JTO Clinical and Research Reports最新文献_第2页

IF 3 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2024-10-16 DOI: 10.1016/j.jtocrr.2024.100739

Nicola Hill MB, BCh, BAO, FRCR, Gerard G. Hanna FRCR, PhD, Gerard M. Walls FRCR, PhD, Jonathan McAleese FRCR

引用次数: 0

S1701, A Randomized Phase 2 Trial of Carboplatin-Paclitaxel With and Without Ramucirumab in Patients With Locally Advanced, Recurrent, or Metastatic Thymic Carcinoma S1701，卡铂-紫杉醇联合或不联合雷莫芦单抗治疗局部晚期、复发性或转移性胸腺癌患者的随机 2 期试验

IF 3 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2024-10-16 DOI: 10.1016/j.jtocrr.2024.100738

Anne S. Tsao MD, MBA , Ming-Hui Hsieh MS , Marianna Koczywas MD , Janet Tu MD , Jonathan Riess MD, MS , Tawee Tanvetyanon MD , Barbara T. Ma MD , Ying-Qi Zhao PhD , Mary W. Redman PhD , Martin J. Edelman MD , David R. Gandara MD , Jhanelle E. Gray MD , Karen L. Kelly MD

Introduction

Thymic carcinoma is a rare and aggressive malignancy with few treatment options. Preclinical studies suggested that targeting the angiogenic pathway may be beneficial in this disease.

Methods

This randomized phase 2 trial enrolled patients with unresectable, locally advanced, recurrent, or metastatic thymic carcinoma. Patients were randomized to receive carboplatin-paclitaxel with or without ramucirumab. The primary end point was progression-free survival (PFS) and secondary end points included response by Response Evaluation Criteria in Solid Tumors, disease control, toxicity, and overall survival. The primary analysis was done using a one-sided 10%-level log-rank test. Target sample size was 66 patients.

Results

Between 2018 and 2022, 21 patients enrolled to ramucirumab plus carboplatin-paclitaxel (RCP, n = 8) and to the control arm (carboplatin-paclitaxel [CP], n = 13) with one patient on CP not meeting eligibility criteria. Owing to slow accrual, the study was terminated early by the Data and Safety Monitoring Board. Of the 20 eligible patients, eight on RCP and nine on CP received protocol treatment. PFS was not statistically different (hazard ratio = 0.51, 80% confidence interval [CI]: 0.24–1.09, p = 0.13). There were no grade 4 or higher treatment-related adverse events with RCP, although 50% experienced grade 3 adverse events, in which one patient had a grade 3 thromboembolic event. Among nine assessable patients for toxicity on CP, one patient (11%) encountered grade 4 neutropenia and one patient (11%) reported grade 3 thromboembolic events. Response rates favored the RCP arm, with an 88% (seven of eight, 80% CI: 59%–99%) response rate compared with 40% (four of 10, 80% CI: 19%–65%) on CP arm (p = 0.04). Disease control rate was higher in the RCP arm (100% versus 70%, p = 0.09). At the time of analysis, as only one death has been reported, overall survival remains immature.

Conclusions

Accrual to this population is challenging, and the study was closed early because of feasibility. Although PFS was not statistically better with RCP, the hazard ratio was 0.51 and the lack of significance was likely due to small sample sizes. Notably, addition of ramucirumab to CP led to higher response rates than CP alone. Future research should consider exploring larger multicenter trials and other combinations to improve outcomes. Challenges in enrollment emphasize the need for innovative strategies and larger collaborations in rare malignancies such as thymic carcinoma.

简介：乳腺癌是一种罕见的侵袭性恶性肿瘤，治疗方法很少。临床前研究表明，靶向血管生成途径可能对这种疾病有益。方法这项随机2期试验招募了无法切除、局部晚期、复发或转移性胸腺癌患者。患者随机接受卡铂-紫杉醇联合或不联合雷莫芦单抗治疗。主要终点是无进展生存期（PFS），次要终点包括实体瘤反应评价标准的反应、疾病控制、毒性和总生存期。主要分析采用单侧10%水平的对数秩检验。目标样本量为66例患者。结果2018年至2022年期间，21例患者加入拉莫单抗加卡铂-紫杉醇治疗组（RCP，n = 8）和对照组（卡铂-紫杉醇[CP]，n = 13），其中1例接受CP治疗的患者不符合资格标准。由于进展缓慢，数据与安全监测委员会提前终止了该研究。在符合条件的 20 名患者中，8 名接受 RCP 治疗的患者和 9 名接受 CP 治疗的患者接受了方案治疗。PFS无统计学差异（危险比=0.51，80%置信区间[CI]：0.24-1.09，P=0.13）。RCP 没有出现 4 级或更高的治疗相关不良事件，但有 50% 的患者出现了 3 级不良事件，其中一名患者出现了 3 级血栓栓塞事件。在 9 名可评估 CP 毒性的患者中，1 名患者（11%）出现了 4 级中性粒细胞减少症，1 名患者（11%）报告了 3 级血栓栓塞事件。RCP 治疗组的应答率更高，为 88%（8 例中的 7 例，80% CI：59%-99%），而 CP 治疗组为 40%（10 例中的 4 例，80% CI：19%-65%）（P = 0.04）。RCP 治疗组的疾病控制率更高（100% 对 70%，p = 0.09）。在进行分析时，由于只报告了一例死亡病例，因此总生存率仍不成熟。虽然 RCP 的 PFS 在统计学上没有更好，但危险比为 0.51，缺乏显著性可能是由于样本量较小。值得注意的是，在 CP 的基础上加用雷莫芦单抗比单用 CP 的反应率更高。未来的研究应考虑探索更大规模的多中心试验和其他组合疗法，以改善疗效。入组方面的挑战凸显了对胸腺癌等罕见恶性肿瘤采取创新策略和扩大合作的必要性。

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引用次数: 0

Real-World Outcomes of Patients With Malignant Pleural Mesothelioma Receiving a Combination of Ipilimumab and Nivolumab as First- or Later-Line Treatment 恶性胸膜间皮瘤患者接受伊匹单抗和 Nivolumab 联合疗法作为一线或二线治疗的实际效果

IF 3 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2024-10-15 DOI: 10.1016/j.jtocrr.2024.100735

Sabine Schmid MD , Lisa Holer MSc , Katrin Gysel MSc , Kira-Lee Koster MD , Sacha I. Rothschild MD , Laura A. Boos MD , Lorenz Frehner MD , Sabine Cardoso Almeida MD , Christian Britschgi MD, PhD , Yannis Metaxas MD , Michael Mark MD , Patrizia Froesch MD , Wolf-Dieter Janthur MD , Anna Allemann MD , Christine Waibel MD , Catherine Von der Mühll-Schill MD , Martin Früh MD , Laetitia A. Mauti MD, PhD

Objectives

On the basis of the positive results of CheckMate-743, first-line (1L) treatment of malignant pleural mesothelioma (MPM) with the combination of ipilimumab and nivolumab (ipi-nivo) has become a standard-of-care. Furthermore, patients who received 1L platinum/pemetrexed chemotherapy are often considered for second or further-line (2L+) ipi-nivo on the basis of MAPS2 results. Here we report on real-world survival and safety outcomes of ipi-nivo for patients with MPM in Switzerland.

Methods

Twelve cancer centers contributed data to this retrospective cohort. Baseline characteristics including age, sex, histology, programmed death-ligand 1 expression, Eastern Cooperative Oncology Group performance status (ECOG PS), and previous/subsequent therapies were collected. The efficacy and safety outcomes were assessed by local investigators.

Results

Of the 109 patients with MPM treated with ipi-nivo between November 2017 and March 2023 (median follow-up of 16.6 months) 75% had epithelioid, 9% biphasic, and 16% sarcomatoid histology. The median age was 72 years; 91% were males, and 83% had an ECOG PS of 0 to 1. Ipilimumab in combination with nivolumab was given as 1L in 43% and as 2L+ treatment in 57% of patients. The objective response rate was 21% in 1L and 15% in 2L+. Median progression-free survival was 6.5 and 2.8 months, respectively. Median overall survival (OS) from the start of ipi-nivo was 12.6 months for 1L and 6.9 months for 2L+. No differences in OS were observed depending on age and programmed death-ligand 1 expression. Nevertheless, the median OS was significantly worse in patients with an ECOG PS of 2 or higher than those with an ECOG PS of 0 to 1 (2.4 versus 11.9 months, p < 0.001). Treatment-related adverse events (TRAEs) of any grade related to ipi-nivo treatment occurred in 65 patients (62%). The highest-grade TRAE was 1 to 2 in 58% of these patients and 3 or higher in 42% Treatment discontinuation due to a TRAE occurred in 22% of patients.

Conclusion

In this real-world cohort of patients with MPM treated with ipi-nivo survival outcomes were inferior to those reported in the CheckMate-743 and MAPS2 trials, whereas safety outcomes were similar.

目的在CheckMate-743取得积极成果的基础上，伊匹单抗和尼夫单抗（ipi-nivo）联合治疗恶性胸膜间皮瘤（MPM）的一线（1L）疗法已成为标准疗法。此外，根据MAPS2的结果，接受过1L铂/培美曲塞化疗的患者通常会被考虑接受二线或三线（2L+）ipi-nivo治疗。在此，我们报告了瑞士 MPM 患者接受 ipi-nivo 治疗的实际生存率和安全性结果。收集的基线特征包括年龄、性别、组织学、程序性死亡配体 1 表达、东部合作肿瘤学组（Eastern Cooperative Oncology Group）表现状态（ECOG PS）以及先前/后续疗法。结果在2017年11月至2023年3月期间接受ipi-nivo治疗的109名MPM患者中（中位随访16.6个月），75%为上皮样组织学，9%为双相组织学，16%为肉瘤样组织学。43%的患者接受了伊匹单抗联合尼妥珠单抗的1L治疗，57%的患者接受了2L+治疗。1L 的客观反应率为 21%，2L+ 的客观反应率为 15%。中位无进展生存期分别为6.5个月和2.8个月。从开始接受ipi-nivo治疗起，1L患者的中位总生存期（OS）为12.6个月，2L+患者的中位总生存期（OS）为6.9个月。根据年龄和程序性死亡配体1表达的不同，OS没有差异。然而，ECOG PS 为 2 或以上的患者的中位 OS 明显低于 ECOG PS 为 0 至 1 的患者（2.4 个月对 11.9 个月，p < 0.001）。65名患者（62%）发生了与ipi-nivo治疗相关的任何级别的治疗相关不良事件（TRAE）。结论在这组接受 ipi-nivo 治疗的 MPM 患者中，实际生存结果不如 CheckMate-743 和 MAPS2 试验报告的结果，但安全性结果相似。

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引用次数: 0

CRYOVATE: A Pilot Study of Lung Cancer Cryoactivation in Combination With Immunotherapy in Advanced NSCLC CRYOVATE：肺癌冷冻激活与免疫疗法相结合治疗晚期 NSCLC 的试点研究

IF 3 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2024-10-15 DOI: 10.1016/j.jtocrr.2024.100737

Antoine Desilets MD, MSc , Gabryella Pinheiro PhD , Wiam Belkaid PhD , Olivier Salko MD , Julie Malo , Eleyine Zarour MD , Adeline Jouquan MSc , Anne-Julie Thibaudeau MSc , Marc-Antoine Nolin MSc , John Stagg PhD , Marie Florescu MD , Mustapha Tehfe MD , Normand Blais MD, MSc , Samer Tabchi MD , Jean Chalaoui MD , Philippe Stephenson MD , Arielle Elkrief MD , Vincent Quoc-Huy Trinh MD, MSc , Bertrand Routy MD, PhD , Moishe Liberman MD, PhD

Introduction

NSCLC is the leading cause of cancer-related mortality. Although immune-checkpoint inhibitors (ICIs) have improved survival in patients with advanced NSCLC, treatment resistance remains a challenge. Cryoactivation, a technique inducing cell death by cycles of freezing and thawing, has the potential to augment tumor responses when combined with ICIs.

Methods

This single-arm phase 1 clinical trial enrolled patients with previously untreated advanced NSCLC and 50% or higher programmed cell death ligand-1 (PD-L1). Patients underwent cryoactivation followed by ICI monotherapy initiated 5 days later. The primary end point was the objective response rate. Co-secondary end points included the safety and feasibility of the procedure and overall survival. Immune cell infiltration by immunohistochemistry was performed on paired pre- and post-treatment samples, with patients dichotomized according to clinical benefit (CB) rate (CB versus no CB [NCB]).

Results

Eight patients were enrolled. Two patients achieved a partial response, yielding an objective response rate of 25%. Median progression-free survival and overall survival were 3.8 and 13.0 months, respectively. The cryoactivation procedure was well tolerated, without grade 3 to 4 adverse events. Post-hoc analysis reported a CB rate of 50%. Immunohistochemistry analysis reported a numerical difference in the cluster of differentiation 8–positive (CD8⁺) T cell infiltration in CB versus NCB in the pre- and post-treatment biopsies (p = 0.09) and an increase in CD8⁺ T cells in the post-treatment biopsies of CB versus NCB (p = 0.03).

Conclusions

Although cryoactivation combined with pembrolizumab was safe and well tolerated in patients with NSCLC, therapeutic benefits were not evident compared with historical cohorts of ICI monotherapy. Correlative analyses validated CD8⁺ T cell recruitment in patients deriving CB.

导言：NSCLC 是癌症相关死亡的主要原因。尽管免疫检查点抑制剂（ICIs）提高了晚期NSCLC患者的生存率，但耐药性仍然是一个挑战。冷冻激活是一种通过冷冻和解冻循环诱导细胞死亡的技术，与 ICIs 联用时有可能增强肿瘤反应。患者接受低温激活，5天后开始接受ICI单药治疗。主要终点是客观反应率。次要终点包括手术的安全性和可行性以及总生存率。免疫组化法对治疗前后的配对样本进行免疫细胞浸润检测，并根据临床获益率（CB）（CB 与无 CB [NCB]）对患者进行二分法。两名患者获得了部分应答，客观应答率为25%。无进展生存期和总生存期的中位数分别为 3.8 个月和 13.0 个月。冷冻激活过程耐受性良好，未出现 3 至 4 级不良反应。事后分析显示，CB率为50%。免疫组化分析表明，在治疗前和治疗后的活组织切片中，CB 与 NCB 的分化簇 8 阳性 (CD8+) T 细胞浸润在数量上存在差异（p = 0.09），而在治疗后的活组织切片中，CB 与 NCB 的 CD8+ T 细胞有所增加（p = 0.03）。结论虽然低温激活联合 pembrolizumab 对 NSCLC 患者安全且耐受性良好，但与 ICI 单药治疗的历史队列相比，治疗效果并不明显。相关分析验证了 CB 患者的 CD8+ T 细胞招募。

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引用次数: 0

Radiotherapy Improves Survival in NSCLC After Oligoprogression on Immunotherapy: A Cohort Study 放疗可提高免疫治疗寡进展后 NSCLC 患者的生存率：队列研究

IF 3 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2024-10-01 DOI: 10.1016/j.jtocrr.2024.100695

Lauren Julia Brown M.B.B.S., MClinTRes, FRACP , Julie Ahn M.B.B.S. , Bo Gao BMedSci M.B.B.S., FRACP, PhD , Harriet Gee M.B.B.S., DPhil, FRANZCR , Adnan Nagrial M.B.B.S., FRACP, PhD , Inês Pires da Silva MD, FRACP, PhD , Eric Hau BSc (Med), M.B.B.S., Grad Cert (Biostat), FRANZCR, PhD

Introduction

The patterns of oligoprogression after first-line immune checkpoint inhibitors (ICIs) for metastatic NSCLC are yet to be well established. An increasing volume of data suggests that directed radiotherapy improves survival outcomes in patients with progression after ICIs.

Methods

A retrospective cohort study was performed on patients with metastatic NSCLC who had completed first-line programmed death-(ligand) 1 inhibitor therapy with or without chemotherapy at two high-volume cancer centers. We sought to characterize the frequency and location of oligoprogression and determine the overall survival (OS) after radiotherapy in this population.

Results

A total of 159 patients were included in the study. At first progression, 62 (39.0%) were classified as undergoing oligoprogression. Multivariate analysis confirmed the presence of brain metastases was associated with an increased likelihood of oligoprogression (OR = 2.44, p = 0.04) with most (63.2%) of these patients experiencing progression intracranially. The presence of liver metastases was associated with a decreased likelihood of oligoprogression (OR = 0.17, p < 0.01). For patients with oligoprogression, those who received radiotherapy had a longer median progression-free survival-2 (PFS2) (17 versus 11.5 mo, HR = 0.51, p = 0.02) and a longer median OS (23 versus 13 mo, HR = 0.40, p < 0.001) compared with those who did not receive radiotherapy. No difference in PFS2 or OS outcomes was observed between patients who received radiotherapy versus those who did not for systemic progression.

Conclusions

In patients with oligoprogressive metastatic NSCLC after treatment with first-line ICIs, radiotherapy significantly improves OS and PFS2 outcomes. Patients with baseline brain metastases are more likely to experience oligoprogression. Further prospective studies in directed, less heterogeneous populations of patients with metastatic NSCLC will be fundamental to optimize management.

导言一线免疫检查点抑制剂（ICIs）治疗转移性NSCLC后的寡进展模式尚未完全确定。越来越多的数据表明，定向放疗可改善 ICIs 治疗后病情进展患者的生存预后。方法：我们在两家大型癌症中心对已完成一线程序性死亡（配体）1 抑制剂治疗并接受或不接受化疗的转移性 NSCLC 患者进行了一项回顾性队列研究。我们试图描述寡进展的频率和位置，并确定该人群放疗后的总生存率（OS）。在首次进展时，62 例（39.0%）患者被归类为寡进展。多变量分析证实，脑转移与寡进展的可能性增加有关（OR = 2.44，P = 0.04），这些患者中的大多数（63.2%）在颅内出现进展。肝转移的存在与寡进展的可能性降低有关（OR = 0.17，p = 0.01）。对于寡进展患者，与未接受放疗者相比，接受放疗者的中位无进展生存期-2（PFS2）更长（17个月对11.5个月，HR = 0.51，p = 0.02），中位OS（23个月对13个月，HR = 0.40，p <0.001）更长。结论在接受一线 ICIs 治疗后的寡进展转移性 NSCLC 患者中，放疗可显著改善 OS 和 PFS2。基线脑转移的患者更容易出现寡进展。在定向的、异质性较低的转移性 NSCLC 患者群体中开展进一步的前瞻性研究将是优化治疗的基础。

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引用次数: 0

Intracranial Response to Selpercatinib After Pralsetinib-Induced Disease Progression in Rearranged During Transfection Fusion-Positive Non-Small-Cell Lung Cancer: Case Report 转染融合重组阳性非小细胞肺癌患者在普拉塞替尼诱导疾病进展后对赛乐西替尼的颅内反应：病例报告

IF 3 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2024-09-17 DOI: 10.1016/j.jtocrr.2024.100730

Illaa Smesseim MD, Tijmen van der Wel MD, Sushil K. Badrising MD, PhD

RET fusion-positive NSCLC accounts for 1% to 2% of lung carcinoma cases. Although two Food and Drug Administration–approved selective RET inhibitors, pralsetinib, and selpercatinib, have revealed efficacy in managing RET fusion-positive NSCLC, this case series is unique in its focus on the intracranial response to selpercatinib after disease progression during pralsetinib treatment. This report contributes to the literature by providing evidence of selpercatinib’s potential as a treatment option in such refractory cases. The patients described in both cases were diagnosed with metastatic RET fusion-positive NSCLC and developed intracranial metastases during pralsetinib treatment. After switching to selpercatinib, both exhibited significant intracranial responses. The first patient reported a reduction in brain metastasis size and maintained a response for over 1.5 years. The second patient also responded intracranially to selpercatinib but unfortunately passed away 8 months later owing to pulmonary hemorrhage, possibly linked to prior radiation treatment. These cases highlight the potential efficacy of selpercatinib in treating intracranial metastases in RET fusion-positive patients with NSCLC after pralsetinib-refractory progression. The key takeaway is that selpercatinib may offer a viable treatment option in such scenarios, although more extensive studies are needed to determine its role as a monotherapy or in combination with other treatments.

RET融合阳性NSCLC占肺癌病例的1%至2%。虽然美国食品和药物管理局批准的两种选择性RET抑制剂普拉塞替尼和色瑞帕替尼在治疗RET融合阳性NSCLC方面具有疗效，但本系列病例的独特之处在于它关注了普拉塞替尼治疗期间疾病进展后对色瑞帕替尼的颅内反应。本报告提供了证据，证明赛乐替尼有可能成为此类难治性病例的治疗选择，从而为文献做出了贡献。两例患者均被诊断为转移性RET融合阳性NSCLC，并在普拉塞替尼治疗期间出现颅内转移。在改用赛帕替尼治疗后，两例患者均出现了明显的颅内反应。第一例患者的脑转移灶缩小，并在超过1.5年的时间里一直保持着这种反应。第二名患者也对赛帕替尼产生了颅内反应，但不幸在8个月后因肺出血去世，这可能与之前的放射治疗有关。这些病例凸显了色瑞帕替尼治疗普拉塞替尼难治性进展后RET融合阳性NSCLC患者颅内转移的潜在疗效。尽管还需要进行更广泛的研究来确定其作为单一疗法或与其他疗法联合使用的作用，但关键的启示是，在这种情况下，赛帕替尼可能是一种可行的治疗选择。

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引用次数: 0

Developing a Conceptual Framework for a Person-Centered Approach to Improving Adherence and Outcomes in Lung Cancer Screening: The Engaged Approach to Lung Cancer Screening: A Brief Report 为以人为本的方法制定概念框架，以改善肺癌筛查的依从性和结果：肺癌筛查的参与式方法》：简要报告

IF 3 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2024-09-17 DOI: 10.1016/j.jtocrr.2024.100728

Margaret M. Byrne PhD , Erin A. Hirsch PhD, MS , Kaitlyn Hoover MS , Jessica H. McCoy RN, BSN , Courtney R. Blair MS , Michelle Futrell RN , Upal Basu Roy PhD, MPH , Jamie L. Studts PhD

Introduction

Translating outcomes from randomized trials of lung cancer screening into community practice settings has been challenging. We developed a framework—the Engaged Approach to Lung Cancer Screening (EA-LCS)—for improving adherence and individual and population health outcomes in LCS.

Methods

Employing community-engaged research, we conducted semistructured interviews with LCS program staff (N = 15) and participants (N = 7) and administered brief surveys to understand LCS adherence. We combined our knowledge of LCS implementation with data to formulate the EA-LCS framework, including principles and strategies instrumental for LCS adherence.

Results

Program staff identified four factors that facilitated adherence: (1) the use of specialized tracking software, (2) the importance of personal connection and a reliable touchpoint, (3) centralized program operations, and (4) standardization and streamlining of reports to participants and clinicians. Participant data identified four factors supporting adherence: (1) a single contact point and information availability, (2) tailored communications, (3) personalized results delivery, and (4) increased scan accessibility. Combined analyses identified three overarching themes in the EA-LCS framework: (1) respect, (2) trust, and (3) engagement.

Conclusions

The EA-LCS conceptual model integrates three foundational principles (person-centeredness, trustworthy relationships, and sustained communications) to enhance LCS adherence. Efforts are underway to translate the EA-LCS framework into materials to support adherence.

导言将肺癌筛查随机试验的结果转化到社区实践环境中具有挑战性。我们开发了一个框架--肺癌筛查参与式方法（EA-LCS）--用于改善肺癌筛查的依从性以及个人和人群的健康结果。方法我们采用社区参与式研究，对肺癌筛查项目的工作人员（15 人）和参与者（7 人）进行了半结构式访谈，并进行了简短的调查，以了解肺癌筛查的依从性。我们将对 LCS 实施情况的了解与数据相结合，制定了 EA-LCS 框架，其中包括对坚持 LCS 有益的原则和策略。结果项目工作人员发现了四个有助于坚持 LCS 的因素：（1）使用专门的跟踪软件；（2）个人联系和可靠接触点的重要性；（3）集中的项目运作；（4）向参与者和临床医生报告的标准化和简化。参与者数据确定了支持坚持使用的四个因素：(1) 单一接触点和信息可用性，(2) 量身定制的沟通，(3) 个性化的结果交付，以及 (4) 扫描可及性的提高。综合分析确定了 EA-LCS 框架的三个首要主题：(1) 尊重；(2) 信任；(3) 参与。结论 EA-LCS 概念模型整合了三个基本原则（以人为本、值得信赖的关系和持续沟通），以提高 LCS 的依从性。目前正在努力将 EA-LCS 框架转化为支持坚持治疗的材料。

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引用次数: 0

Analysis of Baseline Molecular Factors Associated With the Risk of Central Nervous System Progression Among Alectinib-Treated Patients With ALK–Positive NSCLC 与阿来替尼治疗的ALK阳性NSCLC患者中枢神经系统进展风险相关的基线分子因素分析

IF 3 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2024-09-17 DOI: 10.1016/j.jtocrr.2024.100729

Lianxi Song MD , Huan Yan MD , Qinqin Xu MD , Chunhua Zhou MD , Juan Liang MD , Shaoding Lin MD , Ruiguang Zhang MD , Juan Yu MD , Yang Xia MD , Nong Yang MD , Liang Zeng MD , Yongchang Zhang MD

Introduction

Despite receiving alectinib therapy, patients with ALK-positive NSCLC remain at risk of central nervous system (CNS) progression. Our retrospective study aimed to identify baseline clinical and molecular factors associated with the risk of CNS progression in this patient subset.

Methods

We analyzed the clinical, molecular, and imaging data of 318 patients with ALK-positive advanced NSCLC who received alectinib as first-line (1L-alectinib) or second-line (2L-alectinib) therapy at baseline (1L, n = 183; 2L, n = 135) and at disease progression (1L, n = 80; 2L, n = 76).

Results

The incidence rates of CNS progression were 23.7% after 1L-alectinib treatment and 31.6% after 2L-alectinib treatment. Compared with patients who received 1L-alectinib, CNS progression was similar in patients who received 2L-alectinib (p > 0.05). Oligoprogression was detected in 55.0% (44 of 80) of patients who progressed after first-line alectinib, with the remaining 45.0% (36 of 80) having nonoligoprogression. Univariate and multivariate analyses and stepwise regression analyses consistently identified a higher likelihood of CNS progression among (1) patients who received 2L-alectinib than 1L-alectinib, (2) patients with non-3a/b variant ALK fusion than those with echinoderm microtubule-associated protein-like 4–ALK variant 3a/b, and (3) patients with programmed death ligand 1 (PD-L1) tumor proportion score (TPS) of 50% or higher than PD-L1 TPS of less than 50%.

Conclusions

Our study provided real-world evidence that patients who harbored PD-L1 TPS of 50% or higher were more likely to experience CNS progression during alectinib therapy. The association between CNS progression and breakpoint variants warrants further investigation. Our findings suggest that close monitoring and prompt intervention are crucial in prolonging the quality of life of this patient subset.

简介尽管接受了阿来替尼治疗，ALK 阳性 NSCLC 患者仍有中枢神经系统（CNS）恶化的风险。我们的回顾性研究旨在确定与该患者亚群中枢神经系统进展风险相关的基线临床和分子因素。方法我们分析了318例ALK阳性晚期NSCLC患者的临床、分子和影像学数据，这些患者在基线时（1L，n = 183；2L，n = 135）和疾病进展时（1L，n = 80；2L，n = 76）接受了阿来替尼一线（1L-alectinib）或二线（2L-alectinib）治疗。结果1L-alectinib治疗后中枢神经系统进展发生率为23.7%，2L-alectinib治疗后为31.6%。与接受1L-阿来替尼治疗的患者相比，接受2L-阿来替尼治疗的患者中枢神经系统进展情况相似（p > 0.05）。在一线阿来替尼治疗后出现进展的患者中，55.0%（80 人中有 44 人）发现了寡进展，其余 45.0%（80 人中有 36 人）为非寡进展。单变量和多变量分析以及逐步回归分析一致发现，在以下患者中，中枢神经系统进展的可能性更高：（1）接受 2L-alectinib 治疗的患者比接受 1L-alectinib 治疗的患者、(2) 非3a/b变异型ALK融合患者比棘皮微管相关蛋白样4-ALK变异型3a/b患者；以及 (3) 程序性死亡配体1（PD-L1）肿瘤比例评分（TPS）达到或超过50%的患者比PD-L1 TPS低于50%的患者。结论我们的研究提供了真实世界的证据，表明PD-L1 TPS为50%或更高的患者在阿来替尼治疗期间更有可能出现中枢神经系统进展。中枢神经系统进展与断点变异之间的关联值得进一步研究。我们的研究结果表明，密切监测和及时干预对于延长这一患者亚群的生活质量至关重要。

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引用次数: 0

Regarding: “Olloni A, et al. Heart and Lung Dose as Predictors of Overall Survival in Patients With Locally Advanced Lung Cancer. A National Multicenter Study” 关于"Olloni A 等人，局部晚期肺癌患者总生存期的心脏和肺部剂量预测因素。一项全国多中心研究"

IF 3 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2024-09-07 DOI: 10.1016/j.jtocrr.2024.100718

Arno C. Hessels MD, PhD, Mark L. Frederiks MSc, Christina T. Muijs MD, PhD, Peter van Luijk PhD

引用次数: 0

Simultaneous Occurrence of HER2 Mutations in EGFR Mutant NSCLC: Case Reports 表皮生长因子受体突变 NSCLC 中同时出现 HER2 突变：病例报告

IF 3 Q2 ONCOLOGY

JTO Clinical and Research Reports

Pub Date : 2024-09-07 DOI: 10.1016/j.jtocrr.2024.100719

Blerina Resuli MD , Diego Kauffmann-Guerrero MD , Jürgen Behr MD , Amanda Tufman MD

HER2 mutation and amplification have been identified as distinct molecular targets in lung cancer with different therapeutic and prognostic values. The coexistence of HER2 and EGFR mutations is extremely rare, and therefore, no data exist on the best treatment in these cases.

HER2 基因突变和扩增已被确定为肺癌中不同的分子靶点，具有不同的治疗和预后价值。HER2 和表皮生长因子受体（EGFR）突变同时存在的情况极为罕见，因此目前还没有关于这些病例最佳治疗方法的数据。

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