Systemic Therapy Research Articles

Spectrum of Findings Seen in Patients With IDH1/2-Mutant Cholangiocarcinoma.

Cholangiocarcinoma-with a growing incidence rate and poor prognosis-is not an aggressive tumor that is not uncommon. Molecular profiling can reveal actionable aberrations in at least a third of the tumors. This is especially so in the case of intrahepatic cholangiocarcinoma (ICC), where mutations in the isocitrate dehydrogenase 1 and 2 genes (IDH1/2) make up 15%-20% of these tumors. IDH1/2 mutant ICC is a rare disease that has not been adequately reported. To expand the spectrum of findings seen in these patients, we present a single institution case series. We descriptively characterize the clinical, radiological, and histopathological findings of 12 such patients. IDH1/2 mutant ICC was found in elderly women, with two-thirds of patients having additional co-mutations. Anecdotally, patients who did receive systemic and/or locoregional therapies had long-term durable outcomes. Our findings indicate an increasing need to personalize an approach for these patients with specific molecular alterations. With the advent of the IDH1 inhibitor ivosidenib and other inhibitors in this space, IDH1/2 mutation has both prognostic and predictive value. Our series builds upon the patterns and findings seen in these patients.

PIPAC Pharmacologic and Clinical Data.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) emerged as an innovative intraperitoneal chemotherapy delivery system to overcome the issue of limited efficacy of systemic therapies to induce response in peritoneal malignancies. Promising results for patients with mesothelioma peritonei and peritoneal metastasis from gastric, ovarian, colorectal, pancreatic, and hepatobiliary tumors origin are changing the landscape for patients otherwise just facing palliative treatment. Ongoing trials will shed more light on the actual benefits of PIPAC.

National Registry for Childhood Onset Scleroderma I: Insights from the first 341 juvenile localized scleroderma patients

Objectives: There is an under recognition of juvenile-onset localized scleroderma and its extracutaneous manifestations leading to delay in systemic treatment. Our study aims to address this gap by describing the demographics, presentation, associated family history, concurrent autoimmune disease, extracutaneous manifestations, laboratory evaluation, treatment, and course of disease in juvenile-onset localized scleroderma patients enrolled in the National Registry for Childhood Onset Scleroderma. Methods: Participants for this study were derived from the National Registry for Childhood Onset Scleroderma and included 341 patients with juvenile-onset localized scleroderma. Demographic, and prospectively collected outcome measures, such as the Localized Scleroderma Cutaneous Assessment Tool, physical exam findings, laboratory values, and patient-reported outcomes were reviewed. Results: Most patients were female (71%), Caucasian (94%), had a linear subtype (56%), and had the onset of disease at age 7.5 (±4.2) years, and diagnosis 1.9 (±2.6) years after symptom onset. Most patients experienced at least one extracutaneous manifestation (70%), most commonly musculoskeletal (57%), followed by neurological (46%), and ophthalmological (11%). Those with musculoskeletal extracutaneous manifestation have significantly abnormal inflammatory and antibody laboratory values. Of patients with 1-year follow-up, a majority were treated with systemic therapy and globally improved with significant reduction in both modified Localized Scleroderma Skin Index ( p < 0.001) and Localized Scleroderma Damage Index ( p = 0.001). Conclusion: The study highlights need for earlier recognition of juvenile-onset localized scleroderma after demonstrating the delay in diagnosis and frequent extracutaneous manifestations with significant disease burden in a juvenile-onset localized scleroderma cohort. The benefits of systemic treatment and full extracutaneous manifestation screening in juvenile-onset localized scleroderma is supported.

Optimizing Hearing Outcomes in Nasopharyngeal Cancer Survivors in the Era of Modern Radiotherapy and Systemic Therapy.

Intensity-modulated radiation therapy (IMRT) improves disease control and reduces treatment-related toxicity in patients with localized nasopharyngeal carcinoma (NPC). However, due to the proximity of the auditory apparatus to the treatment volume and the frequent incorporation of cisplatin-based chemotherapy, treatment-related sensorineural hearing loss (SNHL) remains a common debilitating complication among NPC survivors. The reported crude incidence of SNHL following IMRT for NPC varies widely at 1-46% due to differences in auditory assessment methods and thresholds, follow-up durations, chemotherapy usage, and patient compositions. International guidelines and radiation dosimetric studies have recommended constraining the cochlear mean dose to less than 44-50 Gy, but the risk of SNHL remains high despite adherence to these constraints. Potential strategies to improve hearing outcomes in NPC survivors include cautious de-escalation of radiotherapy dose and volume, individualization of cochlear constraints, optimization of radiotherapy planning techniques, and the use of substitutes or alternative schedules for cisplatin-based chemotherapy. The addition of immune checkpoint inhibitors to chemoradiotherapy did not impact ototoxicity. Prospective studies that employ both objective and patient-reported auditory outcomes are warranted to test the long-term benefits of various approaches. This article aims to provide a comprehensive review of the incidence and radiation dose-toxicity relationship of SNHL in NPC survivors and to summarize potential strategies to optimize hearing outcomes in relation to nuances in radiotherapy planning and the selection of systemic therapy.

Adult Prostate Sarcoma: Demographics, Treatment Patterns, and Survival.

This study aimed to examine clinicopathologic characteristics, treatment patterns, and survival rates in a contemporary population-based cohort of adult prostate sarcoma patients. In the Surveillance, Epidemiology, and End Results database (2004-2020), adult patients with prostate sarcoma were identified. Descriptive statistics, Kaplan-Meier analyses, smoothed cumulative incidence plots, and Cox regression models were used. Of 125 patients, 45 (36%) harbored leiomyosarcoma, 17 (14%) had rhabdomyosarcoma, 15 (12%) had stromal sarcoma, 17 (14%) had sarcoma not otherwise specified (NOS), and 31 (25%) had other sarcoma subtypes. Metastatic stage was most common in the rhabdomyosarcoma patients (44%) and least common in the leiomyosarcoma (21%) and stromal sarcoma (20%) patients. Most of the rhabdomyosarcoma patients received the combination of systemic and radiation therapy with (24%)or without radical surgery(35%), whereas most of the leiomyosarcoma and stromal sarcoma patients underwent radical surgery with (22 and 13%) or without (22 and 47%) radiation. In the overall population, the median overall survival was 27months. The 5-years overall versus cancer-specific versus other-cause mortality rates were respectively 71 versus 58 versus 13%. In the multivariable Cox regression models, the highest overall mortality was exhibited by the patients with metastatic disease (hazard ratio [HR] 2.87; 95% confidence interval [CI] 1.55-5.31; p < 0.001) or unknown disease stage (HR 2.94; 95% CI 2.20-7.21; p = 0.019). Conversely, of all the histologic subtypes, only stromal sarcoma distinguished itself by lower overall mortality (HR 0.41; 95% CI 0.18-0.96; p = 0.039). Four major histologic subtypes were identified. Among most adult sarcoma patients, treatment patterns vary according to histology, from multimodal therapy to radical prostatectomy alone. These treatment differences reflect equally important heterogeneity in survival patterns.

Current understanding of modulated electro-hyperthermia in cancer treatment

Traditional hyperthermia involves increasing the temperature at the tumor site to above 39 ℃, inducing death in cancer cells. Although hyperthermia is an effective cancer treatment, its clinical application has decreased due to potential complications, including damage to surrounding normal tissue. In recent years, modulated electro-hyperthermia (mEHT) has emerged as an effective and safe treatment modality. mEHT selectively heats tumor cells to 42–43 °C, while reducing the average temperature in the treatment area, including the surrounding normal tissue, compared to conventional methods. Additionally, mEHT may be used in combination with systemic chemotherapy and radiation therapy in tumor treatment, providing a synergistic effect to increase efficacy. As chemotherapy and radiation therapy technologies advance, the application of combined mEHT may improve clinical outcomes. In this study, we review and discuss reports on the clinical outcomes of mEHT combined with chemotherapy and/or radiation therapy, which are established anticancer treatments.

Dosimetric and Clinical Prognostic Factors in Single-Isocenter Linac-Based Stereotactic Radiotherapy for Brain Metastases.

Background/Objectives: To report on predictive factors in Linac-based SRT for single and multiple BM. Methods: Consecutive patients receiving either one or three fractions of single-isocenter coplanar VMAT SRT were retrospectively included. The GTV-PTV margin was 1-2 mm. The delivered target dose was estimated by recalculating the original plans on roto-translated CT according to errors recorded by post-treatment CBCT. The Kaplan-Meier method estimated local progression-free survival (LPFS), intracranial progression-free survival (IPFS), and overall survival (OS). Log-rank and Wilcoxon-Mann-Whitney tests evaluated inter-group differences, whereas Cox regression analysis assessed prognostic factors. Results: Fifty females and fifty males, with a median age of 69 years, received 107 SRTs. A total of 213 BM (range, 1-10 per treatment) with a median volume of 0.22 cc were irradiated with a median minimum BED of 59.5 Gy. The median delivered GTV D95 reduction was -0.3%. The median follow-up was 11 months. Nineteen LP events and a 1-year LC rate of 90.1% were observed. The GTV coverage did not correlate with LC, while the GTV volume was a risk factor for LP, with the 1-year rate dropping to 73% for volumes ≥ 0.88 cc. The median LPFS, IPFS, and OS were 6, 5, and 7 months, respectively. Multivariate analysis showed that patients with melanoma histology and those receiving a second or subsequent systemic therapy line had the worst outcomes, whereas patients with adenocarcinoma histology and mutations showed better results. Conclusions: The accuracy and efficacy of the Linac-based SRT approach for BM were confirmed, but the dose distribution alone failed to predict the treatment response, suggesting that other factors must be considered to maximize SRT outcomes.

Shifting the Paradigm: The Transformative Role of Neoadjuvant Therapy in Early Breast Cancer.

The use of neoadjuvant systemic therapy (NST) has become increasingly important in the treatment of breast cancer because of its various advantages. These include the ability to downstage tumors without compromising locoregional control and the potential to obtain valuable information about clinical and biological response to therapy with implications for individual prognoses. Surgical response assessment paves the way for response-adapted therapy, and pathological complete response (pCR; defined as ypT0/is ypN0) serves as an additional endpoint for drug development trials. Recommended NST regimens commonly consist of anthracyclines and taxane, with dose-dense anthracyclines and weekly paclitaxel often preferred, whenever feasible. For patients with human epidermal growth factor receptor-2 (HER2)-positive tumors, dual anti-HER2 therapy (trastuzumab and pertuzumab) is indicated together with NST in case of elevated risk of recurrence. For patients with triple-negative breast cancer (TNBC), adding carboplatin to NST correlates with improved pCR and survival rates, as does the addition of immune checkpoint inhibitors. For hormone receptor (HR)-positive/HER2-negative cancers, emerging data on NST including immune checkpoint inhibitors may elevate the significance of NST in high-risk luminal breast cancer. Here, we present a synthesis of the results from neoadjuvant clinical trials that aim at optimizing treatment options for patients with high-risk breast cancer.

Tinea capitis, caused by Microsporum canis (felineum) : literature review and clinical cases

According to statistics, tinea capitis remains the main mycological problem in childhood. The spectrum of causative agents of tinea capitis varies depending on the continent. In epidemiological terms, the pathogenic fungus Microsporum canis (felineum)absolutely predominates on the Eurasian continent. A significant problem in the diagnosis and, in particular, in the treatment of microsporia are cases of the disease in very young children: we estimate this most problematic age from 1 to 18 months. Microsporia in children under the age of 1 year is the most relevant in pediatric clinical mycology due to the limited arsenal of topical and systemic medications approved at this age. The clinical case presented in this article demonstrates an example of successful treatment of scalp microsporia in a 7-month-old child who had contraindications to systemic therapy. It should be noted that the duration of treatment in this case was almost 4 months, while the most effective therapy regimens, including systemic drugs, lead to the elimination of pathogenic fungus from the foci on the scalp within 30–45 days.

Surgical treatment of distant metastases of cutaneous melanoma

This article addresses the issue of surgical treatment effectiveness in cases of disseminated melanoma. It is shown that disseminated melanoma can be divided into truly disseminated and oligometastatic processes, where distant metastases are resectable. Previously, surgical intervention was the treatment of choice for patients with resectable distant metastases, however, with the development of new therapeutic approaches, such as immune checkpoint inhibitors and targeted therapies, the role of surgery has become less straightforward. However, tumor burden reduction through surgical removal of metastatic lesions may enhance the immune response. Combined treatment, involving surgical intervention and systemic therapy, has emerged as a new approach in treatment of disseminated melanoma, improving efficacy and prognosis. The article emphasizes the need for further research to determine the optimal approach for treatment in this patient population.

A study on the Prescription Pattern of Antifungal Drugs in Aden-Yemen

Background: Fungal infections are more common in tropical zones; they can be simple, complicated, or even fatal. Studying the prescribing pattern can help physicians provide rational medical care and appropriate patient compliance. The current study aimed to determine the prescription patterns of antifungals in three departments and the distribution of fungal disease to help in developing policies and stewardship in using antifungal medications. Method: This cross-sectional study was conducted over 6 months from March to October 2023. Potential participants were approached in Governorate and private pharmacies, and dermatologic, gynecologic, and dental clinics. Results: The total number of collected prescriptions was 250. The analysis of the demographic characteristics of the involved patients showed that about 166 (66.4%) of the patients were females and 84 (33.65%) were males. Most of the patients are in the age group (19-35 years). Most of the fungal infection was vulvovaginal candidiasis 64(25.6%), Tinea versicolor 38(15.2), Tinea cruris 30(12%), oral candidiasis 21 (8.4 %), Tinea corporis (8.4%) then Tinea pedis and skin candidiasis had equal number 19 (7.6%), followed by tinea capitis 12 (4.8%) and onychomycosis 12 (4.8%). The most prescribed oral medicines were Itraconazole 66 (26.4%), followed by Fluconazole 56 (22.4%), Terbinafine 28 (11.2%), Ketoconazole 29 (11.6%) and Griseofulvin 13 (5.2%). The topical medicines prescribed were as follows: Ketoconazole 98 (39.28%), Clotrimazole 46 (18.4 %), Terbinafine 36 (14.4%), and Miconazole 33 (16.4%). The majority of patients (75%) received a combination of topical and systemic oral therapy. While (25 %) were treated by only topical agents.

Efficacy of pembrolizumab plus lenvatinib as first‐line treatment for metastatic renal cell carcinoma with multiple brain metastases

IntroductionPatients with metastatic renal cell carcinoma have a poor prognosis and its specific pathogenesis remains unelucidated.Case presentationAt 78 years of age, a Japanese male patient was diagnosed with metastatic renal cell carcinoma (cT3N2M1 stage) and multiple brain metastases that were responsive to stereotactic radiation therapy followed by systemic combination induction therapy of pembrolizumab plus lenvatinib. Adverse events, including grade 3 hypertension, grade 2 eruption, and elevated grade 2 fever, were controlled by a dose reduction or suspension of drugs. The patient eventually showed a tolerance for continuing with 8 mg lenvatinib. Fourteen months after the initiation of treatment, and on 8 mg lenvatinib, this patient showed no sign of disease progression at the last follow‐up.ConclusionWe detail the absence of disease progression in a metastatic renal cell carcinoma case with multiple brain metastases more than 1 year after stereotactic radiation therapy followed by first‐line pembrolizumab plus lenvatinib.

Bipolar androgen therapy for treatment of metastatic castration‐resistant prostate cancer: A case series

AbstractIntroductionAdvanced prostate cancer treatment has improved with androgen receptor signaling inhibitors (ARPI), yet many patients develop metastatic castration‐resistant prostate cancer (mCRPC), characterized by sustained androgen receptor (AR) signaling. Bipolar androgen therapy (BAT) introduces supraphysiologic testosterone levels to inhibit tumor growth, offering novel treatment for mCRPC by exploiting AR‐dependent mechanisms.Case PresentationsCase 1: A 53‐year‐old man with mCRPC, post multiple systemic therapies, initiated BAT and pembrolizumab, achieving PSA reduction and improved quality of life before progression. The patient exhibited AR amplification, which may have contributed to favorable response to BAT.Case 2: A 73‐year‐old man with recurrent prostate cancer, stable on ADT and abiraterone, experienced PSA decline with BAT to an undetectable level, maintaining stability post‐therapy discontinuation.Case 3: A 73‐year‐old man with metastatic prostate cancer, initially resistant to enzalutamide, achieved clinical benefit and disease control with BAT, although he did not meet PSA response criteria, patient had remarkable response upon enzalutamide rechallenge.Case 4: A 90‐year‐old man with localized prostate cancer, refractory to multiple treatments, experienced symptom relief and PSA reduction with BAT before progression.ConclusionBAT represents a promising treatment strategy for mCRPC. This case series underscores BAT's potential to induce significant clinical and biochemical responses, resensitize tumors to ARPIs, and improve patients' quality of life. Despite eventual progression in some cases, BAT offers a period of disease control. Further research is needed to optimize patient selection and understand the molecular determinants of BAT responsiveness.

The role of epigenetic factors in childhood atopic dermatitis

Atopic dermatitis (AD) is a genetically determined chronic inflammatory skin disease characterized by itching, relapsing course, age-related features of the lesion morphology and localization. The etiological factors contributing to the development of AD are: allergic reactions, inflammatory reactions in the skin, leading to a barrier disfunction, the affect and interaction of genetic and environmental factors. Epigenetic mechanisms also play a key role in immune regulation. The aim of this work is to study the genome-wide methylation profile in the skin of children with AD in the acute stage, as well as to determine changes in the expression level of immune response genes associated with common signaling pathways during therapy. Whole-genome sequencing was conducted to examine methylation in the skin samples from AD patients and controls. The stages of bioinformatics data processing were carried out. Changes in the expression levels of the TLR2, TLR9, IL4, IL13, CAMP, and DEFB1 genes before and after treatment were carried out using RT-PCR-RT on samples of mononuclear blood cells. When comparing samples from patients with AD and healthy children, changes were shown in the methylation of 2364 regions of genomic DNA with their corresponding specific genes. Among the identified genes, those related to processes associated with the pathogenesis of AD were selected. At the next stage, changes in the expression of the described immunity factors (TLR2, TLR9, IL-4, IL-13, DEFB1, CAMP) were assessed over time according to the type of treatment. For this purpose, patients were divided into 2 groups depending on the prescription of systemic therapy. Three months after treatment, the level of expression for all studied immune factors decreased. However, a significant decrease in expression for almost all parameters (except for the DEFB1 gene) was recorded in the group in which systemic therapy (dupilumab) was used in addition to topical treatment. At the same time, the SCORAD index after treatment improved by an average of 63% and amounted to 17±6.0 points. Thus, systemic therapy aimed at suppressing signaling of IL-4 and IL-13 cytokines indirectly leads to normalization of the expression levels of innate immune factors. Studying the regulation of molecular genetic mechanisms of immunity involved in the processes of inflammation in AD helps to clarify the immunopathogenesis of this disease, determine diagnostic markers and targets for drug therapy.

The Clinical Utilisation and Duration of Treatment with HER2-Directed Therapies in HER2-Positive Recurrent or Metastatic Salivary Gland Cancers.

Salivary gland cancers (SGC) are rare tumours with limited availability of systemic therapies. Some SGC subtypes overexpress HER2, and this represents a potential therapeutic target, but the evidence base is limited. This study sought to analyse real-world data on the efficacy of HER2-directed therapies in SGC. This is a retrospective observational study using anonymised data from commercial compassionate-use access registrations and a privately funded pharmacy prescribing register. Treatment duration was defined as the time from drug initiation to treatment discontinuation. Kaplan-Meier analysis of treatment duration was performed using R for Windows (v4.3.2). A case report is also provided of an exceptional responder. Eighteen patients were identified who received HER2-directed therapies for HER2-positive recurrent/metastatic SGC, and complete data on treatment duration was available for 15/18. Histology was salivary duct carcinoma in 13/18 patients, adenocarcinoma NOS in 4/18, and carcinoma ex pleomorphic adenoma in 1/18. The median treatment duration was 8.3 months (95% CI: 6.41-not reached), and the range was 1.0-47.0 months. Choice of HER2-directed therapy varied, with ado-trastuzumab emtasine being the most common (9/18). At the time of analysis, HER2-directed therapy was ongoing for 9/15, discontinued due to disease progression for 4/15, discontinued due to toxicity for 1/15, and 1/15 was discontinued for an unspecified reason. An exceptional responder experienced a complete response with a treatment duration of 47.0 months. These real-world data are comparable to the median PFS observed with HER2-directed therapies in phase II trials and support the use of HER2-directed therapies in this group.

Metaplastic breast cancer: Experience with ifosfamide based chemotherapy

BackgroundMetaplastic breast cancer (MPBC) is a rare variant of breast cancer and most treatment protocols are based on the guidelines for triple negative breast cancer. However, response to standard anthracycline and taxane based chemotherapy is poor. Published literature on use of ifosfamide based chemotherapy in the first line setting for MPBC is scarce. Patients and methodsWe carried out this record based analysis on MPBC patients treated at our institute with the combination of ifosfamide and Adriamycin (IA) as first line therapy. Patients were analysed for the clinical and demographic profile; pathology and treatment details; and treatment outcomes. ResultsFour patients who received IA chemotherapy were evaluated. Three of the four patients were postmenopausal. The median size of the tumor was 7.5 cm, only one patient had a heavy nodal burden and lung was the most common site of metastases seen in all three patients with metastatic disease. Pathology showed heterogenous, mixed histology with high grade tumors. All patients had triple negative tumors. All four patients underwent mastectomy and received IA chemotherapy as per standard doses. One patient had complete response, one had partial response and one patient progressed after 4 cycles of chemotherapy. The patient with localized disease continues to be disease free till date. Grade 3,4 neutropenia and grade 2 anemia was the most common chemotherapy related toxicity. ConclusionThe response rates in MPBC with IA regimen appear to be similar to the currently used anthracycline-taxane combinations, with slightly more haematological toxicity. Ifosfamide and adriamycin regimen may be considered in MPBC patients as primary or salvage systemic therapy.

Anal carcinoma - exploring the epidemiology, risk factors, pathophysiology, diagnosis, and treatment.

Anal carcinoma is a relatively rare tumor that accounts for approximately 2% of gastrointestinal malignancies and less than 7% of anorectal cancers. Most anal tumors originate between the anorectal junction and the anal verge. Risk factors for the disease include human papillomavirus infection, human immunodeficiency virus, tobacco use, immunosuppression, female sex, and older age. The pathogenesis of anal carcinoma is believed to be linked to human papillomavirus-related inflammation, leading to dysplasia and progression to cancer. Squamous cell carcinoma is the most common type of anal tumor, with an annual incidence of approximately 1 to 2 per 100000 persons. Treatment regarding anal cancer has emerged over time. However, chemoradiation therapy remains the mainstay approach for early localized disease. Patients with metastatic disease are treated with systemic therapy, and salvage surgery is reserved for disease recurrence following chemoradiation. This article aims to provide background information on the epidemiology, risk factors, pathology, diagnosis, and current trends in the management of anal cancer. Future directions are briefly discussed.

Management of Pulmonary Toxicities Associated with Systemic Therapy in Non Small Cell Lung Cancer

Management of Pulmonary Toxicities Associated with Systemic Therapy in Non Small Cell Lung Cancer

Oligometastatic Urothelial Cancer and Stereotactic Body Radiotherapy: A Systematic Review and an Updated Insight of Current Evidence and Future Directions.

Stereotactic body radiation therapy (SBRT) is the most commonly used metastasis-directed therapy (MDT) for oligometastatic urothelial carcinoma (omUC). Despite efforts in defining this disease entity, open questions remain concerning the role of MDT and the use of biomarkers, imaging, and its combination with systemic therapies. The aim of the present systematic review is to provide an updated overview of the current clinical evidence on SBRT for omUC in terms of survival and local control benefits. We also aim to provide updates on controversial areas and future directions in this emerging field. With a systematic approach, following PRISMA recommendations, we searched two databases to identify and select articles published up until March 2024 reporting the use of SBRT for omUC with or without concomitant systemic therapies. Prospective randomized or non-randomized studies as well as retrospective studies were included. Eight studies were selected for data extraction and 293 omUC patients treated with SBRT were collectively analyzed. In metachronous omUC patients, SBRT delivered with ablative doses (BED10 ≥ 78 Gy) was associated with a 2-year overall survival (OS) rate of 50.7% (95% CI 35.1-64.4%). The use of sub-ablative SBRT doses (BED10 = 43.2 Gy) in combination with immunotherapy did not demonstrate significant clinical outcome improvement in two prospective studies. The overall tolerance was good, with only one study reporting toxicity of grade 3 in up to 18% of the patients treated with SBRT in combination with immunotherapy. SBRT is an effective and widely available MDT option in omUC, although this is based on a limited number of studies. Despite the attempt to use SBRT as an immune response trigger in combination with immunotherapy, no significant improvement in survival outcomes has been observed. The integration of new systemic agents with MDT will likely define a new scenario for the treatment of omUC. The review protocol was registered in PROSPERO, ID: CRD42024522381.

The effectiveness and acceptability of systemic enzyme therapy in the complex treatment of vulvovaginitis caused by opportunistic microorganisms: Open-label single-center prospective comparative randomized study

The effectiveness and acceptability of systemic enzyme therapy in the complex treatment of vulvovaginitis caused by opportunistic microorganisms: Open-label single-center prospective comparative randomized study