After a thorough analysis of the latest research findings by Keita Miura and colleagues, we affirm their conclusion that approximately one-third of untreated patients with advanced non–small cell lung cancer (NSCLC) exhibit cachexia before first-line systemic treatment, with different treatment methods having a significant impact on these patients' appetite-related quality of life, weight changes and survival [1]. However, the study may have overlooked some key issues that could affect the accuracy and interpretation of the results.

Firstly, the study failed to exclude patients with severe gastrointestinal diseases, active malignancies other than NSCLC, symptomatic brain metastases or those requiring high-dose steroid treatment. These factors are important variables to consider when assessing the impact of cachexia as they could significantly affect the patient's nutritional status, quality of life and response to treatment [2, 3]. If these patients were not excluded, these conditions could have caused a significant confounding effect on the study's conclusions. For instance, severe gastrointestinal diseases could directly impact appetite and food absorption, similar to the appetite decline and weight loss observed in cachexia. Still, they may not be directly related to cancer or its treatment. This could lead to inaccurate assessments of cachexia as non–cancer-related weight loss could be mistakenly attributed to cancer-related cachexia. Similarly, malignancies other than NSCLC could increase systemic inflammatory responses, promoting the development of cachexia, while symptomatic brain metastases requiring high-dose steroids could induce or exacerbate changes in weight and appetite, thus confounding the assessment of cachexia. Additionally, other side effects of steroid treatment, such as muscle wasting and immunosuppression, could be confounded with the physiological changes of cachexia, further complicating the interpretation of treatment effects and patient prognosis [4]. Therefore, these unexcluded conditions could mask the true effects of cachexia treatment, making it difficult to accurately assess the impact of cachexia on patient quality of life and survival.

Secondly, the study did not record and adjust for pulmonary comorbidities that could significantly affect cachexia, such as baseline chronic obstructive pulmonary disease (COPD) and emphysema. These chronic lung diseases not only affect lung function but could also impact the overall health status of patients, including nutritional status and quality of life, especially in patients with advanced NSCLC. If these key baseline conditions were not recorded and adjusted for, they could introduce significant confounders into the study, affecting the assessment and interpretation of cachexia. COPD and emphysema could lead to breathlessness, reduced activity tolerance and decreased quality of life, symptoms similar to those of cachexia, including weight loss, reduced appetite and muscle wasting (Sepulveda-Loyola et al. 2020). Therefore, failing to consider these chronic lung diseases could overestimate or underestimate the incidence and severity of cachexia, thus affecting the understanding of the relationship between cachexia and treatment outcomes [5, 6]. Additionally, COPD and emphysema could affect a patient's tolerance to treatments and choices of treatment, including chemotherapy, targeted therapy and immunotherapy. For example, severe COPD could limit the ability of patients to receive certain chemotherapeutic drugs as these could further impair lung function. This limitation in treatment choice could affect a patient's treatment response and survival, potentially misattributing treatment effects to the presence of cachexia without proper adjustment for these factors. Furthermore, specifics about completed chemotherapy cycles were not recorded. Previous studies have found that increased severity of cachexia is associated with fewer completed cycles of chemotherapy, suggesting that cachexia could affect a patient's tolerance to chemotherapy and the continuity of treatment. Without recording the number of chemotherapy cycles, this could limit our comprehensive understanding of how cachexia affects the treatment response and prognosis of NSCLC patients. Since the number of chemotherapy cycles is a key indicator of treatment continuity and completeness, the lack of this data could lead to an inability to accurately assess the impact of cachexia on a patient's ability to complete chemotherapy [7]. Cachexia could lead to more treatment-related side effects, such as weight loss, reduced appetite and fatigue, which could affect a patient's ability to complete all planned cycles of chemotherapy. Therefore, not recording the number of chemotherapy cycles could obscure the potential negative impact of cachexia on treatment continuity and effectiveness. Recording the number of chemotherapy cycles is crucial for assessing treatment effects, cumulative toxicity, patient tolerance to treatment and changes in quality of life. In the treatment of advanced NSCLC, the number of chemotherapy cycles could be closely related to the efficacy of the drugs, disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Due to the lack of this data in the documents, we cannot accurately assess the impact of chemotherapy dose density on patient prognosis nor can we understand whether patients need to adjust their treatment plans due to tolerance issues.

Lastly, the study did not focus on the information about the intensity and duration of physical exercise of the participants. Physical exercise is thought to reduce systemic inflammation and promote muscle anabolic metabolism, which is particularly important for cancer patients, as cancer cachexia syndrome often accompanies muscle wasting and systemic inflammation. Physical exercise could mitigate these negative effects by reducing inflammation and promoting muscle health, potentially improving quality of life and survival rates [8]. Additionally, the study did not record the specific use of drugs like Anamorelin or corticosteroids and progestogens for the treatment of cachexia. These drugs are thought to enhance appetite and promote anabolic metabolism, potentially effective for improving symptoms of cachexia in cancer patients, especially Anamorelin as a ghrelin receptor agonist, which could have a positive effect on stimulating appetite and muscle synthesis [9, 10]. While corticosteroids can increase appetite in the short term, long-term use could lead to side effects. Since the study did not record the use of these therapeutic drugs, it is not possible to assess their potential impact on cachexia symptoms, appetite changes, muscle mass and patient survival.

在对 Keita Miura 及其同事的最新研究结果进行全面分析后，我们确认了他们的结论，即大约三分之一未经治疗的晚期非小细胞肺癌 （NSCLC） 患者在一线全身治疗前表现出恶病质，不同的治疗方法对这些患者的食欲相关生活质量、体重变化和生存有显着影响 [1].然而，该研究可能忽略了一些可能影响结果准确性和解释的关键问题。

首先，该研究未能排除患有严重胃肠道疾病、NSCLC 以外的活动性恶性肿瘤、有症状的脑转移或需要大剂量类固醇治疗的患者。这些因素是评估恶病质影响时需要考虑的重要变量，因为它们可能会显着影响患者的营养状况、生活质量和对治疗的反应 [2， 3]。如果不排除这些患者，这些情况可能会对研究结论造成显着的混杂影响。例如，严重的胃肠道疾病会直接影响食欲和食物吸收，类似于在恶病质中观察到的食欲下降和体重减轻。尽管如此，它们可能与癌症或其治疗没有直接关系。这可能导致对恶病质的评估不准确，因为非癌症相关的体重减轻可能被错误地归因于癌症相关的恶病质。同样，NSCLC 以外的恶性肿瘤可能会增加全身炎症反应，促进恶病质的发展，而需要大剂量类固醇的症状性脑转移可能会诱发或加剧体重和食欲的变化，从而混淆恶病质的评估。此外，类固醇治疗的其他副作用，如肌肉萎缩和免疫抑制，可能与恶病质的生理变化混淆，使治疗效果和患者预后的解释进一步复杂化 [4]。因此，这些未排除的情况可能会掩盖恶病质治疗的真实效果，从而难以准确评估恶病质对患者生活质量和生存率的影响。

其次，该研究没有记录和调整可能显着影响恶病质的肺部合并症，例如基线慢性阻塞性肺病 （COPD） 和肺气肿。这些慢性肺病不仅影响肺功能，还可能影响患者的整体健康状况，包括营养状况和生活质量，尤其是晚期 NSCLC 患者。如果这些关键的基线条件没有被记录和调整，它们可能会在研究中引入重要的混杂因素，从而影响恶病质的评估和解释。慢性阻塞性肺病和肺气肿可导致呼吸困难、活动耐受力降低和生活质量下降，症状类似于恶病质的症状，包括体重减轻、食欲下降和肌肉萎缩（Sepulveda-Loyola 等人，2020 年）。因此，不考虑这些慢性肺病可能会高估或低估恶病质的发生率和严重程度，从而影响对恶病质与治疗结果之间关系的理解 [5， 6]。此外，慢性阻塞性肺病和肺气肿会影响患者对治疗的耐受性和治疗选择，包括化疗、靶向治疗和免疫治疗。例如，严重的 COPD 可能会限制患者接受某些化疗药物的能力，因为这些药物可能会进一步损害肺功能。这种治疗选择的限制可能会影响患者的治疗反应和生存率，可能会将治疗效果错误地归因于恶病质的存在，而没有对这些因素进行适当调整。此外，未记录有关已完成化疗周期的细节。 以前的研究发现，恶病质的严重程度增加与完成的化疗周期减少有关，这表明恶病质会影响患者对化疗的耐受性和治疗的连续性。如果不记录化疗周期的数量，这可能会限制我们对恶病质如何影响 NSCLC 患者的治疗反应和预后的全面理解。由于化疗周期数是治疗连续性和完整性的关键指标，因此缺乏这些数据可能导致无法准确评估恶病质对患者完成化疗能力的影响 [7]。恶病质可能导致更多与治疗相关的副作用，例如体重减轻、食欲下降和疲劳，这可能会影响患者完成所有计划化疗周期的能力。因此，不记录化疗周期数可能会掩盖恶病质对治疗连续性和有效性的潜在负面影响。记录化疗周期数对于评估治疗效果、累积毒性、患者对治疗的耐受性和生活质量的变化至关重要。在晚期 NSCLC 的治疗中，化疗周期数可能与药物疗效、疾病控制率 （DCR） 、无进展生存期 （PFS） 和总生存期 （OS） 密切相关。由于文件中缺乏这些数据，我们无法准确评估化疗剂量密度对患者预后的影响，也无法了解患者是否因耐受性问题而需要调整治疗计划。

最后，该研究没有关注有关参与者体育锻炼强度和持续时间的信息。体育锻炼被认为可以减少全身炎症并促进肌肉合成代谢，这对癌症患者尤为重要，因为癌症恶病质综合征通常伴随着肌肉萎缩和全身炎症。体育锻炼可以通过减少炎症和促进肌肉健康来减轻这些负面影响，从而有可能提高生活质量和存活率 [8]。此外，该研究没有记录阿那莫林或皮质类固醇和孕激素等药物治疗恶病质的具体用途。这些药物被认为可以增强食欲和促进合成代谢，可能有效改善癌症患者的恶病质症状，尤其是阿那莫林作为生长素释放肽受体激动剂，它可能对刺激食欲和肌肉合成产生积极影响 [9， 10]。虽然皮质类固醇可以在短期内增加食欲，但长期使用可能会导致副作用。由于该研究没有记录这些治疗药物的使用，因此无法评估它们对恶病质症状、食欲变化、肌肉质量和患者生存率的潜在影响。