider education.

Preferences and Insights for Participation in a Rheumatoid Arthritis Clinical Prevention Trial: A Mixed-Methods Study.

OBJECTIVE: In rheumatoid arthritis (RA), anti-citrullinated protein antibodies (ACPA) can be elevated prior to inflammatory arthritis (IA). The potential to intervene in people with ACPA positivity underpins the development of prevention trials in RA. The Research Participation Influences Study examined factors influencing the decisions of individuals who are ACPA(+) to participate in a prevention trial using qualitative and quantitative methods. METHODS: Individuals with ACPA positivity without IA were provided information regarding their risk for future RA, were provided a description of a clinical prevention trial using hydroxychloroquine, and were asked if they would participate in the trial. After agreeing to or declining participation, they were surveyed on what influenced their decision using Likert scales and open-response questions. RESULTS: Thirty-nine individuals who agreed to trial participation (enrollees) and 31 individuals who declined (nonenrollees) completed surveys. Enrollees expressed greater perceived risk for RA and greater perception of benefit to themselves or others than nonenrollees. Nonenrollees expressed greater concern about medication effects and less personal or family experience with RA than enrollees. There was a higher proportion of first-degree relatives (FDRs) of people with RA in enrollees versus nonenrollees (54% vs. 23%, P = 0.01). CONCLUSION: Enrollees were more likely than nonenrollees to be FDRs, exhibit stronger concern for personal risk for RA, and have less concern about adverse effects. Further exploration is needed to determine why these differences were present, including exploration of symptoms and the role of family history. Understanding these issues will better inform researchers and individuals who are candidates for prevention.

Proteasome-dependent truncation of the negative heterochromatin regulator Epe1 mediates antifungal resistance.

Epe1 histone demethylase restricts H3K9-methylation-dependent heterochromatin, preventing it from spreading over, and silencing, gene-containing regions in fission yeast. External stress induces an adaptive response allowing heterochromatin island formation that confers resistance on surviving wild-type lineages. Here we investigate the mechanism by which Epe1 is regulated in response to stress. Exposure to caffeine or antifungals results in Epe1 ubiquitylation and proteasome-dependent removal of the N-terminal 150 residues from Epe1, generating truncated Epe1 (tEpe1) which accumulates in the cytoplasm. Constitutive tEpe1 expression increases H3K9 methylation over several chromosomal regions, reducing expression of underlying genes and enhancing resistance. Reciprocally, constitutive non-cleavable Epe1 expression decreases resistance. tEpe1-mediated resistance requires a functional JmjC demethylase domain. Moreover, caffeine-induced Epe1-to-tEpe1 cleavage is dependent on an intact cell integrity MAP kinase stress signaling pathway, mutations in which alter resistance. Thus, environmental changes elicit a mechanism that curtails the function of this key epigenetic modifier, allowing heterochromatin to reprogram gene expression, thereby bestowing resistance to some cells within a population. H3K9me-heterochromatin components are conserved in human and crop-plant fungal pathogens for which a limited number of antifungals exist. Our findings reveal how transient heterochromatin-dependent antifungal resistant epimutations develop and thus inform on how they might be countered.

A PRO-cision medicine intervention to personalize cancer care using patient-reported outcomes: intervention development and feasibility-testing.

PURPOSE: PRO-cision medicine refers to personalizing care using patient-reported outcomes (PROs). We developed and feasibility-tested a PRO-cision Medicine remote PRO monitoring intervention designed to identify symptoms and reduce the frequency of routine in-person visits. METHODS: We conducted focus groups and one-on-one interviews with metastatic breast (n = 15) and prostate (n = 15) cancer patients and clinicians (n = 10) to elicit their perspectives on a PRO-cision Medicine intervention's design, value, and concerns. We then feasibility-tested the intervention in 24 patients with metastatic breast cancer over 6-months. We obtained feedback via end-of-study surveys (patients) and interviews (clinicians). RESULTS: Focus group and interview participants reported that remote PRO symptom reporting could alert clinicians to issues and avoid unneeded/unwanted visits. However, some patients did not perceive avoiding visits as beneficial. Clinicians were concerned about workflow. In the feasibility-test, 24/236 screened patients (10%) enrolled. Many patients were already being seen less frequently than monthly (n = 97) or clinicians did not feel comfortable seeing them less frequently than monthly (n = 31). Over the 6-month study, there were 75 total alerts from 392 PRO symptom assessments (average 0.19 alert/assessment). Patients had an average of 4 in-person visits (vs. expected 6.5 without the intervention). Patients (n = 19/24) reported high support on the end-of-study survey, with more than 80% agreeing with positive statements about the intervention. Clinician end-of-study interviews (n = 11/14) suggested that PRO symptom monitoring be added to clinic visits, rather than replacing them, and noted the increasing role of telemedicine. CONCLUSIONS: Future research should explore combining remote PRO symptom monitoring with telemedicine and in-person visits.

Simplifying Survivorship Care Planning: A Randomized Controlled Trial Comparing 3 Care Plan Delivery Approaches.

BACKGROUND: Survivorship care plans seek to improve the transition to survivorship, but the required resources present implementation barriers. This randomized controlled trial aimed to identify the simplest, most effective approach for survivorship care planning. METHODS: Stage 1-3 breast, colorectal, and prostate cancer patients aged 21 years or older completing treatment were recruited from an urban-academic and rural-community cancer center. Participants were randomly assigned, stratified by recruitment site and cancer type 1:1:1 to a mailed plan, plan delivered during a 1-time transition visit, or plan delivered during a transition visit plus 6-month follow-up visit. Health service use data were collected from participants and medical records for 18 months. The primary outcome, receipt of all plan-recommended care, was compared across intervention arms using logistic regression adjusting for cancer type and recruitment site, with P less than .05 considered statistically significant. RESULTS: Of 378 participants randomly assigned, 159 (42.1%) were breast, 142 (37.6%) prostate, and 77 (20.4%) colorectal cancer survivors; 207 (54.8%) from the academic site and 171 (45.2%) from the community site; 316 were analyzable for the primary outcome. There was no difference across arms in the proportion of participants receiving all plan-recommended care: 45.2% mail, 50.5% 1-visit, 42.7% 2-visit (2-sided P = .60). Adherence by cancer type for mail, 1-visit, and 2-visit, respectively, was 52.2%, 53.3%, and 40.0% for breast cancer; 48.6%, 64.1%, and 57.1% for prostate cancer; and 23.8%, 19.0%, and 26.1% for colorectal cancer. There were no statistically significant interactions by recruitment site or cancer type. CONCLUSIONS: This study did not find differences in receipt of recommended follow-up care by plan delivery approach. Feasibility and other factors may determine the best approach for survivorship care planning.

Implementing survivorship care planning in two contrasting health systems: lessons learned from a randomized controlled trial.

OBJECTIVE: Survivorship care plans (SCPs) are recommended to promote appropriate follow-up care, but implementation has been limited. We conducted a randomized controlled trial comparing three SCP delivery models in two health systems. We utilize mixed methods to compare the feasibility and participants' perceived value of the three models. METHODS: Patients completing treatment for stage I-III breast, prostate, or colorectal cancer from one urban-academic and one rural community cancer center were randomized to (1) mailed SCP, (2) SCP delivered during an in-person survivorship visit, or (3) SCP delivered during an in-person survivorship visit plus 6-month follow-up. Clinics had flexibility in intervention implementation. Quantitative data summarize intervention fidelity and protocol deviations. Qualitative interview data provide patients' perspectives on feasibility and intervention value. RESULTS: Of 475 eligible participants approached, 378 (79%) were randomized. Of 345 SCPs delivered, 265 (76.8%) were by protocol. Protocol deviations were more common at the urban-academic center. In post-study qualitative interviews, participants recalled little about the SCP document or visit(s). SCPs were valued for information and care coordination, although their static nature was limiting, and sometimes SCP information differed from that provided elsewhere. Visits were opportunities for care and reassurance, but time and distance to the clinic were barriers. CONCLUSIONS: SCP provision was challenging. Patients were interested in SCP, but not necessarily additional survivorship visits, particularly at the urban-academic hospital. IMPLICATIONS FOR CANCER SURVIVORS: These findings suggest that patients value careful consideration of health care needs during the transition out of treatment; SCP documents are one element of this. For many patients, models without additional visits and dynamic SCPs may be preferred.

Oral lichen nitidus case report.

This case report aims to increase awareness that lichen nitidus may affect the mouth and therefore supports multidisciplinary management, particularly between dermatologists and dental professionals.

Real-Time Gain Control of PET Detectors and Evaluation With Challenging Radionuclides.

Accurate gain control of PET detectors is a prerequisite for quantitative accuracy. A shift in the 511 keV peak position can lead to errors in scatter correction, degrading quantitation. The PET detectors in a PET/MR scanner are subject to thermal transients due to eddy currents induced during gradient-intensive MRI sequences. Since the gain of silicon photomultiplier-based detectors changes with temperature, good gain control is particularly challenging. In this paper we describe a method that utilizes information from the entire singles spectrum to create a real-time gain control method that maintains gain of PET detectors stable within approximately ±0.5% (±2.5 keV) with varying levels of scatter and in the presence of significant thermal transients. We describe the methods used to combine information about multiple peaks and how this algorithm is implemented in a way that permits real-time processing on a field-programmable gate array. Simulations demonstrate rapid response time and stability. A method ("virtual scatter filter") is also described that extracts unscattered photopeak events from phantom data and demonstrates the accuracy of the photopeak for various radionuclides that emit energies in addition to the pure 511 keV annihilation peak. Radionuclides 52 Mn, 55 Co, 64 Cu, 89 Zr, 90 Y, and 124 I are included in the study for their various forms of spectral contamination.

Comparison of machine learning algorithms for the prediction of five-year survival in oral squamous cell carcinoma.

BACKGROUND/AIM: Machine learning analyses of cancer outcomes for oral cancer remain sparse compared to other types of cancer like breast or lung. The purpose of the present study was to compare the performance of machine learning algorithms in the prediction of global, recurrence-free five-year survival in oral cancer patients based on clinical and histopathological data. METHODS: Data were gathered retrospectively from 416 patients with oral squamous cell carcinoma. The data set was divided into training and test data set (75:25 split). Training performance of five machine learning algorithms (Logistic regression, K-nearest neighbours, Naïve Bayes, Decision tree and Random forest classifiers) for prediction was assessed by k-fold cross-validation. Variables used in the machine learning models were age, sex, pain symptoms, grade of lesion, lymphovascular invasion, extracapsular extension, perineural invasion, bone invasion and type of treatment. Variable importance was assessed and model performance on the testing data was assessed using receiver operating characteristic curves, accuracy, sensitivity, specificity and F1 score. RESULTS: The best performing model was the Decision tree classifier, followed by the Logistic Regression model (accuracy 76% and 60%, respectively). The Naïve Bayes model did not display any predictive value with 0% specificity. CONCLUSIONS: Machine learning presents a promising and accessible toolset for improving prediction of oral cancer outcomes. Our findings add to a growing body of evidence that Decision tree models are useful in models in predicting OSCC outcomes. We would advise that future similar studies explore a variety of machine learning models including Logistic regression to help evaluate model performance.

SpEDIT: A fast and efficient CRISPR/Cas9 method for fission yeast.

The CRISPR/Cas9 system allows scarless, marker-free genome editing. Current CRISPR/Cas9 systems for the fission yeast  Schizosaccharomyces pombe rely on tedious and time-consuming cloning procedures to introduce a specific sgRNA target sequence into a Cas9-expressing plasmid. In addition, Cas9 endonuclease has been reported to be toxic to fission yeast when constitutively overexpressed from the strong  adh1 promoter. To overcome these problems we have developed an improved system,  SpEDIT, that uses a synthesised Cas9 sequence codon-optimised for  S. pombe expressed from the medium strength  adh15 promoter. The  SpEDIT system exhibits a flexible modular design where the sgRNA is fused to the 3' end of the self-cleaving hepatitis delta virus (HDV) ribozyme, allowing expression of the sgRNA cassette to be driven by RNA polymerase III from a tRNA gene sequence. Lastly, the inclusion of sites for the  BsaI type IIS restriction enzyme flanking a GFP placeholder enables one-step Golden Gate mediated replacement of GFP with synthesized sgRNAs for expression. The  SpEDIT system allowed a 100% mutagenesis efficiency to be achieved when generating targeted point mutants in the  ade6 +  or  ura4 + genes by transformation of cells from asynchronous cultures.  SpEDIT also permitted insertion, tagging and deletion events to be obtained with minimal effort. Simultaneous editing of two independent non-homologous loci was also readily achieved. Importantly the  SpEDIT system displayed reduced toxicity compared to currently available  S. pombe editing systems. Thus,  SpEDIT provides an effective and user-friendly CRISPR/Cas9 procedure that significantly improves the genome editing toolbox for fission yeast.

Large domains of heterochromatin direct the formation of short mitotic chromosome loops.

During mitosis chromosomes reorganise into highly compact, rod-shaped forms, thought to consist of consecutive chromatin loops around a central protein scaffold. Condensin complexes are involved in chromatin compaction, but the contribution of other chromatin proteins, DNA sequence and histone modifications is less understood. A large region of fission yeast DNA inserted into a mouse chromosome was previously observed to adopt a mitotic organisation distinct from that of surrounding mouse DNA. Here, we show that a similar distinct structure is common to a large subset of insertion events in both mouse and human cells and is coincident with the presence of high levels of heterochromatic H3 lysine nine trimethylation (H3K9me3). Hi-C and microscopy indicate that the heterochromatinised fission yeast DNA is organised into smaller chromatin loops than flanking euchromatic mouse chromatin. We conclude that heterochromatin alters chromatin loop size, thus contributing to the distinct appearance of heterochromatin on mitotic chromosomes.

Epigenetic gene silencing by heterochromatin primes fungal resistance.

Heterochromatin that depends on histone H3 lysine 9 methylation (H3K9me) renders embedded genes transcriptionally silent1-3. In the fission yeast Schizosaccharomyces pombe, H3K9me heterochromatin can be transmitted through cell division provided the counteracting demethylase Epe1 is absent4,5. Heterochromatin heritability might allow wild-type cells under certain conditions to acquire epimutations, which could influence phenotype through unstable gene silencing rather than DNA change6,7. Here we show that heterochromatin-dependent epimutants resistant to caffeine arise in fission yeast grown with threshold levels of caffeine. Isolates with unstable resistance have distinct heterochromatin islands with reduced expression of embedded genes, including some whose mutation confers caffeine resistance. Forced heterochromatin formation at implicated loci confirms that resistance results from heterochromatin-mediated silencing. Our analyses reveal that epigenetic processes promote phenotypic plasticity, letting wild-type cells adapt to unfavourable environments without genetic alteration. In some isolates, subsequent or coincident gene-amplification events augment resistance. Caffeine affects two anti-silencing factors: Epe1 is downregulated, reducing its chromatin association, and a shortened isoform of Mst2 histone acetyltransferase is expressed. Thus, heterochromatin-dependent epimutation provides a bet-hedging strategy allowing cells to adapt transiently to insults while remaining genetically wild type. Isolates with unstable caffeine resistance show cross-resistance to antifungal agents, suggesting that related heterochromatin-dependent processes may contribute to resistance of plant and human fungal pathogens to such agents.

Perineural invasion in oral squamous cell carcinoma: Incidence, prognostic impact and molecular insight.

BACKGROUND: The objective of this study was to characterise the incidence and prognostic correlation of perineural invasion (PNI) in oral squamous cell carcinoma and determine whether nerve growth factor and its receptor tyrosine Kinase A expression could be used as biological markers for PNI. METHODS: A retrospective review of pathology reports of 430 patients with oral squamous cell carcinoma who were treated from 1992 to 2014 in Tayside, Scotland, was carried out. The expression of nerve growth factor and tyrosine kinase A was assessed with immunohistochemistry in 132 tissue sections of oral squamous cell carcinoma. RESULTS: Perineural invasion was identified in 17.4% of oral squamous cell carcinomas. High expression of nerve growth factor and tyrosine kinase A was seen in 84% and 92% of oral squamous cell carcinoma, respectively. Tumours with PNI expressed nerve growth factor and tyrosine kinase A with a greater frequency than tumours without PNI. PNI and high expression of nerve growth factor were significantly associated with pain. PNI was significantly associated with stage IV tumours and poor disease-specific survival. CONCLUSIONS: A higher level of expression of nerve growth factor and tyrosine kinase A may predict PNI and therefore may be considered as biological markers for PNI in oral squamous cell carcinoma. PNI and nerve growth factor overexpression may contribute to the pain generation in oral cancer patients. PNI and nerve growth factor expression can predict the aggressiveness and prognosis of oral squamous cell carcinoma patients.

Unique case of inverted papilloma of septum with nasopharyngeal carcinoma: Is it a metachronous tumour?

Inverted papilloma is a rare and benign tumour. It affects the nasal cavity and paranasal sinuses, has a high rate of recurrence and is associated with malignant transformation. Only few cases of a poorly differentiated carcinoma arising from inverted papilloma have been reported, none of which in the nasopharynx. We report a case of a 37-year-old female, who presented originally in 2012 with inverted papilloma of the nasal septum which was surgically resected. Nasopharyngeal biopsy from 2014 was reported as carcinoma in situ and treated with local endoscopic resection. Three years later she presented with a solitary lesion of the right Eustachian tube opening, confirmed as invasive poorly differentiated carcinoma. Imaging revealed T4 N2b M0 malignancy with skull base and prevertebral space invasion, likely extension into right temporal lobe and malignant adenopathy. Although rare, malignant transformation of inverted papilloma in unusual places should be considered during workup and monitoring of patients.

Hap2-Ino80-facilitated transcription promotes de novo establishment of CENP-A chromatin.

Centromeres are maintained epigenetically by the presence of CENP-A, an evolutionarily conserved histone H3 variant, which directs kinetochore assembly and hence centromere function. To identify factors that promote assembly of CENP-A chromatin, we affinity-selected solubilized fission yeast CENP-ACnp1 chromatin. All subunits of the Ino80 complex were enriched, including the auxiliary subunit Hap2. Chromatin association of Hap2 is Ies4-dependent. In addition to a role in maintenance of CENP-ACnp1 chromatin integrity at endogenous centromeres, Hap2 is required for de novo assembly of CENP-ACnp1 chromatin on naïve centromere DNA and promotes H3 turnover on centromere regions and other loci prone to CENP-ACnp1 deposition. Prior to CENP-ACnp1 chromatin assembly, Hap2 facilitates transcription from centromere DNA. These analyses suggest that Hap2-Ino80 destabilizes H3 nucleosomes on centromere DNA through transcription-coupled histone H3 turnover, driving the replacement of resident H3 nucleosomes with CENP-ACnp1 nucleosomes. These inherent properties define centromere DNA by directing a program that mediates CENP-ACnp1 assembly on appropriate sequences.

Nerve growth factor-induced migration in oral and salivary gland tumour cells utilises the PI3K/Akt signalling pathway: Is there a link to perineural invasion?

OBJECTIVES: The aims of this study were to investigate the role of nerve growth factor on perineural invasion in oral and salivary gland tumour cell lines and whether there is an involvement of PI3K/Akt pathway. MATERIALS AND METHODS: Four cell lines were investigated: HSG and TYS (salivary gland tumours), SAS-H1 (oral squamous cell carcinoma) and HaCaT (human skin keratinocyte). Initially, Boyden chamber assay was done to examine the effect of different concentration of nerve growth factor on cell migration. Western blot/ immunofluorescence techniques were used to investigate the phosphorylation status of the Akt pathway within the cells in response to nerve growth factor. The effect of this growth factor and the addition of an Akt inhibitor on cell morphology and migration were also examined using scatter/scratch assays. RESULTS: Nerve growth factor triggered the PI3K/Akt pathway in oral and salivary tumour cells and induced oral and salivary tumour cell scattering and migration. Inhibitor assays confirmed that oral and salivary gland tumour cell scattering and migration is Akt dependent. CONCLUSIONS: Nerve growth factor can stimulate scattering and migration in cells derived from oral and salivary gland tumours, thereby potentially enhancing perineural invasion. Phosphorylated Akt controls cancer cell migration and scattering. Blocking the Akt pathway may inhibit cell migration and therefore perineural invasion and metastasis.

The SmoCar Study: A Caribbean-Based Multicenter Study on the Prevalence and Disparities Linked to Smoking and Gingival Health.

The aim of the SmoCar (Smoking in the Caribbean) study was to estimate the prevalence of smoking and the disparities in the smoking practices of three regions in the Caribbean: Jamaica, Dominican Republic, and Puerto Rico. The secondary objective was to assess the prevalence and severity of gingivitis in relation to the smoking practices. The study population comprised 1,847 (weighted N = 1,830) individuals (18 years and older) who were volunteer participants from the capitals of Jamaica, Dominican Republic, and Puerto Rico. A structured interview was used to assess the participants' smoking behaviors. The gingival index was used to determine the extent of gingival inflammation. Polytomous regression was used to estimate the adjusted odds ratios (aORs) for smoking status (current, past, or never), according to risk factors (sex, age-group, education, marital status, tooth-brushing frequency, and city of residence). Logistic regression models were used to assess the associations between different smoking status variables and mild to moderate/severe gingivitis. The majority of the participants were never-smokers, with current smokers being found most commonly in Kingston (33.22%), followed by San Juan (12.76%) and Santo Domingo (8.8%). Both current (aOR = 2.22, 95% confidence interval [1.45, 3.40]) and past (aOR = 1.87, 95% confidence interval [1.19, 2.93]) smoking (vs. never smoking) was strongly associated with severe gingivitis. Smoking was the most prevalent in Jamaicans and the least prevalent in Dominicans. The study population of current smokers was found to have a fourfold increased risk of severe gingivitis and a twofold increased risk of moderate gingivitis.

Breast cancer survivorship care plans: what are they covering and how well do they align with national guidelines?

PURPOSE: Survivorship care plans (SCPs) provide key information about cancer treatment history and follow-up recommendations. We describe the completeness of breast cancer SCPs and evaluate guideline concordance of follow-up recommendations. METHODS: We analyzed 149 breast cancer SCPs from two sites, abstracting demographics, cancer/treatment details, surveillance plans, and health promotion advice. SCP recommendations and provided information were compared to American Cancer Society/American Society of Clinical Oncology and National Comprehensive Cancer Network guidelines. RESULTS: SCP information provided in > 90% of the plans included patient age; relevant providers; cancer stage; treatment details; and physical exam, mammogram, and health promotion recommendations. SCP components completed less frequently included post-treatment symptoms/side effects (67%). All SCPs at the community site were uniform but had the potential for oversurveillance if visits occurred every 3 months in years 1-2 or every 6 months in years 3-5 with multiple cancer providers. The academic site recommended three predominant patterns of follow-up: (1) primary care provider every 6-12 months; (2) cancer team every 3-6 months (year 1), every 6-12 months (years 4-5); and (3) alternating oncology providers every 3-6 months (years 1-2) then every 6 months. Compared to guidelines, these patterns recommend under- and oversurveillance at various times. Mammography recommendations showed guideline concordance (annual) for 84%, oversurveillance for 10%, and were incomplete for 6%. SCPs of only 12/79 (15%) women on aromatase inhibitors recommended guideline-concordant bone density testing. CONCLUSIONS: SCP content is more complete for demographic and treatment summary information but has follow-up recommendation gaps. Efforts to improve follow-up recommendations are needed.