Locally-advanced non-small cell lung cancer: shall immunotherapy be a new chance?

Filippi, Andrea Riccardo; Muzio, J. Di; Badellino, Serena; Mantovani, Cristina; Ricardi, Umberto

doi:10.21037/jtd.2017.12.53

Cited by 22 publications

(18 citation statements)

References 36 publications

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“…Reanalysis of survival from recurrence after CRT to death also showed that patients who used ICI had a significantly better survival compared to those who did not (HR: 0.19 [95% CI: 0.068–0.55], P = 0.002). There is an increasing body of preclinical and clinical data regarding the radiotherapy‐induced immunomodulatory effects in the local tumor microenvironment, supporting the combination strategy . Radiotherapy modifies the tumor microenvironment, including enhanced antigen presentation, and the upregulation of tumor programmed death ligand‐1 and major histocompatibility complex class I expression .…”

Section: Discussionmentioning

confidence: 99%

Current status and progress of concurrent chemoradiotherapy in patients with locally advanced non‐small cell lung cancer prior to the approval of durvalumab

et al. 2020

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Background: The standard treatment for patients with unresectable locally advanced (LA) non-small cell lung cancer (NSCLC) is chemoradiotherapy (CRT). Consolidation therapy with durvalumab after CRT demonstrated survival benefits and was approved in Japan in July 2018. The use of immune checkpoint inhibitors (ICIs) is entering routine oncological practice, and here we investigate the feasibility of concurrent CRT for LA-NSCLC patients based on the PACIFIC criteria. Methods: We performed a retrospective study to evaluate the feasibility and efficacy of concurrent CRT prior to the approval of durvalumab. We assessed consecutive patients with LA-NSCLC treated with CRT between January 2012 and June 2018. Results: We analyzed a total of 108 consecutive patients who received radical thoracic radiotherapy and concurrent platinum-based chemotherapy. Of those patients, 105 (97%) completed the planned radiotherapy. Radiation pneumonitis was observed in 93 patients (85%), with a median of 130 days (range: 41-317 days) from the initiation of radiation to the onset of the complication. Among the patients, 74 (69%) were considered eligible for consolidation therapy with durvalumab. The overall response rate was 64%, and the two-year survival rate was 63%. Patients who received an ICI after relapse were associated with significantly better survival than those who did not receive an ICI (two-year survival rate: 87% vs. 41%, respectively; P = 0.001). Conclusions: Prior to the approval of durvalumab, the clinical application of ICIs improved the outcome of patients with relapsed NSCLC after CRT for LA-NSCLC. The management of radiation pneumonitis remains a challenge following the approval of durvalumab.

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Section: Discussionmentioning

confidence: 99%

Current status and progress of concurrent chemoradiotherapy in patients with locally advanced non‐small cell lung cancer prior to the approval of durvalumab

et al. 2020

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“…Minimising radiation induced lung injury is the major potential clinical benefit of the individualised approach of FA planning for the NSCLC patients. Along with the wider availability and proven benefit of immunotherapy for lung cancer patients, there are ongoing trials investigating concurrent immunotherapy and radio-chemotherapy [6] , [25] . The lung toxicity profile of multimodality treatments is yet to be established, as the combination of different treatment modalities could potentially be more toxic.…”

Section: Discussionmentioning

confidence: 99%

Functional perfusion image guided radiation treatment planning for locally advanced lung cancer

Farr

West

Yeghiaian-Alvandi

et al. 2019

Physics and Imaging in Radiation Oncology

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Background and purpose: Functional avoidance radiation therapy (RT) aims at sparing functional lung regions. The purpose of this simulation study was to evaluate the feasibility of functional lung avoidance methodology in RT of lung cancer and to characterize the achievable dosimetry of single photon emission computed tomography (SPECT) guided treatment planning. Materials and methods: Fifteen consecutive lung cancer patients were included and planned for definitive RT of 60-66 Gy in 2-Gy fractions. Two plans were optimized: a standard CT-plan, and functional SPECT-plan. The objective was to reduce dose to the highly functional lung subvolumes without compromising tumour coverage, and respecting dose to other organs at risk. For each patient a 3D-conformal, intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy plans were created for standard and functional avoidance. Standard versus functional dose-volume parameters for functional lung (FL) subvolumes, organs at risk and tumour coverage were compared. Results: The largest dose reduction was achieved with IMRT plans. Functional plans resulted in dose reduction from 9.0 Gy to 6.7 Gy (mean reduction of 2.3 Gy or 26%) to the highest functional subvolume FL80% (95%CI 1.1; 3.5). Dose to FL40% was reduced from 13.3 Gy to 11.6 Gy with functional planning. Dose reduction to FL40% was 1.7 Gy (95%CI 0.9; 2.6). Functional volume of lung receiving over 20 Gy improved by 5% (standard 22%, functional 17%). Dose to organs at risk and tumour coverage were not significantly different between plans. Conclusions: SPECT/CT-guided planning resulted in improved dose-volumetric outcomes for functional lung. This methodology may lead to potential reduction in radiation-induced lung toxicity.

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“…Immune checkpoint inhibitors (ICIs) are a novel class of drugs for the treatment of NSCLC. [6][7][8] ICIs activate the host's immune cells, especially T cells, to target specific tumor cells. ICIs include programmed cell death protein 1 (PD-1), programmed death ligand 1 (PD-L1), and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inhibitors, and have revolutionized the NSCLC treatment landscape.…”

Section: Introductionmentioning

confidence: 99%

Real‐world outcomes of chemoradiotherapy for unresectable Stage III non‐small cell lung cancer: The SOLUTION study

et al. 2020

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There are limited real‐world data on the treatment practices, outcomes, and safety of chemoradiotherapy (CRT) alone in potential candidates for immune checkpoint inhibitors (ICI) for unresectable non‐small cell lung cancer (NSCLC). In this study, we analyzed the safety and efficacy of CRT in patients who underwent CRT and would satisfy the key eligibility criteria for maintenance therapy with durvalumab (eg, no progression after CRT) in real‐world settings (m‐sub) for unresectable Stage III NSCLC between 1 January 2013 and 31 December 2015 at 12 sites in Japan. The m‐sub comprised 214 patients with a median follow‐up of 31.6 months (range 1.9‐65.8 months). Median overall survival (OS) and progression‐free survival (PFS) from completing CRT were 36.4 months (95% confidence interval [CI] 28.1 months to not reached) and 9.5 months (95% CI 7.7‐11.7 months), respectively. Consolidation chemotherapy did not influence OS or PFS. Median PFS was 16.9 vs 9.1 months in patients with vs without epidermal growth factor receptor (EGFR) mutations, with PFS rates of ~20% at 3‐4 years. Pneumonitis was the most common adverse event (according to MedDRA version 21.0J), and about half of events were grade 1. Pneumonitis mostly occurred 10‐24 weeks after starting CRT, peaking at 18‐20 weeks. Esophagitis and dermatitis generally occurred from 0 to 4 weeks, peaking at 2‐4 weeks after starting CRT. Pericarditis was rare and occurred sporadically. In conclusion, the results of the m‐sub provide real‐world insight into the outcomes of CRT, and will be useful for future evaluations of ICI maintenance therapy after CRT.

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Locally-advanced non-small cell lung cancer: shall immunotherapy be a new chance?

Cited by 22 publications

References 36 publications

Current status and progress of concurrent chemoradiotherapy in patients with locally advanced non‐small cell lung cancer prior to the approval of durvalumab

Current status and progress of concurrent chemoradiotherapy in patients with locally advanced non‐small cell lung cancer prior to the approval of durvalumab

Functional perfusion image guided radiation treatment planning for locally advanced lung cancer

Real‐world outcomes of chemoradiotherapy for unresectable Stage III non‐small cell lung cancer: The SOLUTION study

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