Oncologist最新文献

Background: Predicting early treatment response in advanced non-small cell lung cancer (NSCLC) is challenging. Longitudinal monitoring of circulating tumor DNA (ctDNA) can track tumor response to treatments like immune checkpoint blockade (ICB) and correlate with outcomes. This meta-analysis evaluated whether ctDNA clearance or decrease is associated with improved survival across various settings in NSCLC.

Methods: A systematic review of MEDLINE, EMBASE, and Cochrane databases (up to April 2024) identified studies evaluating the impact of ctDNA kinetics on survival outcomes in non-curative NSCLC settings. Pooled hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS) were calculated using a random effects model.

Results: We included 32 studies with 3047 NSCLC patients receiving systemic therapies such as targeted therapy (TT), ICB, and chemotherapy. Meta-analysis of 31 studies showed that ctDNA decrease/clearance was linked to improved PFS (HR: 0.32 [0.26, 0.40], I² = 63%, P < .01). Subgroup analysis indicated strong PFS benefits from ctDNA clearance (HR: 0.27 [0.20, 0.36]). Similar improvements were seen across patients undergoing targeted therapy (HR: 0.34) and ICB (HR: 0.33). Analysis of 25 studies revealed a significant association between ctDNA reduction and better OS (HR: 0.31 [0.23, 0.42], I² = 47%, P < .01). Subgroup findings were consistent for both TT (HR: 0.41) and ICB (HR: 0.32). Sensitivity analysis demonstrated that ctDNA clearance/decrease was consistently associated with improved PFS across study designs and ctDNA analysis methods. There was no significant variation in hazard ratios for PFS based on NSCLC subtypes, smoking status, or sex.

Conclusion: Plasma ctDNA kinetics was associated with improved survival outcomes in patients diagnosed with advanced NSCLC undergoing treatment with TT and ICB.

Background: Gastrointestinal (GI) malignancies remain the culprit behind a substantial portion of cancer-related mortality worldwide, and outcomes for patients with advanced or metastatic GI cancers remain poor despite continued efforts to improve care. In 2024, the ongoing clinical trials to optimize and improve GI cancer care showcased progress in molecular diagnostics, systemic therapies, and localized treatment approaches, providing hope for continued progress toward improved patient outcomes.

Materials and methods: This review summarizes selected updates in GI cancer care from the 2024 ASCO and ESMO Annual Meetings, including both positive and negative trials that, while not universally practice-changing, contribute to shaping GI cancer care, clinical management, or address key questions in the field. The selected trials cover early detection and diagnostic advances, perioperative management, metastatic disease management, and immune checkpoint inhibitor (ICI)'s emerging role in GI cancer.

Results: Various clinical trials in perioperative management and their results continue to reshape or strengthen the current treatment paradigms. The use of ICIs for microsatellite instability-high colorectal cancer (CRC) presented a notable advancement with the potential to improve patient outcomes. Localized treatments such as thermal ablation appear to benefit some patients with CRC and liver metastases.

Conclusions: The collection of trial results presented at the 2024 ASCO and ESMO Annual Meetings denote the ongoing efforts of the medical and scientific community for optimizing GI cancer care. The ongoing efforts of the GI cancer research and patient community provide hope for continued progress toward improved patient outcomes and new standards of care.

Real-world success rate of liquid and tissue-based comprehensive genomic profiling (CGP) is unknown. We analyzed real-world pan-tumor cohorts that underwent CGP during clinical care via FoundationOne CDx (F1CDx) and FoundationOne Liquid CDx (F1LCDx) to determine tissue and liquid sample adequacy based on tumor type. Pan-tumor presequencing adequacy was high (>90%) by both tissue-based F1CDx (median: 92.3%; range: 88.2%-96.9%) and liquid-based F1LCDx (median: 94.8%; range: 86.6%-96.7%). Similarly, postsequencing analysis revealed that most tissue and liquid samples yielded successful sequencing results with a median sequencing success rate of 97.9% and 98.1% for F1CDx and F1LCDx, respectively. One exception is central nervous system (CNS) tumors, for which F1CDx had dramatically higher sample sufficiency (96.9%) and postsequencing success rate (97.0%) compared with F1LCDx (86.6% and 92.9%, respectively). The pan-tumor median sample-to-success rate was 90.4% (range: 84.8%-94.4%) for F1CDx. The equivalent rate for F1LCDx was slightly higher at 93.2% (range: 80.4%-95.7%). Conversely, when examining the prevalence of F1LCDx results with high tumor fraction (TF≥1%), the sample-to-high TF results rate was dramatically lower (median: 37.7%, range: 2.1% [CNS tumors]-46.0%). In conclusion, except in CNS tumors or when accounting for liquid TF, success rates of F1CDx and F1LCDx are equivalently high. These results may guide informed decision on when to pursue tissue vs liquid testing of patients with cancer.

Background: Programmed-cell death protein 1 (PD-1) inhibitors have emerged as a standard of care treatment among advanced-stage or metastatic cutaneous squamous cell carcinoma (cSCC). Immune-compromised patients and particularly solid organ transplant recipients (SOTRs) are considered at high risk for cSCC. When treated with PD-1 inhibitors, the possibility of organ rejection, autoimmune flare, or insufficient response to treatment is feared. As these patients were excluded from past prospective clinical trials, we aim to describe our institute's experience regarding these patients.

Methods: A retrospective analysis was conducted on cSCC patients treated with PD-1 inhibitors. Comparisons were made between immune-compromised and immune-competent groups, with a subgroup analysis of SOTR.

Results: The study cohort comprised of 133 patients, including 97.8% receiving Cemiplimab with a mean age of 77.2 ± 11.7 years. Immune-compromised patients constituted 26.9% (n = 35) of the cohort, including 10 SOTR (all kidney transplant recipients). Objective response rates (ORRs) and disease control rates (DCR) were comparable between immunocompetent and immunosuppressed patients receiving Cemiplimab (ORR: 76.8% vs 62.9%, P = .12; DCR: 81.1% vs 68.6%, P = .13). SOTR demonstrated an 80% ORR and DCR. Progression-free survival was comparable across all groups. Toxicity rates were similar between immunosuppressed and immunocompetent subgroups (68.6% vs 62.1%, P = .5). Two OTRs (20%) experienced acute graft rejection.

Conclusions: PD-1 inhibitors demonstrate efficacy and safety in immunosuppressed cSCC patients. While effective in SOTR, treatment requires multidisciplinary management due to the potential risk of organ rejection. These findings provide valuable insights into this understudied population and support the use of PD-1 inhibitors in immunosuppressed patients with advanced cSCC.

Background: The efficacy of adjuvant chemotherapy for T1N0M0 triple-negative breast cancer (TNBC) has not been clearly elucidated. Thus, we aimed to evaluate the efficacy of adjuvant chemotherapy for patients with T1a-cN0M0 TNBC.

Patients and methods: Patients newly diagnosed with TNBC between 2011 and 2015 were identified and followed up until the end of 2020 using the Taiwan Cancer Registry. Univariate and multivariate Cox proportional hazards regression analyses were performed to compare the recurrence-free survival (RFS) and OS between patients who received and those who did not receive adjuvant chemotherapy.

Results: Of the 62 483 patients registered during 2011-2015, 1074 patients with T1N0M0 TNBC (T1a, n = 103; T1b, n = 167; and T1c, n = 804) who underwent definitive breast surgery were included. Overall, 850 (79%) patients received adjuvant chemotherapy; these comprised 24.3%, 67.7%, and 88.6% of the patients with T1a, T1b, and T1c disease, respectively. Over a median follow-up of 7.18 years, a significant RFS and OS benefit from adjuvant chemotherapy was observed in the T1c subgroup but not in the T1a and T1b subgroups. However, subgroup analysis of T1b disease indicated that adjuvant chemotherapy yielded an OS benefit to patients with histological grade III disease (adjusted hazard ratio = 0.08, 95% CI, 0.01-0.77; P = .03).

Conclusions: Adjuvant chemotherapy improved the RFS and OS in patients with T1cN0M0 TNBC and improved the OS in patients with histological grade III T1bN0M0 disease. Our study advocates for the utilization of adjuvant chemotherapy in patients diagnosed with T1cN0M0 and histological grade III T1bN0M0 TNBC.

Background: Preclinical data suggest antifungal azole derivatives have antitumor efficacy that may modulate response to immune checkpoint inhibitors (ICIs). We aimed to evaluate the association of azole drugs with overall survival (OS) in a population of patients with non-small cell lung cancer (NSCLC) treated with ICI within the Veterans Health Administration (VHA).

Methods: In this retrospective study, the VA Corporate Data Warehouse was queried for patients diagnosed with NSCLC and treated with ICI from 2010 to 2018. Concomitant oral azole use was defined as dispensation by a VA pharmacy within 90 days of the first ICI infusion. Patients who received azole after 30 days were excluded from the analysis to mitigate immortal time bias. OS was measured from the start of ICI. Cox regression and propensity score matching were used to adjust for confounders.

Results: We identified 3413 patients with NSCLC receiving ICI; 324 (9.5%) were exposed to concomitant azoles. As a group, azole use was not associated with OS (hazard ratio [HR] = 0.96; 95% CI, 0.84-1.09; P = .51). After stratification by azole type, clotrimazole had an association with better OS on univariable (HR = 0.75; 95% CI, 0.59-0.96; P = .024) and multivariable analysis (HR = 0.71; 95% CI, 0.56-0.91; P = .007). Propensity score matching of patients who received clotrimazole vs no azole yielded 101 patients per matched cohort. Clotrimazole was associated with improved OS, although this did not meet the threshold for statistical significance (HR = 0.74; 0.54-1.01; P = .058).

Conclusion: This observational study demonstrated an association between clotrimazole and OS among patients with advanced NSCLC receiving ICI. These findings build upon preclinical evidence and support further investigation into the potential for clotrimazole as a repurposed FDA drug to improve cancer outcomes.

Immune checkpoint inhibitors (ICIs) have advanced the treatment of metastatic melanoma. However, some patients develop ICI-associated toxicities like hepatitis (ie, immune-mediated hepatitis; IMH). Although these toxicities usually resolve with steroids, steroid-refractory events may occur, which may be a major source of morbidity and mortality without obviously defined treatment algorithms. Herein, we present 2 patients with metastatic melanoma who had IMH that was steroid-refractory and only partially mycophenolate-responsive, but fully resolved with budesonide. The case suggests that budesonide is a potential option to treat IMH that is refractory to standard treatments, but further investigation in a larger series is needed to identify the most optimal setting for budesonide use.

Background: The prognosis for patients with pancreatic ductal adenocarcinoma (PDAC) is poor. Secondary brain metastasis (Br-M) occurs in less than 1% of patients. Clinical characteristics and molecular alterations have not been characterized in this rare patients' subset.

Materials and methods: The Foundry software platform was used to retrospectively query electronic health records for patients with Br-M secondary to PDAC from 2005 to 2023; clinical, molecular, and overall survival (OS) data were analyzed.

Results: Br-M was diagnosed in 44 patients with PDAC. Median follow-up was 78 months; median OS from initial PDAC diagnosis was 47 months. Median duration from PDAC diagnosis to Br-M detection was 24 months; median OS from Br-M diagnosis was 3 months. At Br-M diagnosis, 82% (n = 36) of patients had elevated CA19-9. Lung was the most common preexisting metastatic location (71%) with Br-M, followed by liver (66%). Br-M were most frequently observed in the frontal lobe (34%, n = 15), cerebellar region (23%, n = 10), and leptomeninges (18%, n = 8). KRAS mutations were detected in 94.1% (n = 16) of patients who had molecular data available (n = 17) with KRASG12V being the most frequent subtype 47% (n = 8); KRASG12D in 29% (n = 5); KRASG12R in 18% (n = 3). Patients who underwent Br-M surgical resection (n = 5) had median OS of 8.6 months, while median OS following stereotactic radiosurgery only (n = 11) or whole-brain radiation only (n = 20) was 3.3 and 2.8 months, respectively.

Conclusion: Br-M is a late PDAC complication, resulting in an extremely poor prognosis especially in leptomeningeal disease. KRAS was mutated in 94.1% of the patients and the KRASG12V subtype was prevalent.

Background: Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment but can trigger immune-related encephalitis. We report one of the largest case series of patients with immune-related encephalitis and review of the literature.

Methods: Retrospective series of patients with immune-related encephalitis and literature review.

Results: Fourteen patients with cancer treated with ICI (50% combination therapy) developed immune-related encephalitis. Diagnostic testing revealed cerebral spinal fluid (CSF) lymphocytic pleocytosis (85%) and elevated protein (69%), abnormal brain magnetic resonance imaging(MRI) (33%) or brain FDG-PET (25%), electroencephalogram (EEG) abnormalities (30%), and autoantibodies (31%). Encephalitis treatment included: corticosteroids (86%), intravenous immunoglobulin (IVIg) (36%), plasmapheresis (7%), and rituximab (29%). There were no deaths and 12 patients had significant recovery, although long-term complications were observed. All patients discontinued ICI. Longitudinal follow-up demonstrated anti-cancer response to ICI at 3 months (85%) and 6 months post-ICI initiation (77%). A literature review identified 132 patients with immune-related encephalitis. Most were treated with PD-1 inhibitors (18% combination). Common abnormalities included elevated CSF protein (84%) or pleocytosis (77%), abnormal brain MRI (65%), or autoantibodies (47%). Nearly all were treated with corticosteroids, many required additional therapy with IVIg (26%) or rituximab (12%). Most patients had clinical improvement (81%) but a minority (10%) had a clinical relapse after completing corticosteroid taper. ICIs were resumed in 7 patients (5%), with relapse in 3.

Conclusions and relevance: Immune-related encephalitis is treatable and improves with corticosteroids in most cases but may require additional immunosuppression. Re-emergence of encephalitis is rare and does not typically result in adverse outcomes, and this should be considered in neurological immune-related adverse event management guidelines.