Comparative Analysis of Skip Metastasis in Pediatric Osteosarcoma: Clinical Features and Outcomes.

BACKGROUND: Skip metastasis (SM) is a synchronous regional bone metastasis. Using new imaging modalities, the detection of SM is easier and possibly more common. We reviewed patients with SM and compared their characteristics and outcomes to other patients with osteosarcoma treated at our center. METHODS: We reviewed retrospectively children (<18 years) with newly diagnosed osteosarcoma who presented from June 2006 to March 2022. Patients' characteristics, treatment modalities, and outcomes were analyzed. All cases were discussed in a multidisciplinary clinic that included 2 experienced radiologists. RESULTS: We identified 155 patients with osteosarcoma, among which 13 (8.3%) patients had SM detected by MRI. Patients with SM had a median age at diagnosis of 11.2 years (range 7 to 17). Three patients had lung metastasis at diagnosis. Bone scan was positive for the SM in 8 patients (62%). All patients underwent primary tumor resection after neoadjuvant chemotherapy (amputation in 5, limb salvage surgery in 8). Five had postchemotherapy necrosis ≥90% in primary tumor. Seven patients relapsed/progressed (1 local and 6 in the lung), all relapsed patients died of disease. Compared to the rest of the patients, those with SM had similar clinical features to patients without SM; outcomes were similar with no significant differences in event-free survival and overall survival ( P =0.7 and 0.3, respectively). CONCLUSION: In this study, we observed a percentage of patients with SM comparable to previous reports. Patients with SM exhibited clinical features akin to the rest of our patients. Thorough evaluation of imaging studies and multidisciplinary care, coupled with meticulous surgical planning, are crucial for achieving a cure, which remained unjeopardized in our patients with SM.

Presentation and management outcomes of Retinoblastoma among Syrian refugees in Jordan.

Purpose: The humanitarian crisis in Syria has had a profound impact on the entire region. In this study, we report the patterns of presentation and management outcomes of Syrian patients with Retinoblastoma (Rb) treated at a single tertiary cancer center in Jordan. Methods and Materials: This is a retrospective comparative study of Syrian refugees and Jordanian citizens who had Rb between 2011 and 2020. Collected data included patient demographics, presentation, tumor stage, treatment modalities, eye salvage rate, metastasis, and mortality. Results: Thirty Syrian refugees (16 (53%) had bilateral disease) and 124 Jordanian citizens (51(41%) had bilateral disease) were diagnosed with Rb during this period. The median age at diagnosis for refugees was 10 and 32 months for patients with bilateral and unilateral Rb consecutively, compared to 6 and 28 months for citizens. The median lag time between signs of disease and initiation of treatment was 3 months for refugees, compared to 1 month for citizens.Refugees were more likely to present with a more advanced stage (p=0.046). Out of 46 affected eyes in refugees; 32 (70%) eyes were group D or E, while out of 175 affected eyes among citizens; 98 (56%) eyes were group D or E. Therefore, refugees with Rb were more likely to mandate primary enucleation (48%) compared to citizens (25%) (p=0.003). However, out of 24 eyes among refugees who received conservative therapy, 15 (62%) eyes were successfully salvaged, while out of 131 affected eyes among citizens who received conservative therapy, 105 (80%) eyes were successfully salvaged (p=0.06). Two (7%) of the refugees and four (3.2%) of the citizens with Rb died from metastasis. Conclusion: Syrian refugees with Rb presented with more advanced disease due to delay in diagnosis and referral that increased the treatment burden by decreasing the chance for eye globe salvage. However, patients who received the timely intervention had a similar outcome to citizens with Rb; probably a reflection of the management of all patients at a single specialized center. We advocate for the timely referral of refugees with this rare life-threatening tumor to a specialized cancer center for the best possible outcome.

Programmed screening for retinoblastoma enhances early diagnosis and improves management outcome for high-risk children.

PURPOSE: To study the impact of a Retinoblastoma (Rb) screening program in the absence of genetic testing on the management and outcome of high-risk children. METHODS: This is a retrospective, clinical case series of 76 children from families involved in a Rb screening program as they had higher than normal risk as calculated by the conventional ways without genetic testing. Data included calculated risk, method of diagnosis, demographics, tumor features, treatment modalities, and management outcome. RESULTS: Out of the 76 children screened, 46 children were diagnosed with Rb (12 by screening and 34 had signs of Rb), the other 30 were free of disease. Patients diagnosed by screening were younger (mean; 2.4 months vs 15.8 months for the group with signs of Rb), had significantly earlier tumor stage at diagnosis (p = .0001), higher eye salvage rate (p = .0001), less need for systemic chemotherapy (p = .022), and better visual outcome (p = .0017) than the other group. None of the eyes were group D or E, enucleated or irradiated. Six (50%) patients were cured without chemotherapy, and the visual acuity was 0.5 or better in 55% of eyes. Of interest, 71% of tumors were diagnosed by the age of 6 months, 90% by the age of 1 year, and no new tumor appeared after the age of 2 years. CONCLUSION: Even in the absence of genetic testing, screening for children with high risk for Rb is effective in enhancing early diagnosis, improving visual outcome, and increasing eye salvage rate with limited exposure to treatment burden.

Intravitreal Melphalan Chemotherapy for Vitreous Seeds in Retinoblastoma.

OBJECTIVE: To evaluate our experience with intravitreal melphalan chemotherapy as a second-line regimen for RB patients with refractory or recurrent vitreous seeds. METHODS: A retrospective case series of 16 eyes from 16 patients with intraocular RB who received intravitreal melphalan chemotherapy using the antireflux injection technique. Data included demographics, stage at diagnosis, treatment modalities, side effects, eye salvage, and survival. RESULTS: The total number of injections was 64 (median, 3 injections per eye; range, 3-8), and the median age at time of injection was 22 months (range, 9-63 months). Nine (56%) patients were males, and 13 (81%) patients had bilateral RB. Complete response was seen in 13 (81%) eyes: in 9 (100%) eyes with focal vitreous seeds and in 4 (57%) eyes with diffuse vitreous seeds (P=0.062). At a median follow-up of 18 months (range, 6-48 months), the eye salvage rate was 81%, local retinal toxicity confined to the site of injection was seen in 2/3 of the eyes, 2 (12%) eyes had cataract, and none of the patients had orbital recurrence and distant metastasis or was dead. CONCLUSION: Intravitreal melphalan is a promising modality for treatment of vitreous seeds, and the dose of 20-30 µg of melphalan sounds to be safe and effective for refractory and recurrent vitreous seeds.µg of melphalan sounds to be safe and effective for refractory and recurrent vitreous seeds.

Tocilizumab in the treatment of rheumatoid arthritis and beyond.

Rheumatoid arthritis (RA) is a systemic inflammatory disease characterized by joint pain, swelling, stiffness, and progressive destruction of the small joints of the hands and feet. Treatment of RA has improved over the past decade. With multiple cytokines well-known now to play a role in the pathogenesis of RA, including tumor necrosis factor alpha, interleukin (IL)-1ß, and IL-6, many targeted biological treatments against these cytokines have emerged, changing the treatment of this disease. Tocilizumab (TCZ) is a recombinant humanized monoclonal antibody against the IL-6 receptor and has been approved in many countries, including the United States, for the treatment of moderate to severe RA in patients who have not adequately responded to one or more disease-modifying antirheumatic drugs (DMARDs) or cannot tolerate other approved drug classes for RA. The aim of this review is to discuss the role of IL-6 in RA, and to provide an overview of the mode of action, pharmacokinetics, and safety of TCZ. Furthermore, efficacy studies of TCZ as both monotherapy and combination therapy will be evaluated. There have been several important clinical trials evaluating the efficacy and safety of TCZ in RA patients; this review summarizes this data from 14 key trials with emphasis on Phase III trials. Review of these trials provides strong evidence that its use, both as monotherapy and in combination with methotrexate or other DMARDs, is an effective treatment in reducing the signs and symptoms of RA. TCZ showed tolerable safety but care is required for its use since there are some important safety concerns including elevated liver enzymes, elevated low-density lipoprotein, infections, and gastrointestinal perforations. Additionally, given the efficacy of TCZ in the treatment of RA, this review discusses how TCZ may be beneficial in the treatment of other autoimmune diseases, spinal disease, cardiovascular disease, organ transplantation, and malignancies where elevated levels of IL-6 may play a role in the pathogenesis of these diseases.