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BACKGROUND: Since the publication of the original work in 2014, significant progress has been made in the characterization of genomic alterations that drive oncogenic addiction of nonsmall cell lung cancer (NSCLC) and how the immune system can leverage non-oncogenic pathways to modulate therapeutic outcomes. This update evaluates and validates the recent and emerging data for prognostic and predictive biomarkers with therapeutic targets in NSCLC. DATA SOURCES: We performed a literature search from January 2015 to October 2023 using the keywords non-small cell lung cancer, clinical practice guidelines, gene mutations, genomic assay, immune cancer therapy, circulating tumor DNA, predictive and prognostic biomarkers, and targeted therapies. STUDY SELECTION AND DATA EXTRACTION: We identified, reviewed, and evaluated relevant clinical trials, meta-analyses, seminal articles, and published clinical practice guidelines in the English language. DATA SYNTHESIS: Regulatory-approved targeted therapies include those somatic gene alterations of EGFR ("classic" mutations, exon 20 insertion, and rare EGFR mutations), ALK, ROS1, BRAF V600, RET, MET, NTRK, HER2, and KRAS G12C. Data for immunotherapy and circulating tumor DNA in next-generation sequencing are considered emerging, whereas the predictive role for PIK3CA gene mutation is insufficient. CONCLUSIONS: Advances in sequencing and other genomic technologies have led to identifying novel oncogenic drivers, novel resistance mechanisms, and co-occurring mutations that characterize NSCLC, creating further therapeutic opportunities. The benefits associated with immunotherapy in the perioperative setting hold initial promise, with their long-term results awaiting.
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INTRODUCTION: Immune checkpoint inhibitors (ICI) have changed the prognostic outlook for several malignancies. Despite the unprecedented durable responses and improvement in survival outcomes with ICIs, exclusion of oncology patients living with human immunodeficiency virus (HIV) from most ICI-related trials has limited utility of these agents. Clinical outcomes related to concomitant use of antiretroviral therapy and ICI remain unclear. We present a case series based on our institution's experience to address this unmet need of clinical outcomes with ICI in oncology patients living with HIV. METHODS: Electronic medical records were queried to identify patients living with HIV who were also diagnosed with cancer and treated with ICI from May 2019 to September 2022. RESULTS: A total of five patients were on concurrent antiretroviral therapy and immunotherapy. From an efficacy perspective, three patients were observed to have a response (one complete response, one partial response, and one stable disease). There were three patients with known cluster of differentiation (CD4 + ) levels who had an increase in CD4 + cell count with ICI treatment. The HIV viral load remained undetected in most of the patients on ICI treatment. No confirmed immune-related adverse effects were documented for any patients in this review. CONCLUSION: Immune checkpoint inhibitors may be efficacious and tolerable for treatment of cancer in patients living with HIV. Upward trends in CD4 + cell counts observed in this case series suggest that immune checkpoint inhibitors may enhance HIV disease control. Further research is needed for this patient population to supply more robust evidence for clinical practice.
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Small-molecule inhibitors have revolutionized the treatment of chronic lymphocytic leukemia (CLL), a landscape once dominated by chemoimmunotherapy (i.e., an anti-CD20 monoclonal antibody in combination with systemic chemotherapy) in fit and unfit individuals. Key challenges include the management of refractory disease as well as the optimization of the therapy sequence. Decreased responsiveness has been observed with prolonged treatment, especially with Bruton tyrosine kinase (BTK) and phosphatidylinositol 3-kinase (PI3K) inhibitors which are given continuously, while venetoclax, an agent that targets dysregulations in intrinsic apoptosis signaling, has a fixed duration when combined with anti-CD20 monoclonal antibodies or BTK inhibitors. Combination therapy aims to synergistically target different oncogenic signaling pathways to abrogate the proliferation of resistant clones and thereby allows for fixed-duration treatments. An advantage of fixed-duration therapy is the potential to decrease financial and drug-induced toxicities. Sequencing of therapies is important to individualize treatment decisions based on factors such as age, comorbidities, tolerability, and patient preferences. However, to date, there are limited data to guide the rational sequencing or combination of these therapies, since conventional chemoimmunotherapy or chemotherapy regimens were used as comparators against these small-molecule inhibitors in trials that led to their regulatory approvals. In this article, we examined and evaluated the current evidence for sequencing versus the combination of small-molecule inhibitors for CLL by conducting comprehensive searches of the United States National Library of Medicine PubMed database, key meeting abstracts, and clinical practice guidelines. We also summarized findings from expert opinions to elucidate best practices for clinical scenarios with limited evidence to guide treatment selection.
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Antineoplásicos , Leucemia Linfocítica Crônica de Células B , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/genética , Adenina/uso terapêutico , Fosfatidilinositol 3-Quinases/uso terapêutico , Antineoplásicos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Inibidores de Fosfoinositídeo-3 Quinase/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
INTRODUCTION: In clinical practice, waiting 14 days between the administration of pegfilgrastim and subsequent chemotherapy cycle (as recommended by the prescribing information) is sometimes not feasible with multi-cycle dose-dense regimens. This study evaluated the practice related to the use of pegfilgrastim in oncology patients at a multi-hospital health system. METHODS: Patients who received pegfilgrastim as primary prophylaxis following dose-dense chemotherapy scheduled every 14 days were included. The primary endpoint was the impact of <14 elapsed days between pegfilgrastim administration and next chemotherapy cycle on the change in mean absolute neutrophil counts (ANC). A generalized linear mixed-effects model with fixed effects for pegfilgrastim delivery method, elapsed days between pegfilgrastim and chemotherapy (fixed categorical effect for 12, 13, 14 days), and ANC at subsequent cycle was fitted to the change in ANC between chemotherapy cycles. RESULTS: One hundred and sixty four patients with breast cancer who received pegfilgrastim support for dose dense doxorubicin and cyclophosphamide (ddAC) qualified for the model. The mean age was 52 ± 12 years. Eighty-eight percent received pegfilgrastim on-body injector while 13% received pegfilgrastim injection. The mean number of elapsed days between pegfilgrastim and subsequent chemotherapy was 13 ± 0.5 days. The method of pegfilgrastim delivery and elapsed days between pegfilgrastim and chemotherapy administration had no significant effect on the change in ANC (p = 0.8663 and p = 0.8434 respectively); however, patient's age (p = 0.0125) had a significant effect on the change in ANC. CONCLUSION: The study findings suggest safety and efficacy when chemotherapy is administered 12-14 days from pegfilgrastim.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Filgrastim/administração & dosagem , Polietilenoglicóis/administração & dosagem , Adulto , Idoso , Neoplasias da Mama/sangue , Feminino , Filgrastim/efeitos adversos , Humanos , Contagem de Leucócitos , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Polietilenoglicóis/efeitos adversos , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND: Oral cancer therapy-related cardiovascular (CV) toxicity has a wide variety of presentations including arrhythmia, cardiomyopathy, and myocardial infarction, but clinical evidence related to its management is limited. The purpose of this IRB-approved, single-center, retrospective, cohort study was to characterize cardio-oncologic interventions for CV adverse events related to oral oncolytics. METHODS: The cohort included 67 patients who were admitted to a multi-hospital health system between June 1, 2016 and July 31, 2021, had at least one medical record order of oral oncolytics considered to have cardiotoxic potential, and had an ICD10 code for a cardiotoxic event added to their electronic medical records after initiation of oral oncolytics. RESULTS: The majority (97%) had pre-existing cardiovascular disease (CVD) or a CV risk factor. The three most common classes of oral oncolytics were aromatase inhibitors (36%), BCR-ABL inhibitors (16%), and VEGFR inhibitors (13%). New-onset or worsening heart failure (HF) (n = 31), which occurred after a median of 148 days (Interquartile range (IQR) 43-476 days) was the most common cardiotoxic event. The most frequent interventions were pharmacological treatment of the CV adverse event (n = 44) and treatment interruption (n = 18), but guideline-directed medication therapy for HF could be further optimized. CONCLUSION: Pre-existing CVD or CV risk factors predispose oncology patients to CV adverse events. Real-world practice reveals that CV adverse events require temporary interruption of treatment and initiation of pharmacologic treatment. A multidisciplinary, patient-centered approach that includes discussion of risks/benefits of treatment continuation, and initiation of guideline-directed treatment is recommended until high-quality, drug-specific data for monitoring and treatment become available.
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Pancreatic ductal adenocarcinoma (PDAC) is currently the fourth leading cause of death in the United States and is expected to be ranked second in the next 10 years due to poor prognosis and a rising incidence. Distant metastatic PDAC is associated with the worst prognosis among the different phases of PDAC. The diagnostic options for PDAC are convenient and available for staging, tumor response evaluation, and management of resectable or borderline resectable PDAC. However, imaging is crucial in PDAC diagnosis, monitoring, resectability appraisal, and response evaluation. The advancement of medical technologies is evolving, hence the use of imaging in PDAC treatment options has grown as well as the utilization of ctDNA as a tumor marker. Treatment options for metastatic PDAC are minimal with the primary goal of therapy limited to symptom relief or palliation, especially in patients with low functional capacity at the point of diagnosis. Molecular profiling has shown promising potential solutions that would push the treatment boundaries for patients with PDAC. In this review, we will discuss the latest updates from evidence-based guidelines regarding diagnosis, therapy response evaluation, prognosis, and surveillance, as well as illustrating novel therapies that have been recently investigated for PDAC, in addition to discussing the molecular profiling advances in PDAC.
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Background: Immune checkpoint-induced pneumonitis (ICIP) is one of the most fatal adverse events caused by immune checkpoint inhibitors (ICI) and accounts for 35% of anti-PD-[L]1-related deaths. Risk factors including thoracic radiation and use of EGFR tyrosine kinase inhibitors have been identified as contributors to ICIP development. However, there has been very limited information on obstructive pulmonary disease as a risk factor. Objective: The purpose of this study is to evaluate the incidence and management of ICIP in a cohort of patients with pre-existing obstructive pulmonary disease. Methods: This retrospective, descriptive study, includes data from 139 patients between January 1, 2017 and August 31, 2022. Patients included were adult patients 18 years or older, received at least 2 cycles of an immune checkpoint inhibitor, and had a history of an obstructive pulmonary disorder prior to administration. Patients were excluded if they had literature-established risk factors for pneumonitis. Results: The incidence of ICIP was 7.19% (10 out of 139 patients). From a management perspective, 90% of patients had immunotherapy held, 40% received oral steroids, and 70% received intravenous steroids at the time of ICIP identification. After receiving treatment for the initial episode of ICIP, 6 patients restarted immunotherapy and 3 (50%) subsequently experienced a recurrent episode. One patient experienced grade 4 ICIP event and subsequently died from respiratory failure attributed to ICIP. Conclusion: These findings indicate that a pre-existing history of an obstructive pulmonary disorder may be a risk factor for the development of ICIP and subsequent recurrence of ICIP when rechallenged.
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OBJECTIVES: Despite the use of antiviral prophylaxis in recipients of allogeneic hematopoietic cell transplants (HCT), cytomegalovirus (CMV) is a common clinically significant infection and is associated with significant morbidity and mortality in this patient population. Based on current approval, letermovir is initiated within 28 days following allogeneic HCT for CMV seropositive recipients and continued through 100 days post-transplant. However, it is unknown whether patients who receive extended duration CMV prophylaxis with letermovir would result in less CMV reactivation and reactivation compared to those who do not. This study aimed to evaluate the efficacy of letermovir prophylaxis in CMV seropositive patients when continued for greater than 100 days post-allogeneic stem cell transplant. METHODS: A single-center retrospective chart review was conducted on recipients of allogeneic HCT from November 2017 to July 2021. Patients were eligible for inclusion if they were at least 18 years of age, received an allogeneic HCT, CMV seropositive, and initiated letermovir between days 0-28 post-transplant. The primary endpoint of this study is to compare rates of CMV reactivation in patients who stopped letermovir prophylaxis at 100 days post-transplant (standard duration group) versus those who continued letermovir prophylaxis past day 100 (extended duration group). RESULTS: A total of 87 patients met the eligibility criteria for inclusion. The median duration of letermovir prophylaxis was 78 days in the standard duration group versus and 132 days in the extended duration group. There were more CMV reactivations in the standard duration group versus the extended duration group, 28% versus 19% respectively. CMV pneumonitis was observed in one of the patients in the standard duration group. All-cause mortality at day 200 post-transplant was similar between the two groups. CONCLUSION: The results of this study suggest that extended duration letermovir prophylaxis may be associated with less CMV reactivation compared to the standard duration of prophylaxis.
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Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Humanos , Antivirais/uso terapêutico , Estudos Retrospectivos , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/prevenção & controle , Infecções por Citomegalovirus/epidemiologia , Citomegalovirus , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , TransplantadosRESUMO
The rationale for administering immune checkpoint inhibitors (ICIs) in the adjuvant setting is to eradicate micro-metastases and, ultimately, prolong survival. Thus far, clinical trials have demonstrated that 1-year adjuvant courses of ICIs reduce the risk of recurrence in melanoma, urothelial cancer, renal cell carcinoma, non-small cell lung cancer, and esophageal and gastroesophageal junction cancers. Overall survival benefit has been shown in melanoma while survival data are still not mature in other malignancies. Emerging data also show the feasibility of utilizing ICIs in the peri-transplant setting for hepatobiliary malignancies. While ICIs are generally well-tolerated, the development of chronic immune-related adverse events, typically endocrinopathies or neurotoxicities, as well as delayed immune-related adverse events, warrants further scrutiny regarding the optimal duration of adjuvant therapy and requires a thorough risk-benefit determination. The advent of blood-based, dynamic biomarkers such as circulating tumor DNA (ctDNA) can help detect minimal residual disease and identify the subset of patients who would likely benefit from adjuvant treatment. In addition, the characterization of tumor-infiltrating lymphocytes, neutrophil-to-lymphocyte ratio, and ctDNA-adjusted blood tumor mutation burden (bTMB) has also shown promise in predicting response to immunotherapy. Until additional, prospective studies delineate the magnitude of overall survival benefit and validate the use of predictive biomarkers, a tailored, patient-centered approach to adjuvant ICIs that includes extensive patient counseling on potentially irreversible adverse effects should be routinely incorporated into clinical practice.
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PURPOSE: This article aims to increase awareness of, outline pathophysiology for, and offer guidance on supportive care strategies for specific endocrine, neurological, and immunological syndromes associated with paraneoplastic syndromes (PNSs). SUMMARY: PNS refers to remote effects that cannot be attributed to the direct or invasive effects of a malignancy. These syndromes are considered clinically important because they may provide early recognition, diagnosis, and management of the malignancy in a timely manner. Many of their presenting symptoms such as ectopic Cushing's syndrome, hypercalcemia of malignancy (HCM), syndrome of inappropriate secretion of antidiuretic hormone (SIADH), neurological dysfunctions, and paraneoplastic autoimmune thrombocytopenia overlap with those of nonneoplastic disorders, yet their pathogenesis and responses to treatments differ. Management of ectopic Cushing's syndrome due to a PNS consists of treatment of the underlying malignancy and its comorbidities. Drug therapies may include ketoconazole, mitotane, metyrapone, somatostatin analogs, and dopamine agonists. Hypercalcemia may be classified into cases with parathyroid hormone (PTH)-dependent causes or PTH-independent causes such as HCM, in which osteoclast inhibitors may be deployed. Treatments of PNS-mediated SIADH include treatment of the underlying malignancy and strategies to increase serum sodium levels. Amifampridine is now considered the first-line agent for paraneoplastic Lambert-Eaton myasthenic syndrome, whereas steroids, intravenous immune globulin, thrombopoietin receptor agonists (eg, romiplostim, eltrombopag, and avatrombopag), fostamatinib, and rituximab may find their niche in treatment of PNS-mediated autoimmune thrombocytopenia. CONCLUSION: Supportive care for PNSs lends opportunities to pharmacists to add quality, value, and safety.
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Síndrome de Cushing , Hipercalcemia , Síndrome de Secreção Inadequada de HAD , Neoplasias , Síndromes Paraneoplásicas , Púrpura Trombocitopênica Idiopática , Humanos , Hipercalcemia/complicações , Síndrome de Secreção Inadequada de HAD/complicações , Síndrome de Cushing/complicações , Síndromes Paraneoplásicas/diagnóstico , Síndromes Paraneoplásicas/etiologia , Síndromes Paraneoplásicas/terapia , Neoplasias/complicações , Neoplasias/terapia , AutoanticorposRESUMO
Background: More than half of patients with colorectal cancer (CRC) present with metastatic disease or develop recurrent disease on first-line and second-line options. Treatment beyond the second line remains an area of unmet need for patients with progressive or recurrent disease. Methods: We retrospectively reviewed data of adult (>18 years old) patients with mCRC who received regorafenib + 5FU combination therapy at Houston Methodist Hospital with outcomes of interest including response rate, discontinuation due to side effects, and overall survival. Results: Seven patients received regorafenib + 5FU combination therapy for mCRC after receiving at least two other lines of therapy (including at least one fluorouracil-based therapy). Four patients (57%) achieved disease control in 7-12 weeks after therapy initiation while three patients developed recurrent disease. In patients who achieved disease control, no new adverse events were reported among patients with this combination. Conclusion: Regorafenib and Fluorouracil combination could be considered an option beyond the second line for patients with treatment-refractory metastatic colorectal cancer. Further studies, including a prospective trial, are needed to investigate the efficacy and safety of regorafenib plus 5FU therapy compared to other limited available therapies.
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Systemic combination therapy of immune checkpoint inhibitors and vascular endothelial growth factors have provided the basis for improved outcomes in select patients with unresectable or metastatic hepatocellular carcinoma. However, for patients with resectable disease, surgery alone or an orthotopic liver transplant remains the standard of care. Within the realms of transplant oncology, neoadjuvant systemic therapy is currently being evaluated as a potential strategy to improve outcomes in patients with HCC. Here, we report excellent response with significant downstaging in a safe manner after neoadjuvant treatment with atezolizumab and bevacizumab in a patient diagnosed with poorly differentiated HCC. As a result of the significant response observed with safe outcomes, the patient was listed for orthotopic liver transplant (OLT) evaluation and transplanted successfully.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Dor Abdominal/etiologia , Idoso , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Imunoterapia , Neoplasias Hepáticas/tratamento farmacológico , Transplante de Fígado/efeitos adversos , Masculino , Terapia NeoadjuvanteRESUMO
Pancreatic cancer (PC) is a highly malignant and aggressive tumor. Despite medical advancement, the silent nature of PC results in only 20% of all cases considered resectable at the time of diagnosis. It is projected to become the second leading cause in 2030. Most pancreatic cancer cases are diagnosed in the advanced stages. Such cases are typically unresectable and are associated with a 5-year survival of less than 10%. Although there is no guideline consensus regarding recommendations for screening for pancreatic cancer, early detection has been associated with better outcomes. In addition to continued utilization of imaging and conventional tumor markers, clinicians should be aware of novel testing modalities that may be effective for early detection of pancreatic cancer in individuals with high-risk factors. The pathogenesis of PC is not well understood; however, various modifiable and non-modifiable factors have been implicated in pancreatic oncogenesis. PC detection in the earlier stages is associated with better outcomes; nevertheless, most oncological societies do not recommend universal screening as it may result in a high false-positive rate. Therefore, targeted screening for high-risk individuals represents a reasonable option. In this review, we aimed to summarize the pathogenesis, genetic risk factors, high-risk population, and screening modalities for PC.
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Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Programas de Rastreamento , Carcinogênese , Fatores de Risco , Neoplasias PancreáticasRESUMO
BACKGROUND: The management of cholangiocarcinoma is continually reviewed on a current evidence basis to develop practice guidelines and consensus statements. However, the standardized treatment guidelines are still unclear for cholangiocarcinoma patients who are listed for liver transplantation. We aimed to validate and evaluate the potential efficacy of chemotherapy combination of Gemcitabine and Cisplatin as a neo-adjuvant treatment for cholangiocarcinoma patients before liver transplantation. METHODS: In this prospective case series, patients with locally advanced, unresectable, hilar, or intrahepatic cholangiocarcinoma with no evidence of extrahepatic disease or vascular involvement were treated with a combination of neoadjuvant gemcitabine and cisplatin with no radiation. All patients included received chemotherapy prior to being listed for liver transplantation at a single cancer center according to an open-labeled, and center-approved clinical management protocol. The primary endpoints were the overall survival and recurrence-free survival after liver transplantation. RESULTS: Between 1 March 2016, and 15 March 2022, 10 patients (8 males and 2 females) with a median age of 62.71(interquartile range: 60.02-71.87) had a confirmed diagnosis of intrahepatic or hilar cholangiocarcinoma and underwent liver transplantation. Median days of neoadjuvant therapy for a given combination of gemcitabine and cisplatin were 181 (IRQ: 120-250). Nine patients (90%) were reported with no recurrence or metastasis, and only 1 patient had confirmed metastasis (10%); days for metastasis after transplantation were 612 for this patient. All patients received a combination of gemcitabine and cisplatin as neo-adjuvant while awaiting liver transplantation. The median days of follow-up were 851 (813-967). Overall survival was 100% (95% CI 100-100%) at both years one and two; 75% (95% CI 13-96%) at years three to five. One patient died at eight hundred and eighty-five days. No adverse events were reported after liver transplantation including the patient who was confirmed with recurrence. CONCLUSIONS: Our finding demonstrated that neo-adjuvant gemcitabine and cisplatin with no radiation prior to liver transplantation resulted in excellent outcomes for patients with cholangiocarcinoma.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Transplante de Fígado , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos/patologia , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/cirurgia , Cisplatino/uso terapêutico , Desoxicitidina/análogos & derivados , Feminino , Humanos , Masculino , Terapia Neoadjuvante , GencitabinaRESUMO
Background: Cholangiocarcinoma management is constantly being updated in view of existing evidence in order to establish practice guidelines and consensus statements. However, the available treatment guidelines to optimize outcomes for cholangiocarcinoma patients who require liver transplantation are still controversial. This study contributing to the cholangiocarcinoma care field by investigating a new promising neoadjuvant therapy that might be help to grant the liver transplant option to the patients with cholangiocarcinoma. Here, we evaluate and compare the potential efficacy of chemotherapy combination of Gemcitabine plus Cisplatin versus non- Gemcitabine and Cisplatin regimens as a neo-adjuvant treatment for cholangiocarcinoma patients prior to liver transplantation. Methods: In this retrospective study, patients with locally advanced, unresectable, hilar, or intrahepatic cholangiocarcinoma with no evidence of extrahepatic disease or vascular involvement were treated with either the combination of neo-adjuvant Gemcitabine plus Cisplatin with no radiation or other standard options of neo-adjuvant treatment. All patients included received chemotherapy prior to being listed for liver transplantation at a single cancer center in collaboration with the same institution's transplant center according to an open-labeled, and centers-approved clinical management protocol. Patients were listed for liver transplantation if they had a minimum of six months of scans showing response or confirmation of disease stability. The primary endpoints were the overall survival and recurrence-free survival after liver transplantation. This report, which was censored on March 18, 2022. Results: Out of a total of 707 liver transplant recipients were screened, 37 patients were confirmed with a diagnosis of cholangiocarcinoma and only 18 patients (11 males and 7 females) with a median age of 61.83 [interquartile range: 58.27-68.74] met inclusion criteria. Of the 18 patients enrolled, 10 received Gemcitabine/Cisplatin, while 8 patients received either Gemcitabine monotherapy or Capecitabine or FOLFIRI. Months for recurrence after transplantation was 20.1 (IRQ: 20.1-20.1) in the Gemcitabine/Cisplatin group and 9.5 (8.9-12.47) months in the non-Gemcitabine/Cisplatin group (p-value=0.18). Median months of follow-up in the Gemcitabine/Cisplatin group was 28.35 (27.1-32.23) months versus 40.12 (20.6-56.22) months in the non-Gemcitabine/Cisplatin group (p-value=0.33). In non-Gemcitabine/Cisplatin patients, overall survival was 75% (95% CI 31-93%) at both years 1 and 2; 63% (95% CI 23-86%) at years 3 to 5. In Gemcitabine/Cisplatin patients, overall survival was 100% (95% CI 100-100%) at both years 1 and 2; 75% (95% CI 13-96%) at years 3 to 5. Three non-Gemcitabine/Cisplatin patients died at 328 days, 340 days, and 896 days, respectively. One Gemcitabine/Cisplatin patient died at 885 days. Conclusion: Our findings suggest improved overall survival outcomes with Gemcitabine plus Cisplatin as neo-adjuvant treatment with no concomitant radiation compared to non-Gemcitabine/Cisplatin regimens in patients with cholangiocarcinoma prior to liver transplantation.
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Background: Immune checkpoint inhibitor (ICI) therapy has significantly improved outcomes across a range of malignancies. While infections are a well-known contributor to morbidity and mortality amongst patients receiving systemic chemotherapy regimens, little is known about the impact of infections on patients receiving ICI therapy. This study aims to assess incidence, risk factors, and outcomes in patients who develop infections while on pembrolizumab-based therapies for non-small cell lung cancer (NSCLC). Methods: Patients receiving pembrolizumab for stage III/IV NSCLC from 1/1/2017-8/1/2021 across seven hospitals were identified. Incidence and type of infection were characterized. Covariates including baseline demographics, treatment information, treatment toxicities, and immunosuppressive use were collected and compared between infected and non-infected patients. Outcomes included the rate of infections, all-cause hospital admissions, median number of treatment cycles, overall survival (OS), and progression free survival (PFS). Univariable and multivariable analysis with reported odds ratio (OR) and 95% confidence intervals (CI) were utilized to evaluate infection risks. OS and PFS were analyzed by Kaplan−Meier analysis and tested by log-rank test. p-value < 0.05 was considered statistically significant. Results: There were 243 NSCLC patients that met the inclusion criteria. Of these, 111 (45.7%) had one documented infection, and 36 (14.8%) had two or more. Compared to non-infected patients, infected patients had significantly more all-cause Emergency Department (ED) [37 (33.3%) vs. 26 (19.7%), p = 0.016], hospital [87 (78.4%) vs. 53 (40.1%), p < 0.001], and ICU visits [26 (23.4%) vs. 5 (3.8%), p < 0.001], and had poorer median OS (11.53 [95% CI 6.4−16.7] vs. 21.03 [95% CI: 14.7−24.2] months, p = 0.033). On multivariable analysis, anti-infective therapy (OR 3.32, [95% CI: 1.26−8.76], p = 0.015) and ECOG of >1 (OR 5.79, [95% CI 1.72−19.47], p = 0.005) at ICI initiation conferred an increased risk for infections. At last evaluation, 74 (66.7%) infected and 70 (53.0%) non-infected patients died (p = 0.041). Conclusion: Infections occurred in nearly half of patients receiving pembrolizumab-based therapies for NSCLC. Infected patients had frequent hospitalizations, treatment delays, and poorer survival. ECOG status and anti-infective use at ICI initiation conferred a higher infection risk. Infection prevention and control strategies are needed to ameliorate the risk for infections in patients receiving ICIs.
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There have been unique adverse events reported with targeted blockade of programmed death-1 (PD-1), programmed death-ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated protein-4 (CTLA4), including immune mediated toxicities. Recently, there have been reports of hepatitis B reactivation (HBVr) occurring with PD-1/PD-L1 inhibitors, which may result in treatment delays, interruptions, or discontinuation. This retrospective literature review and analysis of the Food and Drug Administration's (FDA) Adverse Events Reporting System (FAERS) queried reported cases of "Hepatitis B reactivation" reported with the PD-1/PD-L1 inhibitors "Pembrolizumab," "Atezolizumab," "Nivolumab," "Durvalumab," "Avelumab," and "Ipilimumab" from initial FDA approval to June 30, 2020. Disproportionality signal analysis was determined by calculating a reporting odds ratio (ROR) and 95% confidence intervals (CI). The ROR was considered significant when the lower and upper limits of the 95% CI were >1 and confirmed by the Fisher exact test (P<0.05). Pembrolizumab had a strong signal associated with HBVr, with a ROR of 2.32 (95% CI: 1.11-4.28) (P=0.013) and was the only statistically significant finding. There were no reports of HBVr with Ipilimumab or Avelumab. Additional prospective studies should be conducted to validate the findings of this retrospective pharmacovigilance analysis to determine the risk of HBVr in patients receiving immune checkpoint inhibitors.
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Vírus da Hepatite B/efeitos dos fármacos , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/metabolismo , Feminino , Humanos , Inibidores de Checkpoint Imunológico/metabolismo , Masculino , Pessoa de Meia-Idade , Neoplasias/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Estudos RetrospectivosRESUMO
Renal dysfunction is a significant risk factor for acyclovir-induced neurotoxicity and altered mentation and myoclonic movements are the most common clinical symptoms observed. In majority of reported cases, neurological sequelae associated with acyclovir-induced neurotoxicity often mimic viral infections of the central nervous system and makes diagnosis of the former challenging. Although plasma concentrations of the drug may not always correlate with neurotoxic symptoms, obtaining serum levels of acyclovir may be helpful in confirming drug-induced neurotoxicity. Hemodialysis has been shown to significantly improve altered mentation in patients with suspected or confirmed acyclovir-induced neurotoxicity. Here, we report a definite case of acyclovir-induced neurotoxicity in a patient with end-stage renal disease. Clinical improvements in neurologic symptoms were observed following discontinuation of the drug and hemodialysis.
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Aciclovir/administração & dosagem , Aciclovir/efeitos adversos , Antivirais/efeitos adversos , Doenças do Sistema Nervoso Central/induzido quimicamente , Falência Renal Crônica/tratamento farmacológico , Antivirais/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Neurotóxicas , Diálise RenalRESUMO
This letter highlights a rare association of anti-HER2 cancer therapy with development of pulmonary arterial hypertension, based on a review of data from the FDA https://bit.ly/2X90xDu.