Overall Survival and Prognostic Factors in Metastatic Triple-Negative Breast Cancer: A National Cancer Database Analysis.

BACKGROUND: Metastatic triple-negative breast cancer (TNBC) is aggressive with poor median overall survival (OS) ranging from 8 to 13 months. There exists considerable heterogeneity in survival at the individual patient level. To better understand the survival heterogeneity and improve risk stratification, our study aims to identify the factors influencing survival, utilizing a large patient sample from the National Cancer Database (NCDB). METHODS: Women diagnosed with metastatic TNBC from 2010 to 2020 in the NCDB were included. Demographic, clinicopathological, and treatment data and overall survival (OS) outcomes were collected. Kaplan-Meier curves were used to estimate OS. The log-rank test was used to identify OS differences between groups for each variable in the univariate analysis. For the multivariate analysis, the Cox proportional hazard model with backward elimination was used to identify factors affecting OS. Adjusted hazard ratios and 95% confidence intervals are presented. RESULTS: In this sample, 2273 women had a median overall survival of 13.6 months. Factors associated with statistically significantly worse OS included older age, higher comorbidity scores, specific histologies, higher number of metastatic sites, presence of liver or other site metastases in those with only one metastatic site (excluding brain metastases), presence of cranial and extra-cranial metastases, lack of chemotherapy, lack of immunotherapy, lack of surgery to distant sites, lack of radiation to distant sites, and receipt of palliative treatment to alleviate symptoms. In the multivariate analysis, comorbidity score, histology, number of metastatic sites, immunotherapy, and chemotherapy had a statistically significant effect on OS. CONCLUSIONS: Through NCDB analysis, we have identified prognostic factors for metastatic TNBC. These findings will help individualize prognostication at diagnosis, optimize treatment strategies, and facilitate patient stratification in future clinical trials.

Diagnosis of Metastatic Non-Small Cell Lung Cancer during Hospitalization: Missed Opportunity for Optimal Supportive Care?

PURPOSE: The usual workup for patients newly diagnosed with advanced non-small cell lung cancer (NSCLC) occurs in the ambulatory setting. A subset of patients present with acute care needs and receive the diagnosis while hospitalized. Palliative therapies are typically initiated when patients are outpatients, even when diagnoses are made when they are inpatients. Lengthy admission, rehabilitation needs after discharge, and readmissions are possible barriers to timely and adequate outpatient follow-up. The outcomes for these patients diagnosed in the hospital are not well characterized. We hypothesized that patients have been ill-served by current treatment patterns, as reflected by low rates of cancer-directed treatment and poor survival. PATIENTS AND METHODS: We performed a retrospective study of new inpatient diagnoses of metastatic NSCLC at our institution between 1 January 2012 and 1 January 2022. The primary outcome was the proportion of patients ultimately receiving cancer-directed therapy. Other outcomes included time to treatment, use of targeted therapy, palliative care/hospice utilization, and overall survival (OS). RESULTS: Seventy-three patients were included, with a median age of 57 years. Twenty-seven patients (37%) ultimately received systemic therapy with a median time from diagnosis to treatment of 37.5 days. Overall, 5.4% patients died while admitted, 6.8% were discharged to a hospice, 21.9% were discharged to a facility, and 61.6% were discharged home. Only 20 patients (27%) received palliative care consultation. The median OS for our entire population was 2.3 months, with estimated 6-month and 1-year OS rates of 32% and 22%, respectively. CONCLUSION: Patients with new inpatient diagnoses of metastatic NSCLC have extremely poor outcomes. Current management strategies resulted in few patients starting systemic therapy, yet most of the patients did not receive palliative care or hospice involvement. These findings demonstrate that there is a high unmet need to optimally support and palliate these patients.

A Review of the Current FDA-Approved Antibody-Drug Conjugates: Landmark Clinical Trials and Indications.

Despite considerable treatment progress, cancer remains among the leading causes of death worldwide. Antibody-drug conjugates (ADCs), a rapidly growing class of systemic therapy, show promise by combining the properties of conventional chemotherapy and targeted therapy. Antibody-drug conjugates have been shown to be more efficacious than traditional chemotherapy. To date, there are 13 ADCs approved by the United States Food and Drug Administration (FDA) for treating various hematological and solid organ cancers. There are several new promising ADCs that are being developed and are in clinical trials. This review provides an overview of the current FDA-approved ADCs, the landmark clinical trials that led to their approval, the common toxicities seen in the landmark trials, the challenges associated with ADCs, and the potential future directions.

Unusual Clinical Presentation of Clear Cell Sarcoma in a Young Woman.

Clear cell sarcoma (CCS) is a rare but aggressive malignancy that typically occurs in young adults and is characterized by soft tissue tumors of the extremities. CCS can be difficult to distinguish from metastatic melanoma based solely on histology and immunohistochemistry (IHC) because of the significant overlap between them. However, it is imperative to get an accurate clinical diagnosis, as it informs disease staging and treatment options for patient care. Present in approximately 75% of CCS cases, the EWSR1 gene rearrangement detected by fluorescence in situ hybridization (FISH) can help with establishing a diagnosis; the underlying reciprocal translocation has never been reported in cutaneous melanoma. We reviewed a case of a young woman who presented with a confusing picture of widespread lymphadenopathy, cutaneous metastases, and electrolyte derangements and was subsequently diagnosed with metastatic CCS.This case suggests possible value in performing molecular testing when a clinical picture does not correspond with what is expected for melanoma. It also raises the question of whether CCS cases may be underreported. This case highlights an uncommon presentation that may not be recognized as a manifestation of CCS by an oncologist who is not a sarcoma specialist. It is unclear how COVID-19 vaccination contributed to her clinical presentation, and it is also unclear whether an early diagnosis would have changed her clinical outcome.

Cerebral Venous Sinus Thrombosis due to Thrombosis with Thrombocytopenia Syndrome Following Ad26.COV2.S: A First Real-World Case Report of a Male Subject.

Thrombosis with Thrombocytopenia Syndrome (TTS) or Vaccine-induced Immune Thrombotic Thrombocytopenia (VITT) had been reported in patients receiving the Ad26.COV2.S vaccination (Johnson & Johnson [J&J]/Janssen) vaccine. They frequently presented with cerebral venous sinus thrombosis (CVST), but venous or arterial thrombosis at other locations can be present. The majority of those affected are younger adult females. Therefore, after a brief pause from April 13-23, 2021, the Centers for Disease Control and Prevention (CDC) and the U.S. Food and Drug Administration (FDA) recommended caution in using this vaccine in females under 50 years. Based on the reported 28 cases of TTS after this vaccination (data till April 21, 2021) by CDC, 22 were females (78%), and 6 were male. None of those males had CVST but had thrombosis at other locations. We report the first case of a young male with TTS and CVST following Ad26.COV2.S vaccine presented with severe headache and diagnosed with acute right transverse and sigmoid cerebral venous sinus thrombosis, multiple right-sided pulmonary emboli, and right hepatic vein thrombosis. He was treated with parenteral anticoagulation with argatroban and intravenous immune globulin with the improvement of his symptoms. A heparin-induced thrombocytopenia with thrombosis (HITT) like syndrome caused by the genesis of a platelet-activating autoantibody against platelet factor 4 (PF4) triggered by adenoviral vector-based COVID-19 vaccinations is understood to be the underlying pathophysiology. TTS with CVST should be considered when patients present with headaches, stroke-like neurological symptoms, thrombocytopenia, and symptom onset 6-15 days after Ad26.COV2.S vaccination.

Biomarkers for Treatment Response in Advanced Prostate Cancer.

Multiple treatment options with different mechanisms of action are currently available for the management of metastatic prostate cancer. However, the optimal use of these therapies-specifically, the sequencing of therapies-is not well defined. In order to obtain the best clinical outcomes, patients need to be treated with the therapies that are most likely to provide benefit and avoid toxic therapies that are unlikely to be effective. Ideally, predictive biomarkers that allow for the selection of the therapies most likely to be of benefit would be employed for each treatment decision. In practice, biomarkers including tumor molecular sequencing, circulating tumor DNA, circulating tumor cell enumeration and androgen receptor characteristics, and tumor cell surface expression (PSMA), all may have a role in therapy selection. In this review, we define the established prognostic and predictive biomarkers for therapy in advanced prostate cancer and explore emerging biomarkers.

Non-secretory multiple myeloma with unusual TFG-ALK fusion showed dramatic response to ALK inhibition.

Non-secretory multiple myeloma (NSMM) constitutes a distinct entity of multiple myeloma characterized by the absence of detectable monoclonal protein and rarely an absence of free light chains in the serum and urine. Given its rarity, the genomic landscape, clinical course, and prognosis of NSSM are not well characterized. Here, we report a case of a patient with relapsed and refractory NSMM with brain metastasis harboring a TFG-ALK fusion showing a dramatic and durable (over two years) response to commercially available anaplastic lymphoma kinase (ALK) inhibitors. The case emphasizes the beneficial role of molecular profiling in this target-poor disease.

Maxillary Osteomyelitis with an Incidental Diagnosis of Maxillary Diffuse Large B-Cell Lymphoma: A Case Report.

Raoultella planticola osteomyelitis is rarely reported in the literature. The most likely source in our case is the oral microbiome secondary to the tooth extraction. Herein we present a case of Raoultella planticola osteomyelitis of the jaw that leads to the diagnosis of diffuse large B-cell lymphoma (DLBCL) of the jaw. A 75-year-old male with no significant medical history, presented to the emergency department with right upper jaw pain after he had a tooth extraction a week before his presentation. Computed tomography (CT) scan of the face showed concerns of right maxillary osteomyelitis with soft tissue swelling and prominent cervical lymph nodes. He underwent a bone biopsy of the maxilla and was started on intravenous ampicillin-sulbactam. His bone culture grew pan-sensitive Raoultella planticola. in addition to that, his bone biopsy revealed diffuse large B-cell lymphoma of the jaw. The patient underwent staging imaging, and he was found to have metastasis to the liver. He was started on chemotherapy and had a good response. In conclusion, Raoultella planticola osteomyelitis is extremely rare. The diagnosis of maxillary DLBCL can be a challenge. Fortunately, our patient had an infection at the same site that led to the diagnosis of DLBCL.

A Case of Rituximab-Induced Acute Thrombocytopenia in a Patient with Splenic Marginal Zone Lymphoma and Chronic Hepatitis C Virus Infection.

BACKGROUND Rituximab is a chimeric monoclonal antibody to CD20 that is used to treat vasculitis, B-cell lymphoproliferative disorders, and B-cell non-Hodgkin lymphoma (NHL). A report is presented of a case of rituximab-induced acute thrombocytopenia (RIAT) in a woman with splenic marginal zone lymphoma (SMZL) and chronic hepatitis C virus (HCV) infection. CASE REPORT A 46-year-old woman with SMZL complicated by chronic HCV infection presented with worsening B symptoms of fever, night sweats, and loss of weight. The patient had a history of recreational drug use. Intravenous treatment with rituximab (dose, 375 mg/m²) commenced with close monitoring in hospital. On the following day, the complete blood count (CBC) showed that her platelet count had dropped from her admission level of 167,000/µl to 7,000/µl, with no change in hemoglobin or white blood cell (WBC) levels. A diagnosis of RIAT was made. The patient was managed conservatively and monitored for the development of potential clinical complications. CONCLUSIONS RIAT is a rare complication of treatment with rituximab and may be poorly recognized. Further studies are needed to determine the incidence and causes of thrombocytopenia in patients treated with rituximab and the possible association with chronic viral infections, including HCV.

Isolated Renal Metastasis from Primary Lung Squamous Cell Carcinoma with Synchronous Small Cell Lung Cancer.

Synchronous multiple primary lung cancer is a unique type of lung carcinomas that are diagnosed with more than two different pathological types in the same or different lung lobes. Isolated metastasis to the kidney is considered rare. Herein, we present a case of a 58-year-old male with a history of chronic obstructive pulmonary disease (COPD) and 40 pack-year of cigarette smoking, who was diagnosed with synchronous small cell lung cancer (SCLC) and squamous cell carcinoma (SCC) with isolated metastasis to the kidney. Isolated kidney metastasis from lung cancer is an infrequent finding; it should be considered when the patient is diagnosed with lung cancer. In the absence of disseminated disease and contraindications, nephrectomy is an option for treatment with chemotherapy or as a palliative measure if the patient is symptomatic.

Hepatocellular Carcinoma with Tumor Thrombus Extending from the Portal Vein to the Right Atrium.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Tumor thrombus formation in advanced HCC stages is common and usually involves the hepatic or portal veins. The formation of tumor thrombus is considered a poor prognostic factor. Herein, we report a rare case wherein the thrombus extended to the inferior vena cava (IVC) reaching the right atrium without affecting the hemodynamic status. This is a 59-year-old male who presented with melena. He was found to have grade 3 esophageal varices with findings suggestive of recent bleeding associated with a large amount of blood in the gastric body that required banding. Computed tomography (CT) of the abdomen and pelvis showed multiple liver masses with an intraluminal IVC mass extending from the hepatic vein into the right atrium. A CT scan of the chest confirmed the presence of a tumor thrombus in the IVC extending to the right atrium. The patient declines surgical intervention and he was discharged. Unfortunately, he passed after a short period of time. In conclusion, tumor thrombus formation is common in HCC. However, expansion of the thrombus to IVC and right atrium is rare and indicates poor prognosis.

A Unique Case of Cryptococcus and Histoplasmosis Co-infection in an HIV-negative Male on Chronic Steroid Therapy.

Histoplasmosis and cryptococcosis are systemic fungal diseases frequently encountered in immunocompromised hosts, particularly in patients with HIV/AIDS with low CD4 counts. However, co-infection with histoplasmosis and cryptococcosis is an uncommon clinical scenario, hence carrying the risk of under diagnosis by medical professionals. For instance, when one infection is identified, most health professionals will have a low suspicion for an additional co-infection. Here, we report the case of a 71-year-old gentleman with a new diagnosis of myasthenia gravis (MG) requiring recent steroid therapy who presented with recurrent respiratory symptoms despite treatment for community acquired pneumonia. Bronchoscopy and bronchoalveolar lavage (BAL) were performed; BAL samples revealed presence of Cryptococcus neoformans and histoplasma antigen (Ag). Serum cryptococcal Ag and urine histoplasma Ag returned positive as well. The patient then required inpatient treatment with amphotericin B, with eventual transition to oral fluconazole at discharge. Pulmonology and Infectious disease consults assisted in appropriate diagnosis and management of this rare presentation. Given the high prevalence of immunocompromised states in a myriad of medical co-morbidities, it is important to highlight this case to create awareness regarding possibility of concomitant systemic fungal diseases.

Comparative proteogenomic characterization of glioblastoma.

Aim: Glioblastoma multiforme (GBM) carries a dismal prognosis. Integrated proteogenomic analysis was performed to understand GBM pathophysiology. Patients & methods: 17 patient samples were analyzed for driver mutations, oncogenes, major pathway alterations and molecular changes at gene and protein level. Clinical, treatment and survival data were collected. Results: Significantly mutated genes included TP53, EGFR, PIK3R1, PTEN, NF1, RET and STAG2. EGFR mutations noted included EGFRvIII-expression, EGFR-L816Q missense mutation-exon 21 and EGFR fusion (FGFR3-TACC3). TP53 mutations were noticed in COSMIC hot-spot driver gene and accompany IDH1 and ATRX mutations suggesting low- to high-grade glioma transformation. Proteomics showed higher (53%) EGFR expression than genomic expression (23%). MGMT methylation was present in two-thirds of cases. Conclusion: This study identifies a distinct biological process that may characterize each GBM differently. Proteogenomic data identify potential therapeutic targets of GBM.

Acute Appendicitis and Small Bowel Obstruction Secondary to Metastatic Breast Cancer.

Breast cancer is the most common cancer in women; it is well-known to metastasize to lymph nodes, lungs, liver, brain, and bones. However, luminal gastrointestinal metastasis is rare, especially to the appendix. Herein, we report a case where cancer metastasized to the ileum and appendix, causing acute appendicitis and small bowel obstruction. This is a 44-year-old female with a history of stage IV metastatic breast cancer to bones, lungs, and ovaries, presented with acute abdominal pain for one day. Her abdomen was soft, distended with generalized tenderness. Computed tomography (CT) of the abdomen and pelvis showed a partial small bowel obstruction and swollen appendix. After her symptoms worsened on conservative treatment, she was taken to the operating room where she was found to have a markedly dilated ileum with signs of acute appendicitis, so she underwent ileocecectomy, appendectomy, and lysis of adhesions. Pathology showed metastatic breast cancer in the appendix with findings consistent with acute appendicitis. She tolerated surgery well without complications. In conclusion, small intestinal and appendiceal metastases of breast cancer are very rare though they should be considered in the differential diagnosis in cancer patients presenting with acute abdominal pain.

A Rare Case of Spontaneous Isolated Dissection of the Superior Mesenteric Artery.

Isolated spontaneous dissection of the superior mesenteric artery (SMA) is a rare entity that is increasingly becoming recognized due to an improvement in imaging techniques. The pathogenesis of a spontaneous SMA dissection has yet to be fully elucidated. Here, we present the case of isolated SMA dissection in a 65-year-old female who was seen in the emergency room with acute substernal chest and left upper quadrant abdominal pain. She was managed for atrial fibrillation with a rapid ventricular response. She underwent computed tomography (CT) angiogram of the chest, abdomen, and pelvis, which revealed focal dissection involving SMA measuring 2.7 cm in width. Vascular surgery recommended conservative management with low-dose daily aspirin and the optimization of blood pressure control. She subsequently was seen as an outpatient with complete resolution of abdominal pain. Given the low incidence rate, vascular surgery evaluation may be required to determine the best course of management. Treatment needs to be individualized for each patient. Since abdominal pain is a common complaint for which patients are seen in each clinical setting, it is important to highlight this case to create awareness regarding the possibility of isolated SMA dissection as one of the underlying etiologies.

Metformin-associated Lactic Acidosis: An Unexpected Scenario.

According to the National Diabetes Statistics Report (2017) by Centers for Disease Control and Prevention (CDC), 9.4% of the US population, approximately 30.3 million people had diabetes while 84.1 million had pre-diabetes as of 2015. In addition to lifestyle changes, the American Diabetes Association recommends metformin as the first-line treatment for type 2 diabetes. Hence, not surprisingly, metformin is a commonly prescribed medication by most healthcare providers in all clinical settings. As a result, it remains essential that all medical professionals be aware of any adverse effects as a result of metformin therapy, no matter how uncommon. We present the case of a 42-year-old lady with type 2 diabetes mellitus who required initial admission to intensive care unit (ICU) after presenting with unilateral back and lower abdominal pain with dysuria and was noted to have an acute kidney injury with a creatinine of 7.45 mg/dL and severe metabolic acidosis with a pH of 6.7 and an anion gap more than 50 mmol/L. Lactic acid was elevated at 24.2 mmol/L. Serum metformin levels were high at 14 mcg/mL (therapeutic range: 1-2 mcg/mL). She required emergent dialysis but subsequently, renal functions recovered. Risk of metformin-associated lactic acidosis (MALA) is reported to be an estimated 6.3 per 100,000 patient-years. Commonly encountered clinical scenarios such as hypoxemia, sepsis, alcohol abuse, renal injury, and shock can precipitate MALA. Early recognition allows timely initiation of appropriate therapy and reduces associated morbidity.

A Rare Case of an Infectious Pseudoaneurysm due to Aspergillus flavus in the Setting of Renal Transplant.

Renal transplant as a treatment option for end-stage renal disease (ESRD) is becoming increasingly prevalent. As with any other surgical intervention, complications may occur, including vascular ones. Pseudoaneurysms are particularly rare, with mycotic aneurysms reported in less than 1% of patients after renal transplant. Here, we present a case of an infected pseudoaneurysm involving the renal artery anastomosis, resulting in the explantation of the transplanted kidney. A 77-year-old man underwent deceased donor renal transplant for ESRD in the setting of diabetes and hypertension. He presented with acute kidney injury; a renal biopsy revealed mild active cellular rejection, treated with high-dose steroids. As renal function continued to deteriorate, a repeat renal biopsy was performed. During ultrasound-guided biopsy of the transplanted kidney, a possible aneurysm proximal to the anastomosis of the renal artery to the right external iliac artery was seen. A pelvic arteriogram showed a large 3 cm x 3.4 cm x 4 cm pseudoaneurysm arising directly off the right external iliac artery with the renal transplant artery filling from the distal side of this aneurysm. The patient was taken to the operation room for a re-exploration of his transplanted kidney and revision of the arterial anastomosis. Intraoperatively, necrotic tissue and purulence within the pseudo-aneurysm were noted with failure to salvage blood supply to the transplanted kidney; both the infected pseudo-aneurysm and renal transplant were resected. A portion of the aneurysm was sent to microbiology for culture; fungal cultures grew Aspergillus flavus. He was treated with isavuconazonium and improved clinically, though he subsequently expired following a sudden cardiac arrest. Given its rarity, most medical professionals will be unfamiliar with this unusual complication in renal transplant patients. Our case highlights the importance of pursuing imaging modalities to help identify vascular complications and discusses how to proceed after diagnosis is made. The importance of knowing this process is paramount in improving future patient outcomes.

Concurrent Cardiac Tamponade and Superior Vena Cava Syndrome: A Concerning Situation.

Diffuse large B-cell lymphoma (DLBCL) is the most commonly diagnosed lymphoma; as per the Surveillance, Epidemiology, and End Results (SEER) database 2006-2015, incidence of DLBCL is 7.0/100,000 per year. Superior vena cava (SVC) syndrome and cardiac tamponade are life-threatening oncological emergencies with an overlap in clinical manifestations. While SVC syndrome may commonly be seen with mediastinal masses, literature search shows only one prior case of cardiac tamponade resulting from DLBCL. Here, we present a case of a patient with a concurrent diagnosis of DLBCL and non-small cell carcinoma of the lung (NSCLC), presenting with respiratory symptoms initially but subsequently worsening with hemodynamic compromise. He was found to have cardiac tamponade secondary to DLBCL and was treated appropriately for it but failed to improve clinically due to co-existing SVC syndrome that was not treated. The patient expired in the intensive care unit (ICU) within 24 hours of acute clinical deterioration. This case highlights that in absence of a clinical suspicion for both conditions, identification of one can lead to an overlooked diagnosis of the other. When associated with hemodynamic instability, urgent intervention is mandatory and failure to recognize and treat either of the two may result in grave outcome. This case attempts to alert medical personnel regarding two major oncological emergencies where an accurate diagnosis and urgent intervention can prevent mortality and morbidity.

Polycythemia in Patients With Hereditary Hemochromatosis: Real or Myth?

BACKGROUND: Hereditary hemochromatosis (HH) is an autosomal recessive disorder affecting iron metabolism, resulting in iron accumulation in tissue parenchymal cells. Missense mutations result in homozygosity or heterozygosity for substitutions in the HFE gene, with the most common being C282Y and H63D. METHODS: With an aim to evaluate an association between polycythemia and HH, retrospective chart review was performed for 152 patients with known HFE mutations. Parameters reviewed included individual HFE genotypes, gender distribution, hemoglobin (Hgb) and hematocrit (Hct) levels, median ferritin levels and whether or not phlebotomy was required. RESULTS: Of 152 patients, 96 (63.2%) were men and 56 (36.8%) were women. Median Hgb and Hct were noted to be higher in men compared to women irrespective of HFE status. Mean age was 60.5 years (range 22 - 93 years). Regarding HFE mutation, 44 (28.9%) patients were C282Y/C282Y, 10 (6.6%) were H63D/H63D and 27 (17.8%) had one copy of each mutation. One patient in the study group was H63D/S65C. Median Hgb and Hct were noted to be 15.5 g/dL and 44.9% respectively in C282Y/C282Y subjects, 16.0 g/dL and 47% in H63D/H63D subjects, 15.8 g/dL and 46% in C282Y/H63D subjects, 16g/dL and 47% in those with single C282Y mutation and 16.6g/dL and 48% in those with single H63D mutation. A total of 67.1% subjects received phlebotomy. A total of 21.7% patients in this cohort were active tobacco users and only 8.6% had an established pulmonary diagnosis, including obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD). Elevated Hgb levels were noted despite absence of an established reason for secondary polycythemia. Anemia was not encountered despite concurrent medical conditions that would usually be associated with anemia, including gastrointestinal bleeding or end-stage renal disease (ESRD). CONCLUSIONS: Elevated Hgb and Hct levels in HH may be secondary to increased iron uptake by erythroid cell precursors in the bone marrow, in setting of increased availability of both transferrin-bound as well as non-transferrin-bound iron (NTBI). Additional studies need to be pursued to explore the association between HFE mutations and secondary polycythemia.

Pembrolizumab in newly diagnosed EBV-negative extranodal natural killer/T-cell lymphoma: A case report.

Extranodal natural killer (NK)/T-cell lymphoma (ENKTL) is a rare subtype of non-Hodgkin's lymphoma with a dismal prognosis. The pathogenesis almost invariably involves Epstein-Barr virus (EBV) infection, although EBV-negative ENKTLs are frequently reported in the western hemisphere. Treatment of these lymphomas consists of aggressive chemotherapy with dexamethasone, methotrexate, ifosfamide, L-asparaginase and etoposide (SMILE regimen). However, the SMILE regimen is poorly tolerated by elderly patients; therefore, treatment options are limited to palliative radiation and chemotherapy and/or hospice care. Recently, binding of programmed death (PD)-1 with its ligand (PD-L1) expressed on tumor cells was shown to downregulate effector T-cell function and may represent a potent mechanism of immune evasion in classical Hodgkin's lymphoma and aggressive B-cell lymphomas. Thus, targeting PD-L1/PD-1 to inhibit effector T-cell signaling may be a promising therapeutic strategy for these NK/T-cell lymphomas. We herein report the clinical efficacy and feasibility of the anti-PD-1 inhibitor pembrolizumab used concurrently with radiation therapy and as maintenance therapy in an elderly female patient. The findings demonstrated that pembrolizumab may be an effective and well-tolerated treatment for this type of lymphoma.