Innovative microbial water quality management in water distribution systems using in-pipe hydropowered UV disinfection: envisioning futuristic water-energy systems.

Hydropower UV disinfection has not been explored as a possible alternative for off-grid disinfection. Hydropowered UV LED technology was developed using off-the-shelf UV-C LEDs and pico - and femto-scale hydro turbine generators and evaluated across point-of-use relevant flow rates. Commercially available UV LED flow through reactors were subjected to microorganism challenge testing with 3 power schemes: wall-plug, hydropower, and hydropower-charged battery. UV LEDs powered by hydropower-charged battery demonstrated similar disinfection as wall-plug powered UV LEDs, achieving 0.5-1.8 MS2 log10 reduction at flow rates 0.5-2.3 L min-1, corresponding to reduction equivalent doses (RED) up to 16 or 30 mJ/cm2 for 254 and 285 nm, respectively. With hydropowered UV LEDs alone, MS2 log10 reduction decreased to <0.3 log10 reduction due to an underperforming and grossly inefficient turbine, with RED of 8 or 18 mJ/cm2 for 254 and 285 nm, respectively. Assessment of existing markets of UV disinfection systems and pico-hydro turbines demonstrated that hydropowered UV systems are already theoretically feasible for scales at point-of-entry (POE) and above. Economic feasibility will improve if turbines and/or UV system efficiencies improve. Prototype hydropower UV LED systems ranged from $145 to 220 depending on the UV LED reactor, and the battery system added $81. This study demonstrates the practicality of sustainable, renewable energy POU UV disinfection technology that can benefit decentralised, off-grid, rural and remote communities. The system may also scale up to provide renewable energy disinfection at larger scales, such as buildings and water distribution systems, for protecting human health in highly populated areas.

Treatment Terminations During Radiation Therapy: A Ten-Year Experience.

PURPOSE: Patients undergoing radiation therapy may terminate treatment for any number of reasons. The incidence of treatment termination (TT) during radiation therapy has not been studied. Herein we present a cohort of TT at a large multi-center radiation oncology department over 10 years. METHODS AND MATERIALS: TTs between 1/2013 and 1/2023 were prospectively analyzed as part of an ongoing departmental quality and safety program. TT was defined as any premature discontinuation of therapy after initiating radiation planning. The rate of TT was calculated as a percentage of all patients starting radiation planning. All cases were presented at monthly morbidity and mortality (MM) conferences with a root cause reviewed (RCA). RESULTS: A total of 1,448 TTs were identified out of 31,199 planned courses of care (4.6%). Six hundred eighty-six (47.4%) involved patients treated with curative intent, while 753 (52.0%) with palliative intent, and 9 (0.6%) for benign disease. The rate of TT decreased from 8.49% in 2013 to 3.02% in 2022 with rates decreasing yearly. The most common disease sites for TT were CNS (21.7%), H&N (19.3%), Thorax (17.5%), and Bone (14.2%). The most common causes of TT were hospice and/or patient expiration (35.9%), patient choice unrelated to toxicity (35.2%), and clinician choice unrelated to toxicity (11.5%). CONCLUSION: This 10-year prospective review of TTs identified a year-over-year decrease in TTs as a percentage of planned patients. This decrease may be associated with the addition of RCA for TTs and discussion monthly at MM rounds, coupled with departmental upstream quality initiatives implemented over time. Understanding the reasons behind TTs may help to decrease preventable TTs. While some TTs may be unavoidable, open discourse and quality improvement changes effectively reduce TT incidents over time.

Elective Irradiation of Retropharyngeal Lymph Nodes as an Indication for Adjuvant Radiation Therapy After Transoral Surgery for Tonsil Cancer.

Treatment of squamous cell carcinoma of the tonsil involves primary radiation therapy (RT) or surgical resection. Historically, if RT was the primary or adjuvant treatment modality, most of the bilateral retropharyngeal lymph nodes (RPLNs) were treated electively with a therapeutic dose for subclinical disease, regardless of whether radiographically pathologic lymph nodes were seen on initial diagnostic imaging. De-escalation strategies include the incorporation of transoral surgery with the goal to either eliminate or reduce the dose of adjuvant RT or chemotherapy. Transoral surgery does not include elective removal of the RPLNs, and no guideline or outcome paper recommends adjuvant RT specifically to electively treat RPLNs. In this Topic Discussion, we discuss pertinent literature and suggest management decisions. The management decisions discussed in this Topic Discussion pertain to only tonsillar primaries and not those of the soft palate or base of the tongue.

Radiation Dose Sensitivity of Subregions of the Larynx to Patient-Reported Swallowing Outcomes.

Purpose: To assess any correlation between swallowing dysfunction and radiation dose to 5 subregions of the larynx. Methods and Materials: A cohort of 136 patients with head and neck cancer, treated with either photon or proton radiation therapy, was assessed using an endpoint of patient-reported swallowing scores, evaluated with the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-H&N35 survey, within 1 month after treatment. Five subregions of the larynx were contoured, and dosimetric metrics were extracted for each subregion as well as the total larynx. Univariate and multivariate logistic regression statistical analyses were used to determine statistical correlation with the dose metrics and clinical variables. Univariate regression models were statistically compared using a non-nested model test. Results: Under univariate analysis, unilateral versus bilateral nodal irradiation (P = .004), concurrent chemotherapy (P = .007), and surgery (P = .015) were statistically significant predictors of poor swallowing score. Unilateral versus bilateral irradiation was statistically significant under multivariate analysis (P = .039). The epiglottis was the most predictive subregion of swallowing score, with a majority (21 of 25) of dosimetric variables being identified as statistically significant. The maximum dose to the epiglottis was the most significant dosimetric variable tested for poor swallowing score in both univariate (P = .003) and multivariate (P = .051) analyses. Comparison of univariate models indicated a general preference for epiglottic variables with the mean dose to the epiglottis being preferred at a statistically significant level in many cases. Conclusions: These results show the relatively increased sensitivity of the epiglottis compared with the rest of the larynx when considering patient-reported decrements in quality-of-life swallowing score and support both the inclusion of the epiglottis in standard larynx contours and the assessment of the epiglottis dose during plan evaluation. Our data suggest that keeping the mean and max doses to the epiglottis <20 to 37 Gy and <53 to 60 Gy, respectively, will reduce swallowing difficulties.

Impact of radiation dose distribution on nutritional supplementation needs in head and neck cancer radiotherapy: a voxel-based machine learning approach.

Objectives: To investigate the relationship between nutritional supplementation and radiation dose to the pharyngeal constrictor muscles and larynx for head and neck (HN) cancer patients undergoing radiotherapy. Methods: We retrospectively analyzed radiotherapy (RT) dose for 231 HN cancer patients, focusing on the pharyngeal constrictors and larynx. We defined nutritional supplementation as feeding tube utilization or >10% weight loss from baseline within 90 days after radiotherapy completion. Using deformable image registration (DIR), we mapped each patient's anatomical structures to a reference coordinate system, and corresponding deformations were applied to dose matrices. Voxel doses were utilized as features for ridge logistic regression models, optimized through 5-fold cross-validation. Model performance was assessed with area under the curve of a receiver operating curve (AUC) and F1 score. We built and compared models using 1) pharyngeal constrictor voxels, 2) larynx voxels, 3) clinical factors and mean regional dose metrics, and 4) clinical factors and dose-volume histogram metrics. Test set AUCs were compared among the models, and feature importance was evaluated. Results: DIR of the pharyngeal constrictors and larynx yielded mean Dice coefficients of 0.80 and 0.84, respectively. Pharyngeal constrictors voxels and larynx voxel models had AUC of 0.88 and 0.82, respectively. Voxel-based dose modeling identified the superior to middle regions of the pharyngeal constrictors and the superior region of larynx as most predictive of feeding tube use/weight loss. Univariate analysis found treatment setting, treatment laterality, chemotherapy, baseline dysphagia, weight, and socioeconomic status predictive of outcome. An aggregated model using mean doses of pharyngeal constrictors and larynx subregions had an AUC of 0.87 and the model using conventional DVH metrics had an AUC of 0.85 with p-value of 0.04. Feature importance calculations from the regional dose model indicated that mean doses to the superior-middle pharyngeal constrictor muscles followed by mean dose to the superior larynx were most predictive of nutritional supplementation. Conclusions: Machine learning modeling of voxel-level doses enables identification of subregions within organs that correlate with toxicity. For HN radiotherapy, doses to the superior-middle pharyngeal constrictors are most predictive of feeding tube use/weight loss followed by the doses to superior portion of the larynx.

Automated target placement for VMAT lattice radiation therapy: enhancing efficiency and consistency.

Objective. An algorithm was developed for automated positioning of lattice points within volumetric modulated arc lattice radiation therapy (VMAT LRT) planning. These points are strategically placed within the gross tumor volume (GTV) to receive high doses, adhering to specific separation rules from adjacent organs at risk (OARs). The study goals included enhancing planning safety, consistency, and efficiency while emulating human performance.Approach. A Monte Carlo-based algorithm was designed to optimize the number and arrangement of lattice points within the GTV while considering placement constraints and objectives. These constraints encompassed minimum spacing between points, distance from OARs, and longitudinal separation along thez-axis. Additionally, the algorithm included an objective to permit, at the user's discretion, solutions with more centrally placed lattice points within the GTV. To validate its effectiveness, the automated approach was compared with manually planned treatments for 24 previous patients. Prior to clinical implementation, a failure mode and effects analysis (FMEA) was conducted to identify potential shortcomings.Main results.The automated program successfully met all placement constraints with an average execution time (over 24 plans) of 0.29 ±0.07 min per lattice point. The average lattice point density (# points per 100 c.c. of GTV) was similar for automated (0.725) compared to manual placement (0.704). The dosimetric differences between the automated and manual plans were minimal, with statistically significant differences in certain metrics like minimum dose (1.9% versus 1.4%), D5% (52.8% versus 49.4%), D95% (7.1% versus 6.2%), and Body-GTV V30% (20.7 c.c. versus 19.7 c.c.).Significance.This study underscores the feasibility of employing a straightforward Monte Carlo-based algorithm to automate the creation of spherical target structures for VMAT LRT planning. The automated method yields similar dose metrics, enhances inter-planner consistency for larger targets, and requires fewer resources and less time compared to manual placement. This approach holds promise for standardizing treatment planning in prospective patient trials and facilitating its adoption across centers seeking to implement VMAT LRT techniques.

Mean Oral Cavity Organ-at-Risk Dose Predicts Opioid Use and Hospitalization during Radiotherapy for Patients with Head and Neck Tumors.

BACKGROUND: Approximately 75% of all head and neck cancer patients are treated with radiotherapy (RT). RT to the oral cavity results in acute and late adverse events which can be severe and detrimental to a patient's quality of life and function. The purpose of this study was to explore associations between RT dose to a defined oral cavity organ-at-risk (OAR) avoidance structure, provider- and patient-reported outcomes (PROs), opioid use, and hospitalization. METHODS: This was a retrospective analysis of prospectively obtained outcomes using multivariable modeling. The study included 196 patients treated with RT involving the oral cavity for a head and neck tumor. A defined oral cavity OAR avoidance structure was used in all patients for RT treatment planning. Validated PROs were collected prospectively. Opioid use and hospitalization were abstracted electronically from medical records. RESULTS: Multivariable modeling revealed the mean dose to the oral cavity OAR was significantly associated with opioid use (p = 0.0082) and hospitalization (p = 0.0356) during and within 30 days of completing RT. CONCLUSIONS: The findings of this study may be valuable in RT treatment planning for patients with tumors of the head and neck region to reduce the need for opioid use and hospitalization during treatment.

Association Between Social Determinants of Health, Distance from Treatment Center, and Treatment Type with Outcomes in Human Papillomavirus Associated Oropharyngeal cancer.

OBJECTIVES: Social determinants of health (SDOH) can influence access to cancer care, clinical trials, and oncologic outcomes. We investigated the association between SDOH, distance from treatment center, and treatment type with outcomes in human papillomavirus associated oropharyngeal squamous cell carcinoma [HPV(+)OPSCC] patients treated at a tertiary care center. STUDY DESIGN: Retrospective review. METHODS: HPV(+)OPSCC patients treated surgically from 2006 to 2021 were selected from our departmental Oropharyngeal Cancer RedCap database. Demographic data, treatment, and oncologic outcomes were extracted. Distance was calculated in miles between the centroid of each patient zip code and our hospital zip code (zipdistance). RESULTS: 874 patients (89 % male; mean age: 58 years) were identified. Most patients (96 %) reported Non-Hispanic White as their primary race. 204 patients (23 %) had a high-school degree or less, 217 patients (25 %) reported some college education or a 2-year degree, 153 patients (18 %) completed a four-year college degree, and 155 patients (18 %) had post-graduate degrees. Relative to those with a high-school degree, patients with higher levels of education were more likely to live further away from our institution (p < 0.0001). Patients who received adjuvant radiation therapy elsewhere lived, on average, 104 miles further away than patients receiving radiation at our institution (Estimate 104.3, 95 % CI 14.2-194.4, p-value = 0.02). In univariable Cox PH models, oncologic outcomes did not significantly differ by zipdistance. CONCLUSIONS: Education level-and access to resources-varied proportionally to a patient's distance from our center. Patients travelling further distances for surgical management of OPSCC were more likely to pursue adjuvant radiation therapy at an outside institution. Distance traveled was not associated with oncologic outcomes. Breaking down barriers to currently excluded populations may improve access to clinical trials and improve oncologic outcomes for diverse patient populations.

Research Publication Rates Are Age- and Era-Dependent for Radiation Oncologists From Highly Ranked NCI-Designated Cancer Centers.

PURPOSE: Quantitative bibliometrics are increasingly used to evaluate faculty research productivity. This study benchmarks publication rates for radiation oncologists from highly ranked National Cancer Institute-designated cancer centers and reveals how productivity changes over the arc of a career and of the field over time. METHODS AND MATERIALS: Peer-reviewed articles from 1970 to 2022 were obtained using Scopus for the 348 radiation oncologists listed as faculty for the top 10 cancer hospitals ranked by US News and World Report in 2022. Bibliometrics were analyzed for authorships (A˙), authorships where the individual was first or last author (F˙L), the monograph equivalent of authorships (M˙E), h-index, and ha-index (an analog to h-index using M˙E in place of publications). Career start was defined as the year of first publication. Bibliometric inflation was explored by analyzing authorship and bibliometric changes between 1990 and 2022. RESULTS: Publication rates peak, with as much as a 500% increase, 20 to 25 years from the start of a career before declining until retirement. At career ages of 1, 10, 20, and 30 years, the median bibliometrics were A˙ = (1.5, 4.1, 6.5, 7.0) year-1, F˙L = (0.5, 0.9, 1.2, 0.6) year-1, M˙E= (0.2, 0.5, 0.7, 0.8) year-1, h-index = (1, 12, 22, 47), and ha-index = (0.4, 4.4, 6.9, 18.4). With regards to authorship patterns across eras, the median number of authors listed per paper increased by 240% between 1990 and 2022. Meanwhile, research productivity per individual as measured by F˙L and M˙E was unchanged. CONCLUSIONS: The research publication rates of the median radiation oncologist change substantially over the course of their career. Productivity improves steadily for more than 2 decades before peaking and declining. The culture of authorship has also changed between 1990 and 2022. The number of authors listed per paper has trended upwards, which has an inflationary effect on the number of authorships and h-index. Meanwhile, the rate of manuscripts published per faculty has not changed.

Assessing the capacity of methylated DNA markers of cervical squamous cell carcinoma to discriminate oropharyngeal squamous cell carcinoma in human papillomavirus mediated disease.

OBJECTIVE: Early identification of human papillomavirus associated oropharyngeal squamous cell carcinoma (HPV(+)OPSCC) is challenging and novel biomarkers are needed. We hypothesized that a panel of methylated DNA markers (MDMs) found in HPV(+) cervical squamous cell carcinoma (CSCC) will have similar discrimination in HPV(+)OPSCC tissues. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded tissues were obtained from patients with primary HPV(+)OPSCC or HPV(+)CSCC; control tissues included normal oropharynx palatine tonsil (NOP) and cervix (NCS). Using a methylation-specific polymerase chain reaction, 21 previously validated cervical MDMs were evaluated on tissue-extracted DNA. Discrimination between case and control cervical and oropharynx tissue was assessed using area under the curve (AUC). RESULTS: 34 HPV(+)OPSCC, 36 HPV(+)CSCC, 26 NOP, and 24 NCS patients met inclusion criteria. Within HPV(+)CSCC, 18/21 (86%) of MDMs achieved an AUC ≥ 0.9 and all MDMs exhibited better than chance classifications relative to control cervical tissue (all p < 0.001). In contrast, within HPV(+)OPSCC only 5/21 (24%) MDMs achieved an AUC ≥ 0.90 but 19/21 (90%) exhibited better than chance classifications relative to control tonsil tissue (all p < 0.001). Overall, 13/21 MDMs had statistically significant lower AUCs in the oropharyngeal cohort compared to the cervical cohort, and only 1 MDM exhibited a statistically significant increase in AUC. CONCLUSIONS: Previously validated MDMs exhibited robust performance in independent HPV(+)CSCC patients. However, most of these MDMs exhibited higher discrimination for HPV(+)CSCC than for HPV(+)OPSCC. This suggests that each SCC subtype requires a unique set of MDMs for optimal discrimination. Future studies are necessary to establish an MDM panel for HPV(+)OPSCC.

Patterns and distribution of regional nodal involvement and recurrence in a surgically treated oropharyngeal squamous cell carcinoma cohort at a tertiary center.

OBJECTIVES: To investigate and describe the patterns of regional metastases and recurrences after surgical treatment of oropharyngeal squamous cell cancer (OPSCC). MATERIALS AND METHODS: Retrospective study of patients diagnosed with OPSCC from 2006 to 2021 at a tertiary referral center. Only patients treated with surgery including a neck dissection were included. Patients with unknown human papillomavirus (HPV) status, prior head and neck cancer, distant metastases, or synchronous head and neck cancer were excluded. RESULTS: A total of 928 patients were included. 89% were males, the average age was 58.6 years (range: 25.2-87.5), 874 (94%) were HPV(+), and 513 (55.3%) had a tonsil cancer. Among cN + patients, the most commonly involved levels at presentation were level II (85.2%), level III (33.3%), and level IV (9.4%). In cN0 patients, metastases were only observed in level II (16.2%) and level III (9.2%). Nodal recurrence occurred in 48 (5.2%) patients after a median time of 1.0 years (interquartile range: 0.6-2.0). Nodal recurrence incidence was similar in HPV(+) and HPV(-) patients (5.0% vs. 7.4%, p = 0.44). The most common levels for regional recurrence were ipsilateral level II (45.8%), contralateral level II (43.8%), and ipsilateral level V (25.0%). Multivariable analysis revealed that pN was a significant predictor for regional recurrence (p = 0.02). CONCLUSION: There is no difference in the distribution of regional metastases and recurrences in HPV(+) and HPV(-) OPSCC patients. Our findings align with the established understanding that regional metastases predominantly manifest in the ipsilateral level II-IV at presentation. Moreover, the data support the clinical recommendation to restrict elective neck dissection in cN0 patients to ipsilateral levels IIa and III, excluding level IIb. Regional recurrence is significantly associated with pN status.

Clinical aspects of spatially fractionated radiation therapy treatments.

PURPOSE: To provide clinical guidance for centers wishing to implement photon spatially fractionated radiation therapy (SFRT) treatments using either a brass grid or volumetric modulated arc therapy (VMAT) lattice approach. METHODS: We describe in detail processes which have been developed over the course of a 3-year period during which our institution treated over 240 SFRT cases. The importance of patient selection, along with aspects of simulation, treatment planning, quality assurance, and treatment delivery are discussed. Illustrative examples involving clinical cases are shown, and we discuss safety implications relevant to the heterogeneous dose distributions. RESULTS: SFRT can be an effective modality for tumors which are otherwise challenging to manage with conventional radiation therapy techniques or for patients who have limited treatment options. However, SFRT has several aspects which differ drastically from conventional radiation therapy treatments. Therefore, the successful implementation of an SFRT treatment program requires the multidisciplinary expertise and collaboration of physicians, physicists, dosimetrists, and radiation therapists. CONCLUSIONS: We have described methods for patient selection, simulation, treatment planning, quality assurance and delivery of clinical SFRT treatments which were built upon our experience treating a large patient population with both a brass grid and VMAT lattice approach. Preclinical research and patient trials aimed at understanding the mechanism of action are needed to elucidate which patients may benefit most from SFRT, and ultimately expand its use.

Clinicopathologic Factors and Their Association with Outcomes of Salivary Duct Carcinoma: A Multicenter Experience.

Purpose: This series reports long-term clinical outcomes of patients with salivary duct carcinoma (SDC), which is associated with a poor prognosis. Methods and Materials: Eighty-nine patients with SDC were treated with curative intent from February 5, 1971, through September 15, 2018. Kaplan-Meier and competing risk analyses were used to estimate locoregional control, distant metastasis-free survival (DMFS), progression-free survival, and overall survival (OS). Cox regression analyses of disease and treatment characteristics were performed to discover predictors of locoregional control, DMFS, and OS. Results: Median follow-up was 44.1 months (range, 0.23-356.67). The median age at diagnosis was 66 years (interquartile range, 57-75). Curative surgery followed by adjuvant radiation therapy was performed in 73 patients (82%). Chemotherapy was delivered in 26 patients (29.2%). The 5-year local recurrence and distant metastasis rates were 27% and 44%, respectively, with death as a competing risk. Distant metastasis was associated with lymph node-positive disease (hazard ratio [HR], 3.16; 95% confidence interval [CI], 1.38-7.23; P = .006), stage IV disease (HR, 4.78; 95% CI, 1.14-20.11; P = .033), perineural invasion (HR, 4.56; 95% CI, 1.74-11.97; P = .002), and positive margins (HR, 9.06; 95% CI, 3.88-21.14; P < .001). Median OS was 4.84 years (95% CI, 3.54-7.02). The 5-year OS was 42%. Reduced OS was associated with lymphovascular space invasion (HR, 3.49; 95% CI, 1.2-10.1; P = .022), perineural invasion (HR, 2.05; 95% CI, 1.06-3.97; P = .033), positive margins (HR, 2.7; 95% CI, 1.3-5.6; P = .011), N2 disease (HR, 1.88; 95% CI, 1.03-3.43; P = .04), and N3 disease (HR, 11.76; 95% CI, 3.19-43.3; P < .001). Conclusions: In this single-institution, multicenter retrospective study, the 5-year survival was 42% in patients with SDC. Lymphovascular space invasion, lymph node involvement, and higher staging at diagnosis were associated with lower DMFS and OS.

Patient Experience Performance at a Primary Cancer Center Versus Affiliated Community Facilities.

Purpose: Patient experience tools are used throughout health care to evaluate physician and departmental performance. In radiation medicine, these tools are important in evaluating patient-specific metrics throughout their care journey. This study compared patient experience outcomes from a central tertiary cancer program with network clinics in a health care network. Methods and Materials: Radiation medicine patient experience surveys (Press Ganey, LLC) were collected from a central facility and 5 network locations from January 2017 through June 2021. Surveys were distributed to patients after treatment completion. The study cohort was divided into the central facility and satellites. Questions were converted to a 0 to 100 scale from the Likert scale (1-5). To compare scores between site types, 2-way analysis of variance tests for the significance of sites adjusted for years of operations and adjustments for multiple comparisons (Dunnett's test) were completed on each question. Results: The number of consecutively returned surveys analyzed was 3777; a response rate of 33.3% was observed. The central site conducted 117,583 linear accelerator, 1425 Gamma Knife, 273 stereotactic radiosurgery, and 830 stereotactic body radiation therapy procedures. All satellites combined conducted 76,788 linear accelerator, 131 Gamma Knife, 95 stereotactic radiosurgery, and 355 stereotactic body radiation therapy procedures. The central facility fared better than the satellites on "Convenience of parking" (95.9 vs 87.9; P = .0001) but worse in other domains of care. Conclusions: All sites yielded exemplary patient experience rates. Community clinics scored higher than the main campus. The higher scores at the network sites require a deeper analysis of factors influencing the central facility, as the survey did not account for varying patient volumes and disparities in care complexity across sites. Attributes to satellites include lower patient volumes and easily navigable layouts. These results counter the impression that increased resources at the main campus create a better patient experience relative to network clinics and suggest that high-volume tertiary facilities will require unique initiatives to improve the patient experience.

Impact of Tumor-Infiltrating Lymphocytes on Disease Progression in Human Papillomavirus-Related Oropharyngeal Carcinoma.

OBJECTIVE: We aim to explore the prognostic value of tumor-infiltrating lymphocytes (TILs) in the primary tumor and metastatic lymph nodes of patients with HPV(+)OPSCC. We hypothesize that TILS density at both sites is associated with disease-free survival in HPV(+)OPSCC. STUDY DESIGN: Matched case-control study among HPV(+)OPSCC patients who underwent intent-to-cure surgery. Cases developed locoregional or distant recurrence. Controls were matched based on age, sex, pathologic T, N, and overall stage, year of surgery, type of adjuvant treatment received, and the Adult Comorbidity Evaluation-27 (ACE-27) score. SETTING: Single tertiary care center, May 2007 to December 2016. METHODS: Tumoral TILs (tTILs) density was defined as % TILs; stromal TILs (sTILs) density was defined as absent/sparse or moderate/dense crowding. Associations between TILs and time to disease progression were assessed using Cox regression models. RESULTS: Forty-four case-control pairs (N = 88) were included: 42 (48%) AJCC pStage I, 39 (44%) pStage II, and 7 (8%) pStage III. tTILs density ≥10% (hazard ratio [HR] 0.41, 95% confidence interval [CI] 0.17-0.99, p = .048) and a moderate/dense sTILs density (HR 0.21, 95% CI 0.06-0.75, p = .016) in the primary tumor were significantly associated with decreased risk of progression. TILs density in the lymph node was associated with decreased risk of progression but did not reach statistical significance. The tTILs and sTILs density correlated strongly between the primary tumor and lymph node. Concordance between the pathologists' was moderate (60%-70%). CONCLUSIONS: In HPV(+)OPSCC, a higher density of tumoral and stromal TILs in the primary tumor and possibly the lymph node may predict a lower risk of disease progression.

Small-Molecule-Mediated Stabilization of PP2A Modulates the Homologous Recombination Pathway and Potentiates DNA Damage-Induced Cell Death.

High-grade serous carcinoma (HGSC) is the most common and lethal ovarian cancer subtype. PARP inhibitors (PARPi) have become the mainstay of HGSC-targeted therapy, given that these tumors are driven by a high degree of genomic instability (GI) and homologous recombination (HR) defects. Nonetheless, approximately 30% of patients initially respond to treatment, ultimately relapsing with resistant disease. Thus, despite recent advances in drug development and an increased understanding of genetic alterations driving HGSC progression, mortality has not declined, highlighting the need for novel therapies. Using a small-molecule activator of protein phosphatase 2A (PP2A; SMAP-061), we investigated the mechanism by which PP2A stabilization induces apoptosis in patient-derived HGSC cells and xenograft (PDX) models alone or in combination with PARPi. We uncovered that PP2A genes essential for cellular transformation (B56α, B56γ, and PR72) and basal phosphatase activity (PP2A-A and -C) are heterozygously lost in the majority of HGSC. Moreover, loss of these PP2A genes correlates with worse overall patient survival. We show that SMAP-061-induced stabilization of PP2A inhibits the HR output by targeting RAD51, leading to chronic accumulation of DNA damage and ultimately apoptosis. Furthermore, combination of SMAP-061 and PARPi leads to enhanced apoptosis in both HR-proficient and HR-deficient HGSC cells and PDX models. Our studies identify PP2A as a novel regulator of HR and indicate PP2A modulators as a therapeutic therapy for HGSC. In summary, our findings further emphasize the potential of PP2A modulators to overcome PARPi insensitivity, given that targeting RAD51 presents benefits in overcoming PARPi resistance driven by BRCA1/2 mutation reversions.

Using 68 Ga-DOTATATE PET for Postoperative Radiosurgery and Radiotherapy Planning in Patients With Meningioma: A Case Series.

BACKGROUND: For patients with either an incompletely resected meningioma or recurrence after surgery, stereotactic radiosurgery is frequently used. MRI is typically used for stereotactic radiosurgery targeting, but differentiating tumor growth from postoperative change can be challenging. 68 Ga-DOTATATE, a positron emission tomography (PET) radiotracer targeting the somatostatin receptor type 2, has been shown to be a reliable meningioma biomarker. OBJECTIVE: To evaluate the impact of 68 Ga-DOTATATE on treatment planning in patients who had previously undergone meningioma resection. METHODS: We present a consecutive case series of 12 patients with pathology-proven meningioma who received a 68 Ga-DOTATATE PET between April 2019 and April 2021. Treatment planning was performed first using MRI. DOTATATE-PET images were then used to assess accurate tumor identification. RESULTS: Ten patients had WHO Grade 2 meningioma, and 2 patients had Grade 1 tumor. Eight patients had recurrent meningiomas, and 4 patients had newly diagnosed disease. Overall, 68 Ga-DOTATATE PET scans altered previously formulated treatment plans in 5 of 12 patients. In addition, 9 of 12 patients had disease foci not appreciated on MRI. CONCLUSION: In this series, incorporating 68 Ga-DOTATATE PET imaging had clinical utility for most patients in whom it was used. It proved particularly adept in demonstrating intraosseous meningiomas, differentiating recurrence from postoperative changes, and identifying subcentimeter disease foci. It is an imaging modality that our center will continue to use as a means of improving postoperative treatment plans after the surgical resection of meningiomas.

Close Margins After Transoral Robotic Surgery for Human Papillomavirus-Positive Oropharyngeal Carcinoma: A Review of the Literature and Practical Recommendations.

The purpose of this article is to summarize the literature and practical recommendations from experienced centers for close margins after transoral robotic surgery for human papillomavirus-positive oropharyngeal carcinoma.

Fluence-based QMRA model for bacterial photorepair and regrowth in drinking water after decentralized UV disinfection.

Ultraviolet disinfection is a promising solution for decentralized drinking water systems such as communal water taps. A potential health risk is enzymatic photorepair of pathogens after UV disinfection, which can result in regrowth of pathogens. Even though photorepair is a known issue, no formal risk assessments have been conducted for photorepair after UV disinfection in drinking water. The main objective was to construct a quantitative microbial risk assessment (QMRA) of photorepair after UV disinfection of drinking water in a decentralized system. UV disinfection and photorepair kinetics for E. coli were modelled using reproducible fluence-based determinations. Impacts of water collection patterns, and wavelength-dependent water container material transmittance, sunlight intensity, and photorepair enzyme absorbance were quantified. After UV disinfection by 16 or 40 mJ/cm2 of < 5-log microorganisms per L, risk of infection did not exceed 1-in-10,000 under conditions permitting E. coli photorepair. Risk from photorepair was less than 1-in-10,000 for photorepair light exposure < 0.75 h throughout the day for UV fluence 16 mJ/cm2 or greater. UV disinfection followed by solar disinfection surpassing photoreactivation during storage reduced risk below 1-in-10,000 for photorepair light exposure > 2.5 h between modelled times of 9 AM - 3 PM. The model can be expanded to other pathogens as UV fluence and photorepair fluence response kinetics become available, and this QMRA can be used to inform the placement of community water access points to reduce risk of photorepair and ensure adequate shelf life of UV disinfected water under safe storage conditions.