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Purpose: AUA guidelines prioritize nephron sparing in patients with preexisting chronic kidney disease (CKD). However, few studies analyze long-term renal function in patients with preoperative severe CKD who undergo extirpative renal surgery. Herein, we compare the hazard of progression to end-stage kidney disease (ESKD) following partial nephrectomy (PN) and radical nephrectomy (RN) among patients with preoperative severe CKD. Materials and Methods: Patients with stage 4 CKD who underwent PN or RN from 1970 to 2018 were identified. A multivariable Fine-Gray subdistribution hazard model was employed to assess associations with progression to ESKD accounting for the competing risk of death. Results: A total of 186 patients with stage 4 CKD underwent PN (n = 71; 38%) or RN (n = 115; 62%) for renal neoplasms with median follow-up of 6.9 years (interquartile range 3.8-14.1). On multivariable analyses adjusting for competing risk of death, the subdistribution hazard ratio (SHR) for older age at surgery (SHR for 5-year increase 0.81; 95% CI 0.73-0.91; P <.001) and higher preoperative estimated glomerular filtration rate (SHR for 5-unit increase 0.63; 95% CI 0.47-0.84; P =.002) was associated with lower hazard of progression to ESKD. There was no significant difference in hazard of ESKD between PN and RN (SHR 0.82; 95% CI 0.50-1.33; P =.4). Conclusions: Among patients with preoperative severe CKD, higher preoperative estimated glomerular filtration rate was associated with lower hazard of progression to ESKD after extirpative surgery for renal neoplasms. We did not observe a significant difference in overall hazard for developing ESKD between PN and RN. [ABSTRACT FROM AUTHOR]

Objective: To quantify the rate of progression in surveilled cysts and assess what factors should indicate delayed resection. Background: Side-branch intraductal papillary mucinous neoplasms (SB-IPMNs) are increasingly discovered, making it challenging to identify which patients require resection, thus avoiding inappropriate treatment. Most incidental lesions are surveyed, yet the consequences of that decision remain uncertain. Methods: A prospectively maintained database of pancreatic cystic neoplasms was queried for patients with SB-IPMN. Patients with ≥ 2 imaging studies >6 months apart were included. Clinically relevant progression (CR-progression) was defined by symptoms, worrisome/high-risk stigmata, or invasive cancer (IC). Growth ≥ 5 mm in 2 years is considered CR-progression; size ≥3 cm alone is not. Results: Between 1997 and 2023, 1337 patients were diagnosed with SB-IPMN. Thirty-seven (2.7%) underwent up-front surgery; 1000 (75.0%) had >6 months of surveillance. The rate of CR-progression was 15.3% (n = 153) based on size increase (n = 63, 6.3%), mainduct involvement (n = 48, 4.8%), symptoms (n = 8, 5.0%), or other criteria (n = 34, 3.4%). At a median follow-up of 6.6 years (interquartile range: 3.0-10.26), 17 patients (1.7%) developed IC. Those with CR-progression developed IC in 11.1% (n = 17) and highgrade dysplasia (HGD) in 6.5% (n = 10). Nearly half of the cancers were not contiguous with the surveyed SB-IPMN. Size ≥3 cm was not associated with HGD/IC (P = 0.232). HGD/IC was least common in CR-progression determined by size growth (6.3%) versus main-duct involvement (24%) or other (43%, P < 0.001) Patients with CR-progression demonstrated improved survival (overall survival) with resection on time-to-event (P < 0.001) and multivariate Cox regression (hazard ratio = 0.205, 0.096-0.439, P < 0.001) analyses. Overall survival was not improved with resection in all patients (P = 0.244). Conclusions: CR-progression for SB-IPMNs is uncommon, with the development of cancer anywhere in the pancreas being rare. Initial size should not drive resection. Long-term and consistent nonoperative surveillance is warranted, with surgery currently reserved for CR-progression, knowing that the majority of these still harbor low-grade pathology. [ABSTRACT FROM AUTHOR]

Purpose: Multiple prognostic models exist to assess survival among patients with metastatic clear cell renal cell carcinoma. However, the relative contribution of histopathological features of the metastasis has not been extensively studied. Herein, we compared models using clinical, primary tumor, and metastatic features to predict cancer-specific survival for patients with surgically resected metastatic clear cell renal cell carcinoma. Materials and Methods: We studied 266 patients who had undergone nephrectomy between 1970 and 2019, and who had a single site of metastasis completely resected. Two versions of the metastatic clear cell renal cell carcinoma score published by Leibovich et al were calculated, using grade and necrosis from the primary tumor and using grade and necrosis from the metastasis. Predictive abilities of these 2 versions and a third model that included metastatic features only were compared using c-indexes from Cox proportional hazards models. Results: A total of 197 patients died from renal cell carcinoma at a median of 2.3 years (IQR 1.1-4.5); median follow-up among survivors was 13.2 years (IQR 10.0-14.5). The Leibovich score using grade and necrosis from the metastasis (c[0.679) had similar predictive ability compared to the original Leibovich score using grade and necrosis from the primary tumor (c[0.675). A third model (c[0.707) demonstrated that metastasectomy within 2 years after nephrectomy, presence of bone metastasis, high grade, and sarcomatoid differentiation in the metastasis were significantly associated with cancer-specific survival. Conclusions: Scoring algorithms calculated using histopathological features of the metastasis can be used to predict cancer-specific survival for patients with surgically resected metastatic clear cell renal cell carcinoma. These findings are of particular importance for instances when primary tumor histopathology is not readily available. [ABSTRACT FROM AUTHOR]

Purpose: Assessments of financial toxicity among patients with metastatic prostate cancer are lacking. Using patient surveys, we sought to identify coping mechanisms and assess characteristics associated with lower financial toxicity. Materials and Methods: Surveys were administered to all patients seen at a single center’s Advanced Prostate Cancer Clinic over a 3-month period. Surveys included the COST-FACIT (COmprehensive Score for Financial Toxicity) and coping mechanism questionnaires. Patients with metastatic disease (lymph nodes, bone, visceral) were included for analysis. Coping mechanisms were compared between patients experiencing low (COST-FACIT >24) vs high (COST-FACIT≤ 24) financial toxicity using Fisher’s exact test. Multivariable linear regression was used to evaluate characteristics associated with lower financial toxicity. Results: Overall, 281 patients met inclusion criteria of which 79 reported high financial toxicity. In multivariable analysis, characteristics associated with lower financial toxicity included older age (estimate: 0.36, 95%CI: 0.21-0.52), applying for patient assistance programs (estimate: 4.42, 95%CI: 1.72-7.11), and an annual income of at least $100,000 (estimate: 7.81, 95%CI: 0.97, 14.66). Patients with high financial toxicity were more likely to decrease spending on basic goods (35% vs 2.5%, P < .001) and leisure activities (59% vs 15%, P > .001), as well as use savings (62% vs 17%, P < .001) to pay for their treatment. Conclusions: In this cross-sectional study, patients with metastatic prostate cancer and high financial toxicity were more likely to decrease spending on basic goods and leisure activities and use savings to pay for care. Understanding the impact of financial toxicity on patients’ lives is crucial to inform shared decisionmaking and interventions designed to mitigate financial toxicity in this population. [ABSTRACT FROM AUTHOR]

Patients commonly use the internet to obtain medical information. Patients in our outpatient setting frequently have incomplete or even incorrect information about hyperthermic intraperitoneal chemotherapy that they have found on the internet. We aimed to assess the quality and content of Web-based information on hyperthermic intraperitoneal chemotherapy using validated and novel scoring systems. The keywords "HIPEC" and "hyperthermic intraperitoneal chemotherapy" were entered into the most commonly used internet search engines (Google, Bing, and Yahoo). The first 10 websites from each search were analyzed. Website quality was assessed using the validated Journal of the American Medical Association benchmark criteria and DISCERN scoring systems. We created a novel hyperthermic intraperitoneal chemotherapy–specific score with surgeon experts in the field. Eighteen unique websites were identified. The majority (78%) were from academic institutions. The mean total DISCERN score for all websites was 41.8 ± 8.4 (maximum possible points = 75). The mean Journal of the American Medical Association and hyperthermic intraperitoneal chemotherapy–specific scores were 1.72 ± 1.13 (maximum possible score = 4) and 11.5 ± 4.5 (maximum possible score = 31), respectively. The lowest Journal of the American Medical Association scores were in the category of authorship. In total, 78% of websites omitted author details; 83% and 78% included the temperature and duration of hyperthermic intraperitoneal chemotherapy, respectively. Only 39% of websites mentioned complications of hyperthermic intraperitoneal chemotherapy. Web-based information on hyperthermic intraperitoneal chemotherapy is of variable content and quality. None of the websites achieved maximum scores using any of the scoring tools. Less than half of the websites provided any information on possible complications of the procedure. These findings should be highlighted to patients using the internet to obtain information about hyperthermic intraperitoneal chemotherapy. [ABSTRACT FROM AUTHOR]

Phosphodiesterase 4 (PDE4) is highly expressed in keratinocytes and immune cells and promotes pro‐inflammatory responses upon activation. The activity of PDE4 has been attributed to various inflammatory conditions, leading to the development and approval of PDE4 inhibitors as host‐directed therapeutics in humans. For example, the topical PDE4 inhibitor, crisaborole, is approved for the treatment of mild‐to‐moderate atopic dermatitis and has shown efficacy in patients with psoriasis. However, the role of crisaborole in regulating the immunopathogenesis of inflammatory skin diseases and infection is not entirely known. Therefore, we evaluated the effects of crisaborole in multiple mouse models, including psoriasis‐like dermatitis, AD‐like skin inflammation with and without filaggrin mutations, and Staphylococcus aureus skin infection. We discovered that crisaborole dampens myeloid cells and itch in the skin during psoriasis‐like dermatitis. Furthermore, crisaborole was effective in reducing skin inflammation in the context of filaggrin deficiency. Importantly, crisaborole reduced S. aureus skin colonization during AD‐like skin inflammation. However, crisaborole was not efficacious in treating S. aureus skin infections, even as adjunctive therapy to antibiotics. Taken together, we found that crisaborole reduced itch during psoriasis‐like dermatitis and decreased S. aureus skin colonization upon AD‐like skin inflammation, which act as additional mechanisms by which crisaborole dampens the immunopathogenesis in mouse models of inflammatory skin diseases. Further examination is warranted to translate these preclinical findings to human disease. [ABSTRACT FROM AUTHOR]

Purpose: The KEYNOTE-564 trial demonstrated that adjuvant pembrolizumab after nephrectomy for clear cell renal cell carcinoma decreased the risk of disease progression and potentially overall mortality as well. Herein, we used a Markov model to weigh the costs, toxicities, and efficacy of pembrolizumab to further investigate its utility. Materials and Methods: Decision-analytic Markov modeling was used to conduct a cost-utility analysis of adjuvant pembrolizumab versus observation after nephrectomy for high-risk clear cell renal cell carcinoma, using data from KEYNOTE-564 to inform model probabilities. Primary outcomes were quality-adjusted life years, Medicare costs, and incremental cost-effectiveness ratios. The willingness-to-pay threshold utilized was $100,000/quality-adjusted life year. Results: At 5 years, adjuvant treatment with pembrolizumab resulted in 0.3 additional quality-adjusted life years at an additional cost of $99,484 relative to observation. Pembrolizumab was found not to be cost-effective at a 5-year time horizon (incremental cost-effectiveness ratio[$326,534). On sensitivity analysis, pembrolizumab became cost-effective if its per cycle cost was <$5,064 (base =$10,278) or its 5-year progression benefit was >18.8% (base 9%). Upon simulation, pembrolizumab was cost-effective for 29% of patients at 5 years. Specifically, we found that pembrolizumab would be cost-effective at 5 years for patients with at least a 59% 5 year risk of progression, which corresponds to a Mayo Progression-free Survival Score ≤10. Conclusions: At current prices, adjuvant pembrolizumab was found to be costeffective only for the highest risk subset of clear cell renal cell carcinoma patients 5 years after treatment, including patients with complete metastasectomy, regional lymph node involvement, or ≤ 7cm pT3 tumors with sarcomatoid features. Longer-term trial data, including overall survival results, are necessary to confirm these extrapolations. [ABSTRACT FROM AUTHOR]

Purpose: Out-of-pocket costs represent an important component of financial toxicity and may impact patients’ receipt of care. Herein, we evaluated patientlevel factors associated with out-of-pocket costs for contemporary advanced prostate cancer treatment options. Materials and Methods: We identified all commercially insured men receiving treatment for advanced prostate cancer between 2007 and 2019 within the OptumLabs Data Warehouse(. Patients were categorized into 3 treatment groups: androgen deprivation monotherapy, novel hormonal therapy, and nonandrogen systemic therapy. The primary outcome was out-of-pocket costs in the first year of treatment. The associations of treatment and patient variables with out-of-pocket costs were assessed using multivariable regression models. All costs were adjusted to reflect 2019 U.S. dollars using the Consumer Price Index. Results: In a cohort of 13,409 men 81% (n [ 10,926) received androgen deprivation monotherapy, 6% (n [ 832) novel hormonal therapy, and 12% (n [ 1,651) nonandrogen systemic therapy. Mean treatment-related out-of-pocket costs in the first year were $165, $4,236, and $994 for androgen deprivation monotherapy, novel hormonal therapy, and nonandrogen systemic therapy, respectively. The adjusted difference in annual treatment-related out-of-pocket costs for novel hormonal therapy and nonandrogen systemic therapy were $2,581 (95% CI: $1,923-$3,240) and $752 (95% CI: $600-$903) higher than androgen deprivation monotherapy, respectively. Patient characteristics associated (P < .05) with higher treatment-related outof-pocket costs included older age (65-74 years), Black race, lower comorbidity scores, and lower household income. Conclusions: Patients receiving novel hormonal therapy for advanced prostate cancer had substantially higher treatment-related out-of-pocket costs. In addition to raising awareness among prescribers, these data support the inclusion of treatment associated financial toxicity in shared decision making for advanced prostate cancer and call attention to subgroups of patients particularly vulnerable to financial toxicity. [ABSTRACT FROM AUTHOR]

Purpose: Conversions from partial to radical nephrectomy are uncommon and reports on this topic are rare. In this study we present a detailed analysis of conversions from partial to radical nephrectomy in a single-institutional contemporary experience and provide an analysis of preoperative risk factors. Materials and Methods: Patients who underwent converted (cases) and completed (controls) partial nephrectomy from 2000 to 2015 were matched 1:1 for analysis. Perioperative imaging was reviewed and RENAL (for radius, exophytic/ endophytic properties, anterior/posterior descriptor, and location relative to the polar line) nephrometry scores were calculated. Reasons for conversions were abstracted from operative reports. Multivariable conditional logistic regression analyses were used to assess preoperative risk factors for conversion. Results: A total of 168 cases (6.1% of all partial nephrectomies) were identified and matched on tumor size, year of surgery, and surgical approach to 168 controls. Conversion rates decreased from 13% in 2000-2003 to 4% in 2012-2015. Oncologic considerations, such as concern for upstaging and positive margins, were the most cited (56%) reasons for conversion. On multivariable analyses, male sex (odds ratio 2.34; P [ .03), Charlson score (odds ratio per 1-unit increase: 1.28; P [ .03), posterior and middle (on anteroposterior axis) location (reference: anterior, odds ratio 2.83, P [ .02 and odds ratio 6.38, P < .001, respectively) and hilar location (reference: peripheral/central, odds ratio 5.61; P < .001) were associated with increased odds of conversion. Conclusions: Rates of conversion from partial to radical nephrectomy in our experience were low and decreased over time. Preoperative characteristics such as hilar, posterior, and middle locations were significantly associated with conversions after controlling for tumor size, and offer guidance for operative planning and patient counseling. [ABSTRACT FROM AUTHOR]

This study aimed to assess the correlation between validated measures of physical status in a prehabilitation regimen with an established frailty score and analyze changes in these measures after completion of a directed prehabilitation program among patients undergoing elective pancreatic resection. Adult patients undergoing pancreatic resection from 2019−2021 were enrolled in a pilot prehabilitation program. Three validated measures of physical status were used: the 6-minute walk test, grip strength, and chair-stand test. The prehabilitation program comprised 7,500 steps, 30 grip strength exercises, and 100 chair-stand exercises daily. Patients' frailty score was calculated using the Modified Johns Hopkins Frailty score. Changes in physical status measures after prehabilitation and postoperative outcomes were compared. Thirty-two patients with a median age of 69.0 years (interquartile range = 59.5−76.3 years) were included. Patients' median duration of participation was 21.5 days (interquartile range = 16−29 days). There was a negative correlation between increasing frailty score and baseline the 6-minute walk test (R2 = 0.17) and chair-stand test (R2 = 0.18). Patients' mean the 6-minute walk test decreased at the end of the prehabilitation program, while grip strength and chair-stand test were unchanged. When stratified by low or intermediate and high frailty scores, the differences in the 6-minute walk test and chair-stand test were unchanged. Hospital duration of stay, complications, and 90-day readmission rates were not different between frailty groups (P >.05). Correlation of physical status measures with frailty score suggests only one of these measures is sufficient to estimate patients' preoperative physical status. A longer, more comprehensive prehabilitation program or an expedited operation are likely the best strategies to improve patient outcomes. [ABSTRACT FROM AUTHOR]

C‐C motif chemokine receptor 2 (CCR2) is an important mediator of myeloid cell chemotaxis during inflammation and infection. Myeloid cells such as monocytes, macrophages, and neutrophils contribute to host defense during orthopedic implant‐associated infections (OIAI), but whether CCR2‐mediated chemotaxis is involved remains unclear. Therefore, a Staphylococcus aureus OIAI model was performed by surgically placing an orthopedic‐grade titanium implant and inoculating a bioluminescent S. aureus strain in knee joints of wildtype (wt) and CCR2‐deficient mice. In vivo bioluminescent signals significantly increased in CCR2‐deficient mice compared with wt mice at later time points (Days 14–28), which was confirmed with ex vivo colony‐forming unit enumeration. S. aureus γ‐hemolysin utilizes CCR2 to induce host cell lysis. However, there were no differences in bacterial burden when the OIAI model was performed with a parental versus a mutant γ‐hemolysin‐deficient S. aureus strain, indicating that the protection was mediated by the host cell function of CCR2 rather than γ‐hemolysin virulence. Although CCR2‐deficient and wt mice had similar cellular infiltrates in the infected joint tissue, CCR2‐deficient mice had reduced myeloid cells and γδ T cells in the draining lymph nodes. Taken together, CCR2 contributed to host defense at later time points during an OIAI by increasing immune cell infiltrates in the draining lymph nodes, which likely contained the infection and prevented invasive spread. [ABSTRACT FROM AUTHOR]

Anti-infection immunotherapy: Antibiotic-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) are increasingly prevalent and difficult to treat. Alphonse et al. show that a pan-caspase inhibitor called Q-VD-OPH functioned as an effective immunotherapy in mouse models of community-acquired MRSA, Streptococcus pyogenes, and Pseudomonas aeruginosa skin infections. Q-VD-OPH reduced apoptosis in neutrophils and monocytes and increased necroptosis in macrophages, thereby increasing TNF production and infection clearance in mice. This work suggests a potential strategy to target bacterial infections without requiring the use of antibiotics. Staphylococcus aureus causes most skin infections in humans, and the emergence of methicillin-resistant S. aureus (MRSA) strains is a serious public health threat. There is an urgent clinical need for nonantibiotic immunotherapies to treat MRSA infections and prevent the spread of antibiotic resistance. Here, we investigated the pan-caspase inhibitor quinoline–valine–aspartic acid–difluorophenoxymethyl ketone (Q-VD-OPH) for efficacy against MRSA skin infection in mice. A single systemic dose of Q-VD-OPH decreased skin lesion sizes and reduced bacterial burden compared with vehicle-treated or untreated mice. Although Q-VD-OPH inhibited inflammasome-dependent apoptosis-associated speck-like protein containing caspase activation and recruitment domain (ASC) speck formation and caspase-1–mediated interleukin-1β (IL-1β) production, Q-VD-OPH maintained efficacy in mice deficient in IL-1β, ASC, caspase-1, caspase-11, or gasdermin D. Thus, Q-VD-OPH efficacy was independent of inflammasome-mediated pyroptosis. Rather, Q-VD-OPH reduced apoptosis of monocytes and neutrophils. Moreover, Q-VD-OPH enhanced necroptosis of macrophages with concomitant increases in serum TNF and TNF-producing neutrophils, monocytes/macrophages, and neutrophils in the infected skin. Consistent with this, Q-VD-OPH lacked efficacy in mice deficient in TNF (with associated reduced neutrophil influx and necroptosis), in mice deficient in TNF/IL-1R and anti-TNF antibody-treated WT mice. In vitro studies revealed that combined caspase-3, caspase-8, and caspase-9 inhibition reduced apoptosis, and combined caspase-1, caspase-8, and caspase-11 inhibition increased TNF, suggesting a mechanism for Q-VD-OPH efficacy in vivo. Last, Q-VD-OPH also had a therapeutic effect against Streptococcus pyogenes and Pseudomonas aeruginosa skin infections in mice. Collectively, pan-caspase inhibition represents a potential host-directed immunotherapy against MRSA and other bacterial skin infections. [ABSTRACT FROM AUTHOR]

Orthopedic implant‐associated infection (OIAI) is a major complication that leads to implant failure. In preclinical models of Staphylococcus aureus OIAI, osteomyelitis and septic arthritis, interleukin‐1α (IL‐1α), IL‐1β, and tumor necrosis factor (TNF) are induced, but whether they have interactive or distinctive roles in host defense are unclear. Herein, a S. aureus OIAI model was performed in mice deficient in IL‐1α, IL‐1β, or TNF. Mice deficient in IL‐1β or TNF (to a lesser extent) but not IL‐1α had increased bacterial burden at the site of the OIAI throughout the 28‐day experiment. IL‐1β and TNF had a combined and critical role in host defense as mice deficient in both IL‐1R and TNF (IL‐1R/TNF‐deficient mice) had a 40% mortality rate, which was associated with markedly increased bacterial burden at the site of the OIAI infection. Finally, IL‐1α‐ and IL‐1β‐deficient mice had impaired neutrophil recruitment whereas IL‐1β‐, TNF‐, and IL‐1R/TNF‐deficient mice all had impaired recruitment of both neutrophils and monocytes. Therefore, IL‐1β and TNF contributed to host defense against S. aureus OIAI and neutrophil recruitment was primarily mediated by IL‐1β and monocyte recruitment was mediated by both IL‐1β and TNF. [ABSTRACT FROM AUTHOR]

Myeloid-derived suppressor cells (MDSCs) are markedly increased in cancer patients and tumor-bearing mice and promote tumor growth and survival by inhibiting host innate and adaptive immunity. In this study, we generated and characterized MDSCs from murine-induced pluripotent stem cells (iPSCs). The iPSCs were co-cultured with OP9 cells, stimulated with GM-CSF, and became morphologically heterologous under co-culturing with hepatic stellate cells. Allogeneic and OVA-specific antigen stimulation demonstrated that iPS-MDSCs have a T-cell regulatory function. Furthermore, a popliteal lymph node assay and autoimmune hepatitis model showed that iPS-MDSCs also regulate immune responsiveness in vivo and have a therapeutic effect against hepatitis. Taken together, our results demonstrated a method of generating functional MDSCs from iPSCs and highlighted the potential of iPS-MDSCs as a key cell therapy resource for transplantation and autoimmune diseases. [ABSTRACT FROM AUTHOR]

Background Schizophrenia is characterized by prominent cognitive deficits, impacting on memory and learning; these are strongly associated with the prefrontal cortex. Objective/hypothesis To combine two interventions, transcranial direct current stimulation (tDCS) over the prefrontal cortex and cognitive training, to examine change in cognitive performance in patients with schizophrenia. Methods A double blind, sham-controlled pilot study of 49 patients with schizophrenia, randomized into real or sham tDCS stimulation groups. Subjects participated in 4 days of cognitive training (days 1, 2, 14, 56) with tDCS applied at day-1 and day-14. The primary outcome measure was change in accuracy on working memory and implicit learning tasks from baseline. The secondary outcome measure was the generalization of learning to non-trained task, indexed by the CogState neuropsychological battery. Data analysis was conducted using multilevel modelling and multiple regressions. Results 24 participants were randomized to real tDCS and 25 to sham. The working memory task demonstrated a significant mean difference in performance in the tDCS treatment group: at day-2 (b = 0.68, CI 0.14–1.21; p = 0.044) and at day-56 (b = 0.71, 0.16–1.26; p = 0.044). There were no significant effects of tDCS on implicit learning. Trend evidence of generalization onto untrained tasks of attention and vigilance task (b = 0.40, 0.43–0.77; p = 0.058) was found. Conclusions This is the first study to show a significant longer-term effect of tDCS on working memory in schizophrenia. Given the current lack of effective therapies for cognitive deficits, tDCS may offer an important novel approach to modulating brain networks to ameliorate cognitive deficits in schizophrenia. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study was to prospectively evaluate the use of daily 2-mm bolus in patients undergoing postmastectomy radiation without reconstruction using optically stimulated luminescence dosimetry and weekly assessment of skin toxicity. Methods and materials We prospectively collected data from the first 49 women treated with a daily 2-mm Superflab bolus during their postmastectomy radiation therapy from 2013 to 2016 at The University of Chicago Comprehensive Cancer Center at Silver Cross. Within the first 3 days of starting radiation therapy, we measured the surface dose in vivo at 5 anatomical locations under the 2-mm bolus on the chest wall. We assessed weekly the acute skin toxicity during radiation using the National Cancer Institute Common Toxicity Criteria. Patients with reconstruction before radiation therapy were excluded. Results Forty-nine women with a mean age of 54.3 years were treated with daily 2-mm bolus to the chest wall following mastectomy. Median follow-up was 32.7 weeks. The mean percentages of prescribed dose (standard deviation) for the median, central, lateral, superior, and inferior optically stimulated luminescence dosimeters were 100.1% (5.6%), 108.1% (6.7%), 98.1% (6.5%), 102.6% (8.9%), and 106.3% (6.6%), respectively. The majority (71.4%) of women experienced a maximum acute National Cancer Institute Common Toxicity Criteria skin toxicity score of 2, with only 12.2% experiencing a score of 3. There were no grade 4 toxicities. There were no local recurrences during our follow-up period. Conclusions A daily 2-mm bolus is a feasible regimen for chest wall bolus during postmastectomy radiation therapy with acceptable dose buildup and skin toxicity. [ABSTRACT FROM AUTHOR]