Oncologist最新文献

Background: Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide, with increasing incidence in US. Improvements in disease management and the increasing incidence of patients with metastatic CRC (mCRC) at younger ages means that more patients survive to continue to the third-line treatment setting. Treatment has evolved beyond chemotherapy with the approval of newer agents, but there is no consensus on the optimized choice or sequencing in this treatment setting. Identification of the drivers of treatment decisions may provide evidence to guide decision making, ensuring that patients receive optimal care. The objective of this study was to evaluate treatment preferences and prescribing patterns for third-line mCRC among community-based physicians.

Methods: This study surveyed community-based physicians in the US who were actively treating patients with mCRC.

Results: Overall survival (OS) and impacts to patient quality of life (QoL) were primary considerations for any third-line treatment for mCRC. Physicians considered OS and progression-free survival (PFS) as extremely important factors when making third-line treatment decisions. Most physicians selected trifluridine-tipiracil (FTD-TPI) combined with bevacizumab as their first treatment choice for third-line mCRC (60%), compared to regorafenib (12%), FTD-TPI monotherapy (8%), capecitabine (8%), and fruquintinib (6%). Physicians identified fatigue, neutropenia, and hand foot syndrome as the most challenging adverse events (AEs) to manage, while hand foot syndrome and allergic reactions were the AEs that would most likely lead physicians to discontinue treatment.

Conclusion: These findings highlight the third-line treatment preferences and prescribing patterns of community-based physicians who are actively treating patients with mCRC.

Background: The incidence of thyroid cancer has increased markedly in recent years, largely driven by well-differentiated thyroid carcinoma (WDTC). WDTC is biologically heterogeneous, with generally favorable prognosis but substantial variability in clinical behavior. Advances in molecular imaging, artificial intelligence-assisted diagnostics, and liquid biopsy have altered diagnostic strategies, while targeted therapy and immunotherapy have expanded treatment options for selected patients with advanced disease. The multidisciplinary team (MDT) model has therefore become an essential component of WDTC management through the integration of expertise from multiple specialties.

Methods: This review examines the role of MDT application in WDTC through analysis of relevant literature and international clinical guidelines, focusing on MDT composition, implementation models, clinical roles across diagnostic and therapeutic pathways, and current limitations. Differences in MDT recommendations among guidelines from various regions were also compared.

Results: MDT involvement supports personalized decision-making in WDTC, particularly in cases with indeterminate diagnosis, risk-adapted treatment selection, recurrent disease, and radioiodine-refractory progression. Persistent challenges include overtreatment of low-risk disease, suboptimal management of high-risk cases, limited MDT implementation in primary hospitals, uneven specialty participation, and variability in decision-making within guideline gray zones.

Conclusion: The MDT model provides a structured framework to improve risk-adapted management of WDTC. Future efforts should prioritize refined risk-stratified MDT models, integration of decision-support tools, and expansion of remote platforms to enhance consistency and quality of management.

Background: Tumor suppressor gene (TSG) alterations prognosticate inferior survival in metastatic hormone-sensitive prostate cancer (mHSPC) and may affect response to therapy. We evaluated association of TSG alterations with overall survival (OS) in mHSPC, stratified by initial treatment.

Methods: We identified veterans with de-novo mHSPC diagnosed from 2017-2023 within the Veterans Health Administration. TSG alterations included loss-of-function alterations in RB1, TP53, and PTEN identified by somatic sequencing through the National Precision Oncology Program. Treatments within 4 months of diagnosis included androgen deprivation therapy (ADT), docetaxel, and androgen receptor pathway inhibitors (ARPIs). Kaplan-Meier and Cox models evaluated relationships between TSG alterations, clinical factors, and OS.

Results: Among 1842 veterans who met criteria, 865 had sequencing within six months. TSG alterations were found in 935 veterans, with the most common alterations being TP53 (36.7%), PTEN (23.4%), and RB1 (4.5%). In veterans sequenced within 6 months, RB1, TP53, and PTEN alterations were associated with mortality with a hazard ratio (95% CI) of 2.86 (1.94-4.21) (p < 0.001), 1.64 (1.30-2.05) (p < 0.001), and 1.52 (1.20-1.91) (p < 0.001), respectively. In the same cohort, median OS (95% CI) was 40.7 months (37.5-NR) with no alterations, 34.1 months (30.3-37.3) with one, and 19.7 months (16.5-25.5) with ≥2 TSG alterations. In veterans with ≥1 alteration and sequencing within six months, combination therapy with ARPIs was associated with decreased mortality, aHR (95% CI) of 0.65 (0.48-0.88, p = 0.005).

Conclusions: TSG alterations were associated with inferior OS in veterans with mHSPC. In this real-world observational study, ARPI-based combination therapy in veterans with TSG alterations was associated with the longest survival.

Background: Neoadjuvant treatment for hormone receptor (HR)-positive breast cancer remains limited, particularly for tumours that are insensitive to neoadjuvant chemotherapy. This study aims to compare the efficacy of neoadjuvant endocrine therapy combined with CDK4/6 inhibitors to that of traditional neoadjuvant chemotherapy.

Patients and methods: A total of 49 patients receiving neoadjuvant endocrine therapy plus CDK4/6 inhibitors and 210 receiving neoadjuvant chemotherapy were enrolled. Magnetic resonance imaging (MRI) was performed to assess tumor responses every 2-3 cycles of treatment. Propensity score matching (PSM) was performed to balance baseline characteristics.

Results: Both before and after PSM, the objective response rate (ORR) in the endocrine therapy group was comparable to that of the traditional chemotherapy group. After matching, the ORR was 64.6% (95% CI: 49.5%-77.8%) in the endocrine group and 56.3% (95% CI: 41.2%-70.5%) in the chemotherapy group (p = 0.532). A higher proportion of patients in the endocrine group achieved to pathological complete or near-complete response (Miller-Payne grades 4-5, 13.5% vs. 10.4%) and post-treatment Ki67 < 5%, indicating a potential long-term benefit. Patients with ≥30% regression in maximal tumor diameter after 2 cycles of chemotherapy were considered chemotherapy-sensitive. Among patients with tumours less sensitive to chemotherapy, sequential treatment with neoadjuvant endocrine therapy plus CDK4/6 inhibitors significantly improved ORR (61.8% vs. 32.4%, p = 0.028), and was associated with greater Ki67 reduction and improve Miller-Payne grades.

Conclusion: Neoadjuvant endocrine therapy is a promising alternative for HR-positive breast cancer, especially for patients with poor response to chemotherapy.

Background: Multiple myeloma (MM) health disparities are well-documented, with non-Hispanic Black (NHB) and male individuals experiencing higher disease burdens than their non-Hispanic White (NHW) or female counterparts. However, no studies have shown that how these disparities translate into differences in life expectancy, particularly for monoclonal gammopathy of undetermined significance (MGUS), a precursor to MM. This study quantified the remaining life years and life years lost associated with MGUS and MM to inform MM prevention and control priorities.

Methods: We developed a discrete-event simulation (DES) model of the natural history of MM, calibrated using nationally representative data on serologic-detected MGUS and registry-based MM. The model was stratified by race and gender (NHB/NHW men and women). Life years lost was computed as the difference in life years between populations without and with MGUS/MM.

Results: Remaining life years for MGUS/MM were 17.8/6.3 (95% prediction interval [PI]: 17.4-18.2/5.9-6.9) for NHB men, 20.1/7.7 (95% PI : 19.7-20.5/7.1-8.3) for NHB women, 20.9/7.3 (95% PI: 20.3-21.4/6.7-8.0) for NHW men, and 23.0/8.5 (95% PI: 22.5-23.6/7.7-9.4) for NHW women. Corresponding life years lost associated with MGUS/MM was 7.6/14.2 (95% PI: 7.3-8.0/13.3-15.1), 8.0/16.0 (95% PI: 7.7-8.4/15.0-17.0), 8.4/16.0 (95% PI: 8.0-8.9/14.7-17.3), and 8.8/18.1 (95% PI: 8.4-9.2/16.9-19.4), respectively.

Conclusion: Substantial racial and gender differences were identified and quantified in disease burden associated with MGUS and MM, which provides concrete targets for MM prevention and control efforts. Our findings underscore the need for tailored strategies to reduce MM disparities, e.g., enhancing disease monitoring among NHB populations and improving treatment adherence among men with MM.

Patients and methods: we retrospectively collected data of patients with HR+/HER2- advanced breast cancer (ABC) treated with endocrine therapy (ET) and a CDK4/6 inhibitor (CDK4/6i) aiming to describe the patterns of post-progression outcomes.

Results: Among 452 evaluable patients 325 were treated in the first-line setting. Median progression-free survival (mPFS) was 22.8 months overall and 29.7 months in patients treated in first-line setting. Factors associated with outcomes in multivariate analysis were the line of CDK4/6i therapy, de novo vs recurrent disease, visceral vs bone-only metastases, and primary endocrine resistance.A total of 300 patients progressed and 250 overall and 156 in the first-line cohort received a subsequent treatment. Visceral progression and CDK4/6i duration <12 months were associated with a higher likelihood of receiving anthracycline or taxanes (AT) as compared to ET ±everolimus (EET). Post-progression PFS (PPFS) and post-progression OS (PPOS) were statistically significantly better with EET and capecitabine (C) over AT overall and in patients with visceral progression. Multivariate analysis confirmed a significant advantage for EET and C, while visceral progression retained a significant impact only on PPOS. After progression to the first post-CDK4/6i treatment C obtained a significant better PPOS as compared to other treatments.

Conclusion: We showed in a large real-world series that most patients with HR+/HER2- ABC failing CDK4/6i and ET unselected for the occurrence of molecular mutations retain endocrine sensitivity and may benefit of a subsequent ET ± a targeted therapy delaying the need for chemotherapy regardless of site of progression and prior CDK4/6i therapy duration.

Background: While a well-designed next-generation sequencing-based DNA (DNA-NGS) comprehensive genomic profiling assay can be robust for detecting genomic rearrangements (RE), concurrent RNA-based NGS (RNA-NGS) may improve overall sensitivity.

Patients & methods: We examined detection rates of tissue sequencing-based companion diagnostic (CDx) RE (ALK, BRAF, FGFR2/3, METEx14, NTRK1/2/3, NRG1, RET, and ROS1) in a retrospective cohort of 5129 patients who received DNA- and RNA-NGS in parallel in order to quantify the added value of concurrent DNA- and RNA-NGS over DNA-NGS alone.

Results: The prevalence of CDx gene RE was 3.3% (N = 171) across solid tumors and 2.0% (N = 101) within approved tumor types (ITT) across both DNA and RNA. 20% of CDx RE ITT and 26% of CDx gene RE across solid tumors were detected with RNA-NGS only. Detection of NRG1 and NTRK fusions was most improved due to the challenges of baiting these genes on DNA-NGS with 67% of NRG1 RE+ non-small cell lung cancer (NSCLC) and 67% of NTRK RE+ solid tumors identified on RNA alone. A small proportion (4% ITT and 5% across all solid tumors) of CDx gene RE were detected in DNA alone in samples in which RNA could not be sequenced.

Conclusion: A higher rate of CDx RE detection-most significantly for NRG1 and NTRK fusions-was observed using concurrent DNA-NGS and RNA-NGS compared to DNA-NGS alone. Our results highlight the complementary nature of these methods. Given the substantial clinical benefit of RE-targeted therapies, an integrated DNA/RNA profiling strategy should be part of routine clinical care.

Importance: Despite the proven efficacy of tropomyosin receptor kinase (TRK) inhibitors in advanced neurotrophic tyrosine receptor kinase (NTRK) fusion-positive sarcomas, chemotherapy remains the default first-line therapy in many developing countries.

Objective: This real-world study directly compares outcomes of TRK inhibitors with chemotherapy.

Design: This was a multicenter, retrospective cohort study.

Setting: 50 children with advanced NTRK fusion-positive sarcomas were analyzed from three study centers (2018-2024).

Intervention: Patients were assigned into two groups according to their choice of treatment,including chemotherapy or TRK inhibitors..

Main outcomes and measures: Endpoints included treatment failure rate, objective response rate (ORR), mutilating surgery, time to treatment failure, and event-free survival (EFS). Subgroup analyses were conducted for infantile fibrosarcoma (IFS) and NTRK-rearranged spindle cell tumors.

Results: The efficacy of TRK inhibitors (n = 37) was markedly superior compared to chemotherapy (n = 13). Treatment failure was almost eliminated (2.7% vs. 61.5%, P < 0.001), and ORR was significantly higher (91.9% vs. 53.8%, P = 0.006). Subgroup analysis revealed that TRK inhibitors prevented mutilating surgery in IFS (0.0% vs. 42.9%, P < 0.001) and improved the ORR in NTRK-rearranged spindle-cell tumors (95.0% vs. 0.0%, P < 0.001) in which chemotherapy was ineffective. TRK inhibition also induced faster tumor shrinkage, smaller preoperative burden, and 40% pathological complete responses. Finally, TRK inhibitor also prolonged the time-to-treatment failure and EFS.

Conclusions and relevance: Upfront TRK inhibition provided faster, deeper responses, avoided mutilating surgeries, and enabled curative resections. These findings support TRK inhibitors as the preferred first-line option for children with NTRK fusion-positive sarcomas.

Purpose: Age and sex are known to influence outcomes in neuroendocrine neoplasms (NENs), yet their molecular determinants remain poorly defined. We queried a real-world dataset of gastrointestinal (GI) tract and pancreatic (P) NENs and characterized their clinical, molecular, and immune profiles.

Methods: One thousand nine hundred thirty-five cases (GI: n = 1431, P: n = 504) of NENs were analyzed using Next Generation or Whole Exome Sequencing of DNA, and 1211/1935 cases (GI: n = 917, P: n = 294) underwent Whole Transcriptome Sequencing. We compared the molecular and immune profile with respect to age and sex.

Results: Older age at diagnosis was associated with worse survival in both GI- and P-NENs. In patients with GI-NENs, there was decreased survival in males compared to females. In GI-NENs, TP53, RB1, FAT1, and KMT2D mutations, as well as immune checkpoint gene (ICG) expressions of LAG3, CD80, and HAVCR2 and M1 macrophages increased with increasing age while APC mutations and M2 macrophages decreased with increasing age. In P-NENs, TP53, RB1, KRAS, and SMAD4 mutations and CD4+ T cells increased with increasing age while MUTYH and NTHL1 mutations and M2 macrophages decreased with increasing age. In GI-NENs, TP53, FBXW7, and TERT (promoter) mutations and genomic loss of heterozygosity (gLOH) were increased in males. In P-NENs, PIK3CA mutations and dMMR/MSI-H were increased in females.

Conclusion: Our study queries one of the largest datasets of GI- and P-NENs to date and highlights distinct age- and sex-specific molecular and immune profiles. Given the exploratory nature of these analyses and borderline significance, these results remain hypothesis-generating, providing an initial framework for future validation studies.