Asia-Pacific journal of clinical oncology最新文献

Aim: To characterize the long-term adverse events (AEs) observed in patients who received lenvatinib.

Methods: We longitudinally assessed long-term AEs in patients with advanced or metastatic radioiodine-refractory differentiated thyroid cancer who had received lenvatinib for more than 1 year. AEs were graded according to the National Cancer Institute Common Terminology Criteria for AEs. Grade 2 AEs were defined as intolerable if a patient complained of distress.

Results: Seventeen patients were treated for more than 1 year. The median age was 69 years. The median duration of lenvatinib treatment was 40 months. Notable intolerable grade 2 and 3 AEs were developed in the following order: hypertension (median day 18; range, day 1-131), diarrhea (median, day 27; range, day 4-1205), hand-foot skin reaction (median, day 33; range, day 20-582), platelet decrease (median, day 57; range, day 15-427), proteinuria (median, day 72; range, day 18-1772), anorexia (median, day 319; range, day 57-1541), and chronic kidney disease (CKD) (median, day 715; range, day 274-1296). After 2 years of administration, the decrease in estimated glomerular filtration rate became remarkable. Grade 3 hypertension occurred in 94.1% (16/17) of patients, of whom 66.8% (11/16) developed intolerable grade 2 proteinuria at a median interval of 35 days. Of these patients, 54.5% (6/11) developed intolerable grade 2 CKD at a median interval of 245 days.

Conclusions: This longitudinal study revealed which AEs appeared and when. The findings provide useful information about when and which AEs we should be attentive to during daily practice.

Background: Polatuzumab vedotin + bendamustine + rituximab (Pola-BR) was recently approved in Malaysia for treating relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). A multicenter retrospective study was conducted to assess the effectiveness of this regimen among patients in a compassionate use program.

Objective: To determine treatment response and survival rates for R/R DLBCL patients treated with Pola-BR in Malaysia.

Methodology: Safety and efficacy data of 23 adults with R/R DLBCL treated with Pola-BR at nine centers in Malaysia (September 2019-February 2021) were used. Of the 23 patients, 13 received six cycles of Pola-BR. The median follow-up was 10 months (1-37 months). The primary endpoint was complete response (CR) rate; secondary endpoints were overall survival (OS), progression-free survival (PFS), and adverse events (AEs).

Results: The overall response rate was 56.5%, with 34.8% achieving CR. The 1-, 2-, and 3-year OS rates were 51.6%, 51.6%, and 44.2%, respectively, with a median OS of 27 months. The 1- and 2-year PFS rates were 48.2% and 41.3%, respectively, with a median PFS of 10 months; 60% of the nonresponders had progressive disease. Cox proportional hazard regression analysis showed that bulky disease was a significant hazard for disease progression. A total of 42 AEs were recorded, of which 66.7% were grade ≥ 3 AEs; 90.5% of the AEs were hematological and resolved with treatment; only one patient succumbed to neutropenic sepsis.

Conclusions: Pola-BR has a favorable safety profile for R/R DLBCL treatment in Malaysia, although larger sample sizes and longer follow-ups are needed to confirm these results.

Aims: Patients with laryngeal and other head and neck cancers face a high risk of developing second primary cancers. This retrospective cohort study evaluated the prognostic value of second primary cancers in laryngeal cancer patients treated with radiotherapy.

Methods: We retrospectively investigated patients with laryngeal cancer who underwent radiotherapy, and evaluated the incidence and relative risk of synchronous and metachronous second primary cancers in a single-institution cohort.

Results: Between January 2007 and December 2021, 138 patients with laryngeal cancer were analyzed. The median follow-up period was 5.2 years. The 5-year overall survival rate was 82.4% and the progression-free survival rate was 71.9%. Synchronous and metachronous second primary cancers were observed in 15 (10.9%) and 38 (27.5%) patients, respectively, during the follow-up period. The cumulative incidence of metachronous second primary cancers was 23.3% at 5 years. Moreover, deaths from laryngeal cancer, other cancers, and noncancer illnesses accounted for 3.6% (5 patients), 12.3% (17 patients), and 10.9% (17 patients), respectively, with most deaths from causes other than laryngeal cancer occurring after the first 5 years. Synchronous second primary cancer was a significant prognostic factor of poor outcomes (hazard ratio, 4.42; 95% confidence interval, 1.93-10.13) on time-independent multivariate analysis, and metachronous second primary cancer was a significant prognostic factor of poor outcomes (hazard ratio, 4.55; 95% confidence interval, 2.09-9.91) in the time-dependent Cox proportional hazards model.

Conclusion: Synchronous and metachronous second primary cancers are significant prognostic factors for patients with laryngeal cancer treated with radiotherapy.

Background: Randomized studies have demonstrated superior overall survival (OS) of pembrolizumab (pembro), both alone and in combination with chemotherapy (chemo) over chemo alone in patients with programmed cell death ligand-1 (PD-L1) ≥ 50% advanced non-small cell lung cancer (NSCLC). We reviewed the real-world outcomes of patients who received pembro-chemo versus pembro only.

Methods: This Australian-based retrospective cohort study used data from patients with advanced NSCLC PD-L1 ≥ 50%, diagnosed between January 2016 and July 2021 and had received first-line pembro-chemo or pembro only. Patients with an EGFR/ALK/ROS1 sensitizing mutation were excluded. Cox proportional-hazards model and Kaplan-Meier methods were used to estimate OS and progression-free survival (PFS).

Results: Of 111 eligible patients, 25 received pembro-chemo and 86 received pembro only. After a median follow-up of 15.7 months, median (95% CI) OS was not reached in the pembro-chemo group versus 15.6 (9.5-21.7) months in the pembro-only group (HR 0.57, 95% CI 0.28-1.16, p = 0.12). Median PFS was 12.4 (6.5-18.3) versus 9.5 (6.3-12.6) months in pembro-chemo versus pembro-only groups, respectively (HR 0.62, 95% CI 0.32-1.18, p = 0.18). Objective response rate (ORR) was higher in the pembro-chemo group (60% vs. 30.3%). There were more hospitalizations in the pembro-chemo group versus pembro-only group, 28% versus 18.6%, but immune-related adverse events were similar (32% vs. 32.6%).

Conclusion: In patients with PD-L1 ≥ 50% advanced NSCLC, addition of chemo to first-line pembro yielded a higher ORR but no additional benefit in PFS or OS, supporting a shared-decision approach. However, higher rates of hospitalizations seen in the pembro-chemo group should warrant caution in use.

Introduction: Access to early-phase cancer clinical trials is heavily skewed toward urban patients treated at tertiary centers, creating significant inequity for regional/rural (R/R) populations. For early drug development (EDD) trials, travel requirements are a major barrier to R/R participation. Growing public and governmental policy pressure on pharmaceutical stakeholders and trial centers has driven the exploration of innovative solutions to improve access. Among these, the teletrial model, which has been effective in later-phase studies, presents an opportunity to address recruitment challenges in phase 1 trials. This article provides practical guidelines for implementing teletrials in EDD.

Methods/results: This review outlines key operational, regulatory, and logistical considerations for phase 1 teletrials, covering site evaluation, ethics and governance, resource allocation, and funding models. Several teletrial frameworks are presented, tailored to the varying capabilities of satellite sites and the complexities of early-phase trials. Lessons learned from successful pilot initiatives are integrated into the recommendations to help guide site conversion and trial design.

Discussion: Phase 1 teletrials are a necessary evolution in clinical trial conduct, driven by increasing demands for equitable access to life-saving therapies. Challenges, including resource-intensive set-up, cost management, and oversight requirements, are acknowledged. However, with proper planning and stakeholder collaboration, teletrials offer significant benefits: increased trial recruitment, improved R/R patient access, and reduced geographic disparities. The expansion of teletrials will be crucial for meeting the recruitment challenges posed by biomarker-driven and rare-disease studies while maintaining safety and scientific integrity.

Background: Hepatocellular carcinoma (HCC) is the most common liver cancer. Exploring non-apoptotic regulated cell death (RCD) offers a strategy to overcome drug resistance. This study investigates a risk model based on non-apoptotic RCD-related genes to predict clinical outcomes and guide immunotherapy.

Methods: We identified genes associated with non-apoptotic RCD in HCC through weighted gene co-expression network analysis (WGCNA) and differential analysis. We then employed non-negative matrix factorization (NMF) clustering to categorize HCC into molecular subtypes related to non-apoptotic RCD and identified differentially expressed genes (DEGs) among these subtypes. We developed a prognostic model utilizing Cox regression and LASSO analysis, stratifying patients into specific risk groups and validating the model's prognostic significance. We subsequently analyzed immune functions and tumor mutation burden (TMB). Finally, we identified potential drugs and evaluated drug sensitivity specific to HCC.

Results: We identified four non-apoptotic RCD genes and classified patients into three subtypes. We observed significant differences in immune characteristics and prognostic outcomes among these groups. Six DEGs emerged as key indicators for risk assessment, leading to a prognostic model. High-risk patients face poorer survival rates and increased mortality. Independent prognostic analyses confirm that these models can effectively predict patient outcomes. Notably, in high-risk patients, immune-related functions appear suppressed, facilitating tumor immune evasion.

Conclusion: We developed a risk model focused on non-apoptotic RCD genes. This model accurately predicts the prognosis for HCC patients. It may also offer new insights for clinical decisions and immunotherapy.

Objective: This study aims to assess the impact of preoperative synchronized lateral lymph node simultaneous integrated boost radiation therapy on the prognosis of T3-4N+ rectal cancer patients.

Methods: A retrospective analysis was performed on 35 patients with rectal cancer from Beijing Luhe Hospital affiliated to Capital Medical University from August 1, 2019 to April 30, 2023, including 22 patients with T3-4N+ rectal cancer, all of whom received the above preoperative therapy: planning gross tumor volume (PGTV): 95% PGTV 55 Gy/2.2 Gy/25 times; planning gross tumor volume of node (PGTVnd): 95% PGTVnd 60 Gy/2.4 Gy/25 times; and planning target volume (PTV): 95% PTV 50 Gy/2 Gy/25 times. Total mesorectal excision (TME) was performed 8-12 weeks after the radiotherapy. The primary endpoints were postoperative pathologic complete response (pCR) rate, downstaging rate, and 1-, 2-, and 3-year local regional recurrence-free survival (LRRFS). The secondary endpoints were anal retention rate, 1-, 2-, and 3-year event-free survival (EFS), overall survival (OS) rates, treatment-emergent adverse events (TEAEs), and perioperative complications.

Results: All 22 patients completed treatment, with pCR rate of 22.7% (5/22), anal preservation rate of 77.3% (17/22), tumor downstaging (T-downstaging) rate of 95.5% (21/22), and nodal downstaging (N-downstaging) rate of 100% (22/22), and 1-year postoperative LRRFS, EFS, and OS rates of 100%, 80%, and 86%, respectively; 2-year LRRFS, EFS, and OS rates of 90%, 63%, and 75%, respectively; and 3-year LRRFS, EFS, and OS rates of 90%, 63%, and 63%, respectively. Only two cases of Grade 3 adverse events occurred, which were clinically manageable and did not require permanent treatment cessation.

Conclusion: This retrospective analysis demonstrated encouraging short-term outcomes, including a 22.7% pCR rate and a 3-year LRRFS of 90%, with manageable toxicity. Nonetheless, these findings should be interpreted with caution due to the limited sample size and absence of a control arm.

Aim: Cervical cancer is caused by persistent infection with the human papillomavirus. This study aimed to investigate whether the changes in serum inflammatory markers between baseline and posttreatment can predict survival in cervical cancer undergoing definitive chemoradiotherapy (CCRT).

Methods: Eighty-one Stage IB-IVA cervical cancer patients treated with definitive CCRT, with serum inflammatory markers obtained at diagnosis and after completion of pre-planned therapy, were included. The percent changes of post-/pretreatment levels × 100% were calculated for neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic inflammation response index (SIRI), and systemic immune-inflammation index (SII). The cutoffs were obtained with the maximal chi-square statistics.

Results: At a median follow-up of 28 months, the 2-year overall survival (OS) was 75.4%. The 2-year OS for patients with low versus high percent change was as follows: post-/pre-NLR (87.7% vs. 67.8%), post-/pre-MLR (75.9% vs. 71.1%), post-/pre-SIRI (76.5% vs. 61.7%), and post-/pre-SII (91.7% vs. 67.2%) (all p < 0.05). The hazard ratios (HR) in multivariate analysis were as follows: post-/pre-NLR (5.53, 95% confidence interval [CI]: 1.65-18.52), post-/pre-MLR (3.39, 95% CI: 1.39-8.26), post-/pre-SIRI (5.11, 95% CI: 1.92-13.57), and post-/pre-SII (6.57, 95% CI: 1.77-24.36) (all p < 0.05).

Conclusion: This study demonstrates the impact of the dynamics of serum inflammatory markers on survival. It has been consistently demonstrated across the markers. To adopt these markers for personalized treatment decisions, a better understanding of their relation with the actual tumor microenvironment is warranted.

Background: The number of elderly patients with non-small cell lung cancer (NSCLC) is rapidly increasing worldwide. Elderly patients with NSCLC are less suited to active treatment than younger patients. Upfront dose reduction (UDR) of the first cycle of first-line treatment is sometimes chosen for elderly patients due to adverse events. We investigated the clinical impact of UDR in elderly NSCLC patients.

Methods: From a prospective database of consecutive NSCLC patients without actionable genomic alterations who received first-line treatment between November 2018 and March 2024, we analyzed 131 patients of ≥65 years of age. Patients were treated with standard-dose chemotherapy between November 2018 and December 2021 and UDR chemotherapy between January 2022 and March 2024. We retrospectively compared the incidence of adverse events and clinical outcomes between the standard-dose and UDR groups.

Results: The incidence of treatment-related death was relatively lower in the UDR group (UDR vs. standard-dose: 3.0 vs. 13.6%; p = 0.0624). There was no significant difference in the incidence of immune-related adverse events between the two groups. The objective response rate was higher in the UDR group (UDR vs. standard-dose: 61.5 vs. 48.5%; p = 0.161). The log-rank analysis showed that the UDR group had significantly longer median progression-free survival/overall survival relative to the standard-dose group.

Conclusions: UDR as a first-line treatment was safe and could be a suitable approach for elderly patients with NSCLC. Further research is needed to evaluate the clinical outcomes in the treatment of elderly NSCLC patients.