Multimodal Treatment Approach Research Articles

Medicinal Plants Derived Green Carbon Dots: Synthesis, Characterization and Their Potential Applications in Cancer Therapy.

This review aims to explore the synthesis, characterization, and potential applications of carbon dots (CDs) derived from medicinal plants for cancer prevention, highlighting their role as a promising alternative in nanotechnological approaches. A comprehensive literature search was conducted to gather information on the synthesis methods, complex matrices, characterization techniques, and potential applications of CDs derived from medicinal plants in cancer therapy. Carbon dots (CDs) have emerged as a subject of significant interest due to their favorable chemical and biological properties. Various precursors, including graphite, carbon black, and organic molecules, are utilized in the synthesis of CDs through chemical or physical methods. Notably, CDs derived from medicinal plants offer environmentally friendly alternatives, leveraging complex matrices such as aqueous, alcoholic, and hydroalcoholic extracts. This review emphasizes the green synthesis approaches, characterization techniques, and diverse applications of CDs, including drug transport, bioimaging, biosensing, and anti-cancer therapies. Furthermore, it highlights the advantages and disadvantages of different synthesis methods, aiding researchers in selecting appropriate techniques for continuous production. Carbon dots (CDs) represent a transformative advancement in nanotheranostics, offering a versatile platform for precise cancer diagnosis and therapy. With inherent anticancer properties, CDs hold promise in photodynamic therapy (PDT) and photothermal therapy (PTT), enabling precise tumor targeting while minimizing systemic toxicity. To address the limitations of standalone PDT and PTT, researchers are exploring multimodal treatment approaches integrating CDs. By leveraging the unique properties of CDs derived from medicinal plants, a new era of precision cancer therapy may be realized, emphasizing enhanced therapeutic outcomes and reduced adverse effects.

The role of radical cystectomy and lymphadenectomy in the management of bladder cancer with clinically positive lymph node involvement.

The role of radical cystectomy and pelvic lymph node dissection in muscle-invasive bladder cancer (MIBC) with clinically positive lymph nodes is debated. This review examines the role of surgery in treating patients with clinical N1 and more advanced nodal involvement (N2-N3) within a multimodal treatment approach. For clinical N1 disease, guidelines typically recommend neoadjuvant chemotherapy followed by surgery. However, for N2-N3 disease, guidelines vary. Advances in diagnostics, systemic therapies, and surgical recovery have improved the prognosis for these patients. Research is increasingly identifying MIBC patients, including those with positive nodes, who may achieve complete pathologic response and long-term survival, supporting the role of surgery even in advanced nodal stages. Managing MIBC with clinically positive lymph nodes, especially in N2-N3 disease, requires a tailored approach. While neoadjuvant chemotherapy followed by radical cystectomy is standard for N1 disease, the role of surgery in advanced nodal stages is growing because of better patient selection and treatment strategies. Emerging evidence suggests that consolidative surgery may improve outcomes in these complex cases.

Oligometastatic non-small cell lung cancer: Impact of local and contemporary systemic treatment approaches on clinical outcome.

Oligometastatic (OMD) non-small cell lung cancer (NSCLC) is a distinct but heterogeneous entity. Current guidelines recommend systemic therapy and consolidation with local ablative therapy (LAT). However, evidence regarding the optimal choice of multimodal treatment approaches is lacking, in particular with respect to the integration of immunotherapy. This real-world study identified 218 patients with OMD NSCLC (2004-2023, prespecified criteria: ≤5 metastases in ≤2 organ systems) from three major German comprehensive cancer centers. Most patients had one (72.5%) or two (17.4%) metastatic lesions in a single (89.9%) organ system. Overall survival (OS) was significantly longer with a single metastatic lesion (HR 0.54, p = .003), and female gender (HR 0.4, p < .001). Median OS of the full cohort was 27.8 months, with 29% survival at 5 years. Patients who had completed LAT to all NSCLC sites, typically excluding patients with early progression, had a median OS of 34.4 months (37.7% 5-year OS rate) with a median recurrence-free survival (RFS) of 10.9 months (13.3% at 5 years). In those patients, systemic treatment as part of first-line therapy was associated with doubling of RFS (12.3 vs. 6.4 months, p < .001). Despite limited follow-up of patients receiving chemo-immunotherapy (EU approval 2018/2019), RFS was greatly improved by adding checkpoint inhibitors to chemotherapy (HR 0.44, p = .008, 2-year RFS 51.4% vs. 15.1%). In conclusion, patients with OMD NSCLC benefitted from multimodality approaches integrating systemic therapy and local ablation of all cancer sites. A substantial proportion of patients achieved extended OS, suggesting a potential for cure that can be further augmented with the addition of immunotherapy.

Excellent RAI therapeutic response on a patient presenting skull metastasis of follicular thyroid cancer after 15 years.

Bone is the second most common site of metastasis for differentiated thyroid carcinoma (DTC). Bone metastasis (BMs) occur in about 10% of patients with DTC and is observed more often in follicular thyroid carcinoma (FTC) (7-28%) than papillary thyroid carcinoma (PTC) (1-7%). Bone metastasis is associated with unfavorable clinical outcomes mainly including skeletal-related events (SREs), such as pathologic fractures, bone pain, spinal cord compressions, and hypercalcemia, which negatively impact the quality of life of patients and reduce their life expectancy. Patients with BMs from DTC require comprehensive and multimodal treatment approaches, including radioiodine (RAI) therapy, palliative care, surgery, external beam radiotherapy, and targeted drug therapy. RAI therapy is the first-line treatment, despite being rather ineffective, especially in large BMs. The response to RAI therapy, either alone or in combination with BM focal treatment depends on iodine avidity. This study reports a rare case of metachronous skull bone metastasis from FTC in a 72-year-old female patient 15 years after initial treatment. The patient had an excellent response to RAI therapy, which resulted in the abnormal uptake disappearing. Following treatment, the patient has been disease-free for six years. This case confirms that a complete response to RAI treatment for BM depends on the degree of dedifferentiation of cancer cells, which highlights the need for long-term follow-up, especially for FTC patients.

Surgical indication and management of obstructive colonic metastasis from primary lung adenocarcinoma: report of a case and review of the literature

BackgroundColonic metastasis from lung cancer is very rare and is typically associated with poor prognosis. Herein, we report the case of a patient who achieved intermediate-term survival using a multimodal treatment approach, including chemotherapy, immunotherapy, radiotherapy, and surgical resection for obstructive colonic metastasis from primary lung adenocarcinoma.Case presentationA woman in her 50s presented with anemia and a positive fecal occult blood test. Computed tomography revealed a tumor in the right upper lobe of the lung with mediastinal lymphadenopathy and wall thickening in the transverse colon. Colonoscopy revealed a stricture involving 50% of the colonic lumen. Biopsy revealed a poorly differentiated adenocarcinoma positive for CK-7 and TTF-1, very focally positive for napsin A, and negative for CK-20 and CDX-2. Furthermore, positron emission tomography/CT (PET/CT) showed a high maximum standardized uptake value (SUVmax) of 8.2 in the iliac bone. Based on these findings, the patient was diagnosed with primary lung adenocarcinoma with simultaneous metastasis to the transverse colon and iliac bone (cT4N3M1c, cStage IVB).After receiving first-line chemotherapy with atezolizumab, pemetrexed, and carboplatin, the tumors shrank after 4 courses. Subsequently, the patient received maintenance therapy with atezolizumab and pemetrexed. However, the tumor enlarged after 10 courses. Second-line chemotherapy with docetaxel and ramucirumab (3 courses) failed to achieve tumor reduction. Colonoscopy revealed an impassable colonic tumor. Nineteen months after diagnosis, surgery was planned for imminent intestinal obstruction.We determined that the colonic tumor was resectable, because laparoscopic exploration revealed no other metastases. The tumor was resected by partial colectomy with ileocolonic anastomosis. The postoperative course was uneventful. Pathological examination revealed a resection margin that was negative for malignancy, and the histological type was consistent with metastatic lung adenocarcinoma.The patient then received nab-paclitaxel therapy; however, she developed symptoms of superior vena cava syndrome after 3 courses. The patient received palliative irradiation (30 Gy/10 fr) followed by nivolumab. She soon developed a solitary brain metastasis, and stereotactic irradiation was planned. After 3 courses of nivolumab, the metastasis was reduced significantly, and stereotactic brain irradiation was canceled. The lung tumor and mediastinal lymphadenopathy gradually shrank, and the patient survived for 13 months after surgery without disease progression.ConclusionsIn this case, surgical resection of colonic metastasis from primary lung adenocarcinoma may have contributed to the short-term prognosis as a bridge-to-next available multimodal treatment.

Clinical and Molecular Risk Factors in Extracranial Malignant Rhabdoid Tumors: Toward an Integrated Model of High-Risk Tumors.

Extracranial malignant rhabdoid tumors (eMRT) are a challenging entity. Despite the use of multimodal treatment approaches, therapy failure occurs in 55% to 67% of these. Molecular markers for identification of patients at increased risk for relapse or refractory (R/R) disease are not available. Clinical characteristics may only insufficiently predict the individual course of disease. Using the EU-RHAB database, we analyzed a cohort of 121 patients with eMRT clinically. For 81 patients, molecular and clinical data were available, which were further complemented with publicly available DNA molecular data from 92 eMRTs. We aimed to delineate molecular risk factors by dissecting the DNA methylome of these tumors. Moreover, we establish clinical characteristics and treatment details of R/R disease in a subcohort of 80 patients. Using consensus hierarchical clustering, we identified three distinct subgroups, one of which (eMRT standard risk) was associated with significantly improved survival, irrespective of germline status and/or localization. At the transcriptome level, this subgroup was characterized by an overexpression of genes involved in muscle development. A relevant proportion of patients developed distant relapses or progressions; the median time to the event was 4 months, underlining the need for early identification and risk stratification of R/R disease. The overall survival was significantly decreased in patients with progressive disease when compared with relapse cases, and reaching complete remission during salvage therapy provided a survival benefit. Our analysis of eMRT in this comprehensive cohort provides novel insights into the patterns of relapse and integrates molecular and clinical risk factors to guide clinical decision-making.

The Pathomechanism and Current Treatments for Chronic Interstitial Cystitis and Bladder Pain Syndrome.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating condition characterized by symptoms such as bladder pain, frequent urination, and nocturia. Pain is typically perceived in the lower abdomen, pelvic floor, or urethra, causing significant discomfort and impacting quality of life. Due to the similarity of its symptoms with those of overactive bladder and acute bacterial cystitis, patients often face misdiagnosis and delayed appropriate treatment. Hunner's (HIC) and non-Hunner's IC (NHIC), each with distinct clinical presentations, urothelial dysfunction, chronic inflammation, and central sensitization and thus multimodal symptomatic treatment approaches, may be the most common pathogeneses of IC/BPS. Treatment of IC/BPS should involve identifying the different clinical phenotypes and underlying pathophysiology causing clinical symptoms and developing strategies tailored to the patient's needs. This review discusses the roles of urine biomarkers, bladder inflammation, and glycosaminoglycans in the pathogenesis of IC/BPS. Various bladder treatment modalities are explored, including glycosaminoglycan replenishment, botulinum toxin A injection, platelet-rich plasma injection, low-energy shock waves, immunosuppression, and low-dose oral prednisolone. Pelvic floor muscle physiotherapy and bladder therapy combined with psychiatric consultation can help alleviate psychological stress and enhance the quality of life of patients with IC/BPS. Elucidating the pathological mechanisms and exploring diverse treatment options would help advance the care of individuals suffering from this challenging bladder condition.

397. TREATMENT OUTCOMES OF IMMUNE CHECKPOINT INHIBITORS AS PRIMARY THERAPY FOR UNRESECTABLE OR RECURRENT ESOPHAGEAL CANCER

Abstract Background For the primary treatment of unresectable or recurrent esophageal cancer, combination therapy with immune checkpoint inhibitors (ICI) such as pembrolizumab (Pem) with CF (cisplatin and 5-fluorouracil), nivolumab (Nivo) with CF, and Nivo with ipilimumab (Ipi) has been shown the significantly improve prognosis compared to standard CF therapy in international collaborative phase III trials. As a result, these ICIs have been approved as primary treatment agents in Japan, with treatment guidelines strongly recommending therapies including ICIs. We evaluated the treatment outcomes at our institute and discussed their utility. Methods We examined the treatment outcomes of 26 esophageal cancer patients who underwent primary treatment with Pem+CF, Nivo+CF, or Nivo+Ipi from January 2018 to January 2023. The median observation period was 7.0 months. Results There were 20 male and 6 female patients, with a median age of 69 years. Histologically, there were 24 cases of squamous cell carcinoma and 2 cases of adenocarcinoma. Of the 26 patients, 9 were postoperative recurrences and 17 were unresectable diseases. They were treated with Pem+CF (12 cases), Nivo+CF (7 cases), or Nivo+Ipi (7 cases) as primary therapy. The initial response was complete response (CR) in 1 case, partial response (PR) in 14 cases, stable disease (SD) in 2 cases, and progressive disease (PD) in 9 cases, resulting in an overall response rate of 57.6%. The median progression-free survival was 5.0 months, and the median overall survival was 15.2 months. There was no significant difference in prognosis according to the regimens. Grade 3 or higher adverse events included neutropenia in 3 cases, pituitary insufficiency in 1 case, and adrenal insufficiency in 1 case. One case with lung metastasis and two cases with para-aortic lymph node metastasis showed disappearance of metastatic lesions after chemotherapy including ICIs, leading to conversion esophagectomy. One case had anastomotic failure, but no other postoperative complications were observed. All patients are currently under observation without recurrence. Conclusion ICIs for unresectable or recurrent esophageal cancer showed a prolongation of prognosis in real-world clinical practice, suggesting their significance as part of a multimodal treatment approach including conversion surgery.

Silk-Derived Protein-4 Versus Vehicle Control in Treating Patients With Moderate to Severe Dry Eye Disease: A Randomized Clinical Trial

In this study the safety and efficacy of silk-derived protein 4 (SDP-4), also known as amlisimod, eye drops against a vehicle control formulation in patients with moderate to severe dry eye disease (DED) was assessed. SDP-4 is a novel, naturally derived, anti-inflammatory wetting agent that enhances coating on the ocular surface. Exploratory Phase 2, 12- and 8-week, serial cohort, multicenter, double-masked, randomized, vehicle-controlled study. In the first cohort (N = 305), patients were randomized 1:1:1:1 to SDP-4 (0.1%, 1%, 3% wt./wt.) or vehicle control and dosed 2 times per day (BID), while in the second cohort patients were randomized 1:1 with 1% wt./wt. SDP-4, the best performing formulation from the first cohort, or vehicle control BID (N = 151). Diagnosed DED patients were treated in the United States between April 2019 and May 2021. The first cohort of subjects had moderate to severe baseline symptoms, while the second cohort had moderate baseline symptoms to study the impact of baseline symptoms on SDP-4 performance. Key sign and symptom end points were mean change from baseline in TBUT and total SANDE score (0-100 visual analog scale) throughout the study. SDP-4 (1%) significantly increased TBUT vs the vehicle control (P < .05) at days 28 and 56 in the first cohort, and patient symptomatology from baseline was reduced by 46% based on subject reported SANDE VAS scores at day 84. Patients with more severe baseline DED symptoms experienced a significantly greater amount of relief than when compared to patients with moderate DED (P < .05). All treatment groups were well tolerated with a 2.6% total discontinuation rate. To the best of our knowledge, this was the first-in-human use of SDP-4 in a clinical trial. SDP-4 is a first-in-class protein ingredient that offers a safe and multi-modal treatment approach for alleviating severe DED symptoms within a novel formulation.

Idiopathic Fusarium Sclerouveitis: A Case Report.

To report a successfully managed case of idiopathic Fusarium sclerouveitis in a healthy patient with no identifiable risk factors. We describe a case of a 79-year-old man who presented with right-sided eye, facial, and head pain. Initial examination revealed temporal scleral thinning, inflammation, and anterior chamber cell/flare. Cultures were positive for Fusarium species. The patient was treated with sub-Tenon amphotericin, intrascleral voriconazole, surgical debridement, Rose Bengal photodynamic therapy, systemic voriconazole and posaconazole, and topical natamycin. The infection resolved and the patient's visual acuity improved to 20/40. Fusarium sclerouveitis can occur without clear risk factors. This case highlights the importance of an aggressive, multimodal treatment approach for successful management.

Low-dose intravitreal injection of 4 mg preservative-free gentamicin and superficial lamellar keratectomy combined with modified Gundersen grafts to control chronic heterochromic iridocyclitis and secondary keratitis in horses.

To describe a combined treatment approach for heterochromic iridocyclitis and secondary keratitis (HIK) in horses. A total of 15 horses (16 eyes). Sixteen eyes from 15 horses (mean age 14.1 years, range 6-26 years) received low-dose (4 mg) intravitreal preservative-free gentamicin injection (IVGI) and modified Gundersen grafts with standing sedation and local anesthesia following a clinical diagnosis of HIK. Additional therapies of suprachoroidal triamcinolone (8 mg) injection, episcleral bromfenac implants, and suprachoroidal cyclosporine implants were performed in individual cases. Leptospira titers were also reported when available. The most frequent ophthalmic findings were pigmented keratic precipitates (n = 15/16 eyes, 94%), corneal edema (n = 14/16 eyes, 88%), and pigmented cells suspended in the anterior chamber (n = 7/16 eyes, 44%). Postoperative treatment generally consisted of topical and systemic NSAIDs, topical antibiotics, and a topical mydriatic agent. Complications included persistent corneal edema (7/16, 44%), corneal ulceration (6/16, 38%), graft failure requiring revision (2/16, 13%), stromal abscess (1/16, 6%), surgery site infection (1/16, 6%), and suspected retinal degeneration following IVGI (1/16, 6%). One case was enucleated 6 months after treatment (1/16, 6%). Of the 12 eyes with at least 3 months of post-treatment follow-up, 10 were comfortable and visual with static or improved symptoms of HIK. This multimodal treatment approach aims to address both the anterior uveitis and endothelial decompensation frequently seen in horses with HIK. The surgery can be performed under standing sedation. Continued evaluation and long-term follow-up is necessary in all horses with HIK.

Chronic Thromboembolic Pulmonary Hypertension

: While the majority of patients have complete resolution of their acute pulmonary embolism (PE) after an adequate course of anticoagulation, some patients remain symptomatic with evidence of chronic PE. Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and Chronic Thromboembolic Pulmonary Disease (CTEPD) are terms that describe symptomatic patients with chronic thromboembolic occlusions of the pulmonary arteries with or without pulmonary hypertension, respectively. Here, we review the definitions, epidemiology, pathobiology, diagnosis and management of CTEPH. The chronic PE in CTEPH is essentially a scar in the pulmonary vasculature and is accompanied by a pulmonary arteriolar vasculopathy. Ventilation-perfusion scanning is the most sensitive screening test for CTEPH, and diagnosis must be confirmed by right heart catheterization (RHC). Treatment decisions require a multidisciplinary team and guidance from additional imaging, usually CT or pulmonary angiography. While pulmonary endarterectomy (PEA) to remove the chronic PE surgically is still the first-line treatment for appropriate candidates, there is an expanding role for balloon pulmonary angioplasty (BPA) and medical treatment, as well as multimodality treatment approaches that incorporate all of those options. New imaging modalities and treatment strategies hold the promise to improve our care and management of CTEPH patients in the future.

The Therapeutic Role of Lamotrigine in Borderline Personality Disorder: A Comprehensive Review of Outcomes, Mechanisms, and Treatment Strategies.

Borderline personality disorder (BPD) is a severe mental health condition characterized by pervasive instability in mood, self-image, and interpersonal relationships, significantly impacting individuals' personal, social, and occupational functioning. Current treatment strategies primarily include psychotherapy and pharmacotherapy, but there remains a need for more effective and targeted pharmacological options. This review examines the therapeutic role of lamotrigine in BPD, focusing on its efficacy, safety, mechanisms of action,and practical treatment strategies. A comprehensive review of the existing literature was conducted, including clinical trials, observational studies, and relevant pharmacological data. Key focus areas included lamotrigine's impact on BPD symptoms, pharmacological profile, and comparative effectiveness with other treatments. Lamotrigine has shown promise in managing BPD symptoms, particularly in stabilizing mood and reducing emotional dysregulation and impulsivity. Clinical trials suggest that lamotrigine can effectively address core symptoms of BPD, with a safety profile generally comparable to other treatments. The medication's mechanism of action, which involves modulation of glutamate release and mood stabilization, aligns with the therapeutic goals for BPD. Lamotrigine represents a potential adjunctive treatment for BPD, offering benefits in mood stabilization and symptom management. Integrating psychotherapy and other pharmacological options should be considered within a multimodal treatment approach. Further research is needed to better understand its long-term efficacy and safety and its role in combination therapy.

Searching For Ideal Definite Treatment of Sinonasal Squamous Cell Carcinoma with Orbit Invasions.

Sinonasal squamous cell carcinoma (SqCC) often invades the orbit. Treatment of sinonasal cancer invading orbit can vary depending on the medical center and the extent of the invasion. The definitive treatment strategy, whether it involves preserving the orbit or not, varies on a case-by-case basis and leads to different outcomes. Currently, a multimodal treatment approach, which includes surgery, chemotherapy (CTx), radiotherapy (RT), or concurrent chemoradiotherapy (CCRT), is frequently employed for sinonasal cancers. This study aims to evaluate the prognosis of sinonasal SqCC with orbit invasion in various perspectives. We conducted a retrospective review of patients with primary sinonasal SqCC invading the orbit who were treated at between 2009 and 2018. We examined factors such as the extent of tumor, orbit invasion, treatment strategies, recurrence rates, and survival rates. Overall survival (OS) and disease-free survival (DFS) rates did not significantly differ based on the grade of orbit invasion. When tumor resection with orbit preservation was performed as definitive treatment, DFS was significantly longer compared to cases where surgery was not the definitive treatment (RT, CCRT). There was no significant difference in DFS between those who underwent orbit exenteration and those who underwent tumor resection with orbit preservation as the definitive treatment. Tumor resection with orbit preservation as the definitive treatment appears to be the preferred approach, leading to prolonged DFS while ensuring survival in cases of SqCC with orbit invasion.

Experiences of patients with endometriosis with a digital health application: a qualitative analysis

BackgroundEndometriosis is a frequent disease in women of reproductive age in which the endometrium occurs outside the uterine cavity. Multimodal treatment approaches are necessary due to loss of quality of life and the chronic nature of the disease. Digital health applications (DiGa) are becoming increasingly important. This research project investigates how a healthcare app can influence the subjective experience of illness in patients with endometriosis.MethodsEmpiric data were collected through semi-structured interviews. Data analysis was carried out using qualitative focussed interview analysis. Reliability was ensured by joint interdisciplinary and interprofessional evaluation of the interviews by experts and those affected.ResultsTen patients with endometriosis and the prescribed healthcare app Endo-App© were examined. Categories were defined from the superordinate categories “Factors influencing the experience of illness” and “Evaluation of the app”. The app provided reliable information, promoted self-efficacy through exercises and strengthened the perception of the individuality of the illness. It helped to minimise nocebo effects from internet research and enabled a positive change of perspective. Patients criticised the time required for data input and had data protection concerns. The educational elements were often seen as redundant. Some patients only used the app briefly, or not at all.ConclusionOnce a DiGa has been prescribed, it may be useful to explain its use on an outpatient basis and validate regular use. Blind re-prescribing of DiGas should be avoided. Younger patients with a recent diagnosis or patients following rehabilitation may benefit more from prescribing.

Insights into Dyspareunia: From Diagnosis to Multimodal Treatment Approaches

Introduction and Purpose: Dyspareunia is a sexual disorder associated with pain in women. It refers to pain related to sexual intercourse. Pain can occur during penetration attempts, during penetration, during intercourse, and shortly after penetration. Studies conducted in the United States indicate that the problem of pain during intercourse affects as much as 10-20% of women. [1] In Poland, this number is estimated to be around 13%.[1] The aim of this review is to delve into the existing literature on the diagnosis of dyspareunia in women and to raise awareness of its extensive nature, emphasizing an interdisciplinary approach to patient care. A Brief Description of the State of Knowledge: The etiology of dyspareunia is multifactorial and may arise from pathological changes in the vulva and vagina, inflammatory changes, contact irritations, as well as vulvar conditions such as lichen sclerosus and flat. [3] Additionally, hormonal changes, pelvic floor injuries, postpartum gynecological procedures also play a significant role. Psychological factors such as trauma, anxiety, and depression are also important [4]. Conclusions: Dyspareunia is a condition that significantly affects the quality of life of women in various ways, thus necessitating effective therapeutic approaches. Collaboration among diverse specialists such as gynecologists, sexologists, psychotherapists, psychiatrists, and physiotherapists is crucial. Further research focusing on multimodal strategies is needed to effectively tailor treatments and mitigate the systemic effects of chronic pain.

Dissecting the Natural Patterns of Progression and Senescence in Pediatric Low-Grade Glioma: From Cellular Mechanisms to Clinical Implications.

Pediatric low-grade gliomas (PLGGs) comprise a heterogeneous set of low-grade glial and glioneuronal tumors, collectively representing the most frequent CNS tumors of childhood and adolescence. Despite excellent overall survival rates, the chronic nature of the disease bears a high risk of long-term disease- and therapy-related morbidity in affected patients. Recent in-depth molecular profiling and studies of the genetic landscape of PLGGs led to the discovery of the paramount role of frequent upregulation of RAS/MAPK and mTOR signaling in tumorigenesis and progression of these tumors. Beyond, the subsequent unveiling of RAS/MAPK-driven oncogene-induced senescence in these tumors may shape the understanding of the molecular mechanisms determining the versatile progression patterns of PLGGs, potentially providing a promising target for novel therapies. Recent in vitro and in vivo studies moreover indicate a strong dependence of PLGG formation and growth on the tumor microenvironment. In this work, we provide an overview of the current understanding of the multilayered cellular mechanisms and clinical factors determining the natural progression patterns and the characteristic biological behavior of these tumors, aiming to provide a foundation for advanced stratification for the management of these tumors within a multimodal treatment approach.

PARP Inhibitors in Brain Metastases from Epithelial Ovarian Cancer through a Multimodal Patient Journey: Case Reports and Literature Review.

Epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy worldwide. Brain metastasis (BM) is quite an uncommon presentation. However, the likelihood of central nervous system (CNS) metastasization should be considered in the context of disseminated disease. The therapeutic management of BMs is an unmet clinical need, to date. We identified, across different cancer centers, six cases of both BRCA wild-type and BRCA-mutated EOCs spreading to the CNS. They presented either with a single brain lesion or with multiple lesions and most of them had intracranial-only disease. All cases received Poly-ADP ribose polymerase inhibitor (PARPi) maintenance, as per clinical practice, for a long time within a multimodal treatment approach. We also provide an insight into the available body of work regarding the management of this intriguing disease setting, with a glimpse of future therapeutic challenges. Despite the lack of unanimous guidelines, multimodal care pathways should be encouraged for the optimal disease control of this unfortunate patient subset. Albeit not being directly investigated in BM patients, PARPi maintenance is deemed to have a valuable role in this setting. Prospective research, aimed to implement worthwhile strategies in the multimodal patient journey of BMs from EOC, is eagerly awaited.

Conservative Management of Occipital Neuralgia Supported by Physical Therapy: A Review of Available Research and Mechanistic Rationale to Guide Treatment.

Conservative management is consistently recommended as a first line intervention for occipital neuralgia (ON); however, there is limited clinical research regarding conservative intervention for ON. This lack of research may lead to underutilization or unwarranted variability in conservative treatment. This article provides mechanism-based guidance for conservative management of ON as a component of a multimodal treatment approach, and discusses the role of the physical therapist in the care team. It also highlights opportunities for further research to refine conservative management of this condition. Published research on conservative interventions specific to ON is limited to very low-quality evidence for the use of TENS. The contemporary shift toward precision pain management emphasizing treatment based on a patient's constellation of clinical features-a phenotype-rather than solely a diagnosis provides more personalized and specifically targeted pain treatment. This paradigm can guide treatment in cases where diagnosis-specific research is lacking and can be used to inform conservative treatment in this case. Various conservative interventions have demonstrated efficacy in treating many of the symptoms and accepted etiologies of ON. Conservative interventions provided by a physical therapist including exercise, manual therapy, posture and biomechanical training, TENS, patient education, and desensitization have mechanistic justification to treat symptoms and causes of ON. Physical therapists have adequate time and skill to provide such progressive and iterative interventions and should be included in a multimodal treatment plan for ON. Further research is required to determine appropriate dosing, sequencing, and progression of conservative treatments.

The role of radiotherapy in multimodal treatment of non-rhabdomyosarcoma soft tissue sarcomas in children: A real life report from a tertiary center.

The current treatment of pediatric non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) is a multimodal risk-based approach. Today, smaller fields and lower doses of radiotherapy (RT) have become standard. In this study, it was aimed to evaluate the treatment outcomes and toxicity profile in children with NRSTS that received RT as a part of multimodal therapy. Twenty-nine patients with pediatric NRSTS treated with neoadjuvant or adjuvant RT between 1998 and 2022 were evaluated retrospectively. Kaplan-Meier method was used for survival analyses. Median follow-up was 36 months (range, 6-291 months). The median neoadjuvant and adjuvant RT doses were 50 Gy (range, 45-66 Gy) and 54 Gy (45-66 Gy), respectively. During follow-up, six (21%) patients developed a local recurrence and 10 (35%) had distant metastasis. The 5-year local control, overall survival (OS), local recurrence-free survival, and distant metastasis-free survival rate was 79%, 67%, 59%, and 61%, respectively. In multivariate analysis, a ≤5-cm tumor, gross tumor resection, Children's Oncology Group (COG) low-risk group, and absence of neoadjuvant chemotherapy were independent favorable prognostic factors for OS. Severe (≥ grade 3) late toxicity was observed in 6 (20%) patients. RT is a crucial component in the multimodal risk-based treatment approach for pediatric NRSTS. However, late toxicity rates are still high and should be improved. Patients with a ≤5-cm tumor, COG low-risk group and treated with gross tumor resection have increased survival rates.