The role of adjuvant radiation therapy in older patients with node-positive vulvar cancer: A national cancer database analysis.

OBJECTIVE: We sought to evaluate whether the survival benefit of adjuvant radiotherapy in patients with node-positive vulvar cancer is maintained in older patients, who comprise a large subgroup of patients with vulvar cancer. METHODS: The National Cancer Database (NCDB) was queried for patients aged 65 years or older, who were diagnosed with vulvar squamous cell carcinoma from 2004 to 2017 and underwent surgery with confirmed node-positive disease. Statistical analysis was performed with propensity-score matching, chi-square test, log-rank test, Kaplan-Meier, and multivariable Cox proportional regression. RESULTS: A total of 2396 patients were analyzed, and 1517 (63.3%) received adjuvant radiotherapy. Median follow-up was 73 months. Median age at diagnosis was 77 years (range 65-90). In the propensity score-matched cohort, five-year overall survival (OS) was 29%. Five-year OS was 33% in patients who received surgery followed by adjuvant radiotherapy and 26% in patients who received surgery alone (p < 0.0001). Multivariable analysis continued to demonstrate a survival benefit associated with the addition of adjuvant radiotherapy (OR 0.77 [95% CI 0.69-00.87], p < 0.001). Adjuvant radiotherapy was associated with improved OS among patients aged 65-84 (5-year OS 35% vs 29%, p = 0.0004), but not in patients aged 85 years and older (5-year OS 20% vs 19%, p = 0.32). CONCLUSION: This NCDB study suggests that in older patients with node-positive vulvar cancer, radiotherapy continues to be a vital component of multimodality therapy. However, a comprehensive and geriatrics-specific approach is crucial for treating older adults with node-positive vulvar cancer, as the benefit of adjuvant radiotherapy may be compromised by treatment-related morbidity/toxicity.

Recent knowledge: Concepts of dermal absorption in relation to skin decontamination.

Skin decontamination is an important step mitigating percutaneous absorption through the stratum corneum (SC), which is also a highly complex process. Thus, understanding diffusion mechanisms and measuring dermal absorption rates are critical to protect humans from toxic exposures. Here, highly varied literature is placed in a biological and clinical perspective in regards to decontamination. Literature from PubMed and Surge Laboratory library files were searched and reviewed for relevance. Recent data have shown multiple layers of SC structural heterogeneity, which results in unique substance partitioning characteristics across the membrane. As such, attempts to model and understand this behavior in alternative in vitro membranes prove difficult. More synthetic and natural membranes are being explored as models for in vivo behavior. In addition, commonly accepted decontamination methods are undergoing risk assessment. These recent and varied literature findings update available knowledge regarding skin decontamination and its challenges, with a focus on dermal absorption.

Effects of soap-water wash on human epidermal penetration.

Skin decontamination is a primary interventional method used to decrease dermal absorption of hazardous contaminants, including chemical warfare agents, pesticides and industrial pollutants. Soap and water wash, the most common and readily available decontamination system, may enhance percutaneous absorption through the "wash-in effect." To understand better the effect of soap-water wash on percutaneous penetration, and provide insight to improving skin decontamination methods, in vitro human epidermal penetration rates of four C(14) -labeled model chemicals (hydroquinone, clonidine, benzoic acid and paraoxon) were assayed using flow-through diffusion cells. Stratum corneum (SC) absorption rates of these chemicals at various hydration levels (0-295% of the dry SC weights) were determined and compared with the results of the epidermal penetration study to clarify the effect of SC hydration on skin permeability. Results showed accelerated penetration curves of benzoic acid and paraoxon after surface wash at 30 min postdosing. Thirty minutes after washing (60 min postdosing), penetration rates of hydroquinone and benzoic acid decreased due to reduced amounts of chemical on the skin surface and in the SC. At the end of the experiment (90 min postdosing), a soap-water wash resulted in lower hydroquinone penetration, greater paraoxon penetration and similar levels of benzoic acid and clonidine penetration compared to penetration levels in the non-wash groups. The observed wash-in effect agrees with the enhancement effect of SC hydration on the SC chemical absorption rate. These results suggest SC hydration derived from surface wash to be one cause of the wash-in effect. Further, the occurrence of a wash-in effect is dependent on chemical identity and elapsed time between exposure and onset of decontamination. By reducing chemical residue quantity on skin surface and in the SC reservoir, the soap-water wash may decrease the total quantity of chemical absorbed in the long term; however, the more immediate accelerated absorption of chemical toxins, particularly chemical warfare agents, may be lethal. Copyright © 2015 John Wiley & Sons, Ltd.

Effect of massage on percutaneous penetration and skin decontamination: man and animal.

CONTEXT: At least 15 factors of percutaneous penetration exist that should be considered when investigating dermal absorption profiles of chemicals. Rubbing is one variable that has been understudied, but may play an important role in understanding overall exposure rates, chemical toxicity, dermal absorption and skin's barrier abilities. OBJECTIVE: This reviews current data related to the role of massage in enhancing percutaneous penetration and skin decontamination as well as highlights the need for further investigation of its role. RESULTS: An in vivo study in rhesus monkeys and guinea pigs measuring amount of drug excreted after being topically applied showed no effect with massage. However, studies measuring permeation rates directly through human and animal skin ex vivo showed rubbing increased flux, reduced skin impedance and increased drug retention in skin. Rubbing also increased effectiveness of reactive skin decontamination lotion (RSDL). CONCLUSION: Massage sometimes influences chemical penetration rates and should be studied thoroughly to clarify the mechanisms and factors involved in the possible enhancing effect. This will also reveal more insight regarding the skin's ability to act as a barrier to exogenous substances and its role in risk assessment. How ex vivo results translate to in vivo behaviors still requires further investigation.

Natural Language Processing for Radiation Oncology: Personalizing Treatment Pathways.

Natural language processing (NLP), a technology that translates human language into machine-readable data, is revolutionizing numerous sectors, including cancer care. This review outlines the evolution of NLP and its potential for crafting personalized treatment pathways for cancer patients. Leveraging NLP's ability to transform unstructured medical data into structured learnable formats, researchers can tap into the potential of big data for clinical and research applications. Significant advancements in NLP have spurred interest in developing tools that automate information extraction from clinical text, potentially transforming medical research and clinical practices in radiation oncology. Applications discussed include symptom and toxicity monitoring, identification of social determinants of health, improving patient-physician communication, patient education, and predictive modeling. However, several challenges impede the full realization of NLP's benefits, such as privacy and security concerns, biases in NLP models, and the interpretability and generalizability of these models. Overcoming these challenges necessitates a collaborative effort between computer scientists and the radiation oncology community. This paper serves as a comprehensive guide to understanding the intricacies of NLP algorithms, their performance assessment, past research contributions, and the future of NLP in radiation oncology research and clinics.

Precision based approach to tailoring radiotherapy in the multidisciplinary management of pediatric central nervous system tumors.

Modern day survivorship from childhood malignancies is estimated to be over 80%. However, central nervous system tumors remain the leading cause of cancer mortality in children and is the most common solid tumor in this population. Improved survivorship is, in part, a result of improved multidisciplinary care, often with a combination of surgery, radiation therapy, and systemic therapy. With improved survival, long term effects of treatment and quality of life impacts have been recognized and pose a challenge to maximize the therapeutic ratio of treatment. It has been increasingly more apparent that precise risk stratification, such as with the inclusion of molecular classification, is instrumental in efforts to tailor radiotherapy for appropriate treatment, generally towards de-intensification for this vulnerable patient population. In addition, advances in radiotherapy techniques have allowed greater conformality and accuracy of treatment for those who do require radiotherapy for tumor control. Ongoing efforts to tailor radiotherapy, including de-escalation, omission, or intensification of radiotherapy, continue to improve as increasing insight into tumor heterogeneity is recognized, coupled with advances in precision medicine employing novel molecularly-targeted therapeutics.

Outcomes of salvage high dose-rate brachytherapy with or without pelvic external beam radiotherapy in patients with palpable local recurrence of prostate cancer after radical prostatectomy.

PURPOSE: This study aims to evaluate the outcomes and toxicities in patients with palpable local recurrence of prostate cancer after radical prostatectomy (RP), who were treated with salvage high dose-rate brachytherapy (HDR-BT) with or without pelvic external beam radiotherapy (EBRT). METHODS: This retrospective review included patients with palpable local recurrence of prostate cancer after RP who underwent salvage HDR-BT at a single institution between 2002 and 2020. HDR-BT regimens included 950 cGy x 2 (N = 4) or 1500 cGy x 1 (N = 2) combined with EBRT; or monotherapy with 950 cGy x 4 (N = 1) or 800 cGy x 2 (N = 1). Toxicity was graded according to CTCAE Version 5.0. RESULTS: A total of 8 patients were included. Median follow-up was 49 months (range: 9-223 months). Median age at time of salvage brachytherapy was 68 years (range: 59-85 years). Seven out of 8 patients were alive at last follow-up. There have been no locoregional recurrences. Three patients developed distant metastatic disease. One patient developed acute grade 3 urinary obstruction requiring catheterization, which lasted for 1 day postbrachytherapy. One patient developed late grade 3 urinary incontinence 18 months after brachytherapy. There were no other grade 2+ toxicities. CONCLUSIONS: This study demonstrates the safety and efficacy of salvage HDR-BT in the setting of palpable local recurrence of prostate cancer after RP, with durable locoregional control and acceptable rates of toxicity. HDR-BT should be further explored as an option for dose-escalated salvage radiotherapy after prior radical prostatectomy.

Safety of accelerated hypofractionated whole pelvis radiation therapy prior to high dose rate brachytherapy or stereotactic body radiation therapy prostate boost.

BACKGROUND: To evaluate acute and late genitourinary and gastrointestinal toxicities and patient reported urinary and sexual function following accelerated, hypofractionated external beam radiotherapy to the prostate, seminal vesicles and pelvic lymph nodes and high dose rate (HDR) brachytherapy or stereotactic body radiation therapy (SBRT) prostate boost. METHODS: Patients at a single institution with NCCN intermediate- and high-risk localized prostate cancer with logistical barriers to completing five weeks of whole pelvic radiotherapy (WPRT) were retrospectively reviewed for toxicity following accelerated, hypofractionated WPRT (41.25 Gy in 15 fractions of 2.75 Gy). Patients also received prostate boost radiotherapy with either HDR brachytherapy (1 fraction of 15 Gy) or SBRT (19 Gy in 2 fractions of 9.5 Gy). The duration of androgen deprivation therapy was at the discretion of the treating radiation oncologist. Toxicity was evaluated by NCI CTCAE v 5.0. RESULTS: Between 2015 and 2017, 22 patients with a median age of 71 years completed accelerated, hypofractionated WPRT. Median follow-up from the end of radiotherapy was 32 months (range 2-57). 5%, 73%, and 23% of patients had clinical T1, T2, and T3 disease, respectively. 86% of tumors were Gleason grade 7 and 14% were Gleason grade 9. 68% and 32% of patients had NCCN intermediate- and high-risk disease, respectively. 91% and 9% of patients received HDR brachytherapy and SBRT prostate boost following WPRT, respectively. Crude rates of grade 2 or higher GI and GU toxicities were 23% and 23%, respectively. 3 patients (14%) had late or persistent grade 2 toxicities of urinary frequency and 1 patient (5%) had late or persistent GI toxicity of diarrhea. No patient experienced grade 3 or higher toxicity at any time. No difference in patient-reported urinary or sexual function was noted at 12 months. CONCLUSIONS: Accelerated, hypofractionated whole pelvis radiotherapy was associated with acceptable GU and GI toxicities and should be further validated for those at risk for harboring occult nodal disease.

Resection with intraoperative cesium-131 brachytherapy as salvage therapy for recurrent brain tumors.

OBJECTIVE: The authors' objective was to examine the safety and efficacy of salvage intracranial cesium-131 brachytherapy in combination with resection of recurrent brain tumors. METHODS: The authors conducted a retrospective chart review of consecutive patients treated with intraoperative intracranial cesium-131 brachytherapy at a single institution. Permanent suture-stranded cesium-131 seeds were implanted in the resection cavity after maximal safe tumor resection. The primary outcomes of interest were local, locoregional (within 1 cm), and intracranial control, as well as rates of overall survival (OS), neurological death, symptomatic adverse radiation effects (AREs), and surgical complication rate graded according to Common Terminology Criteria for Adverse Events version 5.0. RESULTS: Between 2016 and 2020, 36 patients received 40 consecutive cesium-131 implants for 42 recurrent brain tumors and received imaging follow-up for a median (interquartile range [IQR]) of 17.0 (12.7-25.9) months. Twenty patients (55.6%) with 22 implants were treated for recurrent brain metastasis, 12 patients (33.3%) with 16 implants were treated for recurrent atypical (n = 7) or anaplastic (n = 5) meningioma, and 4 patients (11.1%) were treated for other recurrent primary brain neoplasms. All except 1 tumor (97.6%) had received prior radiotherapy, including 20 (47.6%) that underwent 2 or more prior radiotherapy treatments and 23 (54.8%) that underwent prior resection. The median (IQR) tumor size was 3.0 (2.3-3.7) cm, and 17 lesions (40.5%) had radiographic evidence of ARE prior to salvage therapy. Actuarial 1-year local/locoregional/intracranial control rates for the whole cohort and patients with metastases and meningiomas were 91.6%/83.4%/47.9%, 88.8%/84.4%/45.4%, and 100%/83.9%/46.4%, respectively. No cases of local recurrence of any histology (0 of 27) occurred after gross-total resection (p = 0.012, log-rank test). The 1-year OS rates for the whole cohort and patients with metastases and meningiomas were 82.7%, 79.1%, and 91.7%, respectively, and the median (IQR) survival of all patients was 26.7 (15.6-36.4) months. Seven patients (19.4%) experienced neurological death from progressive intracranial disease (7 of 14 total deaths [50%]), 5 (13.9%) of whom died of leptomeningeal disease. Symptomatic AREs were observed in 9.5% of resection cavities (n = 4), of which 1 (2.4%) was grade 3 in severity. The surgical complication rate was 16.7% (n = 7); 4 (9.5%) of these patients had grade 3 or higher complications, including 1 patient (2.4%) who died perioperatively. CONCLUSIONS: Cesium-131 brachytherapy resulted in good local control and acceptable rates of symptomatic AREs and surgical complications in this heavily pretreated cohort, and it may be a reasonable salvage adjuvant treatment for this patient population.

Role of Ki-67, MRE11, and PD-L1 as Predictive Biomarkers for Recurrence Pattern in Muscle-invasive Bladder Cancer.

BACKGROUND/AIM: Muscle invasive bladder cancer (MIBC) is an aggressive disease with high rates of local recurrence following radical cystectomy (RC). Currently, there are no clinically validated biomarkers to predict local only recurrence (LOR) and guide adjuvant treatment decisions. This pilot study evaluated the role of Ki-67, MRE11 and PD-L1 as predictive biomarkers for recurrence patterns in patients undergoing RC for MIBC. PATIENTS AND METHODS: Our institutional cystectomy database containing cases from 1992-2014 was queried for patients with local only recurrence (LOR), and case-matched to patients with distant recurrence (DR) and no recurrence (NR). Clinicopathological data were collected and a tissue microarray was analyzed for presence of Ki-67, MRE11, and PD-L1 using immunofluorescence and immunohistochemistry. RESULTS: Pathologic specimens from 42 patients (18 NR, 16 LOR, and 8 DR) were reviewed. Compared to normal bladder tissue, tumors had increased expression of Ki-67 (p<0.01) and PD-L1 (p<0.05). High Ki-67 was associated with recurrence pattern (local vs. distant) on univariate analysis (p<0.05). Ki-67 cell density varied by recurrence type: LOR (1354 cells/mm2), DR (557 cells/mm2) and NR (1111 cells/mm2) (p=0.034). CONCLUSION: Our selected biomarkers could distinguish MIBC from normal bladder tissue but could not classify samples by recurrence pattern.

Discontinued dermatological drugs in 2014.

INTRODUCTION: Dermatology is a relatively small field concerned with conditions of the hair, skin, nails and their related diseases; yet there is considerable active research and development within the field. Pharmaceutical companies seek more effective treatments through various therapeutic classes and delivery routes. However, 28 drugs have been discontinued for the treatment of dermatologic diseases in 2014. AREAS COVERED: Herein, the authors summarize the details about each discontinued drug in 2014. The dermatological conditions covered are: psoriasis, eczema, leg ulcers, wounds, allergies, acne, scleroderma, lupus erythematosus, urticaria, mastocytosis, epidermolysis bullosa, onychomycosis and one other unspecified disease. The authors also provide suggestions for improving and accelerating the future of dermatological drug development. EXPERT OPINION: It is clear that improved metrics, especially for early assessment, emphasizing clinical relevance, are necessary to increase success rate. Transparency and clear communication within the field is necessary to reduce and salvage the waste that accumulates from these costly studies. Focused attention on how preclinical and early clinical studies failed to indicate subsequent toxicity profiles in patients would accelerate drug development. Distinguishing between disappointing study results and business/financial factors is important when analyzing discontinuations. A reformed approach toward study design would aid both. Ultimately, relevance and practicality for the patient must be kept in mind at all times.