Human Epidermal Growth Factor Receptor 2-Low Breast Cancer Brain Metastases: An Opportunity for Targeted Systemic Therapies in a High-Need Patient Population.

PURPOSE: Trastuzumab deruxtecan is a new treatment option for patients with advanced human epidermal growth factor receptor 2 (HER2)-low breast cancer (BC). Although HER2-low status has been characterized in early and advanced BC, it has yet to be fully characterized in brain metastases (BrM). METHODS: Patients who underwent surgery for BC BrM at Sunnybrook Health Sciences Centre and for whom HER2 status was available on resected BrM were studied. Estrogen receptor, progesterone receptor, and HER2 status were assessed on the basis of ASCO/College of American Pathologists (CAP) guidelines. HER2-zero was defined as immunohistochemistry (IHC) 0; HER2-low was defined as IHC 1+ or IHC 2+ with fluorescence in situ hybridization (FISH)-negative status. HER2-positive (HER2+) was defined as IHC 3+ or IHC 2+ with positive FISH. Clinicopathologic features were recorded. We also assessed the prognostic association between extent of HER2 expression and (1) brain-specific progression-free survival (bsPFS), as well as (2) overall survival (OS). RESULTS: In this retrospective cohort of 102 patients with resected BC BrM, 53% (n = 54) were HER2+, 29.4% (n = 30) were HER2-low, and 17.6% (n = 18) had HER2-zero status. Among BrM that were triple-negative on the basis of ASCO/CAP guidelines, 63.6% (n = 14/22) were reclassified as being HER2-low. Sixty percent (n = 15/25) of BrM that were hormone receptor-positive/HER2-negative (HR+/HER2-) were reclassified as being HER2-low. In total, 51 patients had matched primary breast and BrM tissue available; results of HER2 status when categorized as HER2-zero, HER2-low, and HER2+ were concordant in 82.3% (n = 42/51) of cases (Cohen's kappa, 0.58; P = .07). There was no significant association between HER2-zero, HER2-low, and HER2+ status in BrM and either bsPFS or OS. CONCLUSION: Among patients with surgically resected BrM, a high proportion of those with metastatic triple-negative BC and HR+/HER2- disease have HER2-low BrM with potential to benefit from HER2-targeted therapy.

Brain Metastases in the Setting of Stable Versus Progressing Extracranial Disease Among Patients With Metastatic Breast Cancer.

INTRODUCTION: Women with metastatic breast cancer (BC) are at risk of developing brain metastases (BrM), which may result in significant morbidity and mortality. Given the emergence of systemic therapies with activity in the brain, more breast oncology clinical trials include patients with BrM, but most require extracranial disease progression for trial participation. METHODS: We evaluated the proportion of patients with BC BrM who have intracranial disease progression in the setting of stable extracranial disease in a retrospective cohort study of 751 patients treated between 2008 and 2018 at the Sunnybrook Odette Cancer. Extracranial disease progression was defined as any progression outside of the brain within 4 weeks of a patient's local/regional treatment. Clinical/pathologic characteristics and outcomes were also abstracted from patients' medical records. RESULTS: Of 752 patients in the cohort, 691 were included in our study. Sixty-one patients were excluded due to the presence of a second primary tumor or uncertain tissue origin of the BrM. BC subtype based on the primary tumor was known for 592 (85.6%) patients; 33.1% (n = 196) had HER2+ disease, 40% (n = 237) had HR+/HER2- disease, and 26.9% (n = 159) had triple negative BC. Extracranial disease status was available for 677 patients (98%); 41.1% (n = 284/691) had stable extracranial disease and 56.8% (n = 393/691) had extracranial disease progression within 4 weeks of treatment for BrM. DISCUSSION: A high proportion of patients with BC BrM (41.1%) would be excluded from clinical trials due to stable extracranial disease. Efforts should be made to design trials for this patient population.

Patterns of treatment and outcomes of patients with brain-only metastatic breast cancer.

BACKGROUND: We characterized the risk factors and survival of metastatic breast cancer (MBC) patients with brain metastases (BrM) as the first and only site of disease in a large, retrospective cohort. METHODS: MBC patients treated for BrM with radiation at a quaternary institution between 2005 and 2019 were identified. MBC patients with BrM but without concurrent extracranial metastases (ECM) or leptomeningeal disease (LMD) were classified as brain-only. Factors associated with brain-only MBC, brain-specific progression free survival (bsPFS) and overall survival (OS) were investigated. RESULTS: A total of 691 patients with MBC and BrM were analyzed. Among them, 67 patients (9.7%, n = 67/691) presented with brain-only MBC without concurrent ECM/LMD. Within this subgroup, 40 patients (5.8%, n = 40/691) remained free of any ECM or LMD, while 17 patients (2.5%) developed LMD, and 10 patients (1.4%%) developed ECM with a median follow-up of 8 months (IQR 2-35). Patients with brain-only MBC were more likely to have a single BrM [OR 3.41 (1.62-7.19), p = 0.001] and either HER2+ [OR 3.3 (1.13-9.65), p = 0.03] or TNBC [OR 4.09 (1.42-11.74), p = 0.009] subtypes. Patients who presented with brain-only MBC also had significantly longer OS [HR 0.45, (0.22-0.86), p = 0.008] and a trend toward longer bsPFS [HR 0.67 (0.44-1.03), p = 0.05] compared to those with concurrent ECM/LMD. CONCLUSION: Patients with brain-only MBC had a longer bsPFS and OS than those with ECM. Patients with HER2+ and TNBC were more likely to have brain-only disease compared to those with HR+/HER2- MBC.

Androgen Receptor Is Expressed in the Majority of Breast Cancer Brain Metastases and Is Subtype-Dependent.

We aimed to evaluate the expression of the "targetable" androgen receptor (AR) in breast cancer brain metastases (BrM). An established, retrospective 57-patient cohort with metastatic breast cancer who underwent surgery for BrM at the Sunnybrook Odette Cancer Centre between 1999-2013 was studied. AR expression in BrM samples was assessed in triplicate using immunohistochemistry (IHC). AR positive status was defined as nuclear AR expression ≥ 10% by IHC using the SP107 antibody. The median age of patients was 52 years (range 32-85 years). 28 (49%) of BrM were HER2+, 17 (30%) were hormone receptor positive (HR+)/HER2-, and 12 (21%) were triple negative breast cancers (TNBCs). 56% (n = 32/57) of BrM were AR positive, and median AR expression was 20% (CI 1.6-38.3%). AR expression was different across breast cancer subtypes; AR was most frequently expressed in HER2+ (n = 21/28), followed by HR+/HER2- (n = 9/17), and lowest in TNBC (n = 2/12) BrM (p = 0.003). Patients with AR positive versus AR negative BrM had similar overall survival (12.5 vs. 7.9 months, p = 0.6), brain-specific progression-free survival (8.0 vs. 5.1 months, p = 0.95), and time from breast cancer diagnosis to BrM diagnosis (51 vs. 29 months, p = 0.16). AR is expressed in the majority of breast cancer BrM and represents a potential therapeutic target.

Disclosure of HIV-serodiscordant relationships and association with viral suppression: results from the Positive Plus One study.

BACKGROUND: Little is known about the effects of disclosure of HIV-serodiscordant relationships on clinical outcomes. We aimed to evaluate the effect of relationship disclosure on HIV viral suppression, and hypothesized that disclosure by HIV-positive and HIV-negative partners would be associated with viral suppression in the HIV-positive partner. METHODS: We conducted a Canadian national online and telephone-administered survey of HIV-positive and HIV-negative partners in serodiscordant relationships. The primary outcome was self-reported viral suppression. Multivariable analyses were undertaken using Firth logistic regression. RESULTS: We recruited 540 participants in current serodiscordant relationships (n = 228 HIV-negative; n = 312 HIV-positive). Similar proportions of HIV-positive and HIV-negative partners disclosed their relationship to healthcare professionals (82% v. 76%, p = 0.13). Among HIV-positive partners, disclosure of the relationship to healthcare professionals increased the odds of viral suppression (aOR = 4.7; CI: 2.13, 10.51) after adjusting for age, education, and relationship turmoil due to HIV. Increasing age (aOR = 1.28; 95% CI = 1.07, 1.55) and education (aOR = 2.43; 95% CI = 1.15, 5.26) were also associated with viral suppression. Among HIV-negative partners, relationship disclosure was not associated with viral suppression and HIV-negative heterosexual men were less likely to report that their HIV-positive partners were virally suppressed (aOR = 0.24; CI: 0.09, 0.61). CONCLUSIONS: Disclosure of HIV-serodiscordant status by HIV-positive participants to healthcare professionals was associated with increased odds of viral suppression. Similar effects were not evident among HIV-negative participants. Future work should explore factors that empower relationship disclosure and incorporate them into supportive services for HIV-serodiscordant relationships.

A national recruitment strategy for HIV-serodiscordant partners living in Canada for the Positive Plus One study: a mixed-methods study.

BACKGROUND: With the recent shift in focus to addressing HIV risk within relationships and couple-based interventions to prevent HIV transmission, successful recruitment of individuals involved in HIV-serodiscordant relationships is crucial. This paper evaluates methods used by the Positive Plus One (PP1) study to recruit and collect data on a diverse national sample of dyads and individuals involved in current or past HIV-serodiscordant relationships, discusses the strengths and limitations of the recruitment approach, and makes recommendations to inform the interpretation of study results and the design of future studies. METHODS: PP1 used a multi-pronged approach to recruit adults involved in a current or past HIV-serodiscordant relationship in Canada from 2016 to 2018 to complete a survey and an interview. Upon survey completion, index (first recruited) partners were invited to recruit their primary current HIV-serodiscordant partner. We investigated participant enrollment by recruitment source, participant-, relationship-, and dyad-level sociodemographic characteristics, missing data, and correlates of participation for individuals recruited by their partners. RESULTS: We recruited 613 participants (355 HIV-positive; 258 HIV-negative) across 10 Canadian provinces, including 153 complete dyads and 307 individuals who participated alone, and representing 460 HIV-serodiscordant relationships. Among those in current relationships, HIV-positive participants were more likely than HIV-negative participants to learn of the study through an ASO staff member (36% v. 20%, p < 0.001), ASO listserv/newsletter (12% v. 5%, p = 0.007), or physician/staff at a clinic (20% v. 11%, p = 0.006). HIV-negative participants involved in current relationships were more likely than HIV-positive participants to learn of the study through their partner (46% v. 8%, p < 0.001). Seventy-eight percent of index participants invited their primary HIV-serodiscordant partner to participate, and 40% were successful. Successful recruitment of primary partners was associated with longer relationship duration, higher relationship satisfaction, and a virally suppressed HIV-positive partner. CONCLUSIONS: Our findings provide important new information on and support the use of a multi-pronged approach to recruit HIV-positive and HIV-negative individuals involved in HIV-serodiscordant relationships in Canada. More creative strategies are needed to help index partners recruit their partner in relationships with lower satisfaction and shorter duration and further minimize the risk of "happy couple" bias.

A competing risk analysis of colorectal cancer recurrence after curative surgery.

BACKGROUND: This study examines the effect of prognostic patient and disease characteristics on colorectal cancer (CRC) recurrence after curative resection. We used competing risk analysis with death as a competing risk. This method provides the clinician a perspective into a patient's actual risk of experiencing a recurrence. METHODS: A retrospective cohort study of patients diagnosed with CRC who underwent curative resection for CRC from 2003-2007 at the Royal University Hospital in Saskatoon was completed. The outcome of interest was the first CRC recurrence, either local or distant metastasis. Demographic data, tumor characteristics, adjuvant treatment and follow-up data, date of local recurrence or metastasis were recorded from the medical record. Univariate analysis was completed to look at the relationship between each of the prognostic indicators and recurrence. Multivariable modelling (subdistribution regression modelling) was done to identify the main risk factors in determining recurrence. RESULTS: Of 148 patients, 38 (25.7%) experienced a recurrence, 16 (10.8%) died without evidence of recurrence, and 94 (63.5%) experienced neither outcome. The median follow-up was 30.5 months (interquartile range 10.6-50). In univariable subdistribution regression, T-stage, N-stage, vascular invasion and positive margins were all predictive of cancer recurrence, with p ≤ 0.001, with subdistribution hazard ratios for T4 stage at 11.93, T3 stage at 2.46, N2 stage at 10.58, and presence of vascular invasion at 4.27. N-stage remained as the sole predictor in multivariable regression. Cumulative incidence function (CIF) of recurrence at 48 months after surgery was 15%, 27% and 90% for N1/2, N3 and N4 respectively. CONCLUSION: The highest CIF of recurrence was associated with T4 stage, N2 stage, and vascular invasion. Patient's age, tumour location, type, or histological grade were not found to have a significant effect on the success of CRC surgery in precluding a recurrence.

Brief Report: Syphilis Coinfection Is Not Associated With an Increased Risk of Virologic Failure Among HIV-Positive Men Who Have Sex With Men on Antiretroviral Therapy.

BACKGROUND: Incidence of syphilis continues to increase among HIV-positive men who have sex with men (MSM) in Ontario. Our objective was to determine the effect of acute syphilis on virologic failure (VF) among virally suppressed HIV-positive MSM taking antiretroviral therapy (ART) and determine if the relationship is confounded by drug use. SETTING: The OHTN Cohort Study is a voluntary cohort of people receiving HIV care in Ontario. Syphilis and viral load (VL) data were retrieved via linkage with the provincial laboratory. METHODS: Analyses included 2632 MSM from 2008 to 2015, on ART, with ≥1 questionnaire and 2 consecutive VL of <50 copies per milliliter 6 months apart. VF was defined as (1) VL of ≥1000 copies per milliliter or (2) 2 consecutive VLs of ≥200 copies per milliliter ≥1 month apart. We modeled acute syphilis as a time-varying covariate on VF using Poisson regression. Time-varying drug use was assessed for confounding using an iterative process where potential confounders were removed and then reintroduced into the model. Our model allowed for repeat observations using generalized estimating equations. RESULTS: VF incidence was 3.5 per 100 person-years [95% confidence interval (CI): 3.4 to 4.2]. The rate ratio for VF for acute syphilis was 1.5 (95% CI: 0.9 to 2.4) in the unadjusted model; 1.6 (95% CI: 1.0 to 2.4) in the model adjusted for age, education, region, and income; and 1.2 (95% CI: 0.7 to 1.9) in the final model with additional adjustment for drug use. CONCLUSIONS: Acute syphilis was not associated with VF among virologically suppressed MSM on ART. Consequently, ART may still reduce HIV transmission risk to sexual partners.

Detection of Caries Around Resin-Modified Glass Ionomer and Compomer Restorations Using Four Different Modalities In Vitro.

The aim of this study was to evaluate the ability of visual examination (International Caries Detection and Assessment System-ICDAS II), light-emitting diodes (LED) fluorescence (SPECTRA), laser fluorescence (DIAGNODent, DD), photothermal radiometry and modulated luminescence (PTR-LUM, The Canary System, CS) to detect natural decay beneath resin-modified glass ionomer (RMGIC) and compomer restorations in vitro. Twenty-seven extracted human molars and premolars, consisting of 2 control teeth, 10 visually healthy/sound and 15 teeth with natural cavitated lesions, were selected. For the carious teeth, caries was removed leaving some carious tissue on one wall of the preparation. For the sound teeth, 3 mm deep cavity preparations were made. All cavities were restored with RMGIC or compomer restorative materials. Sixty-eight sites (4 sites on sound unrestored teeth, 21 sound sites and 43 carious sites with restorations) were selected. CS and DD triplicate measurements were done at 2, 1.5, 0.5, and 0 mm away from the margin of the restoration (MOR). SPECTRA images were taken, and two dentists provided ICDAS II scoring for the restored surfaces. The SPECTRA data and images were inconclusive due to signal interference from the restorations. Visual examinations of the restored tooth surfaces were able to identify 5 of the 15 teeth with caries. In these situations, the teeth were ranked as having ICDAS II 1 or 2 rankings, but they could not identify the location of the caries or depth of the lesion. CS and DD were able to differentiate between sound and carious tissue at the MOR, but larger variation in measurement, and poorer accuracy, was observed for DD. It was concluded that the CS has the potential to detect secondary caries around RMGIC and compomer restorations more accurately than the other modalities used in this study.

Twelve Committed Men: the feasibility of a community-based participatory HIV-prevention intervention within a Canadian men's correctional facility.

OBJECTIVES: The intervention objectives were to evaluate and describe the feasibility of using a community-based research (CBR) approach to adapt and implement HIV-prevention materials and tools with incarcerated men. We found no prior published reports about CBR HIV-prevention education in Canadian correctional facilities. METHODS: Twelve members of the correctional Peer Education Committee (PEC) and Aboriginal PEC, whom a correctional nurse identified as being interested in preventive health, were purposively invited to participate. Eight participants were serving life sentences, three were Aboriginal and their education levels ranged from below grade 8 to 11 years of post-secondary education. The setting was a medium-security federal correctional facility, housing 324 men. The intervention was guided by CBR and 'greater involvement of people with AIDS' principles. Participants were invited to attend four workshops, over seven days in May 2014, and to provide their insights regarding future scaled-up CBR HIV prevention. Each workshop included an HIV-prevention presentation and a focus group discussion, two of which were audio-recorded. FINDINGS: All participants attended all sessions. Synthesis of mixed-method findings, with quantitative and qualitative data triangulation, demonstrated two major outcomes: 'new knowledge was generated' regarding feasibility of CBR HIV prevention in a men's correction facility; and 'capacity building occurred' with increased participants' social capital. Thirty incarcerated men requested HIV testing following the intervention, because participants spread their knowledge about HIV prevention to others. Participants asked to become 'health ambassadors' - champion advisors for future scaled-up CBR HIV-prevention intervention for the entire correctional facility. CONCLUSION: CBR HIV prevention is feasible within a Canadian men's correctional facility.

Serosorting and recreational drug use are risk factors for diagnosis of genital infection with chlamydia and gonorrhoea among HIV-positive men who have sex with men: results from a clinical cohort in Ontario, Canada.

OBJECTIVES: Rates of chlamydia and gonorrhoea have been rising in urban centres in Canada, particularly among HIV-positive men who have sex with men (MSM). Our objective was to identify behavioural risk factors for diagnosis with chlamydia and gonorrhoea in this population, with a focus on the HIV status of sexual partners. METHODS: The OHTN Cohort Study follows people in HIV care across Ontario. We restricted the analysis to 1997 MSM who completed questionnaires in 2010-2013 at one of seven clinics that submit all chlamydia and gonorrhoea tests to the provincial public health laboratory; we obtained test results via record linkage. We estimated cumulative incidences using Kaplan-Meier methods and identified risk factors for diagnosis of a composite outcome (chlamydia or gonorrhoea infection) using Cox regression. RESULTS: At follow-up, there were 74 new chlamydia/gonorrhoea diagnoses with a 12-month cumulative incidence of 1.7% (95% CI 1.1% to 2.2%). Risk factors for chlamydia/gonorrhoea diagnosis were: 5+ HIV-positive partners (HR=3.3, 95% CI 1.4 to 7.8; reference=none) and recreational drug use (HR=2.2, 95% CI 1.2 to 3.9). CONCLUSIONS: Heightened risks with recreational drug use and multiple HIV-positive partners suggest that chlamydia/gonorrhoea may have achieved high prevalence in certain sexual networks among HIV-positive MSM. Interventions to promote safer sex and timely testing among MSM are needed.

High incidence of diagnosis with syphilis co-infection among men who have sex with men in an HIV cohort in Ontario, Canada.

BACKGROUND: The re-emergence of syphilis among HIV-positive gay and other men who have sex with men (MSM) requires vigilance. We estimated incidence of and risk factors for first and subsequent syphilis diagnoses among MSM in HIV care in Ontario, Canada. METHODS: We analyzed data from 2,280 MSM under follow-up from 2006 to 2010 in the Ontario HIV Treatment Network Cohort Study (OCS), a multi-site clinical cohort. We obtained syphilis serology results via record linkage with the provincial public health laboratory. Rates were calculated using Poisson regression. RESULTS: First syphilis diagnoses occurred at a rate of 2.0 per 100 person-years (95 % CI 1.7, 2.4; 121 cases) whereas the re-diagnosis rate was 7.5 per 100 person-years (95 % CI 6.3, 8.8; 136 cases). We observed higher rates over time and among men who were aged <30 years, receiving care in the two largest urban centers, or had a previous syphilis diagnosis. Syphilis diagnosis was less common among Indigenous men, men with higher CD4 cell counts, and, for first diagnoses only, among men with less than high school education. CONCLUSIONS: Compared to reported cases in the general male population, incidence of a new syphilis diagnosis was over 300 times greater among HIV-positive MSM but year-to-year changes reflected provincial trends. Re-diagnosis was common, suggesting treatment failure or re-infection. Novel syphilis control efforts are needed among HIV-positive MSM.

Modest rise in chlamydia and gonorrhoea testing did not increase case detection in a clinical HIV cohort in Ontario, Canada.

OBJECTIVES: We described patterns of testing for chlamydia and gonorrhoea infection among persons in specialty HIV care in Ontario, Canada, from 2008 to 2011. METHODS: We analysed data from 3165 participants in the OHTN Cohort Study attending one of seven specialty HIV care clinics. We obtained chlamydia and gonorrhoea test results via record linkage with the provincial public health laboratory. We estimated the proportion of participants who underwent testing annually, the positivity rate among those tested and the proportion diagnosed with chlamydia or gonorrhoea among all under observation. We explored risk factors for testing and diagnosis using multiple logistic regression analysis. RESULTS: The proportion tested annually rose from 15.2% (95% CI 13.6% to 16.7%) in 2008 to 27.0% (95% CI 25.3% to 28.6%) in 2011 (p<0.0001). Virtually all were urine-based nucleic acid amplification tests. Testing was more common among men who have sex with men (MSM), younger adults, Toronto residents, persons attending primary care clinics and persons who had tested in the previous year or who had more clinic visits in the current year. We observed a decrease in test positivity rates over time. However, the annual proportion diagnosed remained stable and in 2011 this was 0.97% (95% CI 0.61% to 1.3%) and 0.79% (95% CI 0.46% to 1.1%) for chlamydia and gonorrhoea, respectively. Virtually all cases were among MSM. CONCLUSIONS: Chlamydia and gonorrhoea testing increased over time while test positivity rates declined and the overall proportion diagnosed remained stable, suggesting that the modest increase in testing did not improve case detection.

Determinants of prevalent human papillomavirus in recently formed heterosexual partnerships: a dyadic-level analysis.

BACKGROUND: We studied features that predict the presence of human papillomavirus (HPV) in a new sexual partnership. METHODS: We analyzed data from the "HPV Infection and Transmission Among Couples Through Heterosexual Activity" (HITCH) Cohort Study of recently formed partnerships ("dyads"). Women aged 18-24 and their male partners were recruited during 2005-2010 in Montreal, Canada. We tested genital swabs for detection of 36 HPV types. We defined HPV in a partnership as the presence of 1 or more HPV types in either or both partners. Using baseline data from 482 dyads, we calculated prevalence ratios to evaluate candidate risk factors. RESULTS: Most women (88%) were unvaccinated. Sixty-seven percent of dyads harbored HPV. For 49% of dyads, both partners were HPV+. HPV was least prevalent in dyads who were in their first vaginal sex relationship (17%) and was virtually ubiquitous in dyads for which both partners had concurrent partners (96%). Dyads that always used condoms with previous partner(s) were 27% (95% confidence interval, 9%-42%) less likely to have HPV. CONCLUSIONS: The finding that condom use limited onward spread to future partners is in support of condom promotion to prevent sexually transmitted infections. Ongoing monitoring of HPV in sexual networks is needed, particularly in populations with suboptimal vaccine coverage.

Patterns of syphilis testing in a large cohort of HIV patients in Ontario, Canada, 2000-2009.

BACKGROUND: Since 2000, reported syphilis cases increased ten-fold in Canada, particularly among men who have sex with men (MSM) co-infected with HIV. We characterized temporal patterns of of syphilis testing in a large cohort of HIV patients in Ontario, Canada. METHODS: We analyzed data from a multi-site cohort of people in HIV care from 2000 to 2009. Data were obtained from medical charts, interviews and record linkage with the syphilis test database at the Public Health Ontario Laboratories. We estimated the proportion that had syphilis testing at least once per year and the period and annual prevalence of reactive tests. RESULTS: Among 4232 participants, the annual proportion tested rose from 2.7% (95%CI 1.9, 3.5) in 2000 to 54.6% (95%CI 52.9, 56.3) in 2009. Testing was most common for participants who were men who have sex with men (MSM), aged <30, recently diagnosed with HIV, were antiretroviral treatment naive, had routine HIV lab testing at least twice in that year, or tested for syphilis in the preceding year. The proportion with at least one reactive test in 2000-09 was 21.0% (95%CI 19.4, 22.7) for MSM, 5.3% (95%CI 3.3, 7.4) for non-MSM males, and 2.6% (95%CI 1.2, 4.0) for women. Among MSM, the annual prevalence of reactive syphilis tests with high RPR titre (≥1:16) peaked at 3.8% in 2009. CONCLUSIONS: The burden of syphilis co-infection rose considerably among HIV-positive MSM, such that by 2009, at least 1 in 5 men had laboratory evidence of current or past infection. Interventions may be needed to boost syphilis testing to achieve goals set by guidelines even in settings with universal health care.

Rectal toxicity and rectal dosimetry in low-dose-rate (125)I permanent prostate implants: a long-term study in 1006 patients.

OBJECTIVE: To describe the acute and late rectal toxicity in 1006 prostate brachytherapy patients implanted 1998-2003. To determine whether rectal dose-volume histogram as well as patient and treatment factors were associated with rectal toxicity. METHODS AND MATERIALS: Median followup was 60.7 months. Rectal dosimetry was calculated as dose-volume histogram of the rectum using Day 28 CT-based dosimetry and expressed as volume of the rectum in cc receiving 50%, 100%, and 150% of the prescription dose (VR(50cc), VR(100cc), and VR(150cc), respectively). Univariate and multivariate analyses were performed to examine the influence of patient, implant, dosimetry, and learning curve factors on the development of acute and late toxicities using a modified Radiation Therapy Oncology Group (RTOG) scale. Acute toxicity was analyzed using logistic regression and late toxicity using Cox proportional hazards regression. Analysis of variance was used to examine the association between rectal toxicity and rectal dose. RESULTS: Rectal dosimetry in 93.5% and rectal toxicity in 96.2% have been recorded. Median VR(100)=1.05cc. Late RTOG Grades 0, 1, 2, 3, and 4 were recorded in 68%, 23%, 7.3%, 0.9%, and 0.2% patients, respectively. On multivariate analysis, acute RTOG ≥2 rectal toxicity was associated with urinary retention (p=0.036) and learning curve (p=0.015); late RTOG ≥2 was associated with the presence of acute toxicity (p=0.0074), higher VR(100) (p=0.030) and learning curve (p=0.027). CONCLUSIONS: Late rectal RTOG ≥2 rectal toxicity in this cohort was 8%. Increased VR(100), presence of acute rectal toxicity, and learning curve were associated with higher rate of late RTOG ≥2 toxicity. Severe late rectal toxicity after prostate brachytherapy was rare.

Malignant bowel obstruction: natural history of a heterogeneous patient population followed prospectively over two years.

CONTEXT: The management of malignant bowel obstruction (MBO) is often challenging and frequently involves multiple treatment modalities, including chemotherapy, surgery, stenting, and symptomatic medical management. OBJECTIVES: To describe the natural history of patients diagnosed with MBO who were admitted to a tertiary level hospital and followed by a multidisciplinary team that included medical oncologists, surgical oncologists, and palliative care specialists. METHODS: Thirty-five patients admitted under medical or surgical oncology with a diagnosis of MBO were followed over a two-year period or until the time of death. Primary malignancies included colon, rectum, pancreas, biliary, breast, bladder, carcinoid, renal cell, gastric, lung, and melanoma. Clinical outcomes of interest included survival, percentage of patients receiving surgery and/or chemotherapy, total parenteral nutrition (TPN), insertion of venting gastrostomy tube, disposition, and rates of readmission to hospital. RESULTS: Median survival was 80 days and three patients were alive at the time of study closure. At our center, 34% of patients underwent surgical intervention, 37% received at least one dose of post-MBO chemotherapy, and 43% received TPN. There was a cohort of patients (17%) who were alive at one year. CONCLUSION: Interventions such as chemotherapy and TPN may be appropriate in a carefully selected subgroup of patients. A collaborative approach is required for the optimal clinical management and palliation of MBO.

Evaluating the Phoenix definition of biochemical failure after (125)I prostate brachytherapy: Can PSA kinetics distinguish PSA failures from PSA bounces?

PURPOSE: To evaluate the prostate-specific antigen (PSA) kinetics of PSA failure (PSAf) and PSA bounce (PSAb) after permanent (125)I prostate brachytherapy (PB). METHODS AND MATERIALS: The study included 1,006 consecutive low and "low tier" intermediate-risk patients treated with (125)I PB, with a potential minimum follow-up of 4 years. Patients who met the Phoenix definition of biochemical failure (nadir + 2 ng/mL(-1)) were identified. If the PSA subsequently fell to ≤0.5 ng/mL(-1)without intervention, this was considered a PSAb. All others were scored as true PSAf. Patient, tumor and dosimetric characteristics were compared between groups using the chi-square test and analysis of variance to evaluate factors associated with PSAf or PSAb. RESULTS: Median follow-up was 54 months. Of the 1,006 men, 57 patients triggered the Phoenix definition of PSA failure, 32 (56%) were true PSAf, and 25 PSAb (44%). The median time to trigger nadir + 2 was 20.6 months (range, 6-36) vs. 49 mo (range, 12-83) for PSAb vs. PSAf groups (p < 0.001). The PSAb patients were significantly younger (p < 0.0001), had shorter time to reach the nadir (median 6 vs. 11.5 months, p = 0.001) and had a shorter PSA doubling time (p = 0.05). Men younger than age 70 who trigger nadir +2 PSA failure within 38 months of implant have an 80% likelihood of having PSAb and 20% chance of PSAf. CONCLUSIONS: With adequate follow-up, 44% of PSA failures by the Phoenix definition in our cohort were found to be benign PSA bounces. Our study reinforces the need for adequate follow-up when reporting PB PSA outcomes, to ensure accurate estimates of treatment efficacy and to avoid unnecessary secondary interventions.

A single set of numerical cutpoints to define moderate and severe symptoms for the Edmonton Symptom Assessment System.

Symptom intensity in cancer and palliative care patients is frequently assessed using a 0-10 ranking score. Results are then often grouped into verbal categories (mild, moderate, or severe) to guide therapy. Numerical cutpoints separating these categories are often variable, with previous work suggesting different cutpoints across different symptoms, which is unwieldy for clinical use. The Edmonton Symptom Assessment Symptom (ESAS) assesses nine common symptoms using this 0-10 scale. The primary aim of this study was to examine the relationship between the numerical and verbal scores using the ESAS and to identify a single cutpoint to separate severe from nonsevere symptomatology. A second goal was to similarly identify a cutpoint to separate moderate or severe from none or mild symptom intensity. Consenting patients (n=400) completed both a standard ESAS and an identical form that replaced 0-10 with none, mild, moderate, and severe. Receiver operating characteristic curves were generated to identify the best fit between sensitivity and specificity. For the "severe" ranking, six symptoms had a best fit of 7, with sensitivity for the remaining three symptoms still greater than 80%. For the combined grouping of moderate or severe, results were less uniform. A cutpoint of either 4 or 5 would be supported by our data, with a greater sensitivity using 4 and improved specificity using 5 as the cutpoint. Across all ESAS symptoms, then, 7 or higher represents a severe symptom by patient definition, whereas a cutpoint of either 4 or 5 could reasonably define combined moderate and severe symptoms.

Prevalence and type distribution of human papillomavirus in 5,000 British Columbia women--implications for vaccination.

BACKGROUND: Human papilloma virus (HPV) prevalence studies performed in different regions and population groups across Canada would inform public health decisions regarding implementation of anti-HPV vaccines. METHODS: A total of 8,700 liquid-based specimens from 8,660 women aged 13-86 from throughout British Columbia were collected. DNA was isolated from 4,980 of these samples and assessed for HPV prevalence and type distribution. HPV was detected by PCR analysis using tagged GP5+/6+ consensus primers to amplify the L1 region of HPV; typing was done by bi-directional sequencing of PCR products. RESULTS: Overall HPV prevalence was 16.8% (age adjusted 15.5%). Prevalence of high-risk HPV was 13.9, and 10.7% of samples contained HPV16. HPV prevalence was highest in the youngest group of women (<20 years). One-third of HPV positive samples contained more than one HPV type. Percentages of low-grade (LGIL) and high-grade intraepithelial lesions (HGIL) containing high-risk HPV are 52.3 and 79.4%, respectively. CONCLUSIONS: Overall HPV prevalence in this study is within the range of estimates from other studies. The prevalence of HPV16 is higher than what is found in other Canadian and international studies. HPV16 and HPV18 compose a majority of the high-risk virus in this study. Use of current HPV vaccines could considerably reduce HPV-related conditions including cervical cancer and procedures such as colposcopy.