Non-small cell lung adenocarcinoma is the most common type of lung cancer but is often difficult to treat. New treatment options have emerged with the class of tyrosine kinase inhibitors, but it has ...been found that certain genetic mutations in the epidermal growth factor receptor (EGFR) receptor are not as sensitive to this treatment as others. We present a case of a 78-year-old man who was diagnosed with stage IV non-small cell lung adenocarcinoma with an EGFR exon 20 mutations treated with pemetrexed, nivolumab, and then docetaxel. He has lived over four years after his initial diagnosis. This case illustrates the importance of genetic testing of patients to evaluate for specific gene mutations. It highlights the fact that these patients with exon 20 mutations are not sensitive to tyrosine kinase inhibitor treatment and often respond better to chemotherapeutic agents.
Introduction
Immune agents including anti-programmed death receptor-1 and anti-cytotoxic T-lymphocyte antigen-4 have been associated with numerous immune-related complications. Pembrolizumab, a ...programmed death-1 inhibitor, has been associated with a number of immune-related adverse events such as pneumonitis, colitis, hepatitis, hypophysitis, hyperthyroidism, hypothyroidism, nephritis, and type 1 diabetes.
Case report
We present a rare case of an elderly male on pembrolizumab who suffered from four autoimmune toxicities including type 1 diabetes, pneumonitis, hypothyroidism, and polymyalgia rheumatica likely catalyzed by age-related immune activation.
Management and outcome: Immunotherapy was indefinitely stopped, and patient was started on steroids for the immune-related adverse events with complete resolution of polymyalgia rheumatica. Thyroid dysfunction resolved once he started thyroid replacement therapy. His diabetes is well controlled with insulin and is followed by endocrinology. He continues on prednisone for immune-mediated pneumonitis with a good response with regular monitoring via computed tomography scans and pulmonary consultation.
Discussion
Few cases wherein multiple toxicities are seen within one patient are reported. Aging appears to be a risk factor for immune-related adverse events. Aging is associated with an increased incidence of autoimmunity as programmed death-1 ligand expression represents an important mechanism that tissues use to protect from self-reactive effector T cells. Programmed death-1 blockade breaks this protective mechanism and enhances autoimmune diseases. Therefore, close monitoring and extreme vigilance is warranted while using immune checkpoint inhibitors including pembrolizumab as multiple toxicities can occur within a short span of infusion, especially in elderly individuals. Prompt discontinuation and the use of a multidisciplinary team are prudent to prevent further morbidity and mortality.
Primary bone lymphoma (PBL) is a subtype of lymphoma that exclusively affects skeletal tissue. Despite the relatively common involvement of skeletal structures as a manifestation of non-Hodgkin’s ...lymphoma (NHL), primary and exclusive involvement of the skeletal system is rare. The prevalence of PBL is estimated to be 3–7% amongst primary bone tumors and less than 2% amongst all lymphomas in adults. However, the definition of primary bone lymphoma has been inconsistent over time. Within our institution, we identified four cases of primary bone lymphoma based on diagnostic criteria formed from the general consensus of multiple organizations, including the World Health Organization (WHO) and International Extranodal Lymphoma Study Group (IELSG). Here, we discuss the distinct characteristics amongst these cases in addition to performing a systematic review of current literature regarding this lymphoproliferative entity.
Idiopathic granulomatous mastitis (IGM) is a chronic inflammatory disease of the breast, the etiology of which, has still not been elucidated. There have been several mechanisms proposed to explain ...the pathogenesis. Since the first description of the disease, it has proved itself to be a great diagnostic and therapeutic challenge. It is very often misdiagnosed as cancer, resulting in myriad workup by the physician and great distress to the patient. Clear guidelines as to the management have still not been described. Here, we describe two patients who presented with IGM and have been successfully treated. The first patient was treated with a combination of steroids and antibiotics. The second patient achieved remission of the disease with antibiotics alone. We also propose an algorithm for the management of IGM.
Tumor cells present antigen in the context of negative costimulation and immunosuppressive factors, resulting in the inhibition of T cell activation and immune tolerance. Dendritic cells (DCs) are a ...complex network of antigen presenting cells that play a critical role in maintaining the equilibrium between immune activation directed against pathogens and tolerance necessary to prevent damage mediated by autoreactive T cell clones. DCs uniquely induce primary immune responses through the constitutive and enhanced expression of positive costimulatory molecules and inflammatory cytokines necessary for T cell activation. In this context, the design of a cancer vaccine is based on the effective presentation tumor associated antigens to evoke an antigen specific activated T cell response, and importantly, immune memory. As such, DCs have played a major role in the development of cancer vaccine therapy as critical mediators of antigen presentation reversing a major component of tumor mediated immune suppression. DC based vaccines have involved the loading of individual tumor associated antigens or the use of whole tumor cells and have demonstrated potent induction of tumor specific immunity. The correlation of immune response with clinical outcome and integration of DC vaccines with other immune based therapy is currently being explored.
Background
For cancer patients, coronavirus disease 19 (COVID‐19) infection can lead to delays in cancer therapy both due to the infection itself and due to the need to minimize exposure to other ...patients and to staff. Clearance guidelines have been proposed, but expected time to clearance has not been established.
Methods
We identified all patients at a tertiary care hospital cancer center between 25 March 2020 and 6 June 2020 with a positive nasopharyngeal reverse transcriptase polymerase chain reaction (RT‐PCR) test for the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), a cancer‐related visit within 3 years, and at least one follow‐up assay. We determined the time to clearance using American Society of Clinical Oncology (ASCO), the UK National Institute for Health and Care Excellence (UK‐NICE), and Centers for Disease Control and Prevention (CDC) criteria. A matched non‐cancer comparison cohort was also identified.
Results
Thirty‐two cancer patients were identified. Nineteen were cleared by ASCO criteria, with estimated median time to clearance of 50 days. Fourteen patients resumed chemotherapy prior to clearance. Using UK‐NICE criteria, median time to clearance would have been 31 days, and using CDC criteria, it would have been 13 days. The matched non‐cancer cohort had similar clearance time, but with less frequent testing.
Conclusion
SARS‐CoV‐2 clearance times differ substantially depending on the criteria used and may be prolonged in cancer patients. This could lead to a delay in cancer care, increased use of clearance testing, and extension of infection control precautions.
In this single‐institution retrospective cohort study, the median time to SARS‐CoV‐2 clearance among cancer patients was 50 days using the ASCO/CDC criteria of two negative RT‐PCR assays >24 h apart. Using alternative criteria of one negative RT‐PCR assay (UK‐NICE) or CDC clinical criteria (10 days after first positive RT‐PCR and 3 days after last symptoms), median clearance times were 31 and 13 days, respectively.
Nearly all men with prostate cancer who are treated with androgen deprivation therapy develop disease progression. There is considerable evidence to suggest that CXCL 13 released by tumor cells leads ...to B-cell infiltration into the prostate cells. This B-cell infiltration has been postulated to play a role in development of disease progression following androgen-deprivation therapies. We present a case of a patient who achieved remission of metastatic castrate-resistant prostate cancer after receiving rituximab and bendamustine for the treatment of follicular lymphoma. The findings in this report suggest that further investigation is warranted for utilizing B-cell targeted therapy in delaying progression of castrate-resistant prostate cancer.
Meningiomas are primary CNS tumors that arise from the arachnoid layer of the meninges. Genomic sequencing has revealed that NF2 mutations are the most common genetic alteration seen in meningiomas. ...Meningiomas although usually low grade, can sometimes progress to high grade. A patient who had several recurrences of meningiomas since childhood presented with recurrent headaches. Imaging showed that he had another recurrence of a meningioma. He underwent surgery for resection of the meningioma and histopathology showed NF2 mutation. He was started on everolimus and bevacizumab with good effect. Studies have shown that NF-2 mutated meningiomas have a good response to everolimus and bevacizumab with increased progression-free survival time and progression-free survival time at 6 months.
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