Survival Outcomes With Thoracic Radiotherapy in Extensive-Stage Small-Cell Lung Cancer: A Propensity Score-Matched Analysis of the National Cancer Database

Tian, Sibo; Zhang, Xinyan; Jiang, Renjian; Pillai, Rathi N.; Owonikoko, Taofeek K.; Steuer, Conor E.; Saba, Nabil F.; Pakkala, Suchita; Patel, Pretesh; Belani, Chandra P.; Khuri, Fadlo R.; Ramalingam, Suresh S.; Behera, Madhusmita; Higgins, Kristin

doi:10.1016/j.cllc.2019.06.014

Cited by 18 publications

(23 citation statements)

References 28 publications

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“…10,11 The application of consolidation radiotherapy in selected patients with extensive-stage disease (ED) and a good initial response to chemotherapy have partly contributed to the improved survival rate, but application has been very inconsistent. 12,13 Immunotherapy has resulted in significant progress in the treatment of numerous malignant diseases, including nonsmall cell lung cancer (NSCLC). Expectations for the treatment of small cell lung cancer were high as well.…”

Section: Introductionmentioning

confidence: 99%

Neutrophil-to-lymphocyte ratio can predict outcome in extensive-stage small cell lung cancer

Drpa

Šutić

Baranašić

et al. 2020

Radiology and Oncology

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BackgroundThe neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) were analyzed in various carcinomas and their potential prognostic significance was determined. The objective of present study was to determine the correlation between these parameters and the survival of patients with small cell lung cancer (SCLC), since very few studies have been published on this type of carcinoma.Patients and methodsOne hundred and forty patients diagnosed with SCLC at University Hospital Center Zagreb, between 2012 and 2016 were retrospectively analyzed. Extensive-stage disease (ED) was verified in 80 patients and limited-stage disease (LD) in 60 patients. We analyzed the potential prognostic significance of various laboratory parameters, including NLR, PLR, and LMR, measured before the start of treatment.ResultsDisease extension, response to therapy, chest irradiation and prophylactic cranial irradiation (PCI), as well as hemoglobin, monocyte count, C-reactive protein (CRP), and lactate dehydrogenase (LDH) showed a prognostic significance in all patients. When we analyzed the patients separately, depending on the disease extension, we found that only skin metastases as well as LDH and NLR values, regardless of the cut-off value, had a prognostic significance in ED. Meanwhile, the ECOG performance status, chest irradiation, PCI, and hemoglobin and creatinine values had a prognostic significance in LD.ConclusionsNLR calculated before the start of the treatment had a prognostic significance for ED, while PLR and LMR had no prognostic significance in any of the analyzed groups of patients.

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Section: Introductionmentioning

confidence: 99%

Neutrophil-to-lymphocyte ratio can predict outcome in extensive-stage small cell lung cancer

Drpa

Šutić

Baranašić

et al. 2020

Radiology and Oncology

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“…1 , Table II ). The following 10 compounds were identified: ephedrine hydrochloride ( 1 ), levistilide A ( 2 ), liquiritigenin ( 3 ), pseudoephedrine hydrochloride ( 4 ), paeoniflorin ( 5 ), astilbin ( 6 ), cycloastragenol ( 7 ), diosgenin ( 8 ), rosmarinic acid ( 9 ) and paeonol ( 10 ), by comparing the retention times and MS data with the reference standards.…”

Section: Resultsmentioning

confidence: 99%

“…(A) High-performance liquid chromatography coupled with electrospray mass spectrometry chromatogram of the aqueous extract in positive and negative modes. (B) The product ion mass spectra of ( 1 ) ephedrine hydrochloride, ( 2 ) levistilide A, ( 3 ) liquiritigenin, ( 4 ) pseudoephedrine hydrochloride, ( 5 ) paeoniflorin, ( 6 ) astilbin, ( 7 ) cycloastragenol, ( 8 ) diosgenin, ( 9 ) rosmarinic acid and ( 10 ) paeonol. Conditions: collision gas, ultrahigh-purity helium (He); nebulizer gas (N2), 35 psi; drying gas (N2), 10 L/min; drying temperature, 350°C; HV, 3500 V; mass scan range, 100–2200 m/z; target mass, 500 m/z; compound stability, 100%; and trap drive level, 100%.…”

Section: Figurementioning

confidence: 99%

“…Currently, besides surgery and chemotherapy, radiotherapy remains one of the most commonly used treatment methods for thoracic malignant tumors such as lung cancer, breast cancer, neck cancer and lymphoma ( 1 , 2 ). Radiation-induced normal lung tissue injury is a common complication of chest radiotherapy and is an important reason for the limited application of radiotherapy in patients with thoracic malignancies ( 3 , 4 ).…”

Section: Introductionmentioning

confidence: 99%

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PPM1A as a key target of the application of Jiawei‑Maxing‑Shigan decoction for the attenuation of radiation‑induced epithelial‑mesenchymal transition in type II alveolar epithelial cells

Lin

et al. 2021

Mol Med Rep

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Radiation-induced lung tissue injury is an important reason for the limited application of radiotherapy on thoracic malignancies. Previously, we reported that administration of Jiawei-Maxing-Shigan decoction (JMSD) attenuated the radiation-induced epithelial-mesenchymal transition (EMT) in alveolar epithelial cells (AECs) via TGF-β/Smad signaling. The present study aimed to examine the role of protein phosphatase Mg 2+ /Mn 2+ -dependent 1A (PPM1A) in the anti-EMT activity of JMSD on AECs. The components in the aqueous extract of JMSD were identified by high-performance liquid chromatography coupled with electrospray mass spectrometry. Primary rat type II AECs were treated with radiation (60Co γ-ray at 8 Gy) and JMSD-medicated serum. PPM1A was overexpressed and knocked down in the AECs via lentivirus transduction and the effects of JMSD administration on the key proteins related to TGF-β1/Smad signaling were measured by western blotting. It was found that radiation decreased the PPM1A expression in the AECs and JMSD-medicated serum upregulated the PPM1A expressions in the radiation-induced AECs. PPM1A overexpression increased the E-cadherin level but decreased the phosphorylated (p-)Smad2/3, vimentin and α-smooth muscle actin (α-SMA) levels in the AECs. By contrast, the PPM1A knockdown decreased the E-cadherin level and increased the p-Smad2/3, vimentin and α-SMA levels in the AECs and these effects could be blocked by SB431542 (TGF-β1/Smad signaling inhibitor). JMSD administration increased the E-cadherin level and decreased the p-Smad2/3, vimentin and α-SMA levels in the AECs; however, these effects could be blocked by siPPM1A-2. In conclusion, PPM1A is a key target of JMSD administration for the attenuation of the radiation-induced EMT in primary type II AECs via the TGF-β1/Smad pathway.

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“…Moreover, the RTOG 0937 study and NTR1527 trial emphasized that TRT should be performed for ES-SCLC patients who responded to chemotherapy [8]. Several retrospective analyses also suggested that TRT in combination with chemotherapy was associated with long-term survival [9][10][11][12][13]. Recently, the additional use of TRT has been strongly advocated for certain ES-SCLC patients after chemotherapy treatment in the 2020 NCCN guidelines [14] and in the ASTRO 2020 guidelines [15].…”

Section: Introductionmentioning

confidence: 99%

Clinical Outcomes of Extensive Stage Small Cell Lung Cancer Patients Treated With Thoracic Radiotherapy at Different Timing and Fractionation

Han

2020

Preprint

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Objective: The purpose of this study was to assess whether combined thoracic radiotherapy (TRT) on the basis of chemotherapy (ChT) showed promising anti-tumor activity in extensive-stage small cell lung cancer (ES-SCLC), then to explore practice patterns for radiation time and dose/ fractionation and to identify prognostic factors for patients who would benefit from ChT/TRT.Methods: A total of 492 ES-SCLC patients were included from January 2010 to March 2019, of which 244 patients experienced ChT/TRT. Propensity score matching (PSM) was performed to minimize bias between the ChT/TRT and ChT-alone groups. Patients in ChT/TRT group were categorized into four groups based on the number of induction chemotherapy cycles. For effective dose fractionation calculation, we introduced the time-adjusted biological effective dose(tBED). Categorical variables were analyzed with Chi-square tests and Fisher’s exact tests. Survival rates were computed by the Kaplan-Meier method. Multivariate prognostic analysis was performed with Cox proportional hazard models. Results: Patients who received ChT/TRT were associated with improved OS (18.2 vs 10.8 months), PFS (9.0 vs 6.0 months) and LRFS (12.0 vs 6.0 months) before matching, with similar results after matching. In the ChT/TRT group, the median LRFS times for groups based on radiation time were 12.7, 12.0, 12.7, and 9.0 months, respectively. Earlier TRT had a tendency to prolong PFS (median 10.6 vs 9.8 vs 9.1 vs 7.7 months, respectively, p = 0.1095), as was not seen in OS (median 17.6 vs 19.5 vs 17.2 vs 19.1 months, respectively, p = 0.7224). To note, patients within 6 cycles had better LRFS (p = 0.0006). For radiation dose, patients in high-dose group (tBED>50Gy) had worse OS (median 25.9 vs 22.9, p = 0.0484) and PFS (median 12.1 vs 11.2, p=0.0042) in patients with complete response and partial response (CR and PR) to systemic therapy, but the above-mentioned results were not drawn when the population was confined to those receiving standard fractionation with CR and PR. Conclusion: ChT/TRT could improve survival for ES-SCLC patients. We cautiously recommend that TRT should be performed within 6 cycles and receiving hyperfractionated 45Gy in 30 fractions may be a feasible treatment scheme for ES-SCLC patients.

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Survival Outcomes With Thoracic Radiotherapy in Extensive-Stage Small-Cell Lung Cancer: A Propensity Score-Matched Analysis of the National Cancer Database

Cited by 18 publications

References 28 publications

Neutrophil-to-lymphocyte ratio can predict outcome in extensive-stage small cell lung cancer

Neutrophil-to-lymphocyte ratio can predict outcome in extensive-stage small cell lung cancer

PPM1A as a key target of the application of Jiawei‑Maxing‑Shigan decoction for the attenuation of radiation‑induced epithelial‑mesenchymal transition in type II alveolar epithelial cells

Clinical Outcomes of Extensive Stage Small Cell Lung Cancer Patients Treated With Thoracic Radiotherapy at Different Timing and Fractionation

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