Transmissible venereal tumor of the uterine stump following successful chemotherapy in a 5-year-old mixed-breed dog.

A 5-year-old spayed female mixed-breed dog was referred to the Atlantic Veterinary College (Charlottetown, Prince Edward Island) because of a 7-month history of intermittent pink, mucoid, vulvar discharge. The dog was imported from the Bahamas at 3.5 y of age and had a history of transmissible venereal tumor (TVT) of the vulva that was successfully treated with a course of vincristine chemotherapy. Complete remission was achieved with a disease-free interval of 6 mo before clinical signs recurred. Abdominal ultrasound and CT scan identified a large caudal abdominal mass thought to arise from the uterine stump. An exploratory laparotomy was performed and the mass grossly excised. Histopathology was consistent with a poorly differentiated round cell tumor, and immunohistochemical analysis confirmed TVT as the most likely diagnosis. No further treatment was carried out. Repeat abdominal ultrasound at 4 mo after surgery showed no evidence of mass recurrence. At 8 mo after surgery, the dog was reported to be doing well clinically. Key clinical message: Transmissible venereal tumor should be considered as a differential diagnosis for masses arising from the deep genital tissues of dogs in cases where there is a history of previous TVT. Transmissible venereal tumor should be considered even in dogs that have had complete resolution of a primary mass after chemotherapy.

Tumeur vénérienne transmissible du moignon utérin à la suite d'une chimiothérapie réussie chez un chien croisé de 5 ans.Une chienne de race mixte de 5 ans, stérilisée, a été référée au Atlantic Veterinary College (Charlottetown, Île-du-Prince-Édouard) en raison d'antécédents de pertes vulvaires roses, mucoïdes et intermittentes depuis 7 mois. Le chien a été importé des Bahamas à l'âge de 3,5 ans et avait des antécédents de tumeur vénérienne transmissible (TVT) de la vulve qui a été traitée avec succès par une chimiothérapie à la vincristine. Une rémission complète a été obtenue avec un intervalle sans maladie de 6 mois avant la réapparition des signes cliniques. L'échographie abdominale et la tomodensitométrie ont identifié une grosse masse abdominale caudale qui proviendrait du moignon utérin. Une laparotomie exploratoire a été réalisée et la masse excisée. L'histopathologie était compatible avec une tumeur à cellules rondes peu différenciée et l'analyse immunohistochimique a confirmé la TVT comme le diagnostic le plus probable. Aucun autre traitement n'a été effectué. Une échographie abdominale répétée 4 mois après la chirurgie n'a montré aucun signe de récidive massive. Huit mois après l'opération, la chienne se portait bien cliniquement.Message clinique clé:Les tumeurs vénériennes transmissibles doivent être considérées comme un diagnostic différentiel pour les masses provenant des tissus génitaux profonds des chiens dans les cas où il existe des antécédents de TVT. Une tumeur vénérienne transmissible doit être envisagée même chez les chiens dont la masse primaire a complètement disparu après chimiothérapie.(Traduit par Dr Serge Messier).

Lower urinary dysfunction as a long-term effect of childhood vincristine treatment, with potential influences by sex and dose.

Vincristine (VCR) is one of the most widely used chemotherapy agents in treating pediatric cancer. Nonetheless, it is known to cause dose-dependent neurotoxicity which can impact virtually every organ system. Despite its widespread use, the precise impact of VCR on the lower urinary tract (LUT) remains inadequately elucidated. Our initial clinical and translational investigations suggest a sex-specific influence of childhood VCR exposure on LUT function. Thus, the current study aimed to investigate the late effects of systemic VCR exposure on LUT physiology and the underlying mechanisms, focusing on dosage and male-sex, employing juvenile CD-1 mice as a model. Male mice subjected to VCR exhibited augmented functional bladder capacity accompanied by frequent non-void contractions during awake cystometry, alongside mast cell accumulation within the bladder, compared to the saline-treated control group. Noteworthy functional changes were observed in bladder strips from the VCR group, including decreased nerve-mediated contraction, heightened contractile responses to cholinergic and purinergic agonists, enhanced responsiveness to histamine-primarily via histamine receptor 1 (Hrh1)-and an augmented relaxation effect with compound 48/80 (a mast cell degranulator), relative to the control group. Significant changes in gene expression levels associated with neuroinflammation and nociception were observed in both the bladder and lumbosacral dorsal root ganglia (Ls-DRG) of the VCR group. These findings suggest that VCR exposure during childhood, particularly in males, triggers neuroimmune responses in the bladder and Ls-DRG, amplifying responsiveness to neurotransmitters in the bladder, thereby contributing to LUT dysfunction characterized by a mixed bladder phenotype as a late effect during survivorship.

Co-delivery of oncolytic virus and chemotherapeutic modality: Vincristine against prostate cancer treatment: A potent viro-chemotherapeutic approach.

Prostate cancer is a prevalent carcinoma among males, and conventional treatment options are often limited. Cytotoxic chemotherapy, despite its drawbacks, remains a mainstay. We propose a targeted co-delivery approach using nanoscale delivery units for Oncolytic measles virus (OMV) and vincristine (VC) to enhance treatment efficacy. The HA-coated OMV + VC-loaded TCs nanoformulation is designed for targeted oncolytic activity in prostate cancer. The CD44 expression analysis in prostate cancer cell lines indicates a significantly high expression in PC3 cells. The optimization of nanoformulations using Design of Expert (DOE) is performed, and the preparation and characterization of HA-coated OMV + VC-loaded TCs nanoformulations are detailed showing average particle size 397.2 ± 0.01 nm and polydispersity index 0.122 with zeta potential 19.7 + 0.01 mV. Results demonstrate successful encapsulation efficiency with 2.4 × 106 TCID50/Ml and sustained release of OMV and VC from the nanoformulation for up to 72 h. In vitro, assays reveal potent anticancer activity at 10 ± 0.71% cell viability in PC3 cells compared to 73 ± 0.66% in HPrEC and significant morphological changes at 90 µg/ml in dose and time-dependent manner. The co-formulation showed positive cell death 49.5 ± 0.02% at 50 µg PI/ml in PBS and 54.3% cell cycle arrest at the G2/M phase, 8.1% G0/G1 and 5.7% at S phase, with significant mitochondrial membrane potential (MMP) at 50 µg/ml, as assessed by flow cytometry (FACS). The surface-integrating ligand approach enhances the targeted delivery of the oncolytic virus and chemotherapeutic drug, presenting a potential alternative for prostate cancer treatment and suggested that co-administering VC and OMV in a nanoformulation could improve therapeutic outcomes while reducing chemotherapeutic drug doses.

Pharmacogenetic Testing or Therapeutic Drug Monitoring: A Quantitative Framework.

BACKGROUND: Pharmacogenetic profiling and therapeutic drug monitoring (TDM) have both been proposed to manage inter-individual variability (IIV) in drug exposure. However, determining the most effective approach for estimating exposure for a particular drug remains a challenge. This study aimed to quantitatively assess the circumstances in which pharmacogenetic profiling may outperform TDM in estimating drug exposure, under three sources of variability (IIV, inter-occasion variability [IOV], and residual unexplained variability [RUV]). METHODS: Pharmacokinetic models were selected from the literature corresponding to drugs for which pharmacogenetic profiling and TDM are both clinically considered approaches for dose individualization. The models were used to simulate relevant drug exposures (trough concentration or area under the curve [AUC]) under varying degrees of IIV, IOV, and RUV. RESULTS: Six drug cases were selected from the literature. Model-based simulations demonstrated that the percentage of patients for whom pharmacogenetic exposure prediction is superior to TDM differs for each drug case: tacrolimus (11.0%), tamoxifen (12.7%), efavirenz (49.2%), vincristine (49.6%), risperidone (48.1%), and 5-fluorouracil (5-FU) (100%). Generally, in the presence of higher unexplained IIV in combination with lower RUV and IOV, exposure was best estimated by TDM, whereas, under lower unexplained IIV in combination with higher IOV or RUV, pharmacogenetic profiling was preferred. CONCLUSIONS: For the drugs with relatively low RUV and IOV (e.g., tamoxifen and tacrolimus), TDM estimated true exposure the best. Conversely, for drugs with similar or lower unexplained IIV (e.g., efavirenz or 5-FU, respectively) combined with relatively high RUV, pharmacogenetic profiling provided the most accurate estimate for most patients. However, genotype prevalence and the relative influence of genotypes on the PK, as well as the ability of TDM to accurately estimate AUC with a limited number of samples, had an impact. The results could be used to support clinical decision making when considering other factors, such as the probability for severe side effects.

Intestinal T-cell lymphomas NOS presenting as a polypoidal lesion: A case report.

RATIONALE: Intestinal T-cell lymphomas are exceedingly rare diseases. Intestinal T-cell lymphoma NOS, as a "wastebasket" category, is difficult to diagnosis. Endoscopy can identify abnormal mucosa in most patients at a reasonably early stage. Therefore, it is crucial to increase the understanding of endoscopists in terms of the endoscopic characteristics of ITCL. PATIENT CONCERNS: A 74-year-old male alone with wasting as the major complaint, had multiple polypoid lesions in the large intestine. The patient then had endoscopic care. DIAGNOSES: Only 1 polypoid lesion on white-light endoscopy in the sigmoid colon was pathologically diagnosed as intestinal T-cell lymphomas, not otherwise specified (ITCL-NOS). INTERVENTIONS: The patient underwent intensity-reduced CHOP therapy. OUTCOMES: The patient is still with controlled disease but developed chemotherapy-related side effects. LESSONS: In the individual with unexplained anemia and waste, endoscopy should not be delayed. For each of polypoid lesion on white-light endoscopy, the endoscopist need to remain cautious, because every lesion in the same patient can exhibit the independence of histopathological features. Meanwhile, we suggest that endoscopists should routinely observe the terminal ileum, even take biopsy samples if necessary.

Subcutaneous Panniculitis-like T Cell Lymphoma Diagnosed with a Slowly Progressive Course: A Case Report.

Panniculitis is an inflammation that occurs in subcutaneous adipose tissue. Panniculitis includes physical panniculitis (e.g., traumatic) and infectious panniculitis (e.g., bacterial, fungal, subcutaneous panniculitis-like T cell lymphoma [SPCTL], etc.). Accurate diagnosis is crucial due to similar clinical presentation of all types of panniculitis. Here, we report a case of SPCTL which was initially diagnosed with traumatic panniculitis. A 15-year-old male patient was admitted to a previous hospital due to a progressively enlarged right flank and inguinal mass after an abdominal bruise. He was initially diagnosed with traumatic panniculitis, but the mass expanded throughout the chest and abdomen accompanied by a fever of over 11 months. Computed tomography (CT) revealed a subcutaneous mass in the anterior chest and abdominal wall. Fludeoxyglucose F18 (FDG) uptake was observed at those lesions using FDG-positron emission tomography (PET). A biopsy of the mass lesion was performed, during which SPCTL was diagnosed based on pathological examination. He was initially treated with prednisolone and cyclosporine A for two weeks. His fever went down, but subcutaneous mass in the chest and abdominal wall persisted. Therefore, he received a cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen. After 6 courses of CHOP, CT revealed no disease evidence. He remained in complete remission at 30 months of therapy.

Epidemiological, clinical and therapeutic profiles of mantle cell lymphoma cared for in a Moroccan center: a review of 14 cases.

Mantle cell lymphoma (MCL) accounts for 3-10% of non-Hodgkin's lymphomas (NHL). We identified 14 patients with mantle cell lymphoma, with an average number of 3.5 new cases/year. A male predominance was observed with a sex ratio equal to 6. The average age of our patients was 64.4±14.1 years, with an average diagnostic delay of 6.57 months. Regarding the clinical presentation, adenopathy was the most reported physical sign (78.6%) followed by B symptoms (57.1%). Disseminated stages were the most frequent in our series: stages IV (78.5%) and III (7.1%) versus stages I (0%) and II (7.1%). The extra-ganglionic localizations observed were hepatic 5 cases (31.1%), pulmonary 04 cases (25%), medullary 4 cases (25%), pleural 2 cases (12.5%) and prostate 1 case (6.2%). All diagnosed cases are mantle cell lymphomas, of which 12 cases (85.7%) are classical and 2 cases (14.3%) indolent. The high-risk group is, according to international prognostic index (MIPI) MCL prognostic score, the most represented in our series: 0-3 = 6 cases (42.9%), 6-11 = 8 cases (57.1%). The therapeutic protocol chosen 1st line: 9 patients treated with R-DHAP, three with R-CHOP, one with DHAOX and one with R-CVP. Second line: two patients treated with R-DHAP, one after R-CHOP and the other after R-CVP. Two patients received autologous hematopoietic stem cell transplant at the end of the treatment. The evolution was marked by the death of 7 patients, 3 lost to follow-up and 4 still followed. Additionally, the study highlights characteristics and treatment patterns of mantle cell lymphoma, emphasizing its predominance in males, delayed diagnosis, frequent dissemination, and high-risk classification, with chemotherapy as the primary treatment modality and a challenging prognosis contributing to a comprehensive understanding of mantle cell lymphoma presentation and management.

CD20 expression regulates CD37 levels in B-cell lymphoma - implications for immunotherapies.

Rituximab (RTX) plus chemotherapy (R-CHOP) applied as a first-line therapy for lymphoma leads to a relapse in approximately 40% of the patients. Therefore, novel approaches to treat aggressive lymphomas are being intensively investigated. Several RTX-resistant (RR) cell lines have been established as surrogate models to study resistance to R-CHOP. Our study reveals that RR cells are characterized by a major downregulation of CD37, a molecule currently explored as a target for immunotherapy. Using CD20 knockout (KO) cell lines, we demonstrate that CD20 and CD37 form a complex, and hypothesize that the presence of CD20 stabilizes CD37 in the cell membrane. Consequently, we observe a diminished cytotoxicity of anti-CD37 monoclonal antibody (mAb) in complement-dependent cytotoxicity in both RR and CD20 KO cells that can be partially restored upon lysosome inhibition. On the other hand, the internalization rate of anti-CD37 mAb in CD20 KO cells is increased when compared to controls, suggesting unhampered efficacy of antibody drug conjugates (ADCs). Importantly, even a major downregulation in CD37 levels does not hamper the efficacy of CD37-directed chimeric antigen receptor (CAR) T cells. In summary, we present here a novel mechanism of CD37 regulation with further implications for the use of anti-CD37 immunotherapies.

[Primary renal triple expressor DLBCL treated with chemotherapy under continuous hemodialysis and filtration support].

A 69-year-old woman was previously treated with antibiotics for suspected pyelonephritis due to fever but showed limited improvement. Contrast-enhanced CT revealed heterogeneous areas of decreased contrast enhancement in both kidneys, along with an elevated soluble level of the IL-2 receptor (5,090 U/ml), and thus the patient was referred to our department for further evaluation. A percutaneous renal biopsy performed due to suspected malignant lymphoma confirmed lymphoma cell infiltration into the renal interstitium. Immunohistochemical staining was positive for MYC/BCL2/BCL6, leading to the diagnosis of stage IVB primary renal triple expressor diffuse large B cell lymphoma (DLBCL). Due to acute kidney injury, continuous hemodiafiltration (CHDF) was initiated, followed by rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. The patient's renal function improved rapidly, and complete response was achieved after six cycles of R-CHOP. Although DLBCL is a common lymphoma, the primary renal subtype is extremely rare and poses both diagnostic and therapeutic challenges. This case highlights the potential clinical implications of combining CHDF with chemotherapy to achieve complete response despite an initial poor prognosis based on the patient's overall clinical condition and pathology.

[The Reduction of CD4+ T Lymphocytes after the Treatment of Follicular Lymphoma with the Bendamustine Containing Regimen May Predict the Occurrence of Infection and Efficacy].

OBJECTIVE: To investigate the effectiveness, safety, and related prognostic factors of the treatment of follicular lymphoma (FL) with a regimen containing Bendamustine. METHODS: The clinical data of 129 FL patients who were treated with Bendamustine containing regimen were collected from January 1,2020 to October 30,2022 in the Hematology Department of Lianyungang Second People's Hospital and Jiangsu Provincial People's Hospital. The patients were divided into three groups: Bendamustine plus Rituximab (BR), Bendamustine plus Obinutuzumab (GB), Rituximab + Cyclophosphamide + Epirubicin / Doxorubicin + Vindesine + Prednisone (R-CHOP). The efficacy, safety and related prognostic factors of the treatment of FL with a regimen based on Bendamustine were retrospectively analyzed. RESULTS: The ORR was 98% for the BR group, 94% for the GB group, and 72.3% for the R-CHOP group, while the CR rate was 61.2%,70% and 40.4%, respectively. The ORR and CR rates of the R-CHOP group were statistically different from those of the BR group and GB group (P < 0.05). The 3-year PFS rate of the BR group, GB group, and R-CHOP group was 89.6%, 90.9%, 48.9%, respectively. There was a statistically significant difference in 3-year PFS between the R-CHOP group, BR group, and GB group (P < 0.05), while there was no statistically significant difference in 3-year OS（P ＞0.05）. Hematological adverse reactions were mainly bone marrow suppression. Lymphocytes and CD4+T lymphocytes decreased to the lowest level about 6 months after treatment, and the incidence of lymphopenia in BR group and GB group was higher than that in R-CHOP group, with a statistical difference (P < 0.05). The higher incidence of non-Hematological adverse reactions were pulmonary infection, EB virus infection, hepatitis B virus reactivation, and gastrointestinal reactions without statistical difference in 3 groups (P >0.05), and were all controllable. The Receiver operating characteristic of CD4+T lymphocyte count showed that AUC of BR group was 0.802, and the critical value was 258/uL; AUC of GB group was 0.754 with a critical value of 322/uL. CONCLUSION: The treatment of FL with the Bendamustine containing regimen has good efficacy and controllable adverse reactions, but lymphocytopenia was significant after treatment, and the curative efficacy in combination with various CD20 monoclonal antibodies was different. The lowest CD4+T lymphocyte count can be used as a predictive factor for the occurrence of infection and efficacy of the Bendamustine containing regimen for FL.

[A Retrospective Study of R±DHAX Regimen versus R-CHOP Regimen First-Line Treatment of Elderly Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To investigate the clinical efficacy and prognosis of Rituximab combined with DHAX and CHOP regimen in the first-line treatment of elderly patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). METHODS: A total of 36 elderly patients with DLBCL who were admitted and treated with 3 of more courses of treatment from August 2011 to August 2021 were retrospectively analyzed, and they were divided into rituximab±DHAX (R±DHAX) regimen group (18 cases) and rituximab±CHOP (R-CHOP) regimen group (18 cases) according to the treatment plan, and clinical features, efficacy and survival of the patients were observed. RESULTS: Compared with R-CHOP group, patients of the R±DHAX group were older, and had worse performance status and higher IPI score, the differences between two groups in age, ECOG score and IPI score were statistically significant ( P =0.005 P =0.018, P =0.035), but there were no significant differences beween two groups in gender, whether there were B symptoms, whether LDH was elevated, whether there was extranodal involvement, cell origin, bone marrow infiltration, and whether rituximab was combined ( P =0.738, P =1, P =0.315, P =0.305, P =0.413, P =0.177, P =0.711, P =0.229). The efficacy could be evaluated in 36 cases, including CR 14 (38.9%), PR 17 (47.2%), PD 5 (13.9%), and ORR of 86.1% (31/36). There were no statistically significant differences in CRï¼»(27.8%（5/18） vs 50.0%（9/18）; P >0.05ï¼½ and PR ï¼»44.4%（8/18） vs 50.0%（9/18）; P >0.05ï¼½ of R±DHAX group and R-CHOP group, there was statistically significant difference in ORRï¼»72.2%（13/18） vs 100.0%（18/18）; P =0.045ï¼½ between two groups. The 1-year OS of R±DHAX group and R-CHOP group was (38.9±11.5%)% and (94.4±7.4%)%, respectively, 2-year OS was (16.7±8.8)% and (72.2±10.6)%, respectively, and the differences between two groups were statistically significant ( P =0.001, P =0.002). The median survival time in the R±DHAX group was 11 months(95%CI :8.9-13.1), and the median survival time in the R-CHOP group was not reached, and there was a statistically significant difference between the groups (P < 0.001). CONCLUSION: For elderly DLBCL patients, R±DHAX may not be superior to R-CHOP in OS, and ECOG score, IPI score and age may affect the survival of elderly DLBCL patients. However, R±DHAX regimen is safe, tolerable and has a certain efficacy, which can be used as one of the clinical treatment options for elderly DLBCL.

[Comparison of the Prognostic Value of C-Reactive Protein to Albumin Ratio and Glasgow Prognostic Score in Patients with Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To compare the prognostic value of two predictive models based on C-reactive protein (CRP) and albumin (ALB), namely the CRP to ALB ratio (CAR) and the Glasgow prognostic score (GPS), in newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL). METHODS: The data of newly diagnosed DLBCL patients admitted to our center from May 2014 to January 2022 were reviewed. A total of 111 patients who completed at least 4 cycles of R-CHOP or R-CHOP-like chemotherapy with detailed clinical, laboratory data and follow-up information were included. The receiver operating characteristic (ROC) curve was performed to evaluate the predictive value of pre-treatment CAR on disease progression and survival. Furthermore, the association between CAR and baseline clinical, laboratory characteristics of patients was evaluated, and progression-free survival (PFS) and overall survival (OS) were compared between different CAR and GPS subgroups. Finally, the univariate and multivariate COX propor-tional hazard regression models were used to analyze the factors affecting disease outcomes. RESULTS: ROC curve showed that the area under the curve (AUC) of CAR predicting PFS and OS in DLBCL patients was 0.687 (P =0.002) and 0.695 (P =0.005), respectively, with the optimal cut-off value of 0.11 for both predicting PFS and OS. Compared with the lower CAR (<0.11) group, the higher CAR (≥0.11) group had more clinical risk factors, including age >60 years (P =0.025), ECOG score ≥2 (P =0.004), Lugano stage III-IV (P < 0.001), non-germinal center B-cell-like (non-GCB) subtype (P =0.035), elevated lactate dehydrogenase (LDH) ( P < 0.001), extranodal involved site >1 (P =0.004) and IPI score >2 (P < 0.001). The interim response evaluation of patients showed that the overall response rate (ORR) and complete response rate (CRR) in the lower CAR group were both significantly better than those in the higher CAR group (ORR: 96.9% vs 80.0%, P =0.035; CRR: 63.6% vs 32.5%, P =0.008). With a median follow-up of 24 months, patients with lower CAR had significantly longer median PFS and OS than those with higher CAR (median PFS: not reached vs 67 months, P =0.0026; median OS: not reached vs 67 months, P =0.002), while there was no statistical difference in PFS (P =0.11) and OS (P =0.11) in patients with GPS of 0, 1, and 2. Multivariate Cox regression analysis indicated that only sex (male) and IPI score >2 were independent risk factors for both PFS and OS. CONCLUSION: CAR is significantly correlated with disease progression and survival in DLBCL patients; And compared with GPS, CAR has more advantages in predicting disease outcomes in DLBCL patients.

Addition of temsirolimus to chemotherapy in children, adolescents, and young adults with intermediate-risk rhabdomyosarcoma (ARST1431): a randomised, open-label, phase 3 trial from the Children's Oncology Group.

BACKGROUND: The Children's Oncology Group defines intermediate-risk rhabdomyosarcoma as unresected FOXO1 fusion-negative disease arising at an unfavourable site or non-metastatic FOXO1 fusion-positive disease. Temsirolimus in combination with chemotherapy has shown promising activity in patients with relapsed or refractory rhabdomyosarcoma. We aimed to compare event-free survival in patients with intermediate-risk rhabdomyosarcoma treated with vincristine, actinomycin, and cyclophosphamide alternating with vincristine and irinotecan (VAC/VI) combined with temsirolimus followed by maintenance therapy versus VAC/VI alone with maintenance therapy. METHODS: ARST1431 was a randomised, open-label, phase 3 trial conducted across 210 institutions in Australia, Canada, New Zealand, and the USA. Eligible patients were those aged 40 years or younger with non-metastatic FOXO1-positive rhabdomyosarcoma or unresected FOXO1-negative rhabdomyosarcoma disease from unfavourable sites. Two other groups of patients were also eligible: those who had FOXO1-negative disease at a favourable site (excluding orbit) that was unresected; and those who were aged younger than 10 years with stage IV FOXO1-negative disease with distant metastases. Eligible patients had to have a Lansky performance status score of 50 or higher if 16 years or younger and a Karnofsky performance status score of 50 or higher if older than 16 years; all patients were previously untreated. Patients were randomised (1:1) in blocks of four and stratified by histology, stage, and group. Patients received intravenous VAC/VI chemotherapy with a cyclophosphamide dose of 1·2 g/m2 per dose per cycle with or without a reducing dose of intravenous weekly temsirolimus starting at 15 mg/m2 or 0·5 mg/kg per dose for those who weighed less than 10 kg. The total duration of therapy was 42 weeks followed by 6 months of maintenance therapy with oral cyclophosphamide plus intravenous vinorelbine for all patients. Temsirolimus was withheld during radiotherapy and for 2 weeks before any major surgical procedure. The primary endpoint was 3-year event-free survival. Data were analysed with a revised intention-to-treat approach. The study is registered with ClinicalTrials.gov (NCT02567435) and is complete. FINDINGS: Between May 23, 2016, and Jan 1, 2022, 325 patients were enrolled. In 297 evaluable patients (148 assigned to VAC/VI alone and 149 assigned to VAC/VI with temsirolimus), the median age was 6·3 years (IQR 3·0-11·3); 33 (11%) patients were aged 18 years or older; 179 (60%) of 297 were male. 113 (77%) of 148 patients were FOXO1 negative in the VAC/VI group, and 108 (73%) of 149 were FOXO1 negative in the VAC/VI with temsirolimus group. With a median follow-up of 3·6 years (IQR 2·8-4·5), 3-year event-free survival did not differ significantly between the two groups (64·8% [95% CI 55·5-74·1] in the VAC/VI group vs 66·8% [57·5-76·2] in the VAC/VI plus temsirolimus group (hazard ratio 0·86 [95% CI 0·58-1·26]; log-rank p=0·44). The most common grade 3-4 adverse events were anaemia (62 events in 60 [41%] of 148 patients in the VAC/VI group vs 89 events in 87 [58%] of 149 patients in the VAC/VI with temsirolimus group), lymphopenia (83 events in 65 [44%] vs 99 events in 71 [48%]), neutropenia (160 events in 99 [67%] vs 164 events in 105 [70%]), and leukopenia (121 events in 86 [58%] vs 132 events in 93 [62%]). There was one treatment-related death in the VAC/VI with temsirolimus group, categorised as not otherwise specified. INTERPRETATION: Addition of temsirolimus to VAC/VI did not improve event-free survival in patients with intermediate-risk rhabdomyosarcoma defined by their FOXO1 translocation status and clinical factors. Novel biology-based strategies are needed to improve outcomes in this population. FUNDING: The Children's Oncology Group (supported by the US National Cancer Institute, US National Institutes of Health).

Pulmonary metastatic gestational choriocarcinoma following an uncomplicated term pregnancy: a case report.

BACKGROUND: Choriocarcinoma is a highly malignant pregnancy-related trophoblastic neoplasm, characterized by early metastasis to the lungs. Therefore, patients may manifest nongynecological symptoms owing to distant metastases. The incidence of choriocarcinoma after a term pregnancy is really rare (1/160,000 pregnancies). CASE PRESENTATION: We report a case of a 20-year-old Iranian woman, gravida 2 para 1 live 1 abortion 1, who was referred to our gynecology department with sudden onset dyspnea and pain in the left hemithorax the day after her labor. The index pregnancy was without any complications. After the initial workup, the elevation of ß-human chorionic gonadotropin (HCG) levels (> 1,000,000) along with the identification of clinical (vaginal lesions) and radiological evidence of distant metastases (bilateral pulmonary nodes) directed us toward pulmonary metastatic choriocarcinoma diagnosis. After the oncology consult, the etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine chemotherapy regimen was started for the patient. She responded well to the treatment and is currently continuing her chemotherapy process. CONCLUSION: The prognosis of choriocarcinoma is very good if the treatment is started on time. We suggest that clinicians should consider gestational trophoblastic neoplasia in their differential diagnosis of the post-natal period complications, especially after a term and nonmolar pregnancy.

Isolated central nervous system relapse in two adolescents with primary mediastinal large B-cell lymphoma after treatment with R-DA-EPOCH.

The addition of rituximab to standard regimens for primary mediastinal large B-cell lymphoma (PMBCL) has significantly improved overall survival. However, the optimal management of isolated central nervous system (CNS) relapse and role of CNS prophylaxis remains undefined. We present cases of two adolescents with PMBCL who developed isolated CNS relapses. While isolated CNS relapse may be managed with high-dose chemotherapy and autologous stem cell transplant with or without CNS radiotherapy, review of these cases and the literature highlight the need for further work to define risk factors for CNS relapse, and identify patients who may benefit from CNS prophylaxis.

Diffuse Large B-Cell Lymphoma With Cardiac Invasion Presented as Acute Myocardial Infarction and Left Ventricular Hypertrophy: A Case Report.

Primary cardiac lymphoma is an exceedingly rare malignant tumor, with diffuse large B-cell lymphoma (DLBCL) being the most prevalent histological subtype. This disease has non-specific clinical manifestations, making early diagnosis crucial. However, DLBCL diagnosis is commonly delayed, and its prognosis is typically poor. Herein, we report the case of a 51-year-old male patient with DLBCL who presented with recurrent chest tightness for 4 months as the primary clinical symptom. The patient was admitted to the hospital and diagnosed with acute myocardial infarction and left ventricular hypertrophy with heart failure. Echocardiography revealed a progression from left ventricular thickening to local pericardial thickening and adhesion in the inferior and lateral walls of the left ventricle. Finally, pathological analysis of myocardial biopsy confirmed the diagnosis of DLBCL. After treatment with the R-CHOP chemotherapy regimen, the patient's chest tightness improved, and he was discharged. After 2 months, the patient succumbed to death owing to sudden ventricular tachycardia, ventricular fibrillation, and decreased blood pressure despite rescue efforts. Transthoracic echocardiography is inevitable for the early diagnosis of DLBCL, as it can narrow the differential and guide further investigations and interventions, thereby improving the survival of these patients.

Analysis of early response to chemotherapy for non-Hodgkin's lymphoma by quantitative contrast-enhanced ultrasound: A prospective case-control crossectional study.

OBJECTIVE: To investigate the value of quantitative contrast-enhanced ultrasonography (CEUS) in assessing and predicting early therapy response of non-Hodgkin's lymphoma (NHL). METHODS: Fifty-six cases of NHL were studied using CEUS before and after three cycles of R-CHOP / CHOP. Quantitative parameters such as arrival time (ATM), time to peak (TTP), △T = TTP-ATM, area under the gamma curve (Area), curve gradient (Grad), wash-out time (WT), base intensity (BI), peak intensity (PI) and ΔI = PI-BI were compared between the lymphoma and normal lymph nodes before and at mid-treatment, respectively. Changes in quantitative CEUS parameters were also compared between complete response (CR) and incomplete response(non-CR) groups. Besides, the correlation analysis was performed between pretreatment PI and changes in quantitative parameters. RESULTS: After three cycles of R-CHOP/CHOP, S/L (P < 0.001), PI (P = 0.002), ΔI (P < 0.001), Grad (P < 0.001), and Area (P < 0.001) of NHL were significantly decreased. The CR group and non-CR group only differed in ATM before treatment. In contrast, there was no statistical difference in any of the parameters between the two groups at mid-treatment. Finally, a significant correlation was observed between pre-treatment PI and PI△% (r = 0.736, P < 0.001). CONCLUSIONS: CEUS is promising for the assessment of response of NHL to R-CHOP/CHOP. Intra-lesion perfusion changes take precedence over morphological changes suggesting treatment efficacy. Pre-treatment ATM values may help to suggest efficacy outcomes and pre-treatment PI values may be a valid predictor of lymphoma perfusion response.

Indocyanine green-mediated fabrication of urchin-like hydroxyethyl starch nanocarriers for enhanced drug tumor EPR and deep penetration effects.

Effective EPR and tumor penetration are bottlenecks in current nanomedicine therapy. Comosol software was utilized to analyze the motion process of nanoparticles (NPs) with different shapes, from blood vessels to tumor tissue, to address this. By calculation, urchin-like NPs experienced higher drag forces than spherical NPs, facilitating their EPR and tumor penetration effects. Thus, urchin-like indocyanine green-loaded hydroxyethyl starch-cholesterol (ICG@HES-CH) NPs were prepared by leveraging the instability of ICG responding to near-infrared light (NIR). Upon NIR exposure, ICG degraded and partly disintegrated ICG@HES-CH NPs, and its morphology transformed from spherical to urchin-like. Vincristine (VC), as a model drug, was loaded in urchin-like ICG@HES-CH NPs for the treatment of lymphoma. A20 lymphoma cells and 3T3-A20 tumor organoids were employed to investigate the influence of shape on NPs' cellular uptake, penetration pathway, and cytotoxicity. It demonstrated that urchin-like ICG@HES-CH NPs mainly transport across the extracellular matrix through intercellular pathways, easily reaching the deep tumor sites and achieving higher cytotoxicity. In vivo VC distribution and anti-tumor results indicated that urchin-like NPs increased VC EPR and penetration ability, lowering VC neurotoxicity and superior anti-tumor effect. Therefore, urchin-like ICG@HES-CH NPs have great translational potential to be used as chemotherapeutic nanocarriers in anticancer therapy.