For advanced metastatic non-small-lung cancer, the landscape of actionable driver alterations is rapidly growing, with nine targetable oncogenes and seven approvals within the last 5 years. This ...accelerated drug development has expanded the reach of targeted therapies, and it may soon be that a majority of patients with lung adenocarcinoma will be eligible for a targeted therapy during their treatment course. With these emerging therapeutic options, it is important to understand the existing data on immune checkpoint inhibitors (ICIs), along with their efficacy and safety for each oncogene-driven lung cancer, to best guide the selection and sequencing of various therapeutic options. This article reviews the clinical data on ICIs for each of the driver oncogene defined lung cancer subtypes, including efficacy, both for ICI as monotherapy or in combination with chemotherapy or radiation; toxicities from ICI/targeted therapy in combination or in sequence; and potential strategies to enhance ICI efficacy in oncogene-driven non-small-cell lung cancers.
Anemia is a commonly encountered finding either during the preoperative assessment or during the postoperative management of the patient. Anemia often gets overlooked while more emphasis is paid to ...cardiovascular and pulmonary evaluation. Evidence, however, suggests that the presence of anemia in the perioperative period can predispose patients to other complications. Awareness of the consequences of anemia in the perioperative period can lead to better recognition and early management of this potentially modifiable risk factor. In this review, we focus on the effects of anemia on the cardiac, pulmonary, neurologic, cognitive, and functional status outcomes of patients. We also review management strategies that could be employed, depending on the available time and resources.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abdominal pain can arise from numerous sources, including those extra‐abdominal. It is important to obtain additional imaging in the setting of clinical suspicion for malignancy.
Abdominal pain can ...arise from numerous sources, including those extra‐abdominal. It is important to obtain additional imaging in the setting of clinical suspicion for malignancy.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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Background: A written advanced directive (AD) allows patients to indicate their preferences for medical care should they ever lose the ability to make their wishes known. This may take the ...form of a living will or designation of a healthcare surrogate. AD completion rates remain poor on inpatient oncology units, with only 20-40% of patients having an AD. This is despite the fact nearly all cancer patients (95%) believe discussing ADs is an important issue. It has recently been shown that nearly 87% of cancer patients would support a policy in which admitting physicians offered to have a conversation regarding ADs. The goal of our project was to increase the percentage of patients with documented ADs on our inpatient oncology unit from 30% to 50% using the participation of internal medicine residents. Our secondary objective was to initially assess resident knowledge, confidence and skills with AD discussions. Methods: We carried out a prospective QI project in which we first calculated the percentage of consecutive patients on our inpatient oncology unit with documented ADs. After providing educational materials and delivering AD forms to the resident workroom to increase accessibility, we again calculated the percentage of consecutive patients with documented ADs. We also initially surveyed residents about their knowledge, comfort levels, and barriers to having AD discussions with patients. Results: Pre-intervention, 15 out of 50 (30%) consecutive patients on our inpatient oncology unit had documented ADs. Post-intervention, 13 of 27 (48%) consecutive patients in our oncology unit had documented ADs. Most residents felt their knowledge of ADs was average (46.88%, n = 15) or good (28.13%. n = 9). When asked about comfort in filling out ADs with patients, most responded as average (28.13%, n = 9) or poor (28.13%, n = 9). The main barrier to completing ADs was lack of time (25%, n = 20) followed by lack of knowledge (25%, n = 8) and not feeling the responsibility (12.5%, n = 4). Most residents were interested (65.53%, n = 21) or maybe interested (28.13%, n = 9) in further teaching on ADs. Conclusions: Our study showed that AD completion rates on an inpatient oncology unit can be improved using the participation of internal medicine residents. This was done through a standardized approach of housestaff offering to discuss ADs on admission after they had received short small group teaching sessions on AD discussions. Furthermore, we identified that most internal medicine residents had average or poor comfort in initiating advanced care discussions, but were interested in obtaining further knowledge to help discuss ADs with patients.
The improved survival outcomes of patients with non-small-cell lung cancer (NSCLC), largely owing to the improved control of systemic disease provided by immune-checkpoint inhibitors and novel ...targeted therapies, have highlighted the challenges posed by central nervous system (CNS) metastases as a devastating yet common complication, with up to 50% of patients developing such lesions during the course of the disease. Early-generation tyrosine-kinase inhibitors (TKIs) often provide robust systemic disease control in patients with oncogene-driven NSCLCs, although these agents are usually unable to accumulate to therapeutically relevant concentrations in the CNS owing to an inability to cross the blood-brain barrier. However, the past few years have seen a paradigm shift with the emergence of several novel or later-generation TKIs with improved CNS penetrance. Such agents have promising levels of activity against brain metastases, as demonstrated by data from preclinical and clinical studies. In this Review, we describe current preclinical and clinical evidence of the intracranial activity of TKIs targeting various oncogenic drivers in patients with NSCLC, with a focus on newer agents with enhanced CNS penetration, leptomeningeal disease and the need for intrathecal treatment options. We also discuss evolving assessment criteria and regulatory considerations for future clinical investigations.
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GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
Germline mutations driving lung cancer have been infrequently reported in literature, with EGFR T790M being a known germline mutation identified in 1% of NSCLC. Typically, a somatic EGFR mutation is ...acquired to develop lung adenocarcinoma. Osimertinib has become standard-of-care treatment for EGFR T790M-positive lung cancer.
We perform a retrospective analysis through the Lung Cancer Moon Shot GEMINI database at the UT MD Anderson Cancer Center. Of the patients that underwent cfDNA analysis, germline mutations were identified by those with high variant allelic fraction (VAF) approximating 50%, followed by further confirmation on genetic testing.
We identified 22 patients with germline EGFR mutations, with the majority harboring an EGFR T790M mutation (95.5%) and EGFR L858R somatic mutation (50%). Notably, most patients were female (86.4%), non-smokers (81.8%), Caucasian (86.4%), have family history of lung cancer (59.1%), and stage IV at diagnosis (72.7%). A distinct radiographic pattern of small multifocal ground-glass pulmonary nodules was observed in the majority of our cohort (72.7%).
Among the 18 with advanced-stage NSCLC, 12 (66.7%) were treated with first-line osimertinib, demonstrating a median PFS of 16.9 months (95% CI; 6.3-NR). Others were treated with first-line afatinib (11.1%) or chemotherapy (22.2%). Among the 17 patients treated with osimertinib (in first or second-line), mPFS was 20.4 months (95% CI; 6.3-NR) and mOS was 82.0 months (95% CI; 28.4-NR).
Based on our institutional cohort, NSCLC driven by EGFR germline mutations occur more frequently in non-smoking, Caucasian females with multi-focal pulmonary nodules radiographically. Osimertinib for advanced germline EGFR-mutated NSCLC renders similar PFS compared to somatic T790M EGFR-mutated NSCLC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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Background: Radium-223 (Xofigo) has been shown to increase overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) via the phase 3 ALSYMPCA ...study. The side effect of persistent pancytopenia was noted in 2% of the patients, however, the incidence seen in our institutional clinical practice is higher than reported in the literature. This analysis serves to identify predictive factors and thereby help impact future therapy directions in this patient population. Methods: A retrospective analysis was performed analyzing patients with mCRPC who received xofigo at UFHealth in a 3 year span (from January 2014 to January 2017). Data collected included CBC, ECOG functional status, kidney and liver function, evidence of bony disease on imaging, prior chemotherapy regimens, total radiation dose, and PSA. This study was IRB approved. Results: 52 patients with mCRPC were identified, 27 of which received xofigo. 23 patients received treatment at UF, and one was lost to follow-up. 16 patients (73%) completed the full course (6 doses) of xofigo, while 6 did not. 10 patients (45%) developed pancytopenia, with 2 recovering counts within eight months while the other 8 had persistent cytopenias (6 of which were transfusion-dependent). Older age (74.0 ± 8.8 vs 68.7 ± 10.2) and higher ECOG score (1.6 ± 0.7 vs 1.2 ± 0.6) correlated with increased risk of pancytopenia. In addition, a higher percentage of patients who received prior radiation therapy were more likely to develop pancytopenia (90% vs 75%). All patients studied had bony disease and received prior chemotherapy. Conclusions: Albeit with a limited sample size, we found a higher rate of xofigo-induced pancytopenia in our patient population than the 2% reported in the literature. This may influence clinical decision making in the treatment of mCRPC, as pancytopenia may preclude patients from other survival-prolonging therapies. Factors such as age, functional status, and prior radiation therapy are important to keep under consideration prior to xofigo treatment. Additional larger studies are necessary to further quantify this effect.
Post-transplant lymphoproliferative disorder (PTLD) is a well-known complication of hematopoietic stem cell transplant and solid organ transplant. While reduction in immunosuppression (RIS) is the ...first-line treatment for PTLD, outcomes of allograft function as a result of RIS remain understudied. In this retrospective study, we examine rates of allograft rejection and graft failure after RIS in 141 patients diagnosed with PTLD at the University of Florida. Compared to prior literature demonstrating around 32-40% rate of allograft rejection as result of RIS, our institutional analysis revealed a much lower treatment-related allograft rejection rate of 18.4%. Out of the patients who experienced acute allograft rejection, 23.1% ultimately progressed to allograft failure. Interestingly, acute allograft rejection episodes during PTLD treatment were not statistically found to impact overall survival. RIS remains an overall beneficial treatment modality of PTLD due to its low allograft rejection rate relative to treatment rate.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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