Factors influencing multi-disciplinary tumor board recommendations in stage III non-small cell lung cancer

Ronden, M.; Hashemi, S.; Dickhoff, Chris; Haan, Patricia F. de; Becker, Annemarie; Spoelstra, F.; Dahele, Max; Ali, Rania; Tiemessen, M.; Tarasevych, S.; Brink, K. Maassen Van Den; Haasbeek, Cornelis J.A.; Daniels, Johannes M.A.; Laren, Marjolein van; Verbakel, Wilko F.A.R.; Senan, Suresh

doi:10.1016/j.lungcan.2020.12.019

Cited by 14 publications

(15 citation statements)

References 35 publications

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“…The OS values in our real-world cCRT cohort were comparable to those reported in RCT's such as in the control arm of the PACIFIC study [8]. We did not observe an improvement of OS in the sCRT/RT group compared to our earlier cohort, possibly because factors such as comorbidity have the largest influence on OS, and not plan quality or OAR doses [7]. These patients may also be less suitable for aggressive therapy on progression.…”

Section: Discussionsupporting

confidence: 72%

“…In the Netherlands, only a small minority of these patients receive surgery. Surgery is often not feasible due to primary tumor extent, multi-level nodal involvement, or not recommended due to age, comorbidities, or patient’s preference [ 5 , 6 , 7 ]. In fit patients who do not receive surgery, concurrent chemoradiotherapy (cCRT) is preferred over sequential CRT (sCRT) or RT alone, due to better survival.…”

Section: Introductionmentioning

confidence: 99%

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Relationship between Treatment Plan Dosimetry, Toxicity, and Survival following Intensity-Modulated Radiotherapy, with or without Chemotherapy, for Stage III Inoperable Non-Small Cell Lung Cancer

Vries

Ronden

Spoelstra

et al. 2021

Cancers

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Concurrent chemoradiotherapy (cCRT) is the preferred treatment for stage III NSCLC because surgery containing multimodality treatment is often not appropriate. Alternatives, often for less fit patients, include sequential CRT and RT alone. Many reports describing the relationship between overall survival (OS), toxicity, and dosimetry are based on clinical trials, with strict criteria for patient selection. We performed an institutional analysis to study the relationship between dosimetric parameters, toxicity, and OS in inoperable patients with stage III NSCLC treated with (hybrid) IMRT/VMAT-based techniques in routine clinical practice. Eligible patients had undergone treatment with radical intent using cCRT, sCRT, or RT alone, planned to a total dose ≥ 50 Gy delivered in ≥15 fractions. All analyses were performed for two patient groups, (1) cCRT (n = 64) and (2) sCRT/RT (n = 65). The toxicity rate differences between the two groups were not significant, and OS was 29 and 17 months, respectively. For sCRT/RT, no dosimetric factors were associated with OS, whereas for cCRT, PTV-volume, esophagus V50 Gy, and contralateral lung V5 Gy were associated. cCRT OS was significantly lower in patients with esophagitis ≥ G2. The overall rate of ≥G3 pneumonitis was low (3%), and the rate of high-grade esophagitis the OS in this real-world patient population was comparable to those reported in clinical trials. Based on this hypothesis-generating data, more aggressive esophageal sparing merits consideration. Institutional auditing and benchmarking of the planning strategy, dosimetry, and outcome have an important role to play in the continuous quality improvement process.

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Section: Discussionsupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Relationship between Treatment Plan Dosimetry, Toxicity, and Survival following Intensity-Modulated Radiotherapy, with or without Chemotherapy, for Stage III Inoperable Non-Small Cell Lung Cancer

Vries

Ronden

Spoelstra

et al. 2021

Cancers

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“…All patient details were retrospectively extracted from case records and MDT reports and entered into an ethics-approved database. 8 …”

Section: Methodsmentioning

confidence: 99%

“… 7 A recent study in our thoracic oncology network revealed that 60% of patients presenting with a stage III NSCLC between 2015 and 2017 underwent chemoradiotherapy, of which 35% was concurrent and 25% sequential. 8 Patients aged greater than or equal to 70 years and those with a WHO performance score (WHO-PS) greater than or equal to 2 were most likely to not receive a recommendation to undergo either CCRT or surgery combined with other treatment modalities. 8 …”

Section: Introductionmentioning

confidence: 99%

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The Impact of the Availability of Immunotherapy on Patterns of Care in Stage III NSCLC: A Dutch Multicenter Analysis

Ronden

Claessens

Barlo

et al. 2021

JTO Clinical and Research Reports

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Introduction Treatment patterns in stage III NSCLC can vary considerably between countries. The PACIFIC trial reported improvements in progression-free and overall survival with adjuvant durvalumab after concurrent chemoradiotherapy (CCRT). We studied treatment decision-making by three Dutch regional thoracic multidisciplinary tumor boards between 2015 and 2019, to identify changes in practice when adjuvant durvalumab became available. Methods Details of patients presenting with stage III NSCLC were retrospectively collected. Both CCRT and multimodality schemes incorporating planned surgery were defined as being radical-intent treatment (RIT). Results Of 855 eligible patients, most (95%) were discussed at a thoracic multidisciplinary tumor board, which recommended a RIT in 63% (n = 510). Only 52% (n = 424) of the patients finally received a RIT. Predictors for not recommending RIT were age greater than or equal to 70 years, WHO performance score greater than or equal to 2, Charlson comorbidity index greater than or equal to 2 (excluding age), forced expiratory volume in 1 second less than 80% of predicted value, N3 disease, and period of diagnosis. Between 2015 to 2017 and 2018 to 2019, the proportion of patients undergoing CCRT increased from 34% to 42% ( p = 0.02) and use of sequential chemoradiotherapy declined (21%–16%, p = 0.05). Rates of early toxicity and 1-year mortality were comparable for both periods. After 2018, 57% of the patients who underwent CCRT (90 of 159) received adjuvant durvalumab. Conclusions After publication of the PACIFIC trial, a significant increase was observed in the use of CCRT for patients with stage III NSCLC with rates of early toxicity and mortality being unchanged. Since 2018, 57% of the patients undergoing CCRT went on to receive adjuvant durvalumab. Nevertheless, approximately half of the patients were still considered unfit for a RIT.

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Identification of age‐ and immune‐related gene signatures for clinical outcome prediction in lung adenocarcinoma

et al. 2023

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BackgroundThe understanding of the factors causing decreased overall survival (OS) in older patients compared to younger patients in lung adenocarcinoma (LUAD) remains.MethodsGene expression profiles of LUAD were obtained from publicly available databases by Kaplan‐Meier analysis was performed to determine whether age was associated with patient OS. The immune cell composition in the tumor microenvironment (TME) was evaluated using CIBERSORT. The fraction of stromal and immune cells in tumor samples were also using assessed using multiple tools including ESTIMATE, EPIC, and TIMER. Differentially expressed genes (DEGs) from the RNA‐Seq data that were associated with age and immune cell composition were identified using the R package DEGseq. A 22‐gene signature composed of DEGs associated with age and immune cell composition that predicted OS were constructed using Least Absolute Shrinkage and Selection Operator (LASSO).ResultsIn The Cancer Genome Atlas (TCGA)‐LUAD dataset, we found that younger patients (≤70) had a significant better OS compared to older patients (>70). In addition, older patients had significantly higher expression of immune checkpoint proteins including inhibitory T cell receptors and their ligands. Moreover, analyses using multiple bioinformatics tools showed increased immune infiltration, including CD4+ T cells, in older patients compared to younger patients. We identified a panel of genes differentially expressed between patients >70 years compared to those ≤70 years, as well as between patients with high or low immune scores and selected 84 common genes to construct a prognostic gene signature. A risk score calculated based on 22 genes selected by LASSO predicted 1, 3, and 5‐year OS, with an area under the curve (AUC) of 0.72, 0.72, 0.69, receptively, in TCGA‐LUAD dataset and an independent validation dataset available from the European Genome‐phenome Archive (EGA).ConclusionOur results demonstrate that age contributes to OS of LUAD patients atleast in part through its association with immune infiltration in the TME.

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Factors influencing multi-disciplinary tumor board recommendations in stage III non-small cell lung cancer

Cited by 14 publications

References 35 publications

Relationship between Treatment Plan Dosimetry, Toxicity, and Survival following Intensity-Modulated Radiotherapy, with or without Chemotherapy, for Stage III Inoperable Non-Small Cell Lung Cancer

Relationship between Treatment Plan Dosimetry, Toxicity, and Survival following Intensity-Modulated Radiotherapy, with or without Chemotherapy, for Stage III Inoperable Non-Small Cell Lung Cancer

The Impact of the Availability of Immunotherapy on Patterns of Care in Stage III NSCLC: A Dutch Multicenter Analysis

Identification of age‐ and immune‐related gene signatures for clinical outcome prediction in lung adenocarcinoma

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