A Review of the Current Approach and Treatment Landscape for Stage III Non-Small Cell Lung Cancer.

The therapeutic landscape of the management of stage III non-small cell lung cancer (NSCLC) has drastically evolved with the incorporation of immunotherapy and targeted therapy. Stage III NSCLC accounts for one-third of the cases and the treatment strategy of these locally advanced presentations are diverse, ranging from surgical to non-surgical options; with the incorporation of chemo-immunotherapy, radiation, and targeted therapies wherever applicable. The staging of this disease has also changed, and it is essential to have a strong multidisciplinary approach to do justice to patient care. In this article, we aim to navigate the nuanced approaches in the diagnosis and treatment of stage III NSCLC and expand on the evolution of the management of this disease.

Middle Meningeal Artery Embolization in Acute Leukemia Patients Presenting With Subdural Hematoma.

Intracerebral hemorrhage is a potentially fatal complication in patients with acute leukemia and contributing factors include thrombocytopenia and coagulopathy. Patients with acute leukemia may develop subdural hematoma (SDH) spontaneously or secondary to trauma. In patients with acute leukemia and SDH, the surgical evacuation of the hematoma causes significant morbidity and mortality. New approaches and strategies to reduce the need for surgical evacuation are needed to improve outcomes in patients with acute leukemia and intracerebral hemorrhage. We report two cases of acute SDH in patients with acute leukemia successfully treated with middle meningeal artery embolization, a minimally invasive interventional radiology technique, obviating the need for a surgical intervention. The first patient with acute promyelocytic leukemia (APL) presented with coagulopathy and developed an acute SDH after a fall. The second patient with acute myeloid leukemia presented with gum bleeding and also sustained an acute SDH after a fall. Both patients underwent middle meningeal artery embolization for treating their SDHs while actively receiving induction chemotherapy for acute leukemia. Both patients had resolution of their acute SDH and are in remission from their acute leukemia. Middle meningeal artery embolization is a very effective, and within the context of this setting, a novel, minimally invasive technique for management of SDH in acute leukemia patients, which can prevent the need for surgical interventions with its associated comorbidities and high risk of fatal outcomes in patients with acute leukemia and acute SDH.

Reduced-Intensity Anthracycline-Free Chemoimmunotherapy in Elderly Patients With Newly Diagnosed or Relapsed Diffuse Large B-Cell Lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL); it has a cure rate of approximately 50% with standard anthracycline-based chemoimmunotherapy. However, the clinical outcomes of elderly unfit/frail DLBCL patients remain suboptimal due to poor tolerance of anthracycline-containing regimens. Herein, we report a series of seven elderly unfit patients with DLBCL who were treated with a reduced-intensity anthracycline-free chemoimmunotherapy (rituximab, cyclophosphamide, vincristine, and prednisone) regimen combined with lenalidomide (R2-COP). Five patients received R2-COP as first-line therapy, and two patients were treated for relapsed DLBCL. Four patients with newly diagnosed DLBCL and two with relapsed disease achieved complete remission. The R2-COP regimen was well tolerated. Interim positron emission tomography (PET) scans in four patients after two to three cycles showed a complete metabolic response. At a median follow-up of 24 months, six patients remain in complete remission. R2-COP is an effective anthracycline-free regimen with encouraging clinical activity in elderly DLBCL patients who are unfit for standard anthracycline-containing regimens.

Screening for renal cell carcinoma in renal transplant recipients: a single-centre retrospective study.

OBJECTIVES: The primary objective of our study was to evaluate the effectiveness of renal cell carcinoma (RCC) screening in renal transplant (RT) recipients. DESIGN: Single-centre retrospective study. SETTING AND PARTICIPANTS: 1998 RT recipients who underwent RT at Memorial Hermann Hospital (MHH) Texas Medical Center (TMC) between 1 January 1999 and 31 December 2019 were included and we identified 16 patients (0.8%) with RCC. An additional four patients with RCC who underwent RT elsewhere but received follow-up at MHH TMC were also included. Subject races included white (20%), black (50%), Hispanic (20%) and Asian (10%). OUTCOME MEASURES: The RCC stage at diagnosis and outcomes were compared between patients who were screening versus those who were not. RESULTS: We identified a total of 20 patients with post-RT RCC, 75% of whom were men. The median age at diagnosis was 56 years. RCC histologies included clear cell (75%), papillary (20%) and chromophobe (5%). Patients with post-RT RCC who had screening (n=12) underwent ultrasound or CT annually or every 2 years, whereas eight patients had no screening. All 12 patients who had screening had early-stage disease at diagnosis (stage I (n=11) or stage II (n=1)) and were cured by nephrectomy (n=10) or cryotherapy (n=2). In patients who had no screening, three (37.5%) had stage IV RCC at diagnosis and all of whom died of metastatic disease. There was a statistically significant difference in RCC-specific survival in patients who were screened (p=0.01) compared with those who were not screened. CONCLUSION: All RT recipients who had RCC diagnosed based on screening had early-stage disease and there were no RCC-related deaths. Screening is an effective intervention in RT recipients to reduce RCC-related mortality.

Primary Diffuse Large B-Cell Lymphoma of the Bone.

Primary lymphoma of the bone (PLB) is a rare lymphoproliferative neoplasm that can present either as solitary or multiple bone lesions. We report four patients with PLB who were successfully treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by consolidative radiotherapy. All patients achieved a complete remission and had excellent long-term outcomes. PLB has a favorable response to combined modality treatment with chemoimmunotherapy and radiation. Long-term outcomes of PLB tend to be better than those of non-osseous diffuse large B-cell lymphoma.

Metastatic seminoma presenting as neck and axillary lymphadenopathy in an elderly man.

A man in his 60s presented with a gradual progressive right-sided neck mass. Initial core biopsy was inconclusive and he was treated with a short course of oral prednisone for presumed sarcoidosis. Two months later, the patient developed worsening dysphagia, hoarseness of voice, dyspnea, and weight loss. Physical examination revealed bilateral cervical and right axillary lymphadenopathy. A right axillary lymph node excisional biopsy was performed and immunohistochemistry was diffusely positive for OCT4, SALL4, CD117, PLAP, confirming the diagnosis of metastatic seminoma. He received three cycles of bleomycin, etoposide, and cisplatin; bleomycin was omitted for the fourth cycle due to concern for toxicity. Restaging scans after four cycles of chemotherapy showed a favorable response to therapy. Unfortunately, the patient died from bleomycin pulmonary toxicity. This case illustrates a rare and atypical presentation of metastatic seminoma in an elderly patient.

Therapy-related core binding factor acute myeloid leukemia.

Therapy-related acute myeloid leukemia (t-AML) usually stems from exposure of the bone marrow to cytotoxic chemotherapy and/or radiation therapy. t-AML is usually associated with poor overall survival, but occasionally t-AML can involve favorable-risk cytogenetics, including core binding factor AML (CBF-AML), which shows a recurrent chromosomal rearrangement with t(8;21) (q22;22) and 'inv(16) (p13.1;q22)/t(16;16)(p13.1;q22)', leading to 'RUNX1::RUNX1T1 and CBFB::MYH11' fusion genes, respectively. Therapy-related CBF-AML (t-CBF-AML) accounts for 5-15% of CBF-AML cases and tends to have better outcomes than t-AML with unfavorable cytogenetics. Although CBF-AML is sensitive to high-dose cytarabine, t-CBF-AML has worse overall survival than de novo CBF- AML. The objective of this review is to discuss the available data on the pathogenesis, mutations, and therapeutic options in patients with t-CBF-AML.

Acute myeloid leukemia (AML) is a type of cancer of the white blood cells. AML can rarely arise from prior treatment with radiation and/or chemotherapy and are referred to as therapy-related AML (t-AML). Usually t-AML is associated with poor outcomes; however, rarely you may see favorable outcomes with therapy related core binding factor AML. In this paper, we discuss about t-CBF-AML, which is a favorable subtype of t-AML.

Pembrolizumab-Induced Acral Vasculitis.

Immune checkpoint inhibitors (ICIs) have emerged as groundbreaking new therapies for a variety of solid tumors. ICIs stimulate the host immune system to attack cancer cells. However, this nonspecific immune activation can cause autoimmunity across multiple organ systems-this is referred to as an immune-related adverse event. Vasculitis secondary to ICI administration is an extremely rare event seen in <1% of cases. We identified 2 cases of pembrolizumab-induced acral vasculitis at our institution. The first patient, with stage IV adenocarcinoma of the lung, developed antinuclear antibody-positive vasculitis 4 months after initiation of treatment with pembrolizumab. The second patient had stage IV oropharyngeal cancer and presented with acral vasculitis 7 months after starting pembrolizumab. Unfortunately, both cases resulted in dry gangrene and poor outcomes. Here, we discuss the incidence, pathophysiology, clinical features, treatment, and prognosis of patients with ICI-induced vasculitis with the intention of raising awareness about this rare and potentially fatal immune-related adverse event. Early diagnosis and discontinuation of ICIs are critical for improving clinical outcomes in this situation.

B-Lymphoid Blast Phase-Chronic Myeloid Leukemia: Current Therapeutics.

Blast crisis (BC) is one of the most dreaded complications of chronic myeloid leukemia (CML). Fortunately, the incidence of BC has diminished markedly in the BCR-ABL tyrosine kinase inhibitor (TKI) era. The primary objective of initial treatment in BC is to achieve a second chronic phase (CP) and to proceed to an allogeneic stem cell transplantation (SCT) in eligible patients. The clinical outcome of patients with CML BC remains unsatisfactory, even with highly potent TKIs, as remissions are short lived and there is an unmet need for novel therapies. We provide a comprehensive summary reviewing the current management of Lymphoid BC.

Durable Remission in Hodgkin Lymphoma Treated With One Cycle of Bleomycin, Vinblastine, Dacarbazine and Two Doses of Nivolumab and Brentuximab Vedotin.

A 49-year-old woman with systemic lupus erythematosus, lupus nephritis and chronic congestive heart failure presenting with "bulky" cervical lymphadenopathy was diagnosed with classic Hodgkin lymphoma (HL) stage IIIB (positron emission tomography-computed tomography (PET-CT) scan and bone marrow biopsy). She received one cycle of bleomycin, dacarbazine, and vinblastine to debulk the tumor. Given her advanced heart failure, doxorubicin was not administered. After the first cycle of chemotherapy, she was switched to nivolumab plus brentuximab vedotin (BV) and received two doses 4 weeks apart, finishing in July 2019. A restaging PET-CT in June 2019 showed a complete remission (CR). After the second course of treatment, she was unable to tolerate more treatments and hence was placed on a surveillance program. She remains in CR after a follow-up of 3 years. This case highlights the role of a tailored treatment approach to optimize clinical outcomes in uniquely complex clinical circumstances. BV in combination with nivolumab is a reasonable alternative regimen in HL ineligible for cytotoxic chemotherapy.

Mixed-Phenotype Acute Leukemia: Clinical Diagnosis and Therapeutic Strategies.

Mixed-phenotype acute leukemia (MPAL) comprises a heterogenous group of leukemias that are genetically, immunophenotypically, and clinically, diverse. Given the rarity of the disease, the diagnosis and treatment of MPAL is extremely challenging. Recent collaborative efforts have made significant progress in understanding the complex genomic landscape of MPAL. Some retrospective studies support starting ALL-type induction followed by an allogeneic stem cell transplant(allo-sct) in the first complete remission; however, due to the inherent bias of retrospective data and small case series, a prospective validation of AML- and ALL-based regimen, and the incorporation of targeted therapies based on genetics and immunophenotype are warranted. The prognosis of adults and children with MPAL varies; this justifies modulating the intensity of therapy, including the use of allo-sct as a consolidation strategy.

Severe pulmonary toxicity related to carfilzomib use: a rare but serious side effect.

Carfilzomib is a selective proteosome inhibitor that is commonly used in the treatment of relapsed or refractory multiple myeloma. Carfilzomib has been commonly associated with respiratory side effects. It can rarely also cause fatal pulmonary toxicity. We present a case of a man in his 50s with plasma cell leukaemia who was initiated on treatment with carfilzomib and dexamethasone. He developed severe pneumonitis requiring oxygen via a high-flow nasal cannula. After an extensive workup, a temporal relationship between the carfilzomib use and exacerbation of the pulmonary symptoms was found. Carfilzomib was permanently discontinued, and the patient was started promptly on methyl prednisolone with complete resolution of his symptoms. Due to the associated risk of mortality if not detected early, we wish to highlight this rare but serious pulmonary toxicity associated with carfilzomib that was managed with high-dose glucocorticoids.

Glutamic acid decarboxylase (GAD) antibody-positive paraneoplastic stiff person syndrome associated with mediastinal liposarcoma.

Stiff person syndrome (SPS) is a rare, debilitating neurological illness characterised by rigidity and spasms of the axial muscles, causing severe restrictions to mobility. SPS can be classic, partial or paraneoplastic. We report a case of a young woman who presented with seizures and painful spasms of the thoracolumbar muscles who was subsequently diagnosed with SPS. Serological work revealed glutamic acid decarboxylase (GAD) antibodies and imaging showed a large mediastinal mass. The patient underwent surgical resection of the mediastinal mass and final pathology revealed well-differentiated mediastinal liposarcoma. She received five sessions of plasma exchange and her neurological symptoms gradually improved after surgery. This case highlights a rare case of GAD antibody-positive paraneoplastic SPS associated with mediastinal liposarcoma.

Durable remission with Bruton's tyrosine kinase inhibitor therapy in a patient with leptomeningeal disease secondary to relapsed mantle cell lymphoma.

Mantle cell lymphoma (MCL) is an incurable B cell non-Hodgkin's lymphoma with a variable clinical course. Central nervous system (CNS) involvement is a rare and dreaded complication in MCL. We report a case of leptomeningeal relapse of MCL that was successfully treated with a single-agent Bruton's tyrosine kinase inhibitor. A man in his 50s with MCL was treated with six cycles of bendamustine-rituximab, achieving a complete remission (CR) and was subsequently placed on rituximab maintenance for 2 years. Four years later, he was hospitalised with symptoms of organic brain syndrome. Brain MRI and cerebrospinal fluid analysis confirmed CNS relapse of MCL. He was treated with dexamethasone, ibrutinib 560 mg/day and intrathecal cytarabine with improvement in neurological symptoms, and a follow-up MRI showed CR. The patient was later switched to acalabrutinib due to intolerance to ibrutinib. The patient is tolerating this regimen well, remaining in CR 3 years later.

Warm autoimmune haemolytic anaemia seen in association with primary sclerosing cholangitis in the setting of Klebsiella pneumoniae bacteraemia.

Warm autoimmune haemolytic anaemia mediated by warm agglutinins is a rare and heterogeneous disease which can be idiopathic or secondary to an underlying disease. Primary sclerosing cholangitis is a chronic autoimmune cholangiopathy that is very rarely associated with haemolytic anaemia. Infections can also act as triggers for immune haemolytic anaemia. Here, we report a case of a woman in her 50s with a history of primary sclerosing cholangitis and a positive direct antiglobulin test with no evidence of haemolysis who developed overt warm autoimmune haemolytic anaemia in the setting of cholangitis and Klebsiella pneumoniae bacteraemia. She was treated conservatively with appropriate antibiotics and cautious red blood cell transfusion with complete resolution of haemolysis; immunosuppression was avoided given sepsis on presentation. This case highlights a rare association of warm immune haemolytic anaemia in the setting of K. pneumoniae bacteraemia and the role of a tailored treatment approach to treat this heterogeneous disease.

Synchronous Diagnosis of Squamous Cell Carcinoma of the Lung and Mixed Cellularity Hodgkin Lymphoma of the Nasopharynx.

Hodgkin lymphoma (HL) is a highly curable B cell lymphoproliferative neoplasm with a bimodal age distribution. Lung cancer is the leading cause of cancer-related deaths in both sexes. We present a rare case of synchronous squamous cell carcinoma (SCC) of the lung and mixed cellularity HL of the nasopharynx. A gentleman in his 70s presented with right-sided chest pain and shortness of breath. CT of the chest showed a peripheral lung mass, and a biopsy confirmed SCC of the lung. The patient underwent a positron emission tomography/computed tomography (PET/CT) for staging that revealed an 18F-fluorodeoxyglucose (FDG)-avid mass in the nasopharynx. Flexible nasal endoscopy and biopsy of the nasopharyngeal mass revealed mixed cellularity classical HL. The patient was started on chemoimmunotherapy for lung cancer. Unfortunately, two months after initiation of treatment, the patient died from COVID-19 pneumonia and multiorgan failure.

Synchronous Presentation of Autoimmune Hepatitis and Multiple Myeloma.

Autoimmune hepatitis (AIH) is a rare immune-mediated disease predominantly seen in women and triggered by various environmental factors. Rarely, AIH can be triggered by an underlying malignancy. We report a woman in her 60s who presented with markedly abnormal liver biochemical tests. Serology was positive for anti-smooth muscle antibodies and a liver biopsy confirmed AIH. During the hospital course, she developed sepsis and acute renal failure requiring dialysis support. Serum protein electrophoresis (SPEP) showed a monoclonal IgG kappa protein of 1.92 g/dL and a bone marrow biopsy revealed 7% clonal plasma cells. She had lytic lesions on skeletal survey confirming the diagnosis of a coexisting multiple myeloma (MM). Given her markedly abnormal liver chemistries, we decided to treat the AIH first and use the steroids (an important anti-myeloma therapy) as a bridge to the specific treatment of the MM once her clinical condition improved. She was treated with oral prednisone and azathioprine for AIH. One month later, a marked improvement in liver biochemical test results was noted and she was started on oral ixazomib, lenalidomide and dexamethasone. She received palliative radiotherapy to the lumbar spine (L2), left femur, and ischium lesions. This case highlights a rare co-occurrence of AIH and MM, the underlying mechanism of which is unknown.

A Nonpediatric Extraosseous Ewing Sarcoma of the Pancreas: Differential Diagnosis and Therapeutic Strategies.

Extraosseous Ewing's sarcoma is a rare and aggressive malignant tumor with a poor prognosis. The pancreas is an extremely uncommon primary site, with only 27 cases that have been published worldwide. We report a 26-year-old female who presented with 5 days of left upper quadrant pain, nausea, and vomiting. On examination, she was anicteric and had epigastric and left upper quadrant tenderness without guarding, rebound tenderness, or a palpable mass. She had slightly elevated serum aminotransferase and lipase levels. Abdominal computerized tomography revealed a multilobulated tumor arising from the body and tail of the pancreas. A biopsy confirmed a small round cell tumor, and immunohistochemistry was positive for CD99 in approximately 70% of the tumor cells. A fluorescence in situ hybridization (FISH) assay showed a 22q12 rearrangement. She was diagnosed with extraosseous Ewing sarcoma of the pancreas and underwent multiagent neoadjuvant chemotherapy followed by surgical resection, but subsequent imaging revealed evidence of systemic disease progression. She chose to go on hospice care and died a few weeks later.