In today's world, research has evolved a lot in the field of cancer and docetaxel (DTX) has been intensively studied for its ability to cure different types of cancers. However, the intravenous delivery of DTX puts forth various undesirable side effects, while oral delivery has its own solubility and permeability drawbacks. The advancements in research have focused on overcoming these disadvantages by developing novel and efficient DTX-based drug delivery systems. The review aims at identifying challenges faced by DTX and thereby forecasting the different DTX formulations established to surpass them. The successful DTX delivery is mediated by certain efficient nanocarriers, inclusion complexes, etc., effectively destroying the cancerous cells. The current clinical status of these formulations has also been listed in this review. The dedicated efforts of researchers have been fruitful in site-specific targeting of DTX by novel formulations, thus enhancing its antitumor effect. However, this success has been restricted only to preclinical studies and only a few formulations have entered the CTs, while none have received market approval. A deep understanding of the basics of nanoformulations, along with their toxicological insights and flexible production procedures, will help to combat the clinical hurdles faced by them.

Optimizing metaplastic breast cancer (MpBC) management remains an unmet clinical need. Current literature on MpBC response toantibody drug-conjugates is limited to individual case reports and case series. This study investigates outcomes in metastatic MpBC treated withsacituzumab govitecan (SG) and characterizes actionable targets to inform future studies.

Patients (pts) with metastatic triple negative breastcancer (TNBC) treated at the Massachusetts General Hospital Cancer Center between 2000 and 2025 were assessed for MpBC and receipt of SG. MpBCcases were interrogated for biomarkers qualifying for targeted therapy: HER2-low status (IHC 1+/2+), combined positive score (CPS), and targetablegenomic variants based on next-generation sequencing of plasma and/or tissue ordered by the treating provider. Multivariable Cox regression analysisassessed the association of MpBC under SG treatment with progression-free survival (PFS) and overall survival.

MpBC cases (n = 17) had anumerically shorter median PFS under SG compared to non-MpBC TNBC (n = 133) [2.6 vs. 6.8 months, p = 0.16]. While most patients with MpBC hadlimited response to SG monotherapy, two patients on SG + talazoparib had prolonged PFS. Annotation of available genomic and pathology data from allpatients with MpBC (n = 58) revealed targetable alterations including 34/56 patients with HER2-low status, 8/45 patients with germline BRCA1/2mut, and9/30 patients with somatic PIK3CAmut. MpBC response to matched therapies showed variable PFS.

To our knowledge, this study is one ofthe largest analyses of MpBC response to SG and highlights challenges of treating rare diseases at large. Multi-institutional collaboration and inclusive trialdesign are essential to optimize treatments for MpBC.

Intraconal orbital tumors pose significant surgical challenges due to their deep anatomical location and close relationship with critical neurovascular structures. Although the lateral orbitotomy approach (LOA) offers direct access to the intraconal space, comprehensive outcome data from single-center experiences remain limited. This study aimed to evaluate the clinical characteristics, surgical outcomes, and safety profile of patients with intraconal orbital tumors treated via LOA over a ten-year period.

A retrospective analysis was conducted on 27 patients who underwent lateral orbitotomy for intraconal lesions at Gazi University Hospital between January 2013 and January 2023. Patient demographics, presenting symptoms, tumor characteristics, extent of resection, postoperative outcomes, and complications were analyzed.

The cohort consisted of 27 patients, including 12 males and 15 females, with a mean age of 41.0 years. The most common presenting symptoms were exophthalmos (92.6%), visual loss (63.0%), pain (33.3%), and diplopia (25.9%). Cavernous hemangioma was the predominant pathology (77.8%). Gross total resection (GTR) was achieved in 22 patients (81.5%), with significantly smaller tumor volumes compared with the subtotal resection (STR) group (p = 0.0033). All small tumors (< 4.0 cm³) underwent GTR, whereas the rate declined in medium and large tumors (p = 0.0031). Postoperatively, most symptoms improved. Transient postoperative events occurred in 37.0% of patients, most commonly palpebral swelling. No severe complications, or surgery-related mortality were encountered during a median 48-month follow-up.

Lateral orbitotomy is a safe and effective approach for intraconal tumors, providing high GTR rates, consistent symptom improvement, and low morbidity. Its reliable access to lateral and central intraconal compartments supports its continued use in orbital surgery.

Clonality testing using BIOMED-2-based multiplex PCR is widely applied in routine diagnostics, but its interpretation can be complicated by clonal-like peaks arising from non-neoplastic immune responses. In this study, we retrospectively analyzed routine diagnostic cases examined by IGH and TCRB multiplex PCR and assessed both the number of rearranged regions and peak patterns in B-cell lymphoma (N = 291), T-cell lymphoma (N = 48), Classic Hodgkin lymphoma (N = 31), reactive lymphoid hyperplasia (N = 28), and carcinoma (N = 41). The most clinically relevant finding was the frequent detection of apparent IGH clonality in carcinoma, often accompanied by polyclonal background. Clonal IGH peaks were detected in 16 of 35 carcinoma cases (46%), including 7 of 35 cases (20%) with peaks in two or more regions. Among these 16 cases, 11 (69%) showed polyclonal background. In contrast, reactive lymphoid hyperplasia showed much lower IGH positivity, with clonal peaks in 3 of 25 cases (12%) and only 1 of 25 cases (4%) with peaks in two or more regions. More informative than lineage-associated positivity itself were the disease-specific peak patterns, especially the frequent appearance of clonal-like IGH peaks with polyclonal background in carcinoma and the background-rich patterns seen in T-follicular helper cell lymphoma, angioimmunoblastic type/angioimmunoblastic T-cell lymphoma (AITL). These findings indicate that BIOMED-2 clonality assays capture not only neoplastic clones but also disease-specific immune background. Frequent IGH peaks with polyclonal background in carcinoma represent an important diagnostic pitfall and should be interpreted carefully together with the pathological and immunohistochemical results.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) has entered a dual CD123-targeted therapy era following the availability of tagraxofusp and the 2026 approval of pivekimab sunirine-pvzy. This development creates a new clinical problem: treatment can no longer be selected solely by distinguishing targeted therapy from conventional chemotherapy; clinicians must choose between mechanistically distinct CD123 platforms while integrating central nervous system (CNS) management, transplantation, comorbidity, organ function, and prior treatment. This narrative review reframes BPDCN around those decisions. It summarizes the minimum diagnostic and staging information needed before therapy; compares tagraxofusp and pivekimab using response, survival, follow-up, and transplant-bridging data; and proposes scenario-based approaches for newly diagnosed, older or frail, transplant-eligible, and relapsed or refractory patients. Tagraxofusp has the longest disease-specific experience and a defined role as remission induction and a bridge to hematopoietic cell transplantation, but capillary leak syndrome requires stringent selection and cycle-1 monitoring. Pivekimab offers a distinct antibody-drug conjugate platform with once-every-3-week dosing and activity in both treatment-naive and relapsed disease, but hepatotoxicity, including hepatic veno-occlusive disease, is a central limitation. Neither agent has established CNS-protective activity. Baseline cerebrospinal fluid assessment and routine prophylactic intrathecal chemotherapy for CSF-negative patients should therefore be distinguished from intensified therapeutic intrathecal treatment for documented CNS involvement. Early donor search, multidimensional response evaluation, and trial enrollment remain integral. The proposed algorithm is evidence-informed rather than guideline-mandated and highlights where prospective studies are most urgently needed.

Prophylactic administration of systemic antibiotics is widely used to mitigate skin-related adverse events (AEs) during anti-EGFR monoclonal antibody (mAb) therapy for metastatic colorectal cancer (mCRC). However, the optimal duration of prophylaxis remains unclear, and prolonged use may increase risks such as hepatotoxicity and reduced efficacy. In this single-center retrospective study, mCRC patients receiving anti-EGFR mAbs and prophylactic minocycline as part of a standardized outpatient skin care program were analyzed. Patients were classified into 2 groups based on minocycline duration: 8 weeks or >8 weeks. The primary endpoint was the incidence of Grade ≥2 skin-related AEs at weeks 8 and 12. Secondary endpoints included specific AE types, liver dysfunction, and risk factor analysis using multivariate logistic and Cox regression models. Seventy-three patients were included (8-week group: n = 24; >8-week group: n = 49). At week 12, the incidence of Grade ≥2 skin-related AEs was significantly lower in the 8-week group (54.2% vs 81.6%, p = 0.013), particularly for paronychia (16.7% vs 42.9%, p = 0.027). The incidence of liver dysfunction was also lower (16.7% vs 40.8%, p = 0.039). Logistic regression identified younger age and prolonged minocycline use as independent risk factors at week 12, while Cox regression showed age ≥65 years increased risk over the treatment period. Limiting prophylactic minocycline administration to 8 weeks may reduce skin-related AEs and hepatotoxicity. Patient age and treatment duration should be considered when optimizing supportive care protocols for anti-EGFR mAbs therapy.

Single-isocenter multiple-target stereotactic radiation treatments delivered on C-arm linear accelerators are increasingly common due to practical advantages in both accessibility and speed compared to multiple isocenter treatments. Optimization of high-quality treatment plans can be a time-consuming process requiring substantial manual effort. In our institution, the planning workflow for these treatments was entirely manual and involved the generation of optimization structures and repeated recalculation and input of optimization objectives during the iterative optimization process.  Although commercial automated planning solutions are available, their implementation may impose operational constraints, including reliance on specific immobilization and image/surface guidance hardware, motivating the development of an immobilization-independent automation tool for cranial stereotactic treatment plan optimization.

To develop and implement a treatment planning optimization tool for multiple-target cranial stereotactic treatments in the Varian Eclipse treatment planning system, to reduce manual planner input and planning time while improving plan quality.

A software tool was written using the Varian Eclipse Scripting Application Programming Interface to automatically generate target-specific ring structures and facilitate the iterative process of plan generation. Twenty cases were retrospectively re-planned with this tool and compared with the corresponding clinical plans to evaluate plan quality using qualitative and quantitative metrics of conformality and complexity. Automated plans were verified using portal dosimetry to ensure clinical deliverability. For ten cases, a timing study was performed to compare optimization time between the software tool and manual re-optimization.

The automatic optimization tool produced plans with similar modulation and complexity, but consistently lower dosimetric falloff metrics (R_50% and Paddick Gradient Index) than the corresponding clinical plans. All plans passed patient-specific QA (portal dosimetry) following institutional practice. For the ten cases included in the timing study, the software had a mean runtime of 5.8 min (range: 2-12 min), with variation depending on case characteristics such as number of targets and arcs employed. In comparison, manual plan generation required 21.5 min on average (range: 4-49 min).

The automated planning tool produced clinically acceptable, deliverable plans with better dose falloff compared to the previous manual planning approach. The tool is estimated to save an average of 15 min of optimization time per plan.

A treatment planning optimization tool has been developed that provides improvement in both dosimetric plan quality and treatment planning efficiency for single-isocenter multiple-target cranial stereotactic treatments.

Surface Guided Radiation Therapy (SGRT) has become an increasingly important tool that complements x-ray imaging to improve patient safety for setup, respiratory tracking, and motion monitoring. As SGRT is integrated into clinical workflows, its complexity can introduce potential risk of process-related errors. These risks may depend on workflow design, system integration, equipment configuration, and technology specific features. As SGRT continues to expand across a wider range of treatment sites and clinical applications, comprehensive evaluation of institutional workflows is recommended to support safe and effective implementation.

This study aimed to identify and evaluate safety risks associated with the clinical use of SGRT using Failure Mode and Effects Analysis (FMEA). Emphasis was placed on workflow processes, system integration, and equipment-specific characteristics within a clinical environment to inform risk mitigation strategies and support safe implementation.

A multidisciplinary team performed an FMEA of SGRT related procedures and workflows. A process map was developed to define the scope of clinical applications, including tattoo free setup, free-breathing and deep-inspiration breath-hold (DIBH) breast treatments, prone patient positioning and real-time motion monitoring for stereotactic body radiation therapy (SBRT) patients across body sites. For each process step, team members identified potential failure modes associated with the clinical workflow and environment, including the integration of a C-RAD SGRT system with Elekta linear accelerators. Scoring was performed according to AAPM TG-100 guidelines, using severity (S), occurrence (O), and detectability (D) to calculate the Risk Priority Number (RPN). Failure modes were then ranked by RPN, and those with scores greater than or equal to 100 were selected for further analysis and development of mitigation strategies.

Thirty-eight failure modes were identified, with nine having RPN scores greater than or equal to 100 (S = 5-8, O = 2-5, and D = 5-9). High risk failure modes were most associated with the DIBH workflow, particularly respiratory trace acquisition, respiratory trace configuration, and x-ray image verification. Additional high risk failure modes were identified in treatment preparation and system quality assurance processes, including manual data import, template selection, calibration, and daily QA procedures. These risks were primarily associated with workflow-dependent processes involving user interaction and coordination between integrated clinical systems.

This FMEA identified workflow, system integration and equipment related vulnerabilities associated with SGRT implementation. The findings emphasize the importance of risk assessments tailored to specific clinical workflows and treatment environments and support the development of targeted mitigation strategies for safe clinical use.

Splanchnic venous thrombosis (SVT) is a potentially catastrophic manifestation of polycythaemia vera (PV). We report a woman in her 60s with masked PV who had been managed for 5 years with intermittent phlebotomy and aspirin without haematology referral, molecular testing or cytoreductive therapy. Chronic iron deficiency masked erythrocytosis, delaying diagnosis. She presented with extensive thrombosis involving the portal, splenic and superior mesenteric veins complicated by mesenteric ischaemia requiring exploratory laparotomy, jejunal resection and ileostomy. Bone marrow biopsy and JAK2 V617F testing confirmed PV. Therapeutic anticoagulation was initiated with enoxaparin and subsequently transitioned to apixaban, while hydroxyurea achieved sustained haematologic control. Interval imaging demonstrated thrombus regression with persistent cavernous transformation. Given ongoing portal hypertension, oesophageal varices, occasional mild ostomy bleeding and low body weight, anticoagulation was continued indefinitely at reduced intensity with apixaban 2.5 mg twice daily. At 21-month follow-up, the patient remained free of recurrent thrombosis and major bleeding.

The prognosis of myeloid leukaemia associated with Down syndrome (ML-DS) is excellent with reduced-intensity chemotherapy; however, that of refractory or relapsed ML-DS remains dismal. These contrasting outcomes highlight the importance of risk-stratified therapy, based on reliable prognostic factors, to prevent treatment-related mortality and relapse. In addition, novel therapeutic strategies capable of overcoming the poor prognosis of high-risk patients are eagerly anticipated. Based on the results of molecular analyses, in vitro functional assays and anecdotal case reports, azacitidine (AZA), a hypomethylating agent, is a promising candidate for novel therapeutic strategies for high-risk ML-DS.

In this multicentre, single-arm phase II clinical trial, the Japan Children's Cancer Group AML-D24, we will stratify patients with newly diagnosed ML-DS according to age at diagnosis, GATA1 mutation status and treatment response. Patients <24 months of age at the diagnosis with a GATA1 mutation who achieve morphological complete remission and are negative for flow cytometric measurable residual disease at the end of induction will be classified as the low-risk (LR) group and receive less intensive chemotherapy. The other participants, stratified into the non-LR group, will be treated with AZA-combined chemotherapy. The objective of this trial is to evaluate the efficacy and safety of AZA-combined chemotherapy in children with non-LR ML-DS. The primary endpoint is the 3-year event-free survival in the non-LR group. The planned enrolment is 145 patients, including 47 non-LR patients. The study period consists of a 7-year accrual period (including an enrolment suspension period for interim analysis) followed by a 3-year follow-up period for a total duration of 10 years.

This study was approved by the National Hospital Organization Review Board for Clinical Trials (Nagoya, Japan) on 12 May 2025 and was registered in the Japan Registry of Clinical Trials (https://jrct.mhlw.go.jp/latest-detail/jRCTs041250031). Written informed consent will be obtained from all patients and/or their guardians. The results of this study will be disseminated through publication in peer-reviewed journals and presentation at national and international scientific conferences.

jRCTs041250031.