Real-world survey of pneumonitis and its impact on durvalumab consolidation therapy in patients with non-small cell lung cancer who received chemoradiotherapy after durvalumab approval (HOPE-005/CRIMSON)

Saito, Go; Oya, Yuko; Taniguchi, Yoshihiko; Kawachi, Hayato; Fujimoto, Daichi; Matsumoto, Hirotaka; Iwasawa, Shunichiro; Suzuki, Hidekazu; Niitsu, Takayuki; Miyauchi, Eisaku; Yokoi, Takashi; Yokoyama, Toshihide; Uenami, Takeshi; Sakata, Yoshihiko; Arai, Daisuke; Okada, Asuka; Nagata, Kenji; Teraoka, Shunsuke; Kitajima, Masaki

doi:10.1016/j.lungcan.2021.08.019

Cited by 40 publications

(45 citation statements)

References 22 publications

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“…This relation can result from numerous comorbidities, which are independent risk factors. However, this assumption is not clear when analyzing the most extensive trials—probably with the most precise selection of patients [ 6 ]. Another controversial finding concerns the preceding surgery, which we noticed linked with intensified HU changes during the early phase in low-doses (5–10 Gy) and mid-doses (20–40 Gy) for late fibrosis.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, modern radiotherapy methods significantly decrease the highest grades of toxicity. In a recent trial with stage III NSCLC patients who qualified for durvalumab consolidation, the incidence of G3+ pneumonitis was 7% (34% for G2+) [ 6 ]. Similarly, Hu et al [ 7 ] reported G3+ RIP in 1% of patients and Shintani et al [ 8 ] 5% for G3+ (35% for G2+).…”

Section: Introductionmentioning

confidence: 99%

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Normal Lung Tissue CT Density Changes after Volumetric-Arc Radiotherapy (VMAT) for Lung Cancer

Konkol

Bryl

Fechner³

et al. 2022

JPM

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Radiation-induced lung injury remains a significant toxicity in thoracic radiotherapy. Because a precise diagnosis is difficult and commonly used assessment scales are unclear and subjective, there is a need to establish quantitative and sensitive grading methods. The lung tissue density change expressed in Hounsfield units (HUs) derived from CT scans seems a useful numeric surrogate. The study aimed to confirm a dose-response effect on HU value changes (ΔHU), their evolution in time, and the impact of selected clinical and demographic factors. We used dedicated, self-developed software to register and analyze 120 pairs of initial and follow-up CT scans of 47 lung cancer patients treated with dynamic arc radiotherapy. The differences in HU values between CT scans were calculated within discretized dose-bins limited by isodose lines. We have proved the dose-effect relationship, which is well described with a sigmoid model. We found the time evolution of HU changes to suit a typical clinical presentation of radiation-induced toxicity. Some clinical factors were found to correlate with ΔHU degree: planning target volume (PTV), V35 in the lung, patient’s age and a history of arterial hypertension, and initial lung ventilation intensity. Lung density change assessment turned out to be a sensitive and valuable method of grading post-RT lung toxicity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Normal Lung Tissue CT Density Changes after Volumetric-Arc Radiotherapy (VMAT) for Lung Cancer

Konkol

Bryl

Fechner³

et al. 2022

JPM

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show abstract

“…Regarding PFS, a higher lung V20 was a significant unfavourable factor, and a factor of grade 2 or higher RP was not selected. However, grade 2 or higher RP and lung V20 would have relationships because lung V20 is one of the representative risk factors for grade 2 or higher RP, and the importance of lung V20 is evident in this durvalumab era [ 19 – 23 ]. This result is therefore thought to be reasonable, and it is important to reduce lung doses, such as V20, to decrease the risk of developing grade 2 or higher RP.…”

Section: Discussionmentioning

confidence: 99%

Durvalumab after chemoradiotherapy for locally advanced non-small cell lung cancer prolonged distant metastasis-free survival, progression-free survival and overall survival in clinical practice

et al. 2022

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Background In clinical practice, the effect of durvalumab and radiation pneumonitis (RP) on survival after intensity-modulated radiotherapy (IMRT) is not fully understood. The purpose of this retrospective study was to investigate factors related to distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS) after IMRT for locally advanced non-small cell lung cancer (LA-NSCLC). Methods All patients who were treated with conventional fractionated IMRT for LA-NSCLC between April 2016 and March 2021 were eligible. Time-to-event data were assessed by using the Kaplan–Meier estimator, and the Cox proportional hazards model was used for prognostic factor analyses. Factors that emerged after the start of IMRT, such as durvalumab administration or the development of RP, were analysed as time-dependent covariates. Results A total of 68 consecutive patients treated with conventional fractionated IMRT for LA-NSCLC were analysed. Sixty-six patients completed radiotherapy, 50 patients received concurrent chemotherapy, and 36 patients received adjuvant durvalumab. During the median follow-up period of 14.3 months, 23 patients died, and tumour progression occurred in 37 patients, including 28 patients with distant metastases. The 1-year DMFS rate, PFS rate and OS rate were 59.9%, 48.7% and 84.2%, respectively. Grade 2 RP occurred in 16 patients, grade 3 in 6 patients and grade 5 in 1 patient. The 1-year cumulative incidences of grade 2 or higher RP and grade 3 or higher RP were 33.8% and 10.3%, respectively. The results of multivariate analyses showed that durvalumab had a significantly lower hazard ratio (HR) for DMFS, PFS and OS (HR 0.31, p < 0.01; HR 0.33, p < 0.01 and HR 0.32, p = 0.02), respectively. Grade 2 or higher RP showed significance for DMFS and a nonsignificant trend for OS (HR 2.28, p = 0.04 and HR 2.12, p = 0.13), respectively, whereas a higher percentage of lung volume receiving 20 Gy or higher was significant for PFS (HR 2.25, p = 0.01). Conclusions In clinical practice, durvalumab administration following IMRT with concomitant chemotherapy showed a significant survival benefit. Reducing the risk of grade 2 or higher RP would also be beneficial.

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“…When analysing the biggest trials — probably with the most precise selection of patients — this assumption, however, is not that clear [ 12 ]. The influence of sex is also doubtful.…”

Section: Predictors Of Rilimentioning

confidence: 99%

Radiation-induced lung injury — what do we know in the era of modern radiotherapy?

Konkol

Śniatała

Milecki

2022

Rep Pract Oncol Radiother.

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Real-world survey of pneumonitis and its impact on durvalumab consolidation therapy in patients with non-small cell lung cancer who received chemoradiotherapy after durvalumab approval (HOPE-005/CRIMSON)

Cited by 40 publications

References 22 publications

Normal Lung Tissue CT Density Changes after Volumetric-Arc Radiotherapy (VMAT) for Lung Cancer

Normal Lung Tissue CT Density Changes after Volumetric-Arc Radiotherapy (VMAT) for Lung Cancer

Durvalumab after chemoradiotherapy for locally advanced non-small cell lung cancer prolonged distant metastasis-free survival, progression-free survival and overall survival in clinical practice

Radiation-induced lung injury — what do we know in the era of modern radiotherapy?

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