The chemotherapy effect on embryonal rhabdomyosarcoma in a 2-year-old girl in a development country: A rare case

Rhabdomyosarcoma (RMS) is the third most common solid organ malignancy in children after Wilms tumor and neuroblastoma. It is a highly malignant tumor with local tissue invasion and lymphatic and hematogenous metastases. The main treatment for RMS is complete resection with a combination of chemotherapy and radiotherapy. Here, we present the case of a 2-year-old girl who came to the hospital with a complaint of noisy breathing (Stridor) for the past 2 weeks. Intraoral examination showed an oval mass at the base of the tongue that almost closed the airway, felt soft, and had a bump. A computed tomography scan of the neck was performed, and a solid lesion with clear irregular borders was found in the posterior lingua. Incisional biopsy was performed with histopathological results of embryonal RMS. Two weeks after the biopsy, chemotherapy was performed, and the evaluation after two chemotherapy sessions, the mass size was found to have decreased.

PD-L1 and Tumor Mutational Burden Are Not Predictive of Thrombosis in a Cohort of 1,221 Patients with Solid Organ Malignancies

Introduction: Malignancy is a well-known risk factor for thrombosis. While many clinical risk factors for cancer-associated thrombosis have been described, it remains unknown how certain tumor specific observations (such as programmed death ligand 1 expression (PD-L1) and tumor mutational burden (TMB)) correspond to thrombotic risk. To determine the relationship between PD-L1 and TMB quantification and thrombosis in patients with solid tumors, we evaluated a large cohort of clinical samples from an NCI designated cancer center, correlating tissue sample pathology with the development of venous or arterial thromboembolism. Methods: We performed a retrospective cohort study of patients between the ages of 18-89 who underwent histopathologic examination and next generation sequencing for a diagnosis of a solid organ malignancy at the Knight Cancer Institute between June 2019 and Feb 2021. Medical records were reviewed to document clinical and demographic information as well as for the development of thrombosis after cancer diagnosis. Multivariable logistic regression was performed to assess if PD-L1 expression and TMB are independent predictors of thrombosis. Subgroup analysis was then performed to evaluate whether this relationship differed by the organ of the primary malignancy. All analyses were conducted in R (R Core Team 2019). Results: We identified 1,221 patients with solid organ malignancies (mean age 62, 53.6% male). The most common malignancies in the cohort were lung cancer (13.8%), pancreatic cancer (12.3%) and colon cancer (12.3%). Thrombotic events occurred in 206 patients (16.8%) after diagnosis of their malignancy (100 deep vein thrombosis, 42 pulmonary embolism, 46 visceral vein thromboses, 6 superficial vein thromboses, and 11 arterial events). The mean time from initial biopsy to thrombosis was 224 days. TMB (mean 8.5 mutations/Mb) was evaluated in all patients in the cohort, while PD-L1 expression testing (mean 23.0%) was available for 255 patients. On multivariable logistic regression adjusting for age and patient sex, neither TMB (ORadj: 0.97, CI: 0.92-1.03) nor PD-L1 expression (ORadj 1.00, CI: 1.00-1.02) were significant predictors of thrombotic events. Subgroup analysis by primary malignancy type did not demonstrate any specific primary sites for which TMB or PD-L1 were predictive of thrombosis. Discussion: Our analysis found no predictive relationship between TMB and PD-L1 expression with thrombotic events in patients with solid organ malignancy. Further analysis is needed to determine if specific treatment protocols, such as the use of immunotherapy in patients with varying levels of PD-L1 and TMB, alter thrombosis risk. Disclosures Shatzel: Aronora Inc,: Consultancy.

Evaluation of Antibody Response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Immunizations in Patients with B-Cell Malignancies

Background Multiple vaccines have been granted emergency use authorization by the Food and Drug Administration against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Of the currently available vaccines, none have been systematically studied for efficacy or toxicity in patients with immunodeficiency or with immunosuppressed states, such as B cell malignancy. The purpose of the study was to evaluate the immune response to currently available vaccines against COVID-19 in patients with hematologic and solid organ malignancies. Methods This prospective study enrolled 53 patients; 12 with CLL, 10 with multiple myeloma (MM), 11 with non-Hodgkin's lymphoma (NHL) and 21 with a solid organ malignancy. Using a quantitative assay, IgG antibodies to SARS-CoV-2 Spike (S) protein, and nucleocapsid (N) protein by enzyme immunoassay were measured at baseline prior to vaccination and at 2 weeks after completion of vaccination. A fourfold increase in IgG was considered a positive response to vaccination. Through a predesigned survey, patients also self-reported side effects from each dose of vaccination. Results Seroconversion with vaccination was seen in 9/10 (90%) patients with MM, 5/12 (41.7%) patients with CLL, 6/11 (54.1%) patients with NHL, and 17/21 (80.9%) patients with solid organ malignancy. Per univariate analysis, CLL (OR 0.23, 95% CI 0.05-0.88; p= 0.033) was associated with lower odds of seroconversion while NHL (OR 0.48, 95% CI 0.12-1.8; p =0.291), MM (OR 5.33, 95% CI 0.61-46.08; p= 0.128) and solid organ malignancy (OR 2.90, 95% CI 0.79-10.64; p= 0.107) were not. Among patients with hematological malignancies, 5/13 (38.3%) patients treated with rituximab and 2/7 (28.5%) patients on immunoglobulin replacement (IgR) therapy responded to vaccination. This corresponded to reduced odds of seroconversion, 0.18 (95% CI 0.047-0.69; p = 0.013) in patients treated with rituximab and 0.14 (95% CI 0.024-0.826; p=0.030) in patients on IgR. Among patients with solid organ malignancies, treatment with chemotherapy (OR 2.05, 95% CI 0.48-8.61; p=0.320), immunotherapy (OR 4.57, 95% CI 0.52-39.9; p=0.169) or endocrine therapy (OR 1.0) did not lower odds of seroconversion with vaccination. Multivariate analysis revealed patients who received rituximab were less likely to respond to vaccination as compared to patients not previously treated with rituximab (OR 0.22, 95% CI 0.05-0.955; p=0.044). Injection site soreness was the most commonly reported side effect. The only severe side effect occurred in a patient with solid organ malignancy who developed Parsonage Turner syndrome. Conclusion Our study, to the best of our knowledge, is the first study comparing pre and post vaccination IgG titers against the SARS-CoV-2 S protein. Majority of patients with MM and solid organ malignancies, including those receiving active treatment, responded adequately to immunization. Patients with CLL appear less likely to respond to vaccination against COVID-19 as compared to patients with NHL, MM or solid organ malignancies. Previous treatment with rituximab was the most significant risk factor for suboptimal response to vaccination, regardless of underlying hematologic malignancy. These data highlight the importance of continuing risk mitigation strategies against COVID-19 in individuals with hematologic malignancy, particularly those with CLL or on treatment with rituximab. Future research is needed to investigate approaches to provide protective IgG against SARS-CoV-2 in this at-risk population. Figure 1 Figure 1. Disclosures Mustafa: Genentech: Speakers Bureau; GalaxoSmithKline: Speakers Bureau; CSL Behring: Speakers Bureau; Regeneron: Speakers Bureau; AstraZeneca: Speakers Bureau. Walsh: Janssen: Research Funding; Merck: Research Funding; Pfizer: Research Funding. Jamshed: Takeda: Honoraria.

A case report of breast cancer and membranous nephropathy with positive anti phospholipase A2 receptor antibodies

Background Testing for antibodies against podocyte phospholipase A2 receptor-1 (PLA2R) allows clinicians to accurately identify primary membranous nephropathy (MN). Secondary MN is associated with a spectrum of pathology including solid organ malignancy. PLA2R positivity in these patients occurs, although no case of PLA2R-positive MN has been definitively linked to cancer. Case presentation We describe a case of biopsy-proven PLA2R-positive MN, in whom invasive ductal carcinoma of the breast was discovered. The patient underwent surgery and adjuvant chemotherapy (including cyclophosphamide) and went into a sustained complete remission of her nephrotic syndrome. Discussion and conclusions Case series have reported PLA2R positivity in patients with solid organ malignancy associated MN. Our case is unusual as it is a breast malignancy, and the patients nephrotic syndrome and anti-PLA2Rab titres improved with treatment of the cancer. Here we report, to the best of our knowledge, the first case of oestrogen receptor-2 positive breast cancer associated with PLA2R positive MN in a young lady that was treated successfully by treating the malignancy.

Adenoid cystic carcinoma and chronic lymphocytic leukaemia: synchronous presentations in the lung

A 59-year-old male active smoker presented with a 6-month history of cough and breathlessness and was found to have a right upper lobe mass. Histology revealed this to be an adenoid cystic carcinoma (ACC) of the lung, while local lymph node dissection revealed a synchronous diagnosis of chronic lymphocytic leukaemia (CLL). The connection between CLL and solid organ malignancy is well documented, but the reporting of ACC in this context is novel. Mechanisms linking the two processes are revealed with the possibility of causality, and heightened vigilance for the development of primary lung tumours in CLL, and their management, is recommended.

Vaccination Rates and Adherence to Guidelines in Splenectomy Patients: An Observational Cross-sectional Study

Introduction: Splenectomy, whatever the reason, is an absolute indication for vaccination against encapsulated bacteria in order to prevent overwhelming post-splenectomy infections. This study aimed to determine compliance to immunization guidelines for splenectomy in General Surgery Clinics. Materials and Methods: In this observational cross-sectional study, we included patients who underwent splenectomy between April 2016 and April 2018, and recorded the patient data and vaccination status. Results: Splenectomy was performed in 65 patients, 40 (61.5%) were male and median age was 56 (19-90) years. Six of the operations were emergent, 21 were planned and 38 were urgent mostly due to solid organ malignancy. Only 14 (21.5%) patients were vaccinated with Haemophilus influenzae, meningococcal and pneumococcal vaccines according to the guidelines (≥2 weeks before the operation). 14 of the 21 patients (66.6%) who underwent planned splenectomy were vaccinated appropriately. Conclusion: Compliance with vaccination guidelines was low before splenectomy operations. There is a room for improvement particularly for patients undergoing elective splenectomy. A patient-centered team strategy is required to vaccinate patients at the stage of splenectomy planning.