Association between patient-reported outcomes and pathological response in neoadjuvant chemoimmunotherapy—a post hoc analysis of the TD-FOREKNOW trial

Introduction

Patient-reported outcomes (PROs) provide critical insights into symptom burden, functional capacity, and health-related quality of life (HRQoL) from the patient’s perspective. As validated measures of treatment tolerability and patient-centered benefit, PROs have become integral to oncologic research, complementing conventional endpoints such as overall survival (OS) and objective response rate. In resectable non-small cell lung cancer (NSCLC), neoadjuvant chemoimmunotherapy followed by surgery has been associated with improved pathologic complete response (pCR) rates and survival across multiple trials (1-4). The survival benefits associated with pCR have been further confirmed in subsequent studies (5-7). Although HRQoL outcomes from neoadjuvant chemoimmunotherapy trials such as CheckMate 816 and KEYNOTE-671 have been reported, the association between pCR and PROs remains unexplored (8,9). Elucidating whether profound pathological responses induced by neoadjuvant chemoimmunotherapy translate into meaningful improvements in PROs will provide novel scientific evidence for comprehensively evaluating the holistic benefits of this treatment.

The TD-FOREKNOW trial (NCT04338620) is a randomized, open-label, multicenter, phase 2 clinical trial to assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy compared with chemotherapy for patients with resectable stage IIIA or IIIB NSCLC (10). To specifically investigate PRO dynamics during neoadjuvant treatment and the relationship between pathological responses and PROs, we performed a post hoc analysis of PRO data in the TD-FOREKNOW trial, especially in its camrelizumab plus chemotherapy cohort.

Methods

Study design and participants

TD-FOREKNOW, a randomized, open-label, multicenter, phase II clinical trial, was conducted at two tertiary hospitals (Fourth Military Medical University Tangdu Hospital and Shaanxi Provincial Tumor Hospital) in Shaanxi, China. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by The Fourth Military Medical University Tangdu Hospital (No. K202011-02) and Shaanxi Provincial Tumor Hospital (No. 2021-66). Informed consent was taken from all the patients. Detailed study design and results have been reported elsewhere (10).

In this post hoc analysis, we first compared changes of PROs between the camrelizumab plus chemotherapy cohort and chemotherapy cohort in the TD-FOREKNOW trial. To further explore the association between pCR and PROs in neoadjuvant chemoimmunotherapy, patients who underwent surgical resection were stratified into pCR and non-pCR based on pathological response in the camrelizumab plus chemotherapy cohort, and PRO changes were compared between pCR and non-pCR patients.

Procedures

In the original study, camrelizumab (200 mg) was administered intravenously on day 1 of each 3-week cycle for 3 cycles before surgical resection. Neoadjuvant chemotherapy consisted of nab-paclitaxel (130 mg/m² intravenously on days 1 and 8) and platinum (cisplatin, 75 mg/m²; carboplatin, area under the curve, 5; or nedaplatin, 100 mg/m² intravenously on day 1) every 3 weeks for three cycles. Surgery was planned 4–6 weeks after the completion of neoadjuvant treatment. No patient received adjuvant chemotherapy or adjuvant immunotherapy after surgery.

Endpoints

We reported PROs in the TD-FOREKNOW trial post hoc. HRQoL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) (11) and Quality of Life Questionnaire-Lung Cancer Module 13 (QLQ-LC13) (12). Key PRO endpoints were mean score change from baseline evaluated by EORTC QLQ-C30 global health status/quality of life (GHS/QoL), cough (QLQ-LC13, question 1), hemoptysis (QLQ-LC13, question 2) and dyspnea (QLQ-C30, question 8) between pCR patients and non-pCR patients. Supportive PRO endpoints included mean score changes from baseline to weeks 12 and 16 in EORTC QLQ-C30 and EORTC QLQ-LC13 subscales. Time points were selected to represent the neoadjuvant treatment phase (week 12, completed 3 cycles of treatment) and the post-operative phase (week 16, 4 weeks after surgery). HRQoL was assessed using paper-based questionnaires administered by trained site personnel before each drug administration, adverse event evaluation, and disease status update. The EORTC QLQ-C30 was administered first, followed by the QLQ-LC13. Assessments were conducted at five predefined time points: baseline, weeks 4, 7, and 12 during neoadjuvant therapy, and postoperatively at week 16.

Statistical analyses

PRO analyses were performed on the full analysis population, which included patients who received ≥1 dose of study treatment and completed ≥1 PRO assessment. Patients who completed ≥1 item on the PRO instrument were considered to have completed ≥1 PRO assessment. The completion rate referred to the percentage of patients who completed ≥1 PRO assessment in the full analysis population at each time point. Compliance assessed by PRO was defined as the proportion of patients who completed ≥1 item of the questionnaire as expected to complete the questionnaire (i.e., patients who were alive, on medication, transmissible, and scheduled to visit).

We assessed the mean change from baseline to weeks 4, 7, 12 and 16 in the PRO instrument score using a constrained longitudinal data analysis model. PRO score was the response variable, and the covariates were treated with study visits. The inter-group comparisons were reported as the difference in the least square (LS) mean change from baseline with the 95% confidence interval (CI) and nominal P value. Pearson’s χ²-test was used to compare the categorical variables. R (version 4.4.2; The R Foundation for Statistical Computing; http://www.r-project.org) was used for all analyses. P values for all PRO analyses were two-sided and nominal.

Results

Key PRO endpoints

GHS/QoL in TD-FOREKNOW trial

A total of 94 patients were enrolled in the TD-FOREKNOW trial and the full analysis set included 88 patients who completed at least one PRO assessment, with 43 in the camrelizumab plus chemotherapy cohort and 45 in the chemotherapy cohort (Figure 1). Both cohorts had 100% completion rates for the QLQ-C30 and QLQ-LC13 at baseline. The mean and median interval between the surgery date and the last questionnaire administration (week 16) are 28.9±0.9 and 29 [range: 28–30] days. At weeks 4 and 7, the completion rates were 97.7% (42/43) and 100% (45/45), respectively, for both questionnaires. At week 12, the completion rates were 93.0% (40/43) and 95.6% (43/45), and at week 16, they were 90.7% (39/43) and 93.3% (42/45) (Table S1). Baseline mean [standard deviation (SD)] GHS/QoL scores were balanced between the camrelizumab plus chemotherapy cohort [74.2 (17.4)] and the chemotherapy cohort [74.4 (18.8)]. In the camrelizumab plus chemotherapy cohort, LS mean (95% CI) QLQ-C30 GHS/QoL scores decreased from baseline by 4.97 points (−9.93 to −0.02) at week 4, 6.89 points (−13.16 to −0.62) at week 7, 6.95 points (−13.31 to −0.59) at week 12 and 1.97 points (−8.31 to 4.36) at week 16. Conversely, scores in the chemotherapy cohort remained stable relative to baseline, with changes of −1.84 points (−6.62 to 2.94) at week 4, 0.64 points (−5.47 to 6.75) at week 7, and 0.70 points (−5.50 to 6.90) at week 12 and −3.46 points (−9.61 to 2.70) at week 16. The between-group LS mean differences were −3.13 points (95% CI: −10.00 to 3.75; P=0.37) at week 4, −7.53 points (95% CI: −15.15 to 0.08; P=0.053) at week 7, −7.65 points (95% CI: −15.57 to 0.03; P=0.051) at week 12, and 1.48 points (95% CI: −6.38 to 9.35; P=0.71) at week 16 (Table S2).

Figure 1 CONSORT diagram. pCR, pathologic complete response; PRO, patient-reported outcome; QLQ-C30, Quality of Life Questionnaire-Core 30; QLQ-LC, Quality of Life Questionnaire-Lung Cancer Module 13.

PROs between pCR and non-pCR patients in camrelizumab plus chemotherapy cohort

Of the 42 patients in the chemotherapy cohort who underwent surgical resection, only 4 achieved pCR. Due to the limited number of responders, this cohort was not subjected to further analysis. In the camrelizumab plus chemotherapy cohort, 40 of 43 patients proceeded to radical resection. Upon pathological evaluation, 14 patients achieved pCR, whereas 26 patients were classified as non-pCR (Figure 1). The baseline demographic and clinical characteristics—including age, sex, Eastern Cooperative Oncology Group performance status, body mass index, smoking history, histopathological subtype, clinical staging, tumor localization, surgical approach, and extent of resection were balanced between the pCR and non-pCR patients (Table 1). The PRO analysis population included 40 patients who completed at least one PRO assessment. Completion rates were 100.0% for the QLQ-C30 and QLQ-LC13 at baseline. At weeks 4, 7, 12 and 16, the completion rates were 100.0% (14/14) in pCR patients, and were 100.0% (26/26), 100.0% (26/26), 100.0% (26/26) and 96.2% (25/26) in non-pCR patients (Table 2).

Mean changes from baseline in QLQ-C30 GHS/QoL, cough, dyspnea, and hemoptysis scores were evaluated at each visit (Figure 2). Baseline mean (SD) GHS/QoL scores were 73.2 (18.5) in pCR patients and 74.1 (17.5) in non-pCR patients. During the neoadjuvant phase (weeks 4, 7, and 12), mean scores of the GHS/QoL showed a decline from baseline levels. However, a recovery was observed in the postoperative phase. At most assessed time points, patients who achieved a pCR consistently reported higher GHS/QoL scores compared to those without pCR (Figure 2A). The between-group LS mean differences (pCR vs. non-pCR) were 6.3 points (95% CI: −4.7 to 17.3; P=0.25) at week 4, −0.9 point (95% CI: −13.3 to 11.6; P=0.89) at week 7, 0.8 point (95% CI: −12.4 to 14.1; P=0.89) at week 12 and 2.7 points (95% CI: −4.8 to 10.1; P=0.47) at week 16 (Table 3). Besides, changes in GHS/QoL scores were categorized as improved, stable, or worsened using a 20% threshold. We observed that the proportions of patients exhibiting improvement or stability were consistently higher in the pCR group compared with the non-pCR group across all time points (Figure 3).

Figure 2 Mean change from baseline in QLQ-C30 GHS/QoL scores (A), cough scores (B), dyspnea scores (C) and hemoptysis scores (D) by visit. *, P<0.05. GHS/QoL, global health status/quality of life; pCR, pathologic complete response; QLQ-C30, Quality of Life Questionnaire-Core 30; SE, standard error.

Figure 3 Proportions of patients with improved, stable, or worsened GHS/QoL scores in the pCR and non-pCR groups at different time points. Changes were categorized based on a 20% threshold from baseline. GHS/QoL, global health status/quality of life; pCR, pathologic complete response.

Among patients who achieved pCR, cough scores declined progressively during the neoadjuvant phase, reaching their lowest levels at week 7. Conversely, cough scores in non-pCR patients remained consistently elevated relative to baseline (Figure 2B). The between-group LS mean differences peaked [−18.2 (95% CI: −33.0 to −3.5; P=0.02)] at week 12, reflecting the greatest separation in symptom burden at this time point. However, following surgery, cough scores increased significantly in both pCR and non-pCR patients compared to baseline, and the intergroup difference was no longer observed [1.1 (95% CI: −16.9 to 19.1; P=0.90)] (Table S3). Changes in dyspnea scores closely mirrored the trajectory observed for cough scores across both pCR and non-pCR patients (Figure 2C). The between-group LS mean differences were −21.3 (95% CI: −38.3 to −4.3; P=0.02) and 1.1 (95% CI: −17.0 to 19.1; P=0.90) at weeks 12 and 16, respectively (Table S3). Hemoptysis scores declined during the neoadjuvant phase but elevated after surgery (Figure 2D), and no clinically meaningful differences were observed between pCR and non-pCR patients (Table S3). In brief, patients who ultimately achieved pCR exhibited slightly higher GHS/QoL scores and more improvement in pulmonary symptoms (cough and dyspnea) during the neoadjuvant phase. A temporary deterioration of cough, dyspnea, and hemoptysis was reported shortly after surgery in both pCR and non-pCR patients.

Supportive PRO endpoints

In both pCR and non-pCR patients, scores for all functional domains and GHS/QoL exhibited a decline from baseline at week 12 (neoadjuvant phase) with varying degrees. Further reductions in physical and role functioning scores were noted, while other scores were improved, especially in pCR patients at week 16. Across both the neoadjuvant and postoperative phases, pCR patients exhibited less deterioration in functional scales and GHS/QoL scores compared with those in non-pCR patients, with the exception of social functioning during the neoadjuvant phase. Notably, during the postoperative phase, patients achieving pCR demonstrated significant improvements in emotional, cognitive, and social functioning scores, surpassing their respective baseline levels (Figure 4A,4B).

Figure 4 Changes from baseline in QLQ-C30 GHS/QoL and functional scale scores at week 12 (A) and week 16 (B), and QLQ-C30 symptom subscale scores at week 12 (C) and week 16 (D). Higher functional scale scores represent better functioning, whereas higher symptom subscale scores indicate more symptoms; higher GHS/QoL represents better health status/QoL. CI, confidence interval; GHS/QoL, global health status/quality of life; LS, least square; pCR, pathologic complete response; QLQ-C30, Quality of Life Questionnaire-Core 30.

By week 12, both pCR and non-pCR patients exhibited a deterioration in most symptom scales with the exception of dyspnea and diarrhea in pCR patients. Notably, the extent of symptom worsening was generally less pronounced in pCR patients compared to non-pCR patients. By week 16, the pattern of symptom burden and intergroup differences remained largely consistent with those observed during the neoadjuvant phase (Figure 4C,4D).

Discussion

This post hoc study reported PRO dynamics in the TD-FOREKNOW trial and further investigated the relationship between profound pathological responses and PROs in its neoadjuvant camrelizumab plus chemotherapy cohort.

In TD-FOREKNOW trial, GHS/QoL scores in the chemotherapy cohort showed slight fluctuations around the baseline, while scores in the camrelizumab plus chemotherapy cohort declined transiently (Table S2), which is potentially related to a higher incidence of grade 3 or higher adverse events (25.6% vs. 11.1%) in the camrelizumab plus chemotherapy cohort (10). Post-surgery, the camrelizumab plus chemotherapy cohort’s scores increased while the chemotherapy cohort’s scores decreased, narrowing the gap and slightly favoring the camrelizumab plus chemotherapy cohort. This reversal may be due to the reduction of adverse effects from medication and the emergence of surgery-related adverse events (2.5% vs. 33.3%) between the two cohorts (10). In summary, the addition of camrelizumab during neoadjuvant chemotherapy did not significantly impair patients’ quality of life. These results were generally comparable to those observed in the CheckMate 816 and KEYNOTE-671 trial (8,9).

To further investigate the association between pCR and PROs during neoadjuvant chemoimmunotherapy, patients in the camrelizumab plus chemotherapy cohort were stratified into pCR and non-pCR patients. The chemotherapy cohort was excluded from the analysis owing to the limited number of patients who achieved pCR (4 of 42). The trajectory of GHS/QoL scores showed a decline during neoadjuvant therapy followed by a rebound to near-baseline levels postoperatively in both pCR and non-pCR patients. In the context of advanced disease, such a decline is often indicative of disease progression (13-15). However, in the camrelizumab plus chemotherapy cohort, no patient experienced disease progression during treatment, suggesting that the observed decline in GHS/QoL scores was unlikely to be disease-driven. Rather, the temporary deterioration in GHS/QoL is likely attributable to treatment-related adverse events (TRAEs)—particularly chemoimmunotherapy-induced nausea, vomiting, anorexia, alopecia, and dermatologic toxicities—which are known to affect subjective well-being significantly (Table S4). The subsequent postoperative recovery in GHS/QoL scores across both pCR and non-pCR patients further supports this hypothesis. Notably, radical tumor resection may contribute to the mitigation of tumor-related psychological distress as well.

GHS/QoL scores in pCR patients remained consistently higher than those in non-pCR patients as well as their improvement and stability ratio, throughout the neoadjuvant and postoperative phases. Though the incidence and severity of TRAEs were comparable between pCR and non-pCR patients (92.8% vs. 88.5%, Table S4). This finding suggests that tumor regression may independently contribute to better health status, potentially through alleviation of lung cancer-specific symptoms (such as dyspnea and cough) and psychological burden. Complete tumor regression also reduced the complexity of the surgical procedure, thereby leading to fewer surgery-related adverse events (28.6% vs. 42.3%, Table S4). This may explain why pCR patients tend to exhibit slightly higher GHS scores in the postoperative phase.

Time to deterioration (TTD) is closely related to disease progression and is often used as an endpoint to evaluate the quality of life in patients with advanced cancer (16). In the TD-FOREKNOW study, although the questionnaire survey lasted up to 16 weeks, the time span only covered the neoadjuvant treatment phase and 4 weeks post-surgery. During these phases, almost all the patients had their conditions effectively controlled, making it difficult for symptom changes to reflect disease progression accurately. Therefore, TTD was not suitable as an endpoint in this study. Instead, we analyzed and presented the trends in mean scores for cough, dyspnea, and hemoptysis (Figure 2B-2D). A marked reduction in cough scores was observed in pCR patients after two cycles of neoadjuvant therapy, whereas patients in non-pCR patients exhibited persistently elevated cough scores above baseline. Notably, the onset of symptom improvement in pCR patients coincided with the expected pharmacodynamic window of programmed death-1 (PD-1) blockade, typically around 6–8 weeks (17,18), suggesting a temporal alignment between early antitumor activity and symptomatic relief. These findings imply that substantial tumor shrinkage during the neoadjuvant phase may have contributed to cough alleviation, while insufficient regression in non-pCR patients failed to produce similar effects. Dyspnea followed a similar trajectory to cough across both treatment phases. It is common for cough and dyspnea to worsen in the early postoperative period, typically due to lung tissue loss and surgical trauma. Full recovery usually takes approximately 3–6 months. Chest pain, typically associated with pleural, bony, or neural invasion in advanced disease, was infrequently reported in this study due to the low incidence of such invasive features in stage III population. Consequently, it was not considered a suitable endpoint for symptom monitoring. Central-type lung cancer comprised 60% of this cohort and more patients reported hemoptysis than chest pain (37.5% vs. 20%) at baseline. Given its higher incidence, clinical observability, and responsiveness to tumor regression, hemoptysis was selected as a prespecified symptom endpoint in this study. Hemoptysis scores declined substantially during neoadjuvant treatment and rose again following surgery, a pattern consistent with response to systemic therapy and surgical trauma.

During neoadjuvant therapy, both pCR and non-pCR patients exhibited a decline in functional scores across multiple domains relative to baseline, likely attributable to TRAEs. Following surgery, additional reductions were observed in physical and role functioning, reflecting the impact of surgical trauma. However, a notable recovery in cognitive, social, and emotional functioning was seen, particularly in pCR patients, where improvements not only reversed earlier declines but also, in some domains, surpassed baseline levels. Awareness of treatment success likely alleviates disease-related anxiety and fosters a positive perception of future outcomes. This dual physical and psychological relief appears to create a conducive environment for cognitive recovery and encourages patients to resume their social roles more rapidly. In terms of symptom burden, patients experienced varying degrees of deterioration during the neoadjuvant phase; nonetheless, dyspnea and diarrhea scores improved from baseline in pCR patients. While other symptoms showed modest increases in pCR patients, these remained generally lower than those observed in non-pCR patients. These findings suggest that achieving pCR may confer substantial benefits in both symptom and functional domains.

Patients who achieved pCR reported superior HRQoL, which has important implications for clinical practice and trial design. First, our data support pCR as a meaningful endpoint that reflects both tumor control and improved quality of life. Second, the prospect of faster functional recovery provides a strong rationale for neoadjuvant therapy. Finally, patients who do not achieve a pCR may be at higher risk for persistent symptoms and may require additional support to resume their daily activities (19).

The main limitations of this study are: (I) the limited follow-up phase in assessing PROs restricts the evaluation of the long-term efficacy; (II) these post-hoc analyses lack formal statistical testing for some outcomes.

Conclusions

In conclusion, achieving a pCR was associated with improved PROs during neoadjuvant chemoimmunotherapy. These findings suggest that pCR may serve as a valuable marker for patient-centered benefits beyond survival.

Acknowledgments

None.

Footnote

Data Sharing Statement: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-1-1425/dss

Peer Review File: Available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-1-1425/prf

Funding: This study was supported by Jiangsu Hengrui Pharmaceuticals Co., Ltd. It had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-2025-1-1425/coif). X.W. is a current employee of Jiangsu Hengrui Pharmaceuticals Co., Ltd. T.J. reports receiving nonfinancial support from Jiangsu Hengrui Pharmaceuticals Co., Ltd., outside the submitted work. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by The Fourth Military Medical University Tangdu Hospital (No. K202011-02) and Shaanxi Provincial Tumor Hospital (No. 2021-66). Informed consent was taken from all the patients.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Lu S, Zhang W, Wu L, et al. Perioperative Toripalimab Plus Chemotherapy for Patients With Resectable Non-Small Cell Lung Cancer: The Neotorch Randomized Clinical Trial. JAMA 2024;331:201-11. [Crossref] [PubMed]
2. Wakelee H, Liberman M, Kato T, et al. Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer. N Engl J Med 2023;389:491-503. [Crossref] [PubMed]
3. Deutsch JS, Cimino-Mathews A, Thompson E, et al. Association between pathologic response and survival after neoadjuvant therapy in lung cancer. Nat Med 2024;30:218-28. [Crossref] [PubMed]
4. Yue D, Wang W, Liu H, et al. Perioperative tislelizumab plus neoadjuvant chemotherapy for patients with resectable non-small-cell lung cancer (RATIONALE-315): an interim analysis of a randomised clinical trial. Lancet Respir Med 2025;13:119-29. [Crossref] [PubMed]
5. Sorin M, Prosty C, Ghaleb L, et al. Neoadjuvant Chemoimmunotherapy for NSCLC: A Systematic Review and Meta-Analysis. JAMA Oncol 2024;10:621-33. [Crossref] [PubMed]
6. Marinelli D, Nuccio A, Di Federico A, et al. Improved Event-Free Survival After Complete or Major Pathologic Response in Patients With Resectable NSCLC Treated With Neoadjuvant Chemoimmunotherapy Regardless of Adjuvant Treatment: A Systematic Review and Individual Patient Data Meta-Analysis. J Thorac Oncol 2025;20:285-95. [Crossref] [PubMed]
7. Forde PM, Spicer JD, Provencio M, et al. Overall Survival with Neoadjuvant Nivolumab plus Chemotherapy in Lung Cancer. N Engl J Med 2025;393:741-52. [Crossref] [PubMed]
8. Felip E, Wang C, Ciuleanu TE, et al. 932MO Nivolumab (NIVO) plus platinum-doublet chemotherapy (chemo) versus chemo as neoadjuvant treatment for resectable non-small cell lung cancer (NSCLC): Health-related quality of life (HRQoL) outcomes from CheckMate 816. Ann Oncol 2022;33:S973-4.
9. Garassino MC, Wakelee HA, Spicer J, et al. Health-related quality of life (HRQoL) outcomes from the randomized, double-blind phase 3 KEYNOTE-671 study of perioperative pembrolizumab for early-stage non-small-cell lung cancer (NSCLC). J Clin Oncol 2024;42:8012.
10. Lei J, Zhao J, Gong L, et al. Neoadjuvant Camrelizumab Plus Platinum-Based Chemotherapy vs Chemotherapy Alone for Chinese Patients With Resectable Stage IIIA or IIIB (T3N2) Non-Small Cell Lung Cancer: The TD-FOREKNOW Randomized Clinical Trial. JAMA Oncol 2023;9:1348-55. [Crossref] [PubMed]
11. Aaronson NK, Ahmedzai S, Bergman B, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993;85:365-76. [Crossref] [PubMed]
12. Bergman B, Aaronson NK, Ahmedzai S, et al. The EORTC QLQ-LC13: a modular supplement to the EORTC Core Quality of Life Questionnaire (QLQ-C30) for use in lung cancer clinical trials. EORTC Study Group on Quality of Life. Eur J Cancer 1994;30A:635-42. [Crossref] [PubMed]
13. Monk BJ, Tewari KS, Dubot C, et al. Health-related quality of life with pembrolizumab or placebo plus chemotherapy with or without bevacizumab for persistent, recurrent, or metastatic cervical cancer (KEYNOTE-826): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2023;24:392-402.
14. Cescon DW, Schmid P, Rugo HS, et al. Health-related quality of life with pembrolizumab plus chemotherapy vs placebo plus chemotherapy for advanced triple-negative breast cancer: KEYNOTE-355. J Natl Cancer Inst 2024;116:717-27. [Crossref] [PubMed]
15. Mansoor W, Joo S, Norquist JM, et al. Health-related quality-of-life analysis from KEYNOTE-590: pembrolizumab plus chemotherapy versus chemotherapy for advanced esophageal cancer. Oncologist 2024;29:e1324-35. [Crossref] [PubMed]
16. Fiero MH, Roydhouse JK, Bhatnagar V, et al. Time to deterioration of symptoms or function using patient-reported outcomes in cancer trials. Lancet Oncol 2022;23:e229-34. [Crossref] [PubMed]
17. Zhou C, Chen G, Huang Y, et al. Camrelizumab plus carboplatin and pemetrexed versus chemotherapy alone in chemotherapy-naive patients with advanced non-squamous non-small-cell lung cancer (CameL): a randomised, open-label, multicentre, phase 3 trial. Lancet Respir Med 2021;9:305-14. [Crossref] [PubMed]
18. Spicer JD, Garassino MC, Wakelee H, et al. Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab compared with neoadjuvant chemotherapy alone in patients with early-stage non-small-cell lung cancer (KEYNOTE-671): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2024;404:1240-52. [Crossref] [PubMed]
19. Tang L, Wu S, Li X, et al. CACA clinical guideline of holistic psychosocial care for cancer patients. Holistic Integrative Oncology 2025;4:34.