Future oncology最新文献

Background: Atezolizumab plus bevacizumab (atezo+bev) is a standard-of-care 1L treatment for unresectable hepatocellular carcinoma (uHCC). Understanding its adoption and use, clinical outcomes, and subsequent therapies are needed.

Methods: This retrospective cohort study included 550 patients with uHCC in the US who initiated 1L atezo+bev between June 2020 and April 2023. Medical records were abstracted to describe treatment patterns and outcomes.

Results: Of 294 patients who discontinued 1L therapy, 176 patients initiated 2L therapy (2L cohort) and 48 patients didn't initiate 2L therapy after ≥8 weeks of follow-up (No 2L cohort). More of the No 2L cohort had Stage IVb tumors, BCLC stage D, ECOG-PS ≥2, ascites, and hepatic encephalopathy at baseline. The 2L cohort were more likely to discontinue atezo+bev due to disease progression (92.1% vs. 56.3%), and less likely due to toxicity/intolerability (4.0% vs. 10.4%) than the No 2L cohort. OS from 1L atezo+bev initiation was significantly longer in the 2L cohort vs. No 2L cohort (median 23.0 vs. 14.3 months; p < 0.001]).

Conclusions: 1L Atezo+bev was clinically active with 256 patients remaining on therapy at last follow-up. Patients who progressed after 1L atezo+bev benefited from additional systemic therapies. Future research analyzing the comparative effectiveness of 2L therapies is needed.

Introduction: Head and neck squamous cell carcinoma (HNSCC) accounts for approximately 5% of cancer cases worldwide, with more than half of patients presenting with locally advanced (LA) disease. Treatment of LA HNSCC is multimodal and may include concomitant cisplatin-based chemoradiotherapy (CRT) or surgery; however, recurrence rates are high, and there is an unmet need for new treatments. Immune checkpoint inhibitors that target programmed death receptor-1 (PD-1) are standard of care for recurrent/metastatic HNSCC, but outcomes for anti-PD-1 and anti-PD-(ligand [L])1 therapies with CRT in LA HNSCC have been variable. Dostarlimab, an anti-PD-1 therapy approved in advanced endometrial cancer and mismatch repair-deficient solid tumors is being investigated across other tumor types, including HNSCC. JADE is a global, multicenter, double-blind, placebo-controlled, randomized phase 3 study evaluating the efficacy and safety of dostarlimab as post-cisplatin-based CRT sequential therapy in patients with LA unresected PD-L1-expressing HNSCC. JADE seeks to overcome the limitations of previous studies by incorporating both PD-L1 selection and solely sequential administration of dostarlimab soon after CRT.

Methods: The primary endpoint is event-free survival, with overall survival as a key secondary endpoint; safety and tolerability, pharmacokinetics, immunogenicity, biomarkers, and patient-reported outcomes will also be assessed.

Clinical trial registration: www.clinicaltrials.gov identifier is NCT06256588.

Aims: In the absence of head-to-head comparative trials, this study aimed to compare zanubrutinib versus acalabrutinib in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) by calculating number needed to treat (NNT) to avoid one disease progression or death and associated economic impact.

Methods: A health-economic model was developed from US payer perspective using efficacy data from matching-adjusted indirect comparison for overall R/R CLL in base-case analysis, and network meta-analysis for high-risk R/R CLL in the subgroup analysis. The NNT analysis included costs of drug acquisition, adverse event management, medical resource utilization, and subsequent treatment over 24 months. Deterministic sensitivity analyses assessed model uncertainty.

Results: In the base case, zanubrutinib versus acalabrutinib avoided one progression for every 10 patients treated (NNT = 10) and one death for every 15 patients treated (NNT = 15), yielding per-patient cost savings of $7,335 over 24 months. In high-risk R/R CLL subgroup, one progression was avoided per six patients treated (NNT = 6) and one death per 18 patients treated (NNT = 18), with cost savings of $11,533 per patient. Results were robust across sensitivity analyses.

Conclusions: The NNT analysis demonstrates that treatment with zanubrutinib versus acalabrutinib is associated with more favorable clinical and economic outcomes in R/R CLL, especially in high-risk CLL patients.

Background: Adjuvant chemotherapy decision-making in stage II colon cancer remains challenging. Although multidisciplinary tumor boards (MDTs) guide treatment, their recommendations vary. Artificial intelligence (AI) tools such as ChatGPT may support decision-making, but direct comparative evidence with MDTs is limited.

Methods: We retrospectively analyzed 179 patients with stage II colon cancer who underwent surgery between 2019-2024. MDT recommendations (observation, fluoropyrimidine monotherapy, or oxaliplatin-based chemotherapy) were compared with ChatGPT-5 outputs. Clinical factors - including age, ECOG performance status (PS), tumor stage, minor risk factors, and mismatch repair (MMR) status - were incorporated. Agreement was evaluated using Cohen's kappa (κ) and McNemar's test.

Results: Across the three treatment categories, agreement between MDT and AI was moderate (70.4%, κ = 0.542, p < 0.001), while in the binary comparison of adjuvant therapy versus observation, concordance improved to substantial (91.1%, κ = 0.719, p < 0.001). Discordance mainly reflected AI's tendency to escalate therapy. Agreement decreased in patients ≥70 years, those with ECOG PS 2, and those with multiple risk factors.

Conclusions: AI showed moderate agreement with MDTs in detailed three-category recommendations but substantial concordance in binary adjuvant decisions. While AI may serve as a supportive tool, clinical judgment remains essential, particularly for elderly and frail patients.

Aims: This study aimed to evaluate the prognostic value of the systemic immune-inflammation index (SII) and prognostic nutritional index (PNI) for overall survival (OS) in colorectal cancer (CRC) patients with liver metastasis after transcatheter arterial chemoembolization (TACE).

Patients and methods: A retrospective analysis of 270 CRC patients who underwent TACE was conducted. Baseline comparisons were made between survivors (n = 142) and non-survivors (n = 128) focusing on tumor size, AFP, SII, and PNI. Prognostic factors were analyzed using Cox regression, ROC curves, and Kaplan-Meier analysis.

Results: Significant differences in tumor size, AFP, SII, and PNI were found between the two groups. Multivariate Cox regression revealed that larger tumor size (HR = 1.110, p < 0.001), higher AFP (HR = 1.003, p < 0.001), and elevated SII (HR = 1.001, p < 0.001) were associated with poorer OS, while higher PNI (HR = 0.944, p < 0.001) was protective. ROC analysis yielded AUCs of 0.852 for SII and 0.876 for PNI, with a combined model improving to 0.948. Kaplan-Meier showed that high SII (≥1324.165) and low PNI (<40.915) were associated with poorer 3-year OS (p < 0.001).

Conclusions: SII and PNI are valuable prognostic indicators for OS in CRC patients post-TACE. Elevated SII and reduced PNI predict worse outcomes, and their combination enhances survival prediction.

Aim: To review how molecular preselection and combination treatment affects overall response rate (ORR) in pediatric non-central nervous system (CNS) solid tumors treated with tyrosine kinase inhibitors (TKIs).

Methods: A systematic literature review was performed to identify studies reporting ORR (till July 2023). The review was non-registered and non-meta-analytic.

Results: 53 clinical studies involving 306 molecularly preselected patients (16 studies), 513 molecularly not preselected patients on TKI monotherapy (26 studies) and 350 molecularly not preselected patients on combination therapy (15 studies) met prespecified criteria for ORR analysis. According to the MINORS score, methodological quality was moderate to poor. Molecular preselection increased median ORR to TKI monotherapy from 0% [95% CI, 0%, 6%] to 36% [95% CI, 27%, 50%], (p = 0.001). Combination treatment increased median ORR from 0% [95% CI, 0%, 6%] to 14% [95% CI, 5%, 26%] in molecularly unselected population (p = 0.003). Comprehensive molecular characterization was absent, less than 20% of studies investigated molecular aberrations beyond the mechanism of action of tested TKI. Only few studies were terminated due to safety issues.

Conclusions: Molecular background of tumors should be taken into account when using TKIs. The current molecular pre-selection criteria are insufficient and need to be improved.

Background: This study aims to investigate biomarkers for predicting non-SLN metastasis and tumor metastatic burden in patients with 1-2 positive sentinel lymph nodes (SLNs).

Research design and methods: 581 patients with SLN metastasis were enrolled, and their blood biochemical indices and clinical information were tested and analyzed.

Results: Among patients with 1-2 positive SLNs, the SLN positivity rate was higher in the non-SLN metastasis group than in the non-metastasis group. Additionally, thrombin time (TT) and fibrinogen (Fbg) levels were lower in the non-SLN metastasis group compared with the non-metastasis group, with ROC AUC = 0.712. Regarding tumor burden, among patients with 1-2 positive SLNs, the SLN positivity rate was significantly higher in those with metastasis lymph nodes (mLNs) ≥ 4 than in those with <4 mLNs, with ROC AUC = 0.727.

Conclusions: The SLN positivity rate, TT, and Fbg may serve as potential biomarkers for non-SLN metastasis in patients with 1-2 positive SLNs. Additionally, the SLN positivity rate may serve as a potential biomarker for mLNs ≥ 4 in cases with 1-2 positive SLNs and in those with only 1 positive SLN.

Background: Approvals of Bruton's tyrosine kinase inhibitors (BTKis) and other novel agents have changed the Mantle Cell Lymphoma (MCL) treatment paradigm, necessitating assessment of contemporaneous, real-world (rw) treatment and outcomes by line of therapy (LOT).

Methods: Patients diagnosed with MCL on or after 1 January 2012 who initiated first-line (1 L) treatment in the COTA database were eligible, excluding those with concurrent primaries, history of hematologic malignancies, clinical trial participation, or missing/imprecise key dates. Rw time to next treatment (rwTTNT) and overall survival (rwOS) were evaluated using the Kaplan-Meier method from LOT start (index).

Results: Of 499 patients, most were ≥ 50 years (94.8%), male (71.5%), treated in the community (58.7%), and diagnosed with stage III/IV disease (91.2%). The most common 1 L regimen was bendamustine+rituximab (BR)±R maintenance (12.6%/23.0%, respectively). Fifty (10.0%) patients received 1 L autologous stem cell transplant. One hundred and seventy-three patients (34.7%) received 2 L, of which 72 (41.6% of 2 L) received 3 L, of which 29 (40.3% of 3 L) received 4 L +. BTKi monotherapy was the most frequently administered therapy in 2 L (26.0%).Median rwTTNT and rwOS from 1 L to 4 L were 36.8-3.2 and 86.2-8.7 months, respectively.

Conclusions: Outcomes of patients who received 2 L+ for MCL remain poor, highlighting unmet need in the contemporary treatment paradigm.