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Turtle Study: A Phase 2 Study of Durvalumab Plus Carboplatin and Etoposide in Elderly Patients With Extensive-Stage SCLC (LOGiK 2003) 海龟研究:Durvalumab联合卡铂和依托泊苷治疗老年大分期SCLC患者的2期研究(LOGiK 2003)
IF 3 Q2 ONCOLOGY Pub Date : 2025-04-21 DOI: 10.1016/j.jtocrr.2025.100836
Hidenobu Ishii MD, PhD , Koichi Azuma MD, PhD , Yuta Yamanaka MD , Hiroshige Yoshioka MD, PhD , Yukihiro Toi MD , Naoki Shingu MD , Katsuhiko Naoki MD, PhD , Masaki Okamoto MD, PhD , Yuko Tsuchiya-Kawano MD, PhD , Taishi Harada MD , Hiroyuki Inoue MD, PhD , Hiroshi Ishii MD, PhD , Kazunori Tobino MD, PhD , Chiho Nakashima MD, PhD , Yoshifusa Koreeda MD , Yasushi Hisamatsu MD , Shinsuke Tsumura MD , Takashi Inagaki MD , Keiko Mizuno MD, PhD , Takayuki Shimose MMath , Isamu Okamoto MD, PhD

Introduction

The combination of immune checkpoint inhibitors with chemotherapy is the standard treatment for extensive-stage (ES) SCLC. However, its safety for elderly patients is not fully validated. We evaluated the safety and efficacy of durvalumab plus carboplatin and etoposide in elderly patients with ES-SCLC.

Methods

In this prospective, single-arm, multicenter, phase 2 clinical trial, patients with ES-SCLC aged above or equal to 75 years received chemotherapy with up to four cycles of durvalumab 1500 mg on day 1, carboplatin at a dose equivalent to an area under the curve of 5 on day 1, and etoposide 80 mg/m2 on days 1 to 3 every 3 weeks as induction therapy. Maintenance therapy with durvalumab 1500 mg was administered every 4 weeks until disease progression or unacceptable toxicity. The primary end point was safety, and key secondary end points were objective response rate, progression-free survival, overall survival, quality of life, and Geriatric Assessment.

Results

Between August 2021 and February 2023, 40 patients were enrolled at 17 institutions and 38 were assessable for safety and efficacy. Grade 3 or higher adverse events occurred in 36 patients (94.6%). The most common adverse events were hematologic, including grade 3 or higher neutropenia (76.3%) and febrile neutropenia (15.8%). The objective response rate, median progression-free survival, and median overall survival were 89.5%, 5.4 months, and 16.1 months, respectively. No decrease in quality of life or functional assessment scores was observed after treatment.

Conclusion

Durvalumab plus carboplatin and etoposide was tolerable and expected to be effective in elderly patients with ES-SCLC.
免疫检查点抑制剂联合化疗是广泛期(ES) SCLC的标准治疗方法。然而,其对老年患者的安全性尚未得到充分验证。我们评估了durvalumab联合卡铂和依托泊苷治疗老年ES-SCLC患者的安全性和有效性。方法在这项前瞻性、单臂、多中心、2期临床试验中,年龄大于或等于75岁的ES-SCLC患者接受了长达4个周期的化疗,第1天为durvalumab 1500mg,第1天为卡铂,剂量相当于曲线下面积5,第1天为依托泊苷80mg /m2,每3周为第1天至第3天作为诱导治疗。每4周给予durvalumab 1500mg维持治疗,直到疾病进展或不可接受的毒性。主要终点是安全性,关键次要终点是客观缓解率、无进展生存期、总生存期、生活质量和老年评估。结果在2021年8月至2023年2月期间,来自17家机构的40名患者入组,其中38名患者可进行安全性和有效性评估。36例(94.6%)患者发生3级或以上不良事件。最常见的不良事件是血液学,包括3级及以上的中性粒细胞减少(76.3%)和发热性中性粒细胞减少(15.8%)。客观缓解率、中位无进展生存期和中位总生存期分别为89.5%、5.4个月和16.1个月。治疗后未观察到生活质量或功能评估评分下降。结论durvalumab联合卡铂和依托泊苷治疗老年ES-SCLC患者是可耐受的,且有望有效。
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引用次数: 0
Retreatment With Nivolumab and Ipilimumab in Pleural Mesothelioma Following Disease Progression After a Durable Response: Case Series Nivolumab和Ipilimumab治疗胸膜间皮瘤在持续缓解后疾病进展:病例系列
IF 3 Q2 ONCOLOGY Pub Date : 2025-04-21 DOI: 10.1016/j.jtocrr.2025.100835
Illaa Smesseim MD , Paul Baas MD, PhD , Jacobus A. Burgers MD, PhD
The CheckMate 743 trial established nivolumab and ipilimumab as the standard first-line treatment for unresectable pleural mesothelioma. However, optimal management following disease progression after a durable response to dual immunotherapy remains unclear. We report two cases of patients with pleural mesothelioma (epithelioid subtype) initially treated with nivolumab-ipilimumab, achieving prolonged disease control. Both patients experienced disease progression several years after treatment discontinuation and were subsequently retreated with nivolumab-ipilimumab on regulatory approval. In both cases, retreatment resulted in stable disease for at least 12 months. However, immune-related toxicities occurred, with one patient developing recurrent colitis and the other experiencing nephrotic syndrome, ultimately leading to treatment discontinuation. These cases suggest that retreatment with dual immunotherapy may be a viable strategy for selected patients with previous durable responses, although the risk of immune-related toxicity remains significant. Given the lack of prospective data, further research is needed to determine whether rechallenge with nivolumab-ipilimumab offers superior outcomes compared with chemotherapy or best supportive care in this setting. Rechallenging patients with pleural mesothelioma with nivolumab-ipilimumab after a durable response is feasible but associated with immune-related toxicity.
CheckMate 743试验建立了nivolumab和ipilimumab作为不可切除胸膜间皮瘤的标准一线治疗方法。然而,在对双重免疫治疗产生持久反应后,疾病进展后的最佳管理仍不清楚。我们报告了两例胸膜间皮瘤(上皮样亚型)患者最初使用尼伏单抗-伊匹单抗治疗,实现了长期的疾病控制。两名患者在停药几年后均出现疾病进展,随后经监管部门批准使用尼伏单抗-伊匹单抗进行治疗。在这两个病例中,再治疗导致疾病稳定至少12个月。然而,发生了免疫相关的毒性,一名患者出现复发性结肠炎,另一名患者出现肾病综合征,最终导致治疗中断。这些病例表明,尽管免疫相关毒性的风险仍然很大,但对于先前有持久反应的选定患者,双重免疫治疗可能是一种可行的策略。鉴于缺乏前瞻性数据,需要进一步的研究来确定在这种情况下,与化疗或最佳支持治疗相比,nivolumab-ipilimumab的再挑战是否能提供更好的结果。对胸膜间皮瘤患者在持久反应后再用纳武单抗-伊匹单抗治疗是可行的,但与免疫相关的毒性有关。
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引用次数: 0
Combination Therapy With MET Tyrosine Kinase Inhibitor and EGFR Tyrosine Kinase Inhibitor in Patients With MET-Overexpressed EGFR-Mutant Lung Adenocarcinoma MET酪氨酸激酶抑制剂和EGFR酪氨酸激酶抑制剂联合治疗MET过表达EGFR突变型肺腺癌
IF 3 Q2 ONCOLOGY Pub Date : 2025-04-09 DOI: 10.1016/j.jtocrr.2025.100832
Jia-Jun Wu MD , Zhe-Rong Zheng MD , Tse-Hsien Lo MD , Cheng-Hsiang Chu MD , Kun-Chieh Chen MD, PhD , Gee-Chen Chang MD, PhD

Introduction

Dysregulated MET signaling, such as MET overexpression or MET amplification (METamp), is a important mechanism of resistance to EGFR tyrosine kinase inhibitors (TKIs) in patients with EGFR-mutant lung adenocarcinoma (LUAD). Combination therapy with EGFR TKIs and MET TKIs has revealed efficacy in these patients. This study aimed to analyze the real-world experience of TKI combination in patients with EGFR-mutant MET-overexpressed LUAD.

Methods

This retrospective cohort study included patients with advanced EGFR-mutant LUAD who progressed after EGFR TKIs and were treated with combination therapy of EGFR TKIs and MET TKIs (capmatinib or tepotinib). Immunohistochemistry was used to detect MET overexpression.

Results

This study included 27 patients, with a median age of 69 years; 40.7% of the patients were male individuals, and 88.9% never smoked. Overall, the treatment response of the TKI combination reported 29.6% (eight of 27) partial response, 55.6% (15 of 27) stable disease, a median progression-free survival of 7.3 months, and an overall survival of 26.9 months. The adverse events were mostly grade 1 to 2, with only one patient experiencing a grade 3 or greater event, which was peripheral edema. The most common adverse events were hypoalbuminemia (44.4%), increased creatinine (44.4%), and peripheral edema (44.4%). Eight patients underwent next-generation sequencing analysis, and two (25.0%) of them had METamp. Three patients (37.5%) had TP53 mutations, which were the most common concurrent alterations. Those with positive METamp had significantly longer median progression-free survival than those without (25.3 versus 5.8 mo; p = 0.034).

Conclusions

The TKI combination reported clinical activities in patients with advanced EGFR-mutant LUAD resistant to EGFR TKIs and mild toxicity in those with MET overexpression.
MET信号失调,如MET过表达或MET扩增(METamp),是EGFR突变型肺腺癌(LUAD)患者对EGFR酪氨酸激酶抑制剂(TKIs)耐药的重要机制。EGFR TKIs和MET TKIs联合治疗在这些患者中显示出疗效。本研究旨在分析egfr突变met过表达LUAD患者联合TKI的现实体验。方法本回顾性队列研究纳入EGFR TKIs后进展的晚期EGFR突变LUAD患者,并接受EGFR TKIs和MET TKIs联合治疗(卡马替尼或替波替尼)。免疫组织化学检测MET过表达。结果本研究纳入27例患者,中位年龄69岁;40.7%的患者为男性,88.9%的患者从不吸烟。总体而言,TKI联合治疗反应报告29.6%(27例中8例)部分缓解,55.6%(27例中15例)疾病稳定,中位无进展生存期为7.3个月,总生存期为26.9个月。不良事件大多为1 - 2级,只有1例患者出现3级或以上的不良事件,即外周水肿。最常见的不良事件是低白蛋白血症(44.4%)、肌酐升高(44.4%)和外周水肿(44.4%)。8例患者进行了新一代测序分析,其中2例(25.0%)患有METamp。3例患者(37.5%)有TP53突变,这是最常见的并发改变。METamp阳性患者的中位无进展生存期明显长于未阳性患者(25.3个月对5.8个月;P = 0.034)。结论TKI联合治疗对EGFR TKIs耐药的晚期EGFR突变LUAD患者有临床活性,对MET过表达患者毒性较轻。
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引用次数: 0
Outcomes in Patients With Resectable Stage III NSCLC Who Did Not Have Definitive Surgery After Neoadjuvant Treatment—A Retrospective Analysis of the SAKK Trials 16/96, 16/00, 16/01, 16/08, and 16/14: A Brief Report 可切除的III期非小细胞肺癌患者在新辅助治疗后未进行最终手术的结果——对SAKK试验16/96、16/00、16/01、16/08和16/14的回顾性分析:简要报告
IF 3 Q2 ONCOLOGY Pub Date : 2025-04-09 DOI: 10.1016/j.jtocrr.2025.100834
Sabine Raimann MD , Sämi Schär PhD , Stefanie Hayoz PhD , Matthias Guckenberger MD , Tobias Finazzi MD, PhD , Isabelle Opitz MD , Sabine Schmid MD , Michael Mark MD , Alfredo Addeo MD , Laetitia A. Mauti MD, PhD , Daniel C. Betticher MD , Hans-Beat Ris MD , Roger Stupp MD , Alessandra Curioni-Fontecedro MD , Solange Peters MD, PhD , Martin Früh MD , Sacha I. Rothschild MD, PhD , Miklos Pless MD , David König MD

Introduction

Neoadjuvant or perioperative treatment, including an immune checkpoint inhibitor (ICI), has emerged as a new standard for patients with resectable stage III NSCLC. Nevertheless, approximately 20% of patients who start neoadjuvant chemo-immunotherapy will not undergo definitive surgery. Little is known about these patients.

Methods

We analyzed outcomes of patients without definitive surgery from five Swiss Group for Clinical Cancer Research (SAKK) trials that investigated different neoadjuvant treatment modalities in patients with resectable stage III-N2 NSCLC. Study treatment included neoadjuvant cisplatin-docetaxel chemotherapy (with or without radiotherapy), either combined with peri-operative durvalumab in the SAKK 16/14 trial (n = 68) or without an ICI (non-ICI trials, n = 431).

Results

Of the 499 patients, 102 (20%) did not have definitive surgery. Cancellation of surgery occurred in a similar proportion of patients with or without neoadjuvant ICI (19% versus 21%, p = 0.9). Reasons were in non-ICI trials and SAKK 16/14: disease progression (47% and 54%), nonresectability (18% and 8%), medical reasons (17% and 31%), and unknown (18% and 8%), respectively. Of these patients, no patient in SAKK 16/14 and 17 patients (19%) in the non-ICI trials received curative-intended salvage therapy. Three-year overall survival was higher in patients who had definitive surgery compared with those who did not: 78% versus 32% (SAKK 16/14) and 54% versus 10% (non-ICI trials).

Conclusions

In our pooled analysis, patients with definitive surgery had higher survival rates than those without definitive surgery. Prognosis in patients without definitive surgery seems to have improved in the era of ICI.
新辅助或围手术期治疗,包括免疫检查点抑制剂(ICI),已成为可切除的III期NSCLC患者的新标准。然而,大约20%开始新辅助化疗免疫治疗的患者不会接受最终手术。人们对这些病人知之甚少。方法:我们分析了瑞士临床癌症研究小组(SAKK)的五项研究,这些研究调查了可切除的III-N2期非小细胞肺癌患者的不同新辅助治疗方式。研究治疗包括新辅助顺铂-多西紫杉醇化疗(伴或不伴放疗),在SAKK 16/14试验(n = 68)中联合围手术期杜伐单抗或不伴ICI(非ICI试验,n = 431)。结果499例患者中,102例(20%)未行最终手术。有或没有新辅助ICI的患者取消手术的比例相似(19%对21%,p = 0.9)。在非ici试验和SAKK 16/14中,原因分别为:疾病进展(47%和54%)、不可切除(18%和8%)、医学原因(17%和31%)和未知(18%和8%)。在这些患者中,在SAKK 16/14试验中没有患者接受了治疗目的的挽救治疗,在非ici试验中有17例患者(19%)接受了治疗目的的挽救治疗。接受最终手术的患者的三年总生存率高于未接受手术的患者:78%对32% (SAKK 16/14), 54%对10%(非ici试验)。结论在我们的汇总分析中,接受最终手术的患者生存率高于未接受最终手术的患者。在ICI时代,没有明确手术的患者预后似乎有所改善。
{"title":"Outcomes in Patients With Resectable Stage III NSCLC Who Did Not Have Definitive Surgery After Neoadjuvant Treatment—A Retrospective Analysis of the SAKK Trials 16/96, 16/00, 16/01, 16/08, and 16/14: A Brief Report","authors":"Sabine Raimann MD ,&nbsp;Sämi Schär PhD ,&nbsp;Stefanie Hayoz PhD ,&nbsp;Matthias Guckenberger MD ,&nbsp;Tobias Finazzi MD, PhD ,&nbsp;Isabelle Opitz MD ,&nbsp;Sabine Schmid MD ,&nbsp;Michael Mark MD ,&nbsp;Alfredo Addeo MD ,&nbsp;Laetitia A. Mauti MD, PhD ,&nbsp;Daniel C. Betticher MD ,&nbsp;Hans-Beat Ris MD ,&nbsp;Roger Stupp MD ,&nbsp;Alessandra Curioni-Fontecedro MD ,&nbsp;Solange Peters MD, PhD ,&nbsp;Martin Früh MD ,&nbsp;Sacha I. Rothschild MD, PhD ,&nbsp;Miklos Pless MD ,&nbsp;David König MD","doi":"10.1016/j.jtocrr.2025.100834","DOIUrl":"10.1016/j.jtocrr.2025.100834","url":null,"abstract":"<div><h3>Introduction</h3><div>Neoadjuvant or perioperative treatment, including an immune checkpoint inhibitor (ICI), has emerged as a new standard for patients with resectable stage III NSCLC. Nevertheless, approximately 20% of patients who start neoadjuvant chemo-immunotherapy will not undergo definitive surgery. Little is known about these patients.</div></div><div><h3>Methods</h3><div>We analyzed outcomes of patients without definitive surgery from five Swiss Group for Clinical Cancer Research (SAKK) trials that investigated different neoadjuvant treatment modalities in patients with resectable stage III-N2 NSCLC. Study treatment included neoadjuvant cisplatin-docetaxel chemotherapy (with or without radiotherapy), either combined with peri-operative durvalumab in the SAKK 16/14 trial (n = 68) or without an ICI (non-ICI trials, n = 431).</div></div><div><h3>Results</h3><div>Of the 499 patients, 102 (20%) did not have definitive surgery. Cancellation of surgery occurred in a similar proportion of patients with or without neoadjuvant ICI (19% versus 21%, <em>p</em> = 0.9). Reasons were in non-ICI trials and SAKK 16/14: disease progression (47% and 54%), nonresectability (18% and 8%), medical reasons (17% and 31%), and unknown (18% and 8%), respectively. Of these patients, no patient in SAKK 16/14 and 17 patients (19%) in the non-ICI trials received curative-intended salvage therapy. Three-year overall survival was higher in patients who had definitive surgery compared with those who did not: 78% versus 32% (SAKK 16/14) and 54% versus 10% (non-ICI trials).</div></div><div><h3>Conclusions</h3><div>In our pooled analysis, patients with definitive surgery had higher survival rates than those without definitive surgery. Prognosis in patients without definitive surgery seems to have improved in the era of ICI.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 6","pages":"Article 100834"},"PeriodicalIF":3.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cost-Effectiveness of Adjuvant Osimertinib With and Without Chemotherapy for Surgically Resected NSCLC 手术切除的非小细胞肺癌的辅助化疗奥西替尼的成本-效果
IF 3 Q2 ONCOLOGY Pub Date : 2025-04-09 DOI: 10.1016/j.jtocrr.2025.100833
Angelos Vasilopoulos BS , Alexander Pohlman MD , Ayham Odeh MD , K. Robert Shen MD , Julia M. Coughlin MD , Zaid M. Abdelsattar MD, MS, FACS

Introduction

Osimertinib is now approved as adjuvant therapy for stage IB to III NSCLC with EGFR mutations. Nevertheless, this treatment is lengthy and expensive. Its cost-effectiveness profile as monotherapy versus combination with chemotherapy is unknown. In this context, we investigate the cost-effectiveness of adjuvant osimertinib with and without chemotherapy for NSCLC.

Methods

A set of Markov models was established to predict the cost-effectiveness of these different regimens. Data were sourced from the ADAURA trial’s publications and protocols. Health outcomes were quantified as quality-adjusted life-years (QALYs). Costs and incremental cost-effectiveness ratios (ICERs) were estimated in U.S. dollars (USD) and USD per QALY, respectively. Deterministic and probabilistic sensitivity analyses were performed. Data from the Surveillance, Epidemiology, and End Results Program were used to predict additional costs to the U.S. health care system.

Results

Compared with treatment with chemotherapy alone, treatment with osimertinib plus chemotherapy yielded 5.86 QALYs with incremental costs of $414,607.69 (ICER = $380,347.85 per QALY). Treatment with osimertinib alone yielded 6.63 QALYs with an incremental cost of $402,224.32 (ICER = $213,447.59 per QALY). Osimertinib is only likely to be cost-effective if the willingness-to-pay threshold per QALY is $200,000 or more. The price of osimertinib had the strongest influence on cost-effectiveness. On the basis of Surveillance, Epidemiology, and End Results Program data, these practices may cost the U.S. health care system an additional 8.9 billion USD/year.

Conclusions

Adjuvant osimertinib alone is more cost-effective than combination therapy, but only if the willingness-to-pay is high. A reduction in the price of osimertinib would improve its cost-effectiveness profile.
奥西替尼现已被批准作为EGFR突变的IB至III期NSCLC的辅助治疗。然而,这种治疗既漫长又昂贵。其单药与联合化疗的成本效益情况尚不清楚。在这种情况下,我们研究了辅助奥希替尼加化疗和不加化疗治疗非小细胞肺癌的成本效益。方法建立一套马尔可夫模型,预测不同方案的成本-效果。数据来源于ADAURA试验的出版物和方案。健康结果被量化为质量调整生命年(QALYs)。成本和增量成本效益比(ICERs)分别以美元(USD)和每QALY美元估算。进行了确定性和概率敏感性分析。来自监测、流行病学和最终结果项目的数据被用来预测美国医疗保健系统的额外费用。结果与单独化疗治疗相比,奥西替尼联合化疗治疗获得5.86个QALY,增量成本为414,607.69美元(ICER = 380,347.85美元/ QALY)。单独使用奥西替尼治疗产生6.63个QALY,增量成本为402,224.32美元(ICER = 213,447.59美元/ QALY)。只有当每个QALY的支付意愿阈值达到或超过20万美元时,奥西替尼才可能具有成本效益。奥西替尼的价格对成本-效果的影响最大。根据监测、流行病学和最终结果项目的数据,这些做法可能会使美国医疗保健系统每年额外花费89亿美元。结论仅在患者支付意愿高的情况下,单独使用奥希替尼辅助治疗比联合治疗更具成本效益。奥西替尼价格的降低将改善其成本效益。
{"title":"Cost-Effectiveness of Adjuvant Osimertinib With and Without Chemotherapy for Surgically Resected NSCLC","authors":"Angelos Vasilopoulos BS ,&nbsp;Alexander Pohlman MD ,&nbsp;Ayham Odeh MD ,&nbsp;K. Robert Shen MD ,&nbsp;Julia M. Coughlin MD ,&nbsp;Zaid M. Abdelsattar MD, MS, FACS","doi":"10.1016/j.jtocrr.2025.100833","DOIUrl":"10.1016/j.jtocrr.2025.100833","url":null,"abstract":"<div><h3>Introduction</h3><div>Osimertinib is now approved as adjuvant therapy for stage IB to III NSCLC with <em>EGFR</em> mutations. Nevertheless, this treatment is lengthy and expensive. Its cost-effectiveness profile as monotherapy versus combination with chemotherapy is unknown. In this context, we investigate the cost-effectiveness of adjuvant osimertinib with and without chemotherapy for NSCLC.</div></div><div><h3>Methods</h3><div>A set of Markov models was established to predict the cost-effectiveness of these different regimens. Data were sourced from the ADAURA trial’s publications and protocols. Health outcomes were quantified as quality-adjusted life-years (QALYs). Costs and incremental cost-effectiveness ratios (ICERs) were estimated in U.S. dollars (USD) and USD per QALY, respectively. Deterministic and probabilistic sensitivity analyses were performed. Data from the Surveillance, Epidemiology, and End Results Program were used to predict additional costs to the U.S. health care system.</div></div><div><h3>Results</h3><div>Compared with treatment with chemotherapy alone, treatment with osimertinib plus chemotherapy yielded 5.86 QALYs with incremental costs of $414,607.69 (ICER = $380,347.85 per QALY). Treatment with osimertinib alone yielded 6.63 QALYs with an incremental cost of $402,224.32 (ICER = $213,447.59 per QALY). Osimertinib is only likely to be cost-effective if the willingness-to-pay threshold per QALY is $200,000 or more. The price of osimertinib had the strongest influence on cost-effectiveness. On the basis of Surveillance, Epidemiology, and End Results Program data, these practices may cost the U.S. health care system an additional 8.9 billion USD/year.</div></div><div><h3>Conclusions</h3><div>Adjuvant osimertinib alone is more cost-effective than combination therapy, but only if the willingness-to-pay is high. A reduction in the price of osimertinib would improve its cost-effectiveness profile.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 6","pages":"Article 100833"},"PeriodicalIF":3.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The United States’ Early Experience With Lung Cancer Screening—Creation of a National Data Linkage: A Brief Report 美国肺癌筛查的早期经验——国家数据链接的创建:简要报告
IF 3 Q2 ONCOLOGY Pub Date : 2025-03-20 DOI: 10.1016/j.jtocrr.2025.100825
V. Paul Doria-Rose DVM, PhD , Gerard A. Silvestri MD, MS , Danielle D. Durham PhD , Philip Connor BS , Lenka Goldman MSE , Lindsey Enewold PhD, MPH , Farhood Farjah MD, MPH , Eric A. Miller PhD, MSPH , Michael Simanowith MD , Robert A. Smith PhD , Louise M. Henderson PhD, MSPH , Raymond U. Osarogiagbon M.B.B.S., FASCO , Ella A. Kazerooni MD, MS , Andrew Ward PhD, MPH , Paul Pinsky PhD

Introduction

Lung cancer screening has been recommended by the United States Preventive Services Taskforce since 2013. The Centers for Medicare and Medicaid Services coverage decision in early 2015 required data submission to a Centers for Medicare and Medicaid Services–approved registry for facilities to receive payment for screening. Only the American College of Radiology’s Lung Cancer Screening Registry (LCSR) received approval for this purpose. Some LCSR elements, such as race, ethnicity, downstream diagnostic procedures, and cancer outcomes, were underreported.

Methods

To address underreporting, we linked data from the LCSR to Medicare and Surveillance, Epidemiology, and End Results cancer registry data from 2015 to 2021. We created two different cohorts of individuals aged 65 years and older: (1) those who were enrolled in Medicare fee-for-service plans with parts A and B coverage at the time of at least one LCSR-reported screen, and (2) Medicare beneficiaries (regardless of whether fee-for-service or managed care) living within a Surveillance, Epidemiology, and End Results catchment area at the time of at least one LCSR-reported screen. We compared the characteristics of individuals in the linked cohorts with those of all individuals in the LCSR aged 65 years and over.

Results

Demographic, smoking history, and screening examination data elements in the linked data were generally similar to those in the overall LCSR.

Conclusions

On the basis of these results, the linked populations seem to be generally representative of older individuals in the LCSR. These unique data linkages provide an unprecedented opportunity to better understand the early implementation of lung cancer screening in the United States.
自2013年以来,肺癌筛查已被美国预防服务工作组推荐。2015年初,医疗保险和医疗补助服务中心的覆盖范围决定要求向医疗保险和医疗补助服务中心批准的注册中心提交数据,以便接收筛查费用。只有美国放射学院的肺癌筛查登记处(LCSR)获得了这一目的的批准。一些LCSR因素,如种族、民族、下游诊断程序和癌症结局,被低估了。为了解决低报问题,我们将LCSR的数据与2015年至2021年的医疗保险和监测、流行病学和最终结果癌症登记数据联系起来。我们创建了两个不同的65岁及以上的个体队列:(1)在至少一次lcsr报告的筛查中登记了医疗保险按服务收费计划的A部分和B部分覆盖的人;(2)在至少一次lcsr报告的筛查中居住在监测、流行病学和最终结果集区内的医疗保险受益人(无论是否按服务收费或管理医疗)。我们将相关队列中个体的特征与65岁及以上LCSR中所有个体的特征进行了比较。结果关联数据中的人口学、吸烟史和筛查检查数据元素与总体LCSR数据元素基本相似。在这些结果的基础上,相关人群似乎普遍代表了LCSR中的老年人。这些独特的数据联系为更好地了解美国肺癌筛查的早期实施提供了前所未有的机会。
{"title":"The United States’ Early Experience With Lung Cancer Screening—Creation of a National Data Linkage: A Brief Report","authors":"V. Paul Doria-Rose DVM, PhD ,&nbsp;Gerard A. Silvestri MD, MS ,&nbsp;Danielle D. Durham PhD ,&nbsp;Philip Connor BS ,&nbsp;Lenka Goldman MSE ,&nbsp;Lindsey Enewold PhD, MPH ,&nbsp;Farhood Farjah MD, MPH ,&nbsp;Eric A. Miller PhD, MSPH ,&nbsp;Michael Simanowith MD ,&nbsp;Robert A. Smith PhD ,&nbsp;Louise M. Henderson PhD, MSPH ,&nbsp;Raymond U. Osarogiagbon M.B.B.S., FASCO ,&nbsp;Ella A. Kazerooni MD, MS ,&nbsp;Andrew Ward PhD, MPH ,&nbsp;Paul Pinsky PhD","doi":"10.1016/j.jtocrr.2025.100825","DOIUrl":"10.1016/j.jtocrr.2025.100825","url":null,"abstract":"<div><h3>Introduction</h3><div>Lung cancer screening has been recommended by the United States Preventive Services Taskforce since 2013. The Centers for Medicare and Medicaid Services coverage decision in early 2015 required data submission to a Centers for Medicare and Medicaid Services–approved registry for facilities to receive payment for screening. Only the American College of Radiology’s Lung Cancer Screening Registry (LCSR) received approval for this purpose. Some LCSR elements, such as race, ethnicity, downstream diagnostic procedures, and cancer outcomes, were underreported.</div></div><div><h3>Methods</h3><div>To address underreporting, we linked data from the LCSR to Medicare and Surveillance, Epidemiology, and End Results cancer registry data from 2015 to 2021. We created two different cohorts of individuals aged 65 years and older: (1) those who were enrolled in Medicare fee-for-service plans with parts A and B coverage at the time of at least one LCSR-reported screen, and (2) Medicare beneficiaries (regardless of whether fee-for-service or managed care) living within a Surveillance, Epidemiology, and End Results catchment area at the time of at least one LCSR-reported screen. We compared the characteristics of individuals in the linked cohorts with those of all individuals in the LCSR aged 65 years and over.</div></div><div><h3>Results</h3><div>Demographic, smoking history, and screening examination data elements in the linked data were generally similar to those in the overall LCSR.</div></div><div><h3>Conclusions</h3><div>On the basis of these results, the linked populations seem to be generally representative of older individuals in the LCSR. These unique data linkages provide an unprecedented opportunity to better understand the early implementation of lung cancer screening in the United States.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 6","pages":"Article 100825"},"PeriodicalIF":3.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Landscape of MET Exon 14 Skipping Mutations in Patients With Lung Cancer Identified by Next-Generation Sequencing 新一代测序鉴定肺癌患者MET外显子14跳变的格局
IF 3 Q2 ONCOLOGY Pub Date : 2025-03-20 DOI: 10.1016/j.jtocrr.2025.100826
Jia Liao MD , Song Wu MD , Yi Min MD , Yiran Li MD , Yuanhang Nie MD , Quwen Chen MD , Zhiliang Mao MD , Qinglan Zong MS , Ning Gao MS , Ding Zhang PhD , Weiquan Liang MD

Introduction

MET exon 14 (METex14) skipping mutations are observed in approximately 0.9% to 4% of patients with NSCLC. This study aimed to compare the detection rates of METex14 skipping in Chinese patients with lung cancer using DNA-based next-generation sequencing (NGS) with capture-based library construction and synchronous DNA-based and RNA-based NGS with amplicon-based library construction.

Methods

A total of 11,330 tissue samples from 11,330 Chinese patients with lung cancer were included in the study to confirm the presence of METex14 skipping. Simultaneously, MET immunohistochemistry testing was performed on 30 patients.

Results

The highest detection rate of METex14 skipping was observed in the synchronous DNA and RNA-based NGS with amplicon-based library construction, reaching 2.20%. A total of 45 different variants leading to METex14 skipping were detected at the DNA level. These variants were widely distributed across a 197–base pair DNA sequence. In the overall population, the incidence of METex14 skipping was significantly higher in individuals aged 60 years and above (p < 0.0001) and needle biopsy samples (p < 0.0001) and reported no significant association with gender and tumor location. A positive correlation was observed between microsatellite instability–high and METex14 skipping (p < 0.0001).

Conclusions

The mutations causing METex14 skipping exhibit diversity in terms of variant types and are widely distributed across various genomic regions. Synchronous DNA-based and RNA-based NGS is considered the optimal method for detecting METex14 skipping. Furthermore, METex14 skipping is enriched in specific populations, including individuals aged 60 years and above, with advanced-stage disease and a microsatellite instability-high status.
在约0.9%至4%的NSCLC患者中观察到met外显子14 (METex14)跳变。本研究旨在比较基于dna的下一代测序(NGS)与基于捕获的文库构建和同步基于dna和rna的NGS与基于扩增子的文库构建在中国肺癌患者中METex14跳跃性的检出率。方法从11330例中国肺癌患者中抽取11330份组织样本,证实METex14跳变的存在。同时对30例患者进行MET免疫组化检测。结果基于扩增子文库构建的同步DNA和rna NGS中,METex14跳脱检出率最高,达2.20%。在DNA水平上共检测到45种不同的导致METex14跳变的变异。这些变异广泛分布在197个碱基对的DNA序列中。在总体人群中,60岁及以上人群中METex14跳脱的发生率显著较高(p <;0.0001)和针活检样本(p <;0.0001),与性别和肿瘤位置无显著关联。微卫星不稳定性高与METex14跳变呈正相关(p <;0.0001)。结论引起METex14跳变的突变具有多样性,广泛分布于不同的基因组区域。基于dna和rna的同步NGS被认为是检测METex14跳变的最佳方法。此外,METex14跳变在特定人群中丰富,包括60岁及以上的晚期疾病个体和微卫星不稳定-高状态。
{"title":"The Landscape of MET Exon 14 Skipping Mutations in Patients With Lung Cancer Identified by Next-Generation Sequencing","authors":"Jia Liao MD ,&nbsp;Song Wu MD ,&nbsp;Yi Min MD ,&nbsp;Yiran Li MD ,&nbsp;Yuanhang Nie MD ,&nbsp;Quwen Chen MD ,&nbsp;Zhiliang Mao MD ,&nbsp;Qinglan Zong MS ,&nbsp;Ning Gao MS ,&nbsp;Ding Zhang PhD ,&nbsp;Weiquan Liang MD","doi":"10.1016/j.jtocrr.2025.100826","DOIUrl":"10.1016/j.jtocrr.2025.100826","url":null,"abstract":"<div><h3>Introduction</h3><div><em>MET</em> exon 14 (<em>MET</em>ex14) skipping mutations are observed in approximately 0.9% to 4% of patients with NSCLC. This study aimed to compare the detection rates of <em>MET</em>ex14 skipping in Chinese patients with lung cancer using DNA-based next-generation sequencing (NGS) with capture-based library construction and synchronous DNA-based and RNA-based NGS with amplicon-based library construction.</div></div><div><h3>Methods</h3><div>A total of 11,330 tissue samples from 11,330 Chinese patients with lung cancer were included in the study to confirm the presence of <em>MET</em>ex14 skipping. Simultaneously, MET immunohistochemistry testing was performed on 30 patients.</div></div><div><h3>Results</h3><div>The highest detection rate of <em>MET</em>ex14 skipping was observed in the synchronous DNA and RNA-based NGS with amplicon-based library construction, reaching 2.20%. A total of 45 different variants leading to <em>MET</em>ex14 skipping were detected at the DNA level. These variants were widely distributed across a 197–base pair DNA sequence. In the overall population, the incidence of <em>MET</em>ex14 skipping was significantly higher in individuals aged 60 years and above (<em>p</em> &lt; 0.0001) and needle biopsy samples (<em>p</em> &lt; 0.0001) and reported no significant association with gender and tumor location. A positive correlation was observed between microsatellite instability–high and <em>MET</em>ex14 skipping (<em>p</em> &lt; 0.0001).</div></div><div><h3>Conclusions</h3><div>The mutations causing <em>MET</em>ex14 skipping exhibit diversity in terms of variant types and are widely distributed across various genomic regions. Synchronous DNA-based and RNA-based NGS is considered the optimal method for detecting <em>MET</em>ex14 skipping. Furthermore, <em>MET</em>ex14 skipping is enriched in specific populations, including individuals aged 60 years and above, with advanced-stage disease and a microsatellite instability-high status.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 7","pages":"Article 100826"},"PeriodicalIF":3.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144271808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Intensity-Modulated Radiotherapy for Locally Advanced Lung Cancer in the Immunotherapy Era: A Prospective Study WJOG12019L 免疫治疗时代局部晚期肺癌调强放疗:一项前瞻性研究
IF 3 Q2 ONCOLOGY Pub Date : 2025-03-20 DOI: 10.1016/j.jtocrr.2025.100828
Hideyuki Harada MD, PhD , Akito Hata MD , Masahiro Konno PhD , Nobuaki Mamesaya MD, PhD , Kiyoshi Nakamatsu MD, PhD , Koji Haratani MD, PhD , Takaya Yamamoto MD, PhD , Ryota Saito MD, PhD , Hiroshi Mayahara MD, PhD , Masaki Kokubo MD, PhD , Yuki Sato MD , Nobuki Imano MD, PhD , Takeshi Masuda PD, PhD , Haruyuki Fukuda MD, PhD , Toshikatsu Sado MD, PhD , Kenichi Yoshimura PhD , Yasumasa Nishimura MD, PhD , Kazuhiko Nakagawa MD, PhD , Isamu Okamoto MD, PhD , Nobuyuki Yamamoto MD, PhD

Introduction

Chemoradiotherapy (CRT) followed by durvalumab is the standard of care for unresectable locally advanced NSCLC. Limited prospective data have been reported on intensity-modulated radiotherapy (IMRT)–adapted CRT in the immunotherapy era.

Methods

In this multicenter prospective observational study, patients underwent IMRT-adapted CRT (platinum-doublet chemotherapy plus 60 Gy IMRT in 30 fractions under a prespecified radiation protocol), followed by consolidative durvalumab. The primary outcome was the durvalumab introduction rate within 42 days post-CRT.

Results

Thirty-two patients with unresectable locally advanced NSCLC were enrolled between November 2019 and February 2021. Among the 28 evaluable cases, durvalumab was introduced in 24 (85.7%, 90% confidence interval: 70.2%–95.0%) of 28 patients after CRT, achieving the primary end point. All 29 patients who received IMRT completed the scheduled 60 Gy radiotherapy dose. One year of durvalumab treatment was completed in 12 of 24 patients (50%). In the 24 patients who were durvalumab-introduced, the median progression-free survival and overall survival were 20.9 (95% confidence interval: 6.9–not evaluable) months and not reached, respectively. Two-year progression-free survival and overall survival rates were 44% and 73%, respectively. Among the 29 patients in the safety analysis set, there were no treatment-related deaths or grade 4 nonhematological adverse events. Pneumonitis grade 1 was observed in 13 patients (45%), grade 2 in seven (24%), and grade 3 in one (3%).

Conclusions

High durvalumab introduction rate was reported after the completion of IMRT-adapted CRT under a prespecified radiation protocol. Its efficacy has been suggested, with favorable safety profiles, including a low incidence of severe pneumonitis.

Trial Registration

University Hospital Medical Information Network database ID: UMIN000038366
化疗(CRT)加杜伐单抗是不可切除的局部晚期NSCLC的标准治疗方案。在免疫治疗时代,关于调强放疗(IMRT)适应CRT的前瞻性数据报道有限。在这项多中心前瞻性观察研究中,患者接受了适应IMRT的CRT(铂双重化疗加上60 Gy IMRT,在预先指定的放射方案下分为30个部分),然后是巩固杜伐单抗。主要终点是crt后42天内杜伐单抗的引入率。结果在2019年11月至2021年2月期间入组了32例不可切除的局部晚期NSCLC患者。在28例可评估病例中,28例患者中有24例(85.7%,90%置信区间:70.2%-95.0%)在CRT后引入durvalumab,达到主要终点。所有29例接受IMRT的患者均完成了计划的60 Gy放疗剂量。24例患者中有12例(50%)完成了一年的durvalumab治疗。在引入durvalumab的24例患者中,中位无进展生存期和总生存期分别为20.9个月(95%置信区间:6.9 -不可评估)和未达到。两年无进展生存率和总生存率分别为44%和73%。在安全性分析组的29例患者中,没有与治疗相关的死亡或4级非血液学不良事件。1级肺炎13例(45%),2级肺炎7例(24%),3级肺炎1例(3%)。结论在预先设定的放疗方案下完成imrt - CRT后,杜伐单抗引入率较高。它的有效性已被证明具有良好的安全性,包括严重肺炎的低发病率。试验注册大学医院医学信息网数据库ID: UMIN000038366
{"title":"Intensity-Modulated Radiotherapy for Locally Advanced Lung Cancer in the Immunotherapy Era: A Prospective Study WJOG12019L","authors":"Hideyuki Harada MD, PhD ,&nbsp;Akito Hata MD ,&nbsp;Masahiro Konno PhD ,&nbsp;Nobuaki Mamesaya MD, PhD ,&nbsp;Kiyoshi Nakamatsu MD, PhD ,&nbsp;Koji Haratani MD, PhD ,&nbsp;Takaya Yamamoto MD, PhD ,&nbsp;Ryota Saito MD, PhD ,&nbsp;Hiroshi Mayahara MD, PhD ,&nbsp;Masaki Kokubo MD, PhD ,&nbsp;Yuki Sato MD ,&nbsp;Nobuki Imano MD, PhD ,&nbsp;Takeshi Masuda PD, PhD ,&nbsp;Haruyuki Fukuda MD, PhD ,&nbsp;Toshikatsu Sado MD, PhD ,&nbsp;Kenichi Yoshimura PhD ,&nbsp;Yasumasa Nishimura MD, PhD ,&nbsp;Kazuhiko Nakagawa MD, PhD ,&nbsp;Isamu Okamoto MD, PhD ,&nbsp;Nobuyuki Yamamoto MD, PhD","doi":"10.1016/j.jtocrr.2025.100828","DOIUrl":"10.1016/j.jtocrr.2025.100828","url":null,"abstract":"<div><h3>Introduction</h3><div>Chemoradiotherapy (CRT) followed by durvalumab is the standard of care for unresectable locally advanced NSCLC. Limited prospective data have been reported on intensity-modulated radiotherapy (IMRT)–adapted CRT in the immunotherapy era.</div></div><div><h3>Methods</h3><div>In this multicenter prospective observational study, patients underwent IMRT-adapted CRT (platinum-doublet chemotherapy plus 60 Gy IMRT in 30 fractions under a prespecified radiation protocol), followed by consolidative durvalumab. The primary outcome was the durvalumab introduction rate within 42 days post-CRT.</div></div><div><h3>Results</h3><div>Thirty-two patients with unresectable locally advanced NSCLC were enrolled between November 2019 and February 2021. Among the 28 evaluable cases, durvalumab was introduced in 24 (85.7%, 90% confidence interval: 70.2%–95.0%) of 28 patients after CRT, achieving the primary end point. All 29 patients who received IMRT completed the scheduled 60 Gy radiotherapy dose. One year of durvalumab treatment was completed in 12 of 24 patients (50%). In the 24 patients who were durvalumab-introduced, the median progression-free survival and overall survival were 20.9 (95% confidence interval: 6.9–not evaluable) months and not reached, respectively. Two-year progression-free survival and overall survival rates were 44% and 73%, respectively. Among the 29 patients in the safety analysis set, there were no treatment-related deaths or grade 4 nonhematological adverse events. Pneumonitis grade 1 was observed in 13 patients (45%), grade 2 in seven (24%), and grade 3 in one (3%).</div></div><div><h3>Conclusions</h3><div>High durvalumab introduction rate was reported after the completion of IMRT-adapted CRT under a prespecified radiation protocol. Its efficacy has been suggested, with favorable safety profiles, including a low incidence of severe pneumonitis.</div></div><div><h3>Trial Registration</h3><div>University Hospital Medical Information Network database ID: UMIN000038366</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 6","pages":"Article 100828"},"PeriodicalIF":3.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Survival Outcomes of Lung Adenocarcinoma With Intestinal Differentiation in the Era of Immunotherapy 免疫治疗时代肺腺癌肠分化的生存结局
IF 3 Q2 ONCOLOGY Pub Date : 2025-03-20 DOI: 10.1016/j.jtocrr.2025.100827
Micah Tratt BA , Anshu Bandhlish MD , Keith D. Eaton MD, PhD , Ted Gooley PhD , Nicholas Giustini MD , Lei Deng MD

Introduction

Lung adenocarcinoma (LUAD) with intestinal differentiation (LAID) comprises a rare and heterogeneous NSCLC of invasive mucinous, enteric, and colloid characteristics. In the era of chemotherapy, LAID was associated with a poorer prognosis compared with other LUADs. Leveraging the National Cancer Database, we assessed survival outcomes of LAID in the era of immunotherapy.

Methods

The National Cancer Database was queried for stage IV adenocarcinoma cases diagnosed from 2016 to 2019. LAID was defined as invasive mucinous adenocarcinoma, colloid adenocarcinoma, or enteric adenocarcinoma. An unadjusted comparison of survival distributions was performed using a log-rank test and adjusted by Cox multivariable regression.

Results

A total of 40,516 patients were identified, of whom 855 had LAID and 39,661 had other LUAD. Among the cases of LAID, 593 were classified as colloid, 253 as mucinous, and nine as enteric. Patients with LAID had a higher risk of death compared with other LUAD subtypes, with a hazard ratio (HR) of 1.31 (95% confidence interval: 1.21–1.43) and a median survival of 9.19 months and 11.81 months, respectively. This was relatively consistent across all treatment subgroups (HR = 1.40: immunotherapy alone, HR = 1.29: chemoimmunotherapy; HR = 1.25: chemotherapy alone). Patients with LAID treated with chemoimmunotherapy had a median overall survival of 11.16 months, 9.19 months when treated with immunotherapy alone, and 7.09 months when treated with chemotherapy alone.

Conclusions

Compared with other LUADs, LAID remains associated with poorer survival in the era of immunotherapy. Nevertheless, exposure to immunotherapy may be associated with improved survival compared with chemotherapy alone in this rare subgroup.
肺腺癌(LUAD)伴肠分化(lay)是一种罕见的异质性非小细胞肺癌,具有侵袭性粘液、肠和胶质特征。在化疗时代,与其他luad相比,lay的预后较差。利用国家癌症数据库,我们评估了lay在免疫治疗时代的生存结果。方法查询国家癌症数据库2016 - 2019年诊断的IV期腺癌病例。lay被定义为浸润性粘液腺癌、胶质腺癌或肠腺癌。采用log-rank检验对生存分布进行未校正比较,并采用Cox多变量回归进行校正。结果共发现40516例患者,其中855例为lay, 39661例为其他LUAD。其中593例为胶体型,253例为黏液型,9例为肠型。与其他LUAD亚型相比,LAID患者的死亡风险更高,风险比(HR)为1.31(95%可信区间:1.21-1.43),中位生存期分别为9.19个月和11.81个月。这在所有治疗亚组中相对一致(HR = 1.40:单独免疫治疗,HR = 1.29:化学免疫治疗;HR = 1.25:单独化疗)。接受化学免疫治疗的lay患者的中位总生存期为11.16个月,单独接受免疫治疗的中位总生存期为9.19个月,单独接受化疗的中位总生存期为7.09个月。结论在免疫治疗时代,与其他luad相比,lay仍与较差的生存率相关。然而,在这个罕见的亚组中,与单独化疗相比,暴露于免疫治疗可能与生存率的提高有关。
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引用次数: 0
Real-World Validity of Tissue-Agnostic Circulating Tumor DNA Response Monitoring in Lung Cancers Treated With Chemotherapy, Immunotherapy, or Targeted Agents 在接受化疗、免疫治疗或靶向药物治疗的肺癌中,组织不可知循环肿瘤DNA反应监测的真实有效性
IF 3 Q2 ONCOLOGY Pub Date : 2025-03-19 DOI: 10.1016/j.jtocrr.2025.100829
Anne C. Chiang MD, PhD , Russell W. Madison MS , Zoe June Assaf PhD , Alexander Fine PhD , Yi Cao PhD , Ole Gjoerup PhD , Yanmei Huang PhD , Dexter X. Jin PhD , Jason Hughes PhD , Vladan Antic MD, PhD , Amanda Young PhD , David Fabrizio MS , David Shames PhD , Sophia Maund PhD , Alexia Exarchos MPH , Shailendra Lakhanpal MD , Richard Zuniga MD , Lincoln W. Pasquina PhD , Katja Schulze PhD

Introduction

Circulating tumor DNA (ctDNA) monitoring is emerging as a minimally invasive complement to tumor imaging. We evaluated the validity of tissue-agnostic ctDNA quantification across four treatment modalities in NSCLC and SCLC.

Methods

Data from consenting patients were collected from electronic health records as part of the Prospective Clinico-Genomic study (NCT04180176). ctDNA tumor fraction (TF) was retrospectively calculated for plasma collected six to 15 weeks after therapy initiation. TF dynamics were compared among an exploratory cohort, NSCLC and SCLC validity cohorts, and by therapy class.

Results

In on-treatment plasma, undetectable TF was associated with longer real-world progression-free survival and real-world overall survival in exploratory (21.8 versus 8.8 mo; hazard ratio [HR] = 0.35, 95% confidence interval [CI]: 0.24–0.50), validity NSCLC (23.5 versus 9.5 mo; HR = 0.34, 95% CI: 0.22–0.53), and validity SCLC (15.9 versus 8.3 mo; HR = 0.19, 95% CI: 0.08–0.42) cohorts. Equal to or greater than 90% and equal to or greater than 50% TF reduction from baseline was also associated with significantly improved outcomes. ctDNA dynamics differed by treatment class: TF reported greater discriminatory power for selecting tumor responses to immunotherapy and targeted therapy (≥50% decrease in 91% of responders versus 24% of nonresponders) than chemotherapy and chemo-immunotherapy (86% versus 60%). TF dynamics correlated with outcomes, but models of real-world progression-free survival and real-world overall survival were improved when tumor response was included.

Conclusions

Tissue-agnostic monitoring of molecular response on the basis of ctDNA TF dynamics has utility in the real-world setting across four different treatment regimens. These results suggest that ctDNA dynamics may be complementary to tumor imaging in both NSCLC and SCLC to better inform patient care.
循环肿瘤DNA (ctDNA)监测正在成为肿瘤成像的一种微创补充。我们评估了在非小细胞肺癌和小细胞肺癌的四种治疗方式中组织无关的ctDNA量化的有效性。方法作为前瞻性临床基因组研究(NCT04180176)的一部分,从电子健康记录中收集同意患者的数据。回顾性计算治疗开始后6至15周收集的血浆ctDNA肿瘤分数(TF)。在探索性队列、NSCLC和SCLC有效性队列以及治疗班级之间比较TF动态。结果在治疗血浆中,未检测到的TF与探索性患者更长的真实无进展生存期和真实总生存期相关(21.8个月对8.8个月;风险比[HR] = 0.35, 95%可信区间[CI]: 0.24-0.50), NSCLC的有效性(23.5 vs 9.5;HR = 0.34, 95% CI: 0.22-0.53),效度SCLC (15.9 vs 8.3个月;HR = 0.19, 95% CI: 0.08-0.42)。与基线相比,TF减少等于或大于90%,等于或大于50%也与显著改善的结果相关。ctDNA动力学因治疗类别而异:TF报告在选择肿瘤对免疫治疗和靶向治疗的反应(91%的应答者减少≥50%,24%的无应答者减少)比化疗和化疗免疫治疗(86%对60%)具有更大的区别性。TF动力学与结果相关,但当肿瘤反应纳入时,真实世界无进展生存和真实世界总生存模型得到改善。结论基于ctDNA TF动力学的分子反应的组织不可知监测在四种不同治疗方案的现实环境中具有实用价值。这些结果表明,ctDNA动态可能是对NSCLC和SCLC肿瘤成像的补充,以更好地告知患者护理。
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引用次数: 0
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JTO Clinical and Research Reports
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