Imaging-based target volume reduction in chemoradiotherapy for locally advanced non-small-cell lung cancer (PET-Plan): a multicentre, open-label, randomised, controlled trial

Schimek-Jasch, Tanja; Kremp, Stephanie; Schaefer-Schuler, Andrea; Mix, Michael; Küsters, Andreas; Bultel, Y.; Hass, Peter; Fleckenstein, Jochen; Thieme, Alexander; Stockinger, Marcus; Dieckmann, Karin; Miederer, Matthias; Rischke, Hans Christian; Gkika, Eleni; Adebahr, S.; König, Jochem; Grosu, Anca‐Ligia; Weber, W.; Meyer, P.; Hoffmanns, Hans; Nestle, Ursula; Aurisch, R; Schäfer, Wolfgang; Hehr, Thomas; Eschmann, Susanne Martina; Dornoff, W.; Siekmeyer, Birgit; Trampert, L.; Gademann, G.; Brunner, Thomas; Amthauer, A; Ricke, Jens; Pech, Maciej; Rübe, Christian; Kirsch, Carl-Martin; Ezzidin, S.; Schmidberger, Heinz; Schreckenberger, M.; Bamberg, M.; Zips, Daniel; Bares, Roland; Fougère, Christian la; Budach, Volker; Brenner, Walburgis; Beck, Marcus; Gumppenberg, R Freiherr von; Aebersold, Daniel M.; Krause, T.; Feldmann, Horst Jürgen; Hertel, A.; Stüben, Georg; Sciuk, J.; Annweiler, H; Höll, G.; Oehler, W; Schlöcker, I; Baum, R. P.; Kimmig, B.; Dunst, Jürgen; Henze, E.; Lützen, Ulf; Schwaiger, M; Strehle, Katharina; Alberti, Winfried; Piroth, Marc D.; Tosch, Marco; Pötter, Richard; Widder, Joachim; Herold, Christian; Freund, Ulrich; Momm, Felix; Sautter-Bihl, Marie Luise; Tatsch, Klaus; Hildebrandt, Guido; Krause, BJ

doi:10.1016/s1470-2045(20)30013-9

Cited by 123 publications

(68 citation statements)

References 32 publications

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“…In the majority of cases thoracic radiotherapy represents a central part of multi-modal treatment concepts [2]. Several diagnostic and therapeutic advances, such as PETimaging [3,4], improved radiation delivery techniques [5][6][7][8][9], implementation of immunotherapy [10][11][12][13][14][15][16], and molecularly targeted therapy [17][18][19], have led to improved outcome in terms of overall survival, local and distant control as well as quality of life. However, between 10 and 30% of all patients with lung or breast cancer receiving thoracic radiotherapy develop radiation-induced pneumonitis (RIP) as a subacute treatment-associated toxicity, and they are at high risk of developing radiation-induced lung fibrosis (RILF) as late toxicity, although treatmentrelated death is uncommon [5,[20][21][22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Radiation-induced lung toxicity – cellular and molecular mechanisms of pathogenesis, management, and literature review

et al. 2020

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Lung, breast, and esophageal cancer represent three common malignancies with high incidence and mortality worldwide. The management of these tumors critically relies on radiotherapy as a major part of multi-modality care, and treatment-related toxicities, such as radiation-induced pneumonitis and/or lung fibrosis, are important dose limiting factors with direct impact on patient outcomes and quality of life. In this review, we summarize the current understanding of radiation-induced pneumonitis and pulmonary fibrosis, present predictive factors as well as recent diagnostic and therapeutic advances. Novel candidates for molecularly targeted approaches to prevent and/or treat radiation-induced pneumonitis and pulmonary fibrosis are discussed.

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Section: Introductionmentioning

confidence: 99%

Radiation-induced lung toxicity – cellular and molecular mechanisms of pathogenesis, management, and literature review

et al. 2020

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“…With advances in targeted radiotherapy and medical imaging, radiotherapy remains a frontline option for treatment of NSCLC [58]. In the immunotherapy era, there are currently numerous studies combining conventional radiotherapy with immune checkpoint inhibitors for NSCLC [59].…”

Section: Discussionmentioning

confidence: 99%

COMMD1, from the Repair of DNA Double Strand Breaks, to a Novel Anti-Cancer Therapeutic Target

Suraweera

Duijf

Jekimovs

et al. 2021

Cancers

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Lung cancer has the highest incidence and mortality among all cancers, with non-small cell lung cancer (NSCLC) accounting for 85–90% of all lung cancers. Here we investigated the function of COMMD1 in the repair of DNA double strand breaks (DSBs) and as a prognostic and therapeutic target in NSCLC. COMMD1 function in DSB repair was investigated using reporter assays in COMMD1-siRNA-depleted cells. The role of COMMD1 in NSCLC was investigated using bioinformatic analysis, qRT-PCR and immunoblotting of control and NSCLC cells, tissue microarrays, cell viability and cell cycle experiments. DNA repair assays demonstrated that COMMD1 is required for the efficient repair of DSBs and reporter assays showed that COMMD1 functions in both non-homologous-end-joining and homologous recombination. Bioinformatic analysis showed that COMMD1 is upregulated in NSCLC, with high levels of COMMD1 associated with poor patient prognosis. COMMD1 mRNA and protein were upregulated across a panel of NSCLC cell lines and siRNA-mediated depletion of COMMD1 decreased cell proliferation and reduced cell viability of NSCLC, with enhanced death after exposure to DNA damaging-agents. Bioinformatic analyses demonstrated that COMMD1 levels positively correlate with the gene ontology DNA repair gene set enrichment signature in NSCLC. Taken together, COMMD1 functions in DSB repair, is a prognostic maker in NSCLC and is potentially a novel anti-cancer therapeutic target for NSCLC.

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“…In current radio-oncological practice most commonly dose sparing to organs at risk is attempted by limiting the PTV to the primary tumor and the affected lymph node regions, an approach that became known as involved-field radiation therapy (IFRT) [10]. We recognize that there is growing evidence of IFRT not being inferior to elective nodal irradiation (ENI) with respect to locoregional failure [10][11][12]. However, IFRT regularly requires the addition of quite large margins to the GTV: the ESTRO guideline recommends the inclusion of the entire affected lymph node region, or at least the nodal GTV plus a 5-8 mm margin.…”

Section: Discussionmentioning

confidence: 99%

Chemoradiotherapy by intensity-modulated radiation therapy with simultaneous integrated boost in locally advanced or oligometastatic non-small-cell lung cancer—a two center experience

Mantel

Müller²,

Kleine

et al. 2021

Strahlenther Onkol

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Purpose Integrating moderate hypofractionation to the macroscopic tumor with elective nodal irradiation while sparing the organs at risk (OAR) in chemoradiotherapy of locally advanced non-small-cell lung cancer. Methods From 2010–2018, treatment, patient and tumor characteristics of 138 patients from two radiation therapy centers were assessed. Chemoradiotherapy by intensity-modulated radiation therapy (IMRT) with a simultaneous integrated boost (SIB) to the primary tumor and macroscopic lymph node metastases was used. Results A total of 124 (90%) patients received concurrent chemotherapy. 106 (76%) patients had UICC (Union for International Cancer Control) stage ≥IIIB and 21 (15%) patients had an oligometastatic disease (UICC stage IV). Median SIB and elective total dose was 61.6 and 50.4 Gy in 28 fractions, respectively. Furthermore, 64 patients (46%) had an additional sequential boost to the primary tumor after the SIB-IMRT main series: median 6.6 Gy in median 3 fractions. The median cumulative mean lung dose was 15.6 Gy (range 6.2–29.5 Gy). Median follow-up and radiological follow-up for all patients was 18.0 months (range 0.6–86.9) and 16.0 months (range 0.2–86.9), respectively. Actuarial local control rates at 1, 2 and 3 years were 80.4, 68.4 and 57.8%. Median overall survival and progression-free survival was 30.0 months (95% confidence interval [CI] 23.5–36.4) and 12.1 months (95% CI 8.2–16.0), respectively. Treatment-related toxicity was moderate. Radiation-induced pneumonitis grade 2 and grade 3 occurred in 13 (9.8%) and 3 (2.3%) patients. Conclusions Chemoradiotherapy using SIB-IMRT showed promising local tumor control rates and acceptable toxicity in patients with locally advanced and in part oligometastatic lung cancer. The SIB concept, resulting in a relatively low mean lung dose, was associated with low numbers of clinically relevant pneumonitis. The overall survival appears promising in the presence of a majority of patients with UICC stage ≥IIIB disease.

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Imaging-based target volume reduction in chemoradiotherapy for locally advanced non-small-cell lung cancer (PET-Plan): a multicentre, open-label, randomised, controlled trial

Cited by 123 publications

References 32 publications

Radiation-induced lung toxicity – cellular and molecular mechanisms of pathogenesis, management, and literature review

Radiation-induced lung toxicity – cellular and molecular mechanisms of pathogenesis, management, and literature review

COMMD1, from the Repair of DNA Double Strand Breaks, to a Novel Anti-Cancer Therapeutic Target

Chemoradiotherapy by intensity-modulated radiation therapy with simultaneous integrated boost in locally advanced or oligometastatic non-small-cell lung cancer—a two center experience

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