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.

Current management of uncommon EGFR mutations in non-small cell lung cancer.

Epidermal growth factor receptor (EGFR) mutations are frequently implicated in non-small cell lung cancer (NSCLC). Though these typically involve exon 19 in-frame deletions or L858R mutations in exon 21, uncommon EGFR mutations comprise 10-15 % of all EGFR mutations. These most frequently include G719X mutations in exon 18, L861Q mutations in exon 21, S768I mutations in exon 20, and in-frame insertions and/or duplications in exon 20. It is crucial to understand these distinct variants and their specific responses to active treatment options to optimize care. In this review, we discuss these uncommon mutations in depth and dissect the current literature regarding their treatment outcomes and subsequent evidence-based management guidelines.

Durvalumab Outcomes in Stage III Non-small Cell Lung Cancer: A Single-institution Study.

BACKGROUND/AIM: The PACIFIC trial demonstrated improved survival in patients with unresectable stage III non-small cell lung cancer (NSCLC) treated with durvalumab following definitive concurrent chemoradiotherapy (CRT). This study sought to explore real-world outcomes with durvalumab consolidation therapy at our institution. PATIENTS AND METHODS: We retrospectively identified patients diagnosed with stage III NSCLC at our institution from January 2012 to January 2022. We created two cohorts: one who received durvalumab following definitive CRT and a historical one who did not. Primary outcomes of interest included median progression-free survival (PFS) and overall survival (OS). Additionally, we performed subgroup analysis on the durvalumab cohort to explore the associations between survival and time to durvalumab initiation, PD-L1 expression, and neutrophil-to-lymphocyte ratio (NLR). RESULTS: We identified 79 patients with locally advanced NSCLC who were not surgical candidates. Patients treated with durvalumab (n=44) had significantly improved survival compared to the historical cohort (n=35) including a median PFS of 17.4 months versus 8.0 months (p=0.0019) and a median OS of 37.0 months versus 17.0 months (log-rank p-value=0.07, Wilcoxon p-value=0.02). Within the durvalumab group, outcomes did not significantly differ between those who initiated therapy before or after 42 days of finishing CRT, between various PD-L1 expression levels, or between high or low NLR. CONCLUSION: Patients who received durvalumab as consolidation therapy following definitive CRT demonstrated significantly improved survival compared to a historical cohort who did not receive durvalumab. Furthermore, durvalumab appears to benefit patients regardless of time to initiation, PD-L1 expression, or NLR.

Novel Heterozygous Missense Variants in Diacylglycerol Kinase Epsilon and Complement Factor I: Potential Pathogenic Association With Atypical Hemolytic Uremic Syndrome.

Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy (TMA), which copresents with microangiopathic hemolytic anemia, thrombocytopenia, and kidney injury. While typical HUS is normally preceded by infections such as Shiga-toxin-producing Escherichia coli, atypical HUS (aHUS) has a genetic component that leads to dysregulation of the alternative complement pathway. We report a case of a 69-year-old female who developed aHUS after undergoing an elective knee surgery. Genetic testing revealed novel mutations affecting diacylglycerol kinase epsilon (DGKE) protein and complement factor I (CFI) that were not reported before as pathogenic. The patient was treated with eculizumab, leading to the complete resolution of TMA with no lasting organ damage.

Safety Profile of Mutant EGFR-TK Inhibitors in Advanced Non-Small Cell Lung Cancer: A Meta-analysis.

Background: Despite the use of platinum-based chemotherapy, lung cancer continues to be the leading cause of cancer-related death in the world. To overcome the rate of lung cancer-related death, scientists discovered advanced therapies, including mutant epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitors. Observations: We conducted a meta-analysis to determine the safety profile of mutant EGFR-TK inhibitors in the management of advanced non-small cell lung cancer (NSCLC). Included in this study are 9 phase 3 randomized controlled trials designed to study the safety profile of mutant EGFR-TK inhibitors in patients with advanced NSCLC. The study showed that mutant EGFR-TK inhibitors have an incidence of adverse effects that is less reported when compared with platinum-based chemotherapy. Conclusions: We recommend continuing using mutant EGFR-TK inhibitors in patients with advanced NSCLC especially in patients having mutant EGFR receptors. Adverse effects caused by mutant EGFR-TK inhibitors are significant but are usually tolerable and can be avoided by reducing the dosage of it with each cycle or by skipping or delaying the dose until patient is symptomatic.

Novel targeted therapies for advanced non-small lung cancer.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer accounting for almost 80%-85% of all lung cancer cases. Unfortunately, more than half of the patients will be diagnosed with advanced disease at the time of presentation, which makes their disease incurable. Historically, the 5 year overall survival for advanced NSCLC was 5%. However, there has been a significant increase in our understanding of the genetic basis of NSCLC, which has led to development of both immunotherapy and targeted therapy agents. This has improved the 5 year overall survival to become within the range of 15%-50% depending on certain mutations and biomarkers. Over the last decade the United States Food and Drug Administration (FDA) has approved almost 20 new targeted therapies and clinical trials are still undergoing to evaluate more novel agents. In this review, we will present recent updates on novel targeted therapies.

Surgical management of patients with von Willebrand disease: summary of 2 systematic reviews of the literature.

von Willebrand disease (VWD) is the most common inherited bleeding disorder. The management of patients with VWD who are undergoing surgeries is crucial to prevent bleeding complications. We systematically summarized the evidence on the management of patients with VWD who are undergoing major and minor surgeries to support the development of practice guidelines. We searched Medline and EMBASE from inception through October 2019 for randomized clinical trials (RCTs), comparative observational studies, and case series that compared maintaining factor VIII (FVIII) levels or von Willebrand factor (VWF) levels at >0.50 IU/mL for at least 3 days in patients undergoing major surgery, and those with options for perioperative management of patients undergoing minor surgery. Two authors screened and abstracted data and assessed the risk of bias. We conducted meta-analyses when possible. We evaluated the certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. We included 7 case series for major surgeries and 2 RCTs and 12 case series for minor surgeries. Very-low-certainty evidence showed that maintaining FVIII levels or VWF levels of >0.50 IU/mL for at least 3 consecutive days showed excellent hemostatic efficacy (as labeled by the researchers) after 74% to 100% of major surgeries. Low- to very-low-certainty evidence showed that prescribing tranexamic acid and increasing VWF levels to 0.50 IU/mL resulted in fewer bleeding complications after minor procedures compared with increasing VWF levels to 0.50 IU/mL alone. Given the low-quality evidence for guiding management decisions, a shared-decision model leading to individualized therapy plans will be important in patients with VWD who are undergoing surgical and invasive procedures.

Bleeding assessment tools in the diagnosis of VWD in adults and children: a systematic review and meta-analysis of test accuracy.

Von Willebrand disease (VWD) can be associated with significant morbidity. Patients with VWD can experience bruising, mucocutaneous bleeding, and bleeding after dental and surgical procedures. Early diagnosis and treatment are important to minimize the risk of these complications. Several bleeding assessment tools (BATs) have been used to quantify bleeding symptoms as a screening tool for VWD. We systematically reviewed diagnostic test accuracy results of BATs to screen patients for VWD. We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies, reference lists of relevant reviews, registered trials, and relevant conference proceedings. Two investigators screened and abstracted data. Risk of bias was assessed using the revised tool for the quality assessment of diagnostic accuracy studies and certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework. We pooled estimates of sensitivity and specificity. The review included 7 cohort studies that evaluated the use of BATs to screen adult and pediatric patients for VWD. The pooled estimates for sensitivity and specificity were 75% (95% confidence interval, 66-83) and 54% (29-77), respectively. Certainty of evidence varied from moderate to high. This systematic review provides accuracy estimates for validated BATs as a screening modality for VWD. A BAT is a useful initial screening test to determine who needs specific blood testing. The pretest probability of VWD (often determined by the clinical setting/patient population), along with sensitivity and specificity estimates, will influence patient management.

Current Management of Refractory Germ Cell Tumors.

PURPOSE OF REVIEW: Germ cell tumors (GCTs) are the most common solid tumors affecting men between ages of 20 and 34 years. Most of the cases, even in advanced disease, will have good prognosis. However, around 20-30% of advanced disease will be refractory or develop relapse after treatment. Herein, we review the current management of refractory/relapsed GCTs. RECENT FINDINGS: Salvage treatment of GCTs has been a controversial topic for the last few decades. Conventional dose chemotherapy (CDCT), high-dose chemotherapy (HDCT) with stem cell infusion, and surgical salvage were proven to be effective and curative options in some cases. The international randomized trial (TIGER) will ultimately answer which chemotherapy approach may be optimal. Furthermore, the usage of immunotherapy is still under investigation with limited data so far in the setting of relapsed/refractory GCTs. Curative paradigms including with CDCT and HDCT are possible, although novel approaches beyond HDCT are still needed to eliminate mortality from this disease.

Venous thromboembolism prophylaxis in inflammatory bowel disease flare-ups.

BACKGROUND: Inflammatory bowel disease (IBD) is a set of chronic inflammatory diseases associated with significant morbidity. Generally, IBD patients have twice the risk of venous thromboembolism (VTE) compared to healthy controls. VTE in IBD is associated with greater morbidity and mortality. This is compounded by the underutilization of pharmacological anticoagulation in hospitalized patients with IBD. One study showed that half the IBD patients who developed VTE were not receiving any thrombotic prophylaxis. METHOD: We carried out a retrospective chart review of VTE prophylaxis use and safety in patients admitted with IBD flare-up between 2014 and 2017. RESULTS: We evaluated 233 patients (mean age 36.7 years; 53.6% male). Of these patients, 55.2% were Caucasian and 40.5% were African American; 72.5% had Crohn's disease and 21% ulcerative colitis. About one-third of our patients were on chronic steroids. Pharmacological prophylaxis was used in 39.7% of the patients. This significantly correlated with male sex, recent surgery, history of VTE, smoking, and chronic steroid use. Meanwhile, hematochezia, aspirin use, and a history of gastrointestinal bleeding were correlated with less use of pharmacological prophylaxis. Patients receiving pharmacological prophylaxis showed no difference in the incidence of bleeding events. CONCLUSIONS: Multiple factors were associated with the use of pharmacological prophylaxis in hospitalized patients, including sex, steroid use, history of VTE events or gastrointestinal bleeding, and hematochezia. The incidence of major bleeding was not significantly greater in IBD patients receiving pharmacological prophylaxis.

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.

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.

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 Case of Prostate Cancer Presenting with Rash.

Mixed cryoglobulinemia (MC) is well known for its association with chronic hepatitis C virus (HCV) infection. However, it has also been linked to autoimmune disorders and hematological malignancies, particularly of B-cell lymphoid origin. Association with solid malignancies is poorly described in the literature. Non-HCV-related MC, in the setting of prostate cancer, has been reported only twice. Here, we describe a case of MC in a prostate cancer patient complicated by membranoproliferative glomerulonephritis (MPGN) that responded well to plasma exchange therapy and treatment with both corticosteroids and rituximab.

Diffuse Large B-cell Lymphoma Presenting as Bilateral Renal Masses: Successful Treatment with Dose-adjusted REPOCH (Rituximab, Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin) Chemotherapy Regimen.

Diffuse large B-cell lymphoma (DLBL) is an aggressive type of non-Hodgkin lymphoma (NHL). Renal involvement in NHL is not uncommon in advanced stages; however, it is rare to have kidneys affected early in the course of the disease. Usual chemotherapy regimen for DLBL is rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone (R-CHOP). This is a case of a 50-year-old female diagnosed with DLBL who presented with bilateral renal involvement at disease onset and also underwent complete remission after six cycles of dose-adjusted rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (DA-REPOCH). Limited data exist on outcomes of patients with DLBL and renal disease who are treated with high-intensity regimes such as DA-REPOCH. It would be worth looking further into outcomes of DLBL patients especially with renal involvement on DA-REPOCH. Multicenter trials are required to demonstrate which of the two chemotherapy regimens (R-CHOP vs. DA-REPOCH) have better progression-free survival in this particular subset of patients.

Current updates in management of Clostridium difficile infection in cancer patients.

BACKGROUND: Clostridium difficile infection (CDI) is a significant health burden, now recognized as the leading cause of acquired diarrhea in patients receiving antibiotic therapy. Complications of infection with this pathogen include severe diarrhea, causing electrolyte imbalances, dehydration, hemodynamic instability, toxic megacolon, shock, and death. Hence it is extremely paramount to stay updated on management options for this infection, especially in cancer patients. REVIEW: This article presents an in-depth review of literature on the treatment modalities available for CDI in cancer patients. Relevant articles highlighting therapeutic and symptomatic management of CDI patients with underlying malignancy have been summarized. CONCLUSIONS: Despite the current options available, more studies are needed to assess the newer therapeutic options that are being employed for populations other than cancer patients.

Cladribine in the remission induction of adult acute myeloid leukemia: where do we stand?

The combination of cytarabine and an anthracycline has been the standard of care for the induction of remission in acute myeloid leukemia (AML). The response to treatment and survival of adult patients with AML are still variable and depend on multiple factors. Therefore, there have been many efforts to improve the response to treatment and survival rates by either increasing the cytarabine dose or adding a third agent to the standard induction chemotherapy regimen. Unfortunately, attempts to improve response and survival have been mostly unsuccessful. Recent clinical trials and retrospective studies explored the addition of cladribine to standard induction chemotherapy for AML. Some of these studies showed higher rates of complete remission, and one showed improved survival. In this review, we will discuss the antileukemic properties of cladribine and summarize the recent clinical data regarding its incorporation into the induction therapy for adult AML.

Clostridium difficile infection in oncology patients: epidemiology, pathophysiology, risk factors, diagnosis, and treatment.

Clostridium difficile infection (CDI) is one of the most common healthcare-associated infections in the United States. Its incidence has been increasing in the recent years despite preventative measures. CDI increases annual expenses by 1.5 billion dollars. Cancer patients are at higher risk to acquire CDI, as explained by their frequent exposure to risk factors. CDI in cancer patients is associated with higher mortality rates and prolonged hospitalization. Furthermore, CDI affects the course of the disease by delaying treatments such as chemotherapy. Chemotherapeutics drugs are considered independent risk factors for CDI. This review discusses Clostridium difficile infection in cancer patients, including those who are receiving chemotherapy. Herein, we summarize recent data regarding the epidemiology, risk factors, including chemotherapy regimens, pathogenesis, diagnostic techniques and treatment options, including newer agents. Method: A literature search was performed using the PubMed and Google Scholar databases. The MeSH terms utilized in different combinations were 'clostridium difficile', 'neoplasia/cancer/oncology', 'chemotherapy', 'diagnosis', and 'treatment', in addition to looking up each treatment option individually to generate a comprehensive search. The articles were initially screened by title alone, followed by screening through abstracts. Full texts of pertinent articles (including letters to editors, case reports, case series, cohort studies, and clinical trials) were included in this review.

Posterior reversible encephalopathy syndrome while receiving irinotecan with fluorouracil and folinic acid for metastatic gastric cancer.

Posterior reversible encephalopathy syndrome (PRES) is a clinical-radiographic syndrome with seizures, headache, altered mental status and visual disturbances. It is typically associated with posterior cerebral white matter oedema on neuroimaging. There is an increasing number of cases of PRES reported with different chemotherapeutic protocols. However, PRES is rarely reported in association with irinotecan, fluorouracil and folinic acid (FOLFIRI). We report a 28-year-old female patient with a history of Stage IV gastric cancer who presented with abdominal pain and recurrent vomiting that was thought to be related to a partial intestinal obstruction secondary to peritoneal metastasis. Eventually, she was treated with FOLFIRI. A few hours after initiation of the fluorouracil infusion in the second cycle, she developed a tonic-clonic seizure. MRI of the brain showed multiple bilateral T 2 and flair hyperintense cortical and subcortical lesions suggestive of PRES. Other causes of PRES were excluded, as well as brain metastasis. Unfortunately, the patient developed septic shock and died a few days after her presentation.