Averting an Outbreak of SARS-CoV-2 in a University Residence Hall through Wastewater Surveillance.

A wastewater surveillance program targeting a university residence hall was implemented during the spring semester 2021 as a proactive measure to avoid an outbreak of COVID-19 on campus. Over a period of 7 weeks from early February through late March 2021, wastewater originating from the residence hall was collected as grab samples 3 times per week. During this time, there was no detection of SARS-CoV-2 by reverse transcriptase quantitative PCR (RT-qPCR) in the residence hall wastewater stream. Aiming to obtain a sample more representative of the residence hall community, a decision was made to use passive samplers beginning in late March onwards. Adopting a Moore swab approach, SARS-CoV-2 was detected in wastewater samples just 2 days after passive samplers were deployed. These samples also tested positive for the B.1.1.7 (Alpha) variant of concern (VOC) using RT-qPCR. The positive result triggered a public health case-finding response, including a mobile testing unit deployed to the residence hall the following day, with testing of nearly 200 students and staff, which identified two laboratory-confirmed cases of Alpha variant COVID-19. These individuals were relocated to a separate quarantine facility, averting an outbreak on campus. Aggregating wastewater and clinical data, the campus wastewater surveillance program has yielded the first estimates of fecal shedding rates of the Alpha VOC of SARS-CoV-2 in individuals from a nonclinical setting. IMPORTANCE Among early adopters of wastewater monitoring for SARS-CoV-2 have been colleges and universities throughout North America, many of whom are using this approach to monitor congregate living facilities for early evidence of COVID-19 infection as an integral component of campus screening programs. Yet, while there have been numerous examples where wastewater monitoring on a university campus has detected evidence for infection among community members, there are few examples where this monitoring triggered a public health response that may have averted an actual outbreak. This report details a wastewater-testing program targeting a residence hall on a university campus during spring 2021, when there was mounting concern globally over the emergence of SARS-CoV-2 variants of concern, reported to be more transmissible than the wild-type Wuhan strain. In this communication, we present a clear example of how wastewater monitoring resulted in actionable responses by university administration and public health, which averted an outbreak of COVID-19 on a university campus.

Impact of COVID-19 on drowning patterns in the Great Lakes region of North America.

The COVID-19 pandemic significantly altered personal and group behaviors that may directly or indirectly affect other public health issues. This paper examines if and how COVID-19 indirectly influenced beach safety and drownings within the Great Lakes region using daily drowning data from 2020 in comparison to historical trends in drownings pre-COVID. Results suggest that the number of beach drownings in the Great Lakes region was significantly greater compared to the pre-COVID period of 2010-2019. Statistically significant increases in drownings were observed in Lake Michigan (+14), Lake Ontario (+11) and Lake Huron (+4), while no change and a slight decrease was observed in Lake Superior and Lake Erie respectively. Drownings were lower than the historical average early in the pandemic but began to increase as stay-at-home orders were lifted through June and July. It is argued that the increase in drowning is due to a combination of reduced local lifeguard resources, cancelled swimming lessons, large beach crowds, warm weather, high-water levels and self-isolation fatigue. Whether in the Great Lakes region or elsewhere around the world, beach safety cannot be sacrificed in a future public health emergency by budget cuts or by reducing the focus of lifeguards with enforcement of social distancing.

Image-guided tandem and cylinder brachytherapy as monotherapy for definitive treatment of inoperable endometrial carcinoma.

OBJECTIVES: Management of endometrial cancer consists of surgical staging with adjuvant therapy guided by risk factors, though some women cannot undergo surgery due to comorbidities. We present a series of women treated with definitive high-dose rate image-guided tandem and cylinder brachytherapy (HDR-IGBT) alone. METHODS: Patients with grade 1-2, clinical stage I endometrial adenocarcinoma, <50% myometrial invasion, and tumor≤2cm were reviewed. Definitive treatment consisted of 5-6 fractions HDR-IGBT alone with CT- or MRI-based planning. Local-regional control (LRC) was defined as complete imaging response and/or cessation of vaginal bleeding. RESULTS: From 2007 to 2016, 45 patients were treated to a median dose of 37.5Gy. The median gross tumor volume (GTV) and clinical target volume (CTV) were 5.9cm3 (range, 0.7-18.7) and 80.9cm3 (17.2-159.0), respectively. The median cumulative dose to 90% (D90) of the GTV was 132.8Gy (76.5-295.6) equivalent 2Gy dose, and the median CTV D90 was 49.7Gy (34.5-57.2). Median follow-up among living patients was 18.6months (3.0-64.3). Cessation of vaginal bleeding occurred in 98%. Among those with post-treatment MRI (64%), complete radiographic response was demonstrated in 90%. The 2-year LRC, cancer-specific survival, and overall survival rates were 90%, 86%, and 97%, respectively. No grade 3+ acute or late toxicity was observed. CONCLUSIONS: HDR-IGBT alone for treatment of early-stage, medically inoperable endometrial cancer is feasible with excellent response rates and clinical results. This approach also allows sparing of critical organs and ensures target coverage, which contributed to the low toxicity rate and high LRC in comparison with 2D point-based series.

Mapping of dose distribution from IMRT onto MRI-guided high dose rate brachytherapy using deformable image registration for cervical cancer treatments: preliminary study with commercially available software.

PURPOSE: For patients undergoing external beam radiation therapy (EBRT) and brachytherapy, recommendations for target doses and constraints are based on calculation of the equivalent dose in 2 Gy fractions (EQD2) from each phase. At present, the EBRT dose distribution is assumed to be uniform throughout the pelvis. We performed a preliminary study to determine whether deformable dose distribution mapping from the EBRT onto magnetic resonance (MR) images for the brachytherapy would yield differences in doses for organs at risk (OARs) and high-risk clinical target volume (HR-CTV). MATERIAL AND METHODS: Nine cervical cancer patients were treated to a total dose of 45 Gy in 25 fractions using intensity-modulated radiation therapy (IMRT), followed by MRI-based 3D high dose rate (HDR) brachytherapy. Retrospectively, the IMRT planning CT images were fused with the MR image for each fraction of brachytherapy using deformable image registration. The deformed IMRT dose onto MR images were converted to EQD2 and compared to the uniform dose assumption. RESULTS: For all patients, the EQD2 from the EBRT phase was significantly higher with deformable registration than with the conventional uniform dose distribution assumption. The mean EQD2 ± SD for HR-CTV D90 was 45.7 ± 0.7 Gy vs. 44.3 Gy for deformable vs. uniform dose distribution, respectively (p < 0.001). The dose to 2 cc of the bladder, rectum, and sigmoid was 46.4 ± 1.2 Gy, 46.2 ± 1.0 Gy, and 48.0 ± 2.5 Gy, respectively with deformable dose distribution, and was significantly higher than with uniform dose distribution (43.2 Gy for all OAR, p < 0.001). CONCLUSIONS: This study reveals that deformed EBRT dose distribution to HR-CTV and OARs in MR images for brachytherapy is technically feasible, and achieves differences compared to a uniform dose distribution. Therefore, the assumption that EBRT contributes the same dose value may need to be carefully investigated further based on deformable image registration.

Image-based three-dimensional conformal brachytherapy for medically inoperable endometrial carcinoma.

PURPOSE: Definitive radiotherapy is a viable option for medically inoperable patients with early stage endometrial cancer. We present our experience using image-based brachytherapy (BT). METHODS AND MATERIALS: Patients with medically inoperable clinical Stage I endometrial adenocarcinoma received definitive BT with or without external beam radiotherapy. High-dose-rate BT was delivered using MRI- or CT-based planning for each fraction. For patients with an MRI, gross tumor volume (GTV) was contoured although dose was still prescribed to the clinical treatment volume (CTV), including the entire uterus, cervix, and upper 1-2 cm of vagina. Equivalent 2 Gy doses (EQD2) were calculated. RESULTS: Thirty-eight patients were treated from 2007 to 2013, 20 receiving BT alone with a median dose of 37.5 Gy in five to six fractions. For combined therapy, median external beam and BT doses were 45 and 25 Gy in four to five fractions. With 15-month median followup, the 2-year actuarial local control and overall survival were 90.6% and 94.4%. No Grade 2-5 late toxicities were observed. Mean CTV D90 EQD2 for BT alone and combined therapy was 48.6 ± 5.6 and 72.4 ± 6.0 Gy, whereas mean GTV D90 EQD2 was 172.3 ± 59.6 and 138.0 ± 64.6 Gy. CONCLUSIONS: Image-based BT is feasible for medically inoperable early stage endometrial cancer with excellent early results. Despite low CTV doses, high doses delivered to GTV with BT likely accounts for high local control. Endometrial cancer guidelines for image-based planning are needed to define target volumes based on risk with differential dose delivery.

Dosimetric comparison of multichannel with one single-channel vaginal cylinder for vaginal cancer treatments with high-dose-rate brachytherapy.

PURPOSE: To compare the three-dimensional (3D) image (CT/MR)-based planning with a multichannel vaginal cylinder (MVC) to a single-channel vaginal cylinder (SVC) for the treatment of vaginal cancer. METHODS AND MATERIALS: A total of 20 consecutive patients were treated with 3D CT/MR image-based high-dose-rate (HDR) brachytherapy using an MVC. All patients received external beam radiation therapy before HDR brachytherapy. A brachytherapy dose of 20-25Gy of more than five fractions was delivered to clinical target volume (CTV). Retrospectively, treatment plans for all patients were generated using the central channel only to mimic an SVC applicator. The SVC plans were optimized to match CTV coverage with MVC plans. Dose homogeneity index as well as bladder, rectum, sigmoid, and urethral doses were compared. RESULTS: The mean D90 for CTV was 74.2Gy (range: 48.8-84.1Gy). The mean (±standard deviation) of dose homogeneity index for MVC vs. SVC was 0.49 (±0.19) and 0.52 (±0.23), respectively (p=0.09). Mean bladder 0.1, 1, and 2cc doses for MVC vs. SVC were 69 vs. 71.2Gy (p=0.35), 61.4 vs. 63.8Gy (p=0.1), and 59.5 vs. 60.9Gy (p=0.31), respectively. Similarly, mean rectum 0.1, 1, and 2cc doses for MVC vs. SVC were 67.2 vs. 75.4Gy (p=0.005), 60.0 vs. 65.6Gy (p=0.008), and 57.3 vs. 62.0Gy (p=0.015), respectively, and mean sigmoid doses were 56.3 vs. 60.5Gy (p=0.10), 50.9 vs. 53.1Gy (p=0.09), and 49.1 vs. 50.7Gy (p=0.10), respectively. CONCLUSION: The 3D CT-/MR-based plan with MVC may provide better dose distribution in the management of certain clinical situations of vaginal cancer requiring intracavitary brachytherapy, especially in minimizing potential late rectal complications.

Prostate-specific antigen spikes with ¹³¹Cs brachytherapy. Is there a difference with other radioisotopes?

PURPOSE: There is a suggestion that a dose-rate effect exists for the prostate-specific antigen (PSA) spike after brachytherapy. ¹³¹Cs is a newer radioisotope with a half-life of 9.7 days that is being used for prostate brachytherapy. There is no published data on the PSA spike with this radioisotope and the goal of this study was to quantify PSA spikes with ¹³¹Cs and compare it with published data for other isotopes. METHODS AND MATERIALS: We have been maintaining a prospective database for all patients treated with ¹³¹Cs prostate brachytherapy at our institution. We selected patients for whom followup PSA was available for at least 24 months. The PSA spike was defined as an increase of 0.2 ng/mL, followed by a decline to prespike level. RESULTS: One hundred twenty-three patients had monotherapy, whereas 32 had external beam radiation therapy followed by a brachytherapy boost. Median followup was 36 months and mean numbers of PSAs obtained were 7. Forty-six (29.7%) patients had a PSA spike. The mean time and duration for the PSA spike were 12.5 and 8.8 months, respectively. The mean magnitude of increase and mean PSA value at increase were 0.63 and 1.56 ng/mL, respectively. CONCLUSIONS: The incidence of a PSA spike in our series is consistent with reported numbers for other radioisotopes. The occurrence of the spike at 12.5 months appears to be at the early end of the spectrum reported for (125)I, but the duration and magnitude are similar to other radioisotopes.

Three-dimensional image-based high-dose-rate interstitial brachytherapy for vaginal cancer.

PURPOSE: To evaluate dosimetric and clinical outcomes of three-dimensional (3D) image-based high-dose-rate (HDR) interstitial brachytherapy (HDRB) in patients with vaginal cancers. METHODS AND MATERIALS: Thirty patients with vaginal cancers were treated with HDRB using Syed-Neblett template. CT scan was done after placement of needles for confirmation of placement and treatment planning. The target volume and organs at risk, including clinical target volume (CTV), rectum, bladder, and sigmoid colon, were contoured on CT scans. Twenty-eight (93.3%) patients received external beam radiation therapy at a median 45 (24.0-50.4)Gy in 12-28 fractions, followed by HDRB at 3.75-5.0Gy per fraction in five fractions. Total doses for CTV and organs at risk from external beam radiation therapy and HDRB were summated and normalized to a biologically equivalent dose of 2Gy per fraction. RESULTS: Seventeen patients (56.7%) with primary vaginal cancer and 13 patients (43.3%) with recurrent vaginal cancers were treated with 3D HDRB. The mean CTV was 39.3±25.7 cm(3), and the median tumor diameter was 3.3 (1.3-8.0)cm. The median biologically equivalent dose of 2Gy per fraction for 2cc of bladder, rectum, and sigmoid was 55.0, 56.3, 50.0Gy, respectively. The median D(90) for high-risk CTV was 74.3 (36.3-81.1)Gy. The mean volume receiving 100%, 150%, and 200% of prescribed dose was 90.7±10.0%, 41.3±14.6%, and 17.7±8.3%, respectively. With a median followup of 16.7 months, the respective 1-/2-year locoregional and overall survival rates were 84.4%/78.8% and 82.1%/70.2%, respectively. There were no Grade ≥3 gastrointestinal complications. Late complications of Grade 3 vaginal ulceration and Grade 4 vaginal necrosis were seen in two cases. CONCLUSIONS: Initial results of 3D HDRB using our fractionation schedule in the treatment of vaginal cancers showed good local response with acceptable morbidities.

Direct and indirect mortality in Florida during the 2004 hurricane season.

Previous studies have shown that natural disasters, and hurricanes in particular, have led to more deaths than those usually documented in short post-storm surveys. Such indirect deaths, thought to be related to dietary, stress or pre-existing medical conditions, can exceed the number of direct deaths and may persist for weeks or even months beyond the event itself. In the present study, cumulative sum of deviations plots are used to quantify the number of direct and indirect deaths resulting from Hurricanes Charley, Frances, Ivan and Jeanne that made landfall in Florida in 2004. Results suggest that there was an elevated mortality for up to 2 months following each storm, resulting in a total of 624 direct and indirect deaths attributable to the storm. Trauma-related deaths that can be associated directly with the storm account for only ∼4% of the total storm-related mortality, while indirect mortality accounts for most storm-related deaths. Specifically, a large percentage of the elevated mortality was associated with heart (34%) and cancer-related deaths (19%), while diabetes (5%) and accident-related deaths (9%) account for a smaller but still significant percentage of the elevated mortality. The results further suggest that the elevated mortality was the result of additional deaths that would not have otherwise occurred within that 5 month period, and not simply a clustering of deaths that were inevitable between 1 August and 31 December 2004. The elevated mortality identified in this study is significantly greater than the official count of 31 direct and 113 indirect deaths resulting from the four hurricanes combined. This suggests a need for improved mortality counts and surveillance in order to better evaluate and identify effective prevention policies, and to identify preventable deaths.

Dosimetric analysis of 3D image-guided HDR brachytherapy planning for the treatment of cervical cancer: is point A-based dose prescription still valid in image-guided brachytherapy?

The purpose of this study was to analyze the dosimetric outcome of 3D image-guided high-dose-rate (HDR) brachytherapy planning for cervical cancer treatment and compare dose coverage of high-risk clinical target volume (HRCTV) to traditional Point A dose. Thirty-two patients with stage IA2-IIIB cervical cancer were treated using computed tomography/magnetic resonance imaging-based image-guided HDR brachytherapy (IGBT). Brachytherapy dose prescription was 5.0-6.0 Gy per fraction for a total 5 fractions. The HRCTV and organs at risk (OARs) were delineated following the GYN GEC/ESTRO guidelines. Total doses for HRCTV, OARs, Point A, and Point T from external beam radiotherapy and brachytherapy were summated and normalized to a biologically equivalent dose of 2 Gy per fraction (EQD2). The total planned D90 for HRCTV was 80-85 Gy, whereas the dose to 2 mL of bladder, rectum, and sigmoid was limited to 85 Gy, 75 Gy, and 75 Gy, respectively. The mean D90 and its standard deviation for HRCTV was 83.2 ± 4.3 Gy. This is significantly higher (p < 0.0001) than the mean value of the dose to Point A (78.6 ± 4.4 Gy). The dose levels of the OARs were within acceptable limits for most patients. The mean dose to 2 mL of bladder was 78.0 ± 6.2 Gy, whereas the mean dose to rectum and sigmoid were 57.2 ± 4.4 Gy and 66.9 ± 6.1 Gy, respectively. Image-based 3D brachytherapy provides adequate dose coverage to HRCTV, with acceptable dose to OARs in most patients. Dose to Point A was found to be significantly lower than the D90 for HRCTV calculated using the image-based technique. Paradigm shift from 2D point dose dosimetry to IGBT in HDR cervical cancer treatment needs advanced concept of evaluation in dosimetry with clinical outcome data about whether this approach improves local control and/or decreases toxicities.

Impact of transrectal ultrasound- and computed tomography-based seed localization on postimplant dosimetry in prostate brachytherapy.

PURPOSE: To study the impact of seed localization, as performed by different observers using linked (125)I seeds, on postimplant dosimetry in prostate brachytherapy and, to compare transrectal ultrasound (TRUS)-based with CT-based approach for the dosimetric outcomes. METHODS AND MATERIALS: Nineteen permanent prostate implants were conducted using linked (125)I seeds. Postimplant TRUS and CT images were acquired and prostate glands were, after implantation, delineated on all images by a single oncologist, who had performed all 19 seeding procedures. Six observers independently localized the seeds on both TRUS and CT images, from which the principle dosimetric parameters V(100) (volume of prostate that received the prescribed dose), V(150) (volume of prostate that received 150% of the prescribed dose), and D(90) (minimal dose delivered to 90% of the prostate) were directly calculated for each patient. A single-factor analysis of variance was first applied to determine interobserver variability in seed localization. A nonparametric comparison of the approach using TRUS and CT was then carried out by the Wilcoxon paired-sample test. RESULTS: Analysis from the analysis of variance for TRUS showed that the null hypothesis for equal means, could not be rejected for all six observers based on a significance level alpha=0.05. TRUS-based and CT-based approaches were then cross compared by the Wilcoxon paired-sample test, which suggested that the null hypothesis was insignificant for V(100) and D(90), but was significant for V(150). CONCLUSIONS: Both TRUS- and CT-imaging modalities provided indistinguishable postimplant dosimetry results as far as V(100) and D(90) were concerned. There was comparable observer independence between TRUS- and CT-based seed localization for linked-seed implant procedures. With other advantages that TRUS-imaging modality had over CT in the evaluation of postimplant dosimetry, TRUS would be a preferred choice in conjunction with linked seeds for intraoperative procedures in prostate brachytherapy.

The use of mixed-integer programming for inverse treatment planning with pre-defined field segments.

Complex intensity patterns generated by traditional beamlet-based inverse treatment plans are often very difficult to deliver. In the approach presented in this work the intensity maps are controlled by pre-defining field segments to be used for dose optimization. A set of simple rules was used to define a pool of allowable delivery segments and the mixed-integer programming (MIP) method was used to optimize segment weights. The optimization problem was formulated by combining real variables describing segment, weights with a set of binary variables, used to enumerate voxels in targets and critical structures. The MIP method was compared to the previously used Cimmino projection algorithm. The field segmentation approach was compared to an inverse planning system with a traditional beamlet-based beam intensity optimization. In four complex cases of oropharyngeal cancer the segmental inverse planning produced treatment plans, which competed with traditional beamlet-based IMRT plans. The mixed-integer programming provided mechanism for imposition of dose-volume constraints and allowed for identification of the optimal solution for feasible problems. Additional advantages of the segmental technique presented here are: simplified dosimetry, quality assurance and treatment delivery.