Adjuvant Therapy Research Articles

The use of a long-acting muscarinic antagonist in the treatment of asthma: A tertiary asthma center experience.

We aimed to investigate the frequency and sociodemographic and clinical distinguishing features of asthmatic patients in whom long-acting muscarinic antagonists (LAMA) were added to maintenance therapy in our clinic. In this cross-sectional study, data on sociodemographic, phenotypic, and clinical characteristics of patients with asthma using Steps 4 and 5 medications, who were followed up in our center for at least 1 year, were obtained from file records. Whether the patients received add-on LAMA for at least 6 months was also noted. A total of 279 patients with asthma using Steps 4 and 5 medications (female/male: 215/64) with a mean age of 50.84 ± 12.42 years were included in the study. Seventy-nine (28.3%) patients (female/male: 60/19) with a mean age of 52.45 ± 11.61 years used LAMA as an add-on treatment; 28 (37.8%) at Step 4 and 51 (24.8%) at Step 5. In Steps 4 and 5, there was no difference in terms of age, sex, body mass index, smoking status, being allergic or eosinophilic, phenotype, and asthma onset between patients with and without add-on LAMA. Asthma control in the previous year was better, and minimum forced expiratory volume in 1s (FEV1) was lower in patients with LAMA than in those without in Step 4 (P = 0.001 and P = 0.030, respectively). In Step 5, the rate of being well-controlled was higher in those without add-on LAMA (P < 0.001). The number of exacerbations in the previous year was higher, and minimum and maximum FEV1 were lower in patients with add-on LAMA (P < 0.001 and P < 0.001, respectively). Our study showed that add-on LAMA treatment was effective in increasing asthma control in patients using Step 4 medication independent of baseline characteristics and asthma phenotype.

The impact of high exposure to perfluoroalkyl substances and risk for hormone receptor-positive breast cancer – A Swedish cohort study

IntroductionPerfluoroalkyl substances (PFAS) are persisting chemicals with endocrine disruptive and carcinogenic properties. Previous studies involving cohorts with high PFAS exposure have not shown an increased risk of breast cancer. Research on PFAS and breast cancer according to hormone receptor status is limited. This study aims to investigate the association between PFAS exposure and hormone receptor-positive breast cancer. Materials and MethodsIn 2013, high levels of PFAS (sum of PFAS > 10,000 ng/L), dominated by perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS) were found in the drinking water from one of the two waterworks in Ronneby, Sweden. Breast cancer diagnoses and information of adjuvant endocrine therapy were retrieved from the Swedish Cancer Register and The Prescribed Drug Register 2006–2016 for a cohort of women residing in the municipality between 1985 and 2013 (n = 24,509). Individual exposure was assessed based on municipality waterworks distribution data linked to annual residential addresses. Cox proportional hazards models were used in the analysis. The highest achieved educational level was used as an indicator of socioeconomic position. Sensitivity and subgroup analysis were performed for prepubertal exposure and diagnosis before or after age 50 (assumed menopause). ResultsThere were 313 cases of malignant breast cancer among women ≤ 85 years between 2006 and 2016. Of these, 224 cases (72 %) were considered hormone receptor-positive based on the first prescription of adjuvant endocrine therapy, antiestrogens (40 %) or aromatase inhibitor (60 %). Among women ever living at a residential address with high PFAS exposure, the hazard ratio (HR) for breast cancer classified as hormone receptor-positive was 0.84; 95 % confidence interval (CI) 0.61, 1.14. Findings were similar before and after menopause. ConclusionHigh PFAS exposure from drinking water, dominated by PFOS and PFHxS, was not associated with an elevated risk of hormone receptor-positive breast cancer.

Recaticimab as Add-On Therapy to Statins for Nonfamilial Hypercholesterolemia: The Randomized, Phase 3 REMAIN-2 Trial

BackgroundCurrently available antiproprotein convertase subtilisin/kexin type 9 monoclonal antibodies can effectively decrease low-density lipoprotein cholesterol (LDL-C) levels, but require frequent dosing. Recaticimab is a novel humanized monoclonal antibody against proprotein convertase subtilisin/kexin type 9. In a phase 1b/2 trial, recaticimab as add-on to stable statins showed robust LDL-C reduction with a dosing interval up to every 12 weeks (Q12W) in patients with hypercholesterolemia. ObjectivesREMAIN-2 (REcaticiMab Add-on therapy In patients with Nonfamilial hypercholesterolemia) aimed to assess the efficacy and safety of 48-week treatment with recaticimab as add-on therapy to statins in nonfamilial hypercholesterolemia. MethodsREMAIN-2 was a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial. During the run-in period, patients received stable moderate or high-intensity statin, with or without cholesterol absorption inhibitors (ezetimibe) or fenofibrate, for ≥4 weeks. Patients with an LDL-C of ≥1.8 mmol/L (if with atherosclerotic cardiovascular disease [ASCVD]) or ≥2.6 mmol/L (if without ASCVD) were then randomized (2:2:2:1:1:1) to receive recaticimab 150 mg every 4 weeks (Q4W), 300 mg every 8 weeks (Q8W), or 450 mg Q12W, or matching placebo injections (Q4W, Q8W, or Q12W) for 48 weeks. The primary efficacy endpoint was percentage change from baseline to week 24 in LDL-C level. ResultsA total of 689 randomly assigned patients received treatment (mean age, 55.8 years; male, 64.4%; ASCVD history, 69.5%; concomitant ezetimibe, 11.2%; mean baseline LDL-C, 2.8 mmol/L). Percentage change in LDL-C from baseline to week 24 was significantly more pronounced with recaticimab vs placebo (P < 0.0001), with least-squares mean differences of −62.2% (95% CI: −67.0% to −57.4%), −59.7% (95% CI: −65.0% to −54.4%), and −53.4% (95% CI: −58.7% to −48.2%) for the 150 mg Q4W, 300 mg Q8W, and 450 mg Q12W regimens, respectively. The decreases in LDL-C with recaticimab were maintained through week 48. Secondary lipid variables, including non–high-density lipoprotein cholesterol, apolipoprotein B, and lipoprotein(a) also favored the recaticimab groups. During the treatment period, the incidence of treatment-related adverse events (28.5% vs 26.6%) and serious treatment-related adverse events (0.4% vs 0.4%) was similarly low in both the recaticimab and placebo groups. ConclusionsRecaticimab as add-on to stable statin therapy significantly decreased LDL-C levels at week 24 and sustained the decreases through week 48, providing a novel therapeutic alternative with a dosing interval of up to every 12 weeks in patients with nonfamilial hypercholesterolemia.

Ophthalmic Surgeries at a Nigerian Teaching Hospital from the Perspectives of Undergraduate Medical Education

BackgroundAn appraisal of the profile of ophthalmic surgeries performed at Ladoke Akintola University of Technology Teaching Hospital (LAUTECHTH), Ogbomosho, Nigeria over a seven-year period with a view to harnessing their potentials for maximising ophthalmic experiences of medical students. MethodsA retrospective review of ophthalmic surgery records over a seven-year period (2013 – 2019) at LAUTECHTH. ResultsThere were 386 eye surgeries, mean ophthalmic surgeries: 4 - 5/month or 55/year. Most (329, 85.2%) surgeries were performed on individuals aged at least 45 (range 10 - 95) years with slight male dominance (1.1:1). The most common indication for surgery was cataract (307, 79.6%). Most surgeries were elective (362, 93.8%) and performed under local anaesthesia (367, 95.1%). Despite the highest number of surgeries being performed in the months of April and September; and lowest during the months of May and October; there was fair distribution across and over the years. Small incision cataract surgery with or without intraocular lens implant (307, 79.6%) was the most common surgery followed by pterygium excision with adjuvant therapy (37, 9.6%). ConclusionThe study showed a broad spectrum of eye surgeries, including cataract and pterygium, performed at the teaching hospital, encompassing common conditions that lead to visual impairment or blindness. This exposure provides valuable training opportunities for undergraduate medical students to become physicians especially those aspiring to become ophthalmologists. However, there is a need to increase the overall volume of eye surgeries to enhance the learning experience and potentially influence career choices.

Homologous recombination deficiency score is an independent prognostic factor in esophageal squamous cell carcinoma.

Homologous recombination deficiency (HRD) represents an impairment in the homologous recombination repair (HRR) pathway, crucial for repairing DNA double-strand breaks and contributing to genomic instability in cancer. The HRD score may be a more reliable biomarker than HRR-related gene mutations for identifying patients sensitive to poly(ADP-ribose) polymerase inhibitors. Despite its relevance in various cancers, the HRD score remains underexplored in esophageal squamous cell carcinoma (ESCC). We retrospectively analyzed HRD scores in 96 ESCC patients, examining correlations with clinical characteristics and survival outcomes, and validated our findings using the TCGA dataset. Genomic sequencing utilized a custom superHRD next-generation sequencing panel, and HRD scores were calculated from 54,000 single-nucleotide polymorphisms using Kruskal-Wallis rank-sum tests and two cut-off points for analysis. Higher HRD scores correlated with advanced tumor stages, recurrence, and mutations in TP53 and ABCB1, while APC mutations were linked to lower HRD scores. Patients with high HRD scores had significantly shorter disease-free survival (p = 0.013) and a trend toward shorter overall survival (OS) (p = 0.005), particularly those not receiving adjuvant therapy. Conversely, HRD-high patients undergoing adjuvant therapy showed a trend toward longer OS (p = 0.015). Multivariate analysis identified HRD as an independent prognostic factor (hazard ratio = 2.814 for recurrence, p = 0.015). Validation with the TCGA dataset supported these findings. This study highlights the associations between HRD scores, clinical characteristics, and genomic mutations in ESCC, suggesting HRD as a potential prognostic biomarker. HRD assessment may aid in patient stratification and personalized treatment strategies, warranting further investigation to validate the therapeutic implications of HRD scores in ESCC.

Fragmented care, Commission on Cancer Accreditation and Overall Survival in Patients Receiving Surgery and Chemotherapy for Lung Cancer

Patients may receive their adjuvant therapy at a facility different than where they had their lung cancer operation. Whether this fragmentation of care affects outcomes is unclear. We used the National Cancer Database to identify lung cancer patients undergoing resection and adjuvant chemotherapy from 2006-2020. We stratified patients into those receiving fragmented care or not, and further divided fragmented care patients by the Commission on Cancer (CoC) accreditation status of the hospital. Fragmented care refers to patients receiving surgery and chemotherapy at different institutions. These institutions can be either CoC accredited or not. The main outcome was overall survival. We used Kaplan-Meier analysis to estimate survival and multivariable and Cox proportional models to identify associations. Of 65,369 patients, 32,494(49.7%) had fragmented care, with the majority(70.4%) receiving their chemotherapy at a non-CoC accredited facility. Factors associated with fragmented care were white(adjusted odds ratio(aOR)=1.34;p<0.001), lower comorbidity index(aOR=1.11;p<0.001), having a private insurance(aOR=1.11;p<0.001), and a higher median income(aOR=1.24;p<0.001). Fragmented care was associated with worse overall survival(Median survival=60vs65 months;p<0.001) compared to single center care. When care was fragmented, receiving adjuvant chemotherapy at CoC accredited centers had higher 5-year overall survival rates compared to those fragmented care at non-CoC centers(Median survival=71vs55 months;p<0.001). The majority of lung cancer patients have their care fragmented to non-CoC accredited centers and this is associated with worse outcomes. Regionalization, achieving CoC accreditation, or improved patient access may be necessary to allow select patients to receive closer care while maintaining outcomes.

Clinical and histomorphometric evaluation of the vagina following treatment with CO2 laser, radiofrequency, and promestriene for genitourinary syndrome of menopause in breast cancer survivors on adjuvant therapy

Clinical and histomorphometric evaluation of the vagina following treatment with CO2 laser, radiofrequency, and promestriene for genitourinary syndrome of menopause in breast cancer survivors on adjuvant therapy

Pediatric Mesenchymal Tumor With MN1::TAF3 Fusion.

MN1 fusion is emerging as oncogenic in soft-tissue tumors. Here, we provided detailed clinicopathological documentation of a tumor with MN1::TAF3 fusion. The tumor developed on the face of an 8-year-old boy and did not recur or metastasize for 5 years after surgery without adjuvant therapy. Histologically, the tumor predominantly comprised sheets and nests of atypical, mildly pleomorphic epithelioid cells. Mallory body-like eosinophilic cytoplasmic inclusions, small round cells, and fascicles of spindle cells were focally observed. Mitotic activity was high, and focal necrosis was present. Immunohistochemically, the tumor was positive for cytokeratin AE1/AE3 in the epithelioid cell component but otherwise showed nonspecific phenotypes. Targeted RNA sequencing identified an in-frame MN1 (exon 1)::TAF3 (exon 3) fusion transcript. We validated the transcript with reverse transcription-polymerase chain reaction, Sanger sequencing, and MN1 break-apart fluorescence insitu hybridization. MN1::TAF3 was previously listed without details in a large-scale sequencing study involving a pediatric round cell sarcoma in the orbit, raising the possibility that these tumors might form a coherent group.

Circulating tumor DNA status and dynamics predict recurrence in patients with resected extrahepatic cholangiocarcinoma

Background & AimsSurgery is the only curative therapeutic option for resectable extrahepatic cholangiocarcinoma (eCCA), but recurrence is common, and prognosis is poor. There is an unmet clinical need for improved decision-making regarding adjuvant chemotherapy (ACT). Here we evaluated the usefulness of monitoring longitudinal circulating tumor DNA (ctDNA) for minimal residual disease (MRD) in patients of the STAMP trial, which compares the efficacy of adjuvant capecitabine (CAP) versus gemcitabine plus cisplatin (GemCis). MethodsBetween July 2017 and November 2020, 101 patients were randomized 1:1 to receive GemCis (n=50) or CAP (n=51). Efficacy outcomes were analyzed with an extended follow-up of 19 months from the previous report. From a biomarker cohort of 89 patients, longitudinal plasma samples (n=254) were prospectively collected post-surgery before adjuvant chemotherapy (ACT), and on-ACT at 12 and 24 weeks from cycle 1 day 1 (C1D1). ctDNA was evaluated using a personalized, tumor-informed, 16-plex PCR-NGS assay and was correlated with clinical outcomes. ResultsIn the extended follow-up analysis, median disease-free survival (DFS) and overall survival (OS) did not significantly differ between the CAP and GemCis groups. Significantly inferior DFS was associated with ctDNA-positivity before ACT (HR, 1.8; p=0.029), on-ACT at 12 weeks from C1D1 (HR, 7.72; p<0.001), on-ACT at 24 weeks from C1D1 (HR, 5.24; p<0.001), and anytime post-surgery (HR, 3.81; p<0.001). Analysis of pre-treatment to on-treatment ctDNA dynamics revealed that serially ctDNA-negative patients exhibited a significantly longer DFS compared to those with sustained ctDNA-positivity (HR, 6.7; p<0.001) or who turned ctDNA-positive (HR, 5.8; p<0.001). ConclusionIn patients with resected eCCA, ctDNA status and dynamics predicted recurrence during adjuvant therapy, and may help optimize clinical decision-making. Impact and implicationsThe findings from this study highlight the critical role of ctDNA as a prognostic biomarker and monitoring tool for patients with resected extrahepatic cholangiocarcinoma (eCCA). By demonstrating the superiority of ctDNA to predict disease recurrence compared to conventional biomarkers such as CA 19-9 and CEA, this study underscores its potential in guiding decision-making during adjuvant chemotherapy. These results may be crucial to refine post-surgical treatment strategies and improve patient outcomes. The practical application of ctDNA monitoring could lead to more personalized treatment approaches, enabling timely interventions based on minimal residual disease (MRD) status. Clinical Trial Registration numberNCT03079427

[Translated article] Can 3D-printed patient-specific instruments improve local control and overall survival in pelvic sarcoma? A clinical validation study

Background and objectives 3D-printed patient-specific instruments (PSIs), also known as 3D guides, have been shown to improve accuracy in resection of pelvic tumors in cadaver studies and achieve better surgical margins in vivo. This study evaluates the clinical impact of 3D-printed guides on medium-term local and distant disease control, as well as disease-free and overall survival in patients.Material and methods A cohort study included 25 patients with primary pelvic or sacral sarcomas: 10 in the 3D group and 15 in the control group, with a median follow-up of 47 months. Demographic and clinical data, including tumor histology, stage, resection technique, associated reconstruction, adjuvant therapies, and complications, were evaluated. Surgical margins (free, marginal, and contaminated) and relapse-free and overall survival curves were analyzed.Results The 3D group achieved a higher rate of free margins (80% vs 66.7%, p = 0.345). Local recurrence (50% vs 60%, P=.244) and distant disease relapse (20% vs 47%, p = 0.132) rates were lower in the 3D group. At the end of the follow-up, the 3D group had a higher overall survival rate (60% vs 40%, p = 0.327). The complication rate was similar in both groups, with a deep infection rate of 40%.Conclusions The use of 3D guides in resecting primary pelvic tumors not only achieves a higher rate of free margins compared to conventional techniques but also shows a trend towards higher local, distant, and overall disease-free survival. Further studies with larger sample sizes and higher levels of evidence are necessary to validate these clinical trends.

Evaluating efficacy and safety of Saffron add-on treatment in improvement of motor and depressive symptoms of patients with Parkinson’s disease: a randomized, double-blind, placebo-controlled clinical trial

AimEvidence has highlighted neuroprotective effects of saffron in animal models of Parkinson’s disease (PD). The present study investigated the efficacy and safety of add-on saffron on motor and depressive symptoms of patients with PD. MethodsThis study was an 8-week, randomized, double-blind, and parallel-group clinical trial. Known cases of PD with depression were randomized to receive either a routine treatment (levodopa or levodopa-equivalent dose of a dopamine agonist) plus saffron capsule (15 mg bid) or routine treatment plus placebo. All participants were assessed using the Hamilton Depression Rating Scale (HAMD), Geriatric Depression Scale-30 (GDS-30), item 3 of Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part 1, MDS-UPDRS part 3, and H and Y scale at baseline and at week 8. ResultsA total of 52 patients (25 in saffron and 27 in placebo groups) were included. Our results demonstrated that saffron could not improve motor symptoms of PD patients (F=0.53, df=1, p=0.424). However, repeated-measures analysis showed a significant effect of time × treatment (F=8.24, df=1, p=0.006) on HAMD scores, indicating a greater improvement of depressive symptoms in saffron compared to placebo groups. Our study showed nonsignificant findings regarding the secondary outcome measures (GDS-30, item 3 of MDS-UPDRS part 1, and H and Y scale). We showed that treatment with saffron is safe in PD. ConclusionWe substantiated that add-on treatment with saffron significantly improved depression, but not motor symptoms, in PD. Further trials with larger sample sizes and longer follow-ups are needed to confirm our findings.

The Combined Effect of Hypoxia Activation and Radiosensitization by a Multifunctional Nanoplatform System Enhances the Therapeutic Efficacy of Chemoradiotherapy in Pancreatic Cancer

BackgroundPancreatic cancer is a highly malignant tumor, which is still a major global health problem. Chemotherapy and radiotherapy are regularly used in adjuvant therapy for pancreatic cancer but their therapeutic efficacy is limited. MethodsIn the present study, nanoparticle（MSN-AuNPs） was used as a drug carrier loaded with tirapazamine(TPZ) and hyaluronic acid (HA) to synthesize a multifunctional nanoplatform HA@TPZ-MSN-AuNPs (HTMA) for hypoxia activation and radiotherapy sensitization, which can be combined with radiotherapy therapy and synergistically enhance the therapeutic effect in pancreatic cancer. The anti-tumor performance of the nano platform was verified by in vivo and in vitro experiments. ResultFirst, the HA@TPZ-MSN-AuNPs (HTMA) was successfully synthesized. Drug release experiments showed that acidic environment and hyaluronidase promoted drug release in the nanoplatform. In vitro experiments, CCK-8, live-dead staining, clonal formation assay and flow cytometry confirmed the combined anti-tumor effect of hypoxia activation and radiotherapy sensitization with HTMA. In the drug uptake experiment, the nanoplatform showed the function of targeting and binding pancreatic cancer cells. In vivo, HTMA demonstrated good antitumor properties and good biocompatibility. ConclusionsThe nanoplatform had a good targeting effect and synergistic anti-tumor effect. The combination of hypoxia activation and radiotherapy sensitization is a promising strategy for the treatment of pancreatic cancer.

5-Fluorouracil/curcumin loaded silk fibroin hydrogel for the adjuvant therapy in colorectal cancer

This study employed silk fibroin (SF) as a carrier material to encapsulate curcumin (CUR) and 5-fluorouracil (5-FU), forming a highly effective drug-loaded hydrogel. The process involved mixing SF solution containing 5-FU with curcumin solution dissolved in acetone (AC), leading to the formation of composite drug-loaded nanospheres with particle sizes ranging from 77.87 nm to 299.22 nm, demonstrated enhanced permeability and retention (EPR) effects, enabling passive targeting of solid tumors. After the formation of the nanospheres, they were dispersed into a solution containing SF and polyethylene glycol (PEG). Following gelation and PEG removal, a SF hydrogel loaded with 5-FU and CUR (5-FU/CUR@SF hydrogel) was obtained. Results indicated that the 5-FU/CUR@SF hydrogel exhibited excellent drug release properties, with 5-FU and CUR achieving sustained release of 59.66 ± 3.76 % and 47.94 ± 5.03 %, respectively, over a 400-h of sustainable releasing period. Human colorectal cancer cell line (HT-29) and normal human colon epithelial cell line (NCM-460) were cultured with the 5-FU/CUR@SF hydrogel, resulting an apoptosis rate of only 17.38 ± 1.98 % for NCM-460 cells, whereas the apoptosis rate for HT-29 cells significantly increased to 72.31 ± 2.18 %, and its cell viability dropped to 59.77 ± 0.55 %. These findings suggest that the 5-FU/CUR@SF hydrogel exhibits low cytotoxicity toward normal NCM-460 cells, while exerting significant and sustained inhibitory effects on HT-29 cancer cells. In conclusion, the SF-based drug-loaded composite hydrogel holds great potential as a novel adjuvant therapeutic strategy for the treatment of CRC.

Patterns of adjuvant therapy for endometrial cancer with sentinel lymph node biopsy

Patterns of adjuvant therapy for endometrial cancer with sentinel lymph node biopsy

Defining a parameter to select the best radiotherapy technique in patients with right breast cancer after conservative surgery: Evaluation of high doses and risk of radio-induced second tumors to the ipsilateral lung

PurposeIn the adjuvant right breast radiation therapy, after breast-conserving surgery, we wanted to look for a parameter that would help in the choice between the 3D-CRT or VMAT techniques, considering the risk of pneumonia to the ipsilateral lung (IL) linked to high doses. We also investigated the risk of second tumors in the IL related to the VMAT low doses. MethodsWe examined twenty-five 3D-CRT and thirty-five VMAT technique plans, between September 2022 and September 2023.We collected the MAximum Thickness of Ipsilateal Lung (MATIL) included between lateral and medial target borders for evaluating the risk of pneumonia due to the high dose (V20Gy), finally we calculated the Excess of Absolute Risk related to the second tumor risk due to the low dose. ResultsVMAT technique showed a better dose conformity than 3D-CRT. We detected a linear relationship between the V20Gy and MATIL of the IL only for the 3D-CRT technique; over a threshold value of MATIL the 3D-CRT is disadvantaged compared to the VMAT in terms of the risk of toxicity to the IL. We calculated that for every Gy more in average dose, a 12 % increase in the risk of induced cancer is expected. ConclusionsIn the adjuvant right breast RT, the MATIL is a good surrogate parameter to predict the need to use a VMAT technique to limit high doses to IL. VMAT technique, according to the IL second tumor estimated risk, seems justified.

ASO Author Reflections: It Does Not Matter Whether Radical Prostatectomy is Performed in High-Risk Localized Disease or at the Oligometastatic Stage.

Radical prostatectomy (RP) alone has traditionally been considered insufficient for patients with high-risk localized prostate cancer (HRPC) owing to the frequent need for adjuvant salvage radiotherapy or androgen deprivation therapy (ADT) following surgery. Previously, systemic therapy, such as ADT, was the standard treatment for metastatic prostate cancer (PC) patients; RP was not considered viable for these patients. However, since 2015, there has been a recognition that metastatic PC patients can be categorized based on the extent of their metastases, leading to the consideration of RP for some metastatic cases. In recent years, the concept of cytoreductive RP has gained traction; studies suggest that it may improve survival rates in metastatic PC patients through mechanisms, such as tumor debulking and enhancement of the immune response. A meta-analysis of retrospective studies has shown that cytoreductive RP is associated with higher cancer-specific survival rates at 1-year, 3-year, and 5-year intervals compared with systemic therapy alone. In our study, which followed HRPC and oligometastatic PC patients for an average of 46 months, we observed biochemical recurrence in 17.8% of HRPC and 13% of oligometastatic patients, with overall survival rates of 96.4% and 87%, respectively. Although prospective or randomized studies are still lacking, current retrospective studies, including our own, suggest promising outcomes for RP in HRPC and oligometastatic patients. With the increasing prevalence of robotic surgery, improved pelvic anatomy observation, and growing surgical confidence, the realization of prospective randomized study results may not be far off.

T-cell Responses to Individualized Neoantigen Therapy mRNA-4157 (V940) Alone or in Combination with Pembrolizumab in the Phase 1 KEYNOTE-603 Study.

mRNA-4157 (V940) is an individualized neoantigen therapy targeting up to 34 patient-specific tumor neoantigens to induce T-cell responses and potentiate antitumor activity. We report mechanistic insights into the immunogenicity of mRNA-4157 via characterization of T-cell responses to neoantigens from the first-in-human, phase 1, KEYNOTE-603 study (NCT03313778) in patients with resected non-small cell lung cancer (Part A: 1-mg mRNA-4157, n = 4) or resected cutaneous melanoma (Part D: 1-mg mRNA-4157 + 200-mg pembrolizumab, n = 12). Safety, tolerability, and immunogenicity were assessed. All patients experienced ≥1 treatment-emergent adverse event; there were no grade 4/5 adverse events or dose-limiting toxicities. mRNA-4157 alone induced consistent de novo and strengthened preexisting T-cell responses to targeted neoantigens. Following combination therapy, sustained mRNA-4157-induced neoantigen-specific T-cell responses and expansion of cytotoxic CD8 and CD4 T cells were observed. These findings show the potential of a novel mRNA individualized neoantigen therapy approach in oncology. Significance: The safety and immunogenicity results from this phase 1 study of mRNA-4157 as adjuvant monotherapy or combination therapy with pembrolizumab show generation of de novo and enhancement of existing neoantigen-specific T-cell responses and provide mechanistic proof of concept to support further development of mRNA-4157 for patients with resected solid tumors. See related commentary by Berraondo et al., p. 2021.

Ten-year outcomes of a phase III, multicenter, randomized controlled trial (SHIP0804) with three-month neoadjuvant androgen deprivation prior to 125I-seed transperineal prostate brachytherapy followed by nil versus nine-month adjuvant hormonal therapy in patients with intermediate-risk prostate cancer

Ten-year outcomes of a phase III, multicenter, randomized controlled trial (SHIP0804) with three-month neoadjuvant androgen deprivation prior to 125I-seed transperineal prostate brachytherapy followed by nil versus nine-month adjuvant hormonal therapy in patients with intermediate-risk prostate cancer

ASO Author Reflections: Survival Benefit of Adjuvant Systemic Therapy After Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma.

ASO Author Reflections: Survival Benefit of Adjuvant Systemic Therapy After Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma.

A novel stability-indicating chromatographic quantification of the antiparkinsonian drug safinamide in its pharmaceutical formulation employing HPTLC densitometry and ion-pair HPLC–DAD

Parkinson's disease (PD) emerges as a notable health concern among the elderly population. Safinamide mesylate (SAF) is a novel and emerging add-on therapy in PD treatment. The stability of innovative drug formulations and the development of appropriate stability-indicating methods are of great importance to modern pharmaceutical analysis. The current work has established novel comprehensive stability-indicating chromatographic approaches, HPTLC coupled with densitometric quantification and HPLC–DAD, for the selective assay of SAF in pharmaceutical formulation along with its synthetic precursor impurity; 4-hydroxy benzaldehyde (4-HBD) in presence of its stress induced degradation products. The stability of SAF was investigated under different stress conditions. It was found that SAF is likely to undergo acid, base hydrolysis, and oxidative degradation. Using mass spectrometry and infrared spectroscopy, the structures of the forced degradation products were confirmed and elucidated. The dissolution behavior of Parkimedine® Tablets was also monitored in the FDA suitable medium. Multiple assessment tools were used to evaluate the environmental sustainability of the proposed methods and the reported one. The greenness tools included Complex-GAPI and AGREE metrics. In addition, the innovative concepts of "blueness" and "whiteness" evaluation were incorporated through the newly introduced BAGI and RGB12 algorithms, respectively.