Palliative thoracic radiation therapy for non-small cell lung cancer: 2018 Update of an American Society for Radiation Oncology (ASTRO) Evidence-Based Guideline

Moeller, Benjamin J.; Balagamwala, E.H.; Chen, Aileen B.; Creach, Kimberly M.; Giaccone, Giuseppe; Koshy, Matthew; Zaky, Sandra S.; Rodrigues, George

doi:10.1016/j.prro.2018.02.009

Cited by 57 publications

(41 citation statements)

References 21 publications

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“…Palliative (chemo) radiotherapy is an important component of care for many patients with NSCLC [8]. Sequential plus concurrent palliative chemoradiotherapy improves survival compared with chemotherapy alone [18], but it increases toxicity, particularly radiation esophagitis.…”

Section: Discussionmentioning

confidence: 99%

“…Multimodality treatment of non-small cell lung cancer (NSCLC) has become more effective in recent years, e.g., due to stereotactic ablative radiotherapy for stage I disease [1,2] and oligometastatic stage IV disease [3][4][5], and immunotherapy for stage III and IV disease [6,7]. Patients with stage III disease who are unfit for radical chemoradiotherapy should be considered for reduced-intensity palliative chemoradiotherapy [8][9][10]. One of the downsides of chemoradiotherapy is its potential to induce painful acute esophagitis [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

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Risk factors for esophagitis after hypofractionated palliative (chemo) radiotherapy for non-small cell lung cancer

et al. 2020

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Introduction: Esophagitis influences quality of life and might cause treatment interruption and hospitalization. Previous studies of risk factors focused on curative treatment for non-small cell lung cancer (NSCLC), which often involves concomitant chemoradiation (CRT). Given the uncertainty around extrapolation of dose constraints, we analyzed risk factors in patients treated with hypofractionated palliative regimens. Patients and methods: A retrospective review of 106 patients treated with palliative radiotherapy or CRT between 2009 and 2017 was performed. Inclusion criteria: prescribed total dose 30-54 Gy, dose per fraction 2.5-4 Gy, esophageal dose > 1 Gy. Uni-and multivariate analyses were performed in 97 eligible patients to identify predictive factors for acute esophagitis grade ≥ 1 (CTCAE 5.0). Results: Forty percent of patients were treated with 15 fractions of 2.8 Gy (42 Gy) and 28% also received chemotherapy according to the CONRAD study regimen (induction and concomitant Carboplatin/Vinorelbine) published by the Norwegian Lung Cancer Group. Thirty-four percent were treated with 10 fractions of 3 Gy. Stage IV NSCLC was present in 47%. Esophagus Dmax was 39 Gy (population median) and Dmean 15 Gy. Overall 31% of patients developed esophagitis (26% grade 2-3, no grade 4-5). Several dosimetric parameters correlated with the risk of esophagitis (Dmax, Dmean, D5cc, V20, V30, V35, V40). Dmax outperformed other dosimetric variables in multivariate analysis. Furthermore, concomitant chemotherapy significantly increased the risk of esophagitis, while oral steroid medication reduced it. In patients with Dmax ≥40 Gy a reduced Dmean (≤20 Gy) was beneficial. Conclusion: In order to reduce esophagitis after hypofractionated palliative treatment lower doses than those recommended in curative NSCLC settings are preferable. Besides esophageal dose, CRT is the main risk factor for esophagitis. Additional work is needed to confirm that steroids are able to modify the risk (or to rule out confounding effects of baseline variables not included in our database).

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Risk factors for esophagitis after hypofractionated palliative (chemo) radiotherapy for non-small cell lung cancer

et al. 2020

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“…More than one-half of patients with NSCLC are diagnosed with locally advanced (stage III) and advanced (stage IV) disease. The prognosis for lung cancer remains poor, with overall 5 year survival of 14% [2]. The role of curative-intent radiotherapy (RT) is well established in locally advanced and early stage NSCLC [3].…”

Section: Introductionmentioning

confidence: 99%

The p53–53BP1-Related Survival of A549 and H1299 Human Lung Cancer Cells after Multifractionated Radiotherapy Demonstrated Different Response to Additional Acute X-ray Exposure

Pustovalova

Alhaddad

Сметанина

et al. 2020

IJMS

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Radiation therapy is one of the main methods of treating patients with non-small cell lung cancer (NSCLC). However, the resistance of tumor cells to exposure remains the main factor that limits successful therapeutic outcome. To study the molecular/cellular mechanisms of increased resistance of NSCLC to ionizing radiation (IR) exposure, we compared A549 (p53 wild-type) and H1299 (p53-deficient) cells, the two NSCLC cell lines. Using fractionated X-ray irradiation of these cells at a total dose of 60 Gy, we obtained the survived populations and named them A549IR and H1299IR, respectively. Further characterization of these cells showed multiple alterations compared to parental NSCLC cells. The additional 2 Gy exposure led to significant changes in the kinetics of γH2AX and phosphorylated ataxia telangiectasia mutated (pATM) foci numbers in A549IR and H1299IR compared to parental NSCLC cells. Whereas A549, A549IR, and H1299 cells demonstrated clear two-component kinetics of DNA double-strand break (DSB) repair, H1299IR showed slower kinetics of γH2AX foci disappearance with the presence of around 50% of the foci 8 h post-IR. The character of H2AX phosphorylation in these cells was pATM-independent. A decrease of residual γH2AX/53BP1 foci number was observed in both A549IR and H1299IR compared to parental cells post-IR at extra doses of 2, 4, and 6 Gy. This process was accompanied with the changes in the proliferation, cell cycle, apoptosis, and the expression of ATP-binding cassette sub-family G member 2 (ABCG2, also designated as CDw338 and the breast cancer resistance protein (BCRP)) protein. Our study provides strong evidence that different DNA repair mechanisms are activated by multifraction radiotherapy (MFR), as well as single-dose IR, and that the enhanced cellular survival after MFR is reliant on both p53 and 53BP1 signaling along with non-homologous end-joining (NHEJ). Our results are of clinical significance as they can guide the choice of the most effective IR regimen by analyzing the expression status of the p53–53BP1 pathway in tumors and thereby maximize therapeutic benefits for the patients while minimizing collateral damage to normal tissue.

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“…Fractionation schemes utilised varied from 10 Gy/one fraction up to doses more typically associated with the curative intent setting, such as 60 Gy/30 fractions [ 10 ]. Current Royal College of Radiologists (RCR) and American Society for Radiation Oncology (ASTRO) guidance suggest the use of palliative regimens with doses up to 39 Gy/13 fractions and 42 Gy/14 fractions, respectively, for patients with NSCLC [ 14 , 15 ]. Longer fractionation schemes can inconvenience patients with multiple hospital visits towards the end of their lives and also have healthcare resource implications.…”

Section: Introductionmentioning

confidence: 99%

“…From the literature, the following factors have been found to be significantly correlated with survival during multivariable analysis: T and N status, extrathoracic disease status, lactate dehydrogenase levels, completion of planned treatment, leukocyte count and C-reactive protein levels [ 10 , 12 , 13 , 17 , 19 , 20 ]. These factors have not been consistently examined through the literature and when included they are not always reproducibly significant and as such they are not incorporated in commonly used guidelines [ 14 , 15 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Palliative Lung Radiotherapy: Higher Dose Leads to Improved Survival?

et al. 2020

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Aims Choosing the optimal palliative lung radiotherapy regimen is challenging. Guidance from The Royal College of Radiologists recommends treatment stratification based on performance status, but evidence suggests that higher radiotherapy doses may be associated with survival benefits. The aim of this study was to investigate the effects of fractionation regimen and additional factors on the survival of palliative lung cancer radiotherapy patients. Materials and methods A retrospective univariable ( n = 925) and multivariable ( n = 422) survival analysis of the prognostic significance of baseline patient characteristics and treatment prescription was carried out on patients with non-small cell and small cell lung cancer treated with palliative lung radiotherapy. The covariates investigated included: gender, age, performance status, histology, comorbidities, stage, tumour location, tumour side, smoking status, pack year history, primary radiotherapy technique and fractionation scheme. The overall mortality rate at 30 and 90 days of treatment was calculated. Results Univariable analysis revealed that performance status ( P < 0.001), fractionation scheme ( P < 0.001), comorbidities ( P = 0.02), small cell histology ( P = 0.02), ‘lifelong never’ smoking status ( P = 0.01) and gender ( P = 0.06) were associated with survival. Upon multivariable analysis, only better performance status ( P = 0.01) and increased dose/fractionation regimens of up to 30 Gy/10 fractions ( P < 0.001) were associated with increased survival. Eighty-five (9.2%) and 316 patients (34%) died within 30 and 90 days of treatment, respectively. Conclusion In this retrospective single-centre analysis of palliative lung radiotherapy, increased total dose (up to and including 30 Gy/10 fractions) was associated with better survival regardless of performance status.

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Palliative thoracic radiation therapy for non-small cell lung cancer: 2018 Update of an American Society for Radiation Oncology (ASTRO) Evidence-Based Guideline

Cited by 57 publications

References 21 publications

Risk factors for esophagitis after hypofractionated palliative (chemo) radiotherapy for non-small cell lung cancer

Risk factors for esophagitis after hypofractionated palliative (chemo) radiotherapy for non-small cell lung cancer

The p53–53BP1-Related Survival of A549 and H1299 Human Lung Cancer Cells after Multifractionated Radiotherapy Demonstrated Different Response to Additional Acute X-ray Exposure

Palliative Lung Radiotherapy: Higher Dose Leads to Improved Survival?

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