Outcomes of aggressive concurrent radiochemotherapy in highly selected septuagenarians with stage IIIB non-small cell lung carcinoma: Retrospective analysis of 89 patients

Topkan, Erkan; Parlak, Eda; Topuk, Savaş; Güler, Ozan Cem; Selek, Uğur

doi:10.1016/j.lungcan.2013.05.002

Cited by 13 publications

(5 citation statements)

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“…Nevertheless, the secondary analysis of RTOG 9410 [ 20 ] demonstrated that in patients treated with CRT, the median OS was longer for patients aged ≥ 70 years (22.4 months vs. 15.5 months, p -value not provided). Numerous recent trials [ 21 – 23 ] suggested that CRT yielded similar treatment outcome for fit older patients compared with younger patients, which agreed with our results that the elderly (age ≥ 60 years) were non-inferior to the young (age < 60 years) with respect to OS. The reason why age < 60 years acted as a negative predictor for PFS is unknown.…”

Section: Discussionsupporting

confidence: 92%

Consolidation chemotherapy may improve survival for patients with locally advanced non-small-cell lung cancer receiving concurrent chemoradiotherapy - retrospective analysis of 203 cases

Li-pin

et al. 2015

BMC Cancer

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BackgroundFor patients with locally advanced non-small-cell lung cancer (LA-NSCLC), the role of consolidation chemotherapy (CCT) following concurrent chemoradiotherapy (CRT) is partially defined. The aim of this study was to evaluate the efficacy and toxicity of CCT.MethodsThe characteristics of LA-NSCLC patients treated with curative concurrent CRT from 2001 to 2010 were retrospectively reviewed.ResultsAmong 203 patients, 113 (55.7 %) patients received CCT. The median number of delivered CCT was 3 and 89.4 % patients completed ≥2 cycles. The OS was significantly better for patients in the CCT group compared with that in the non-CCT group (median OS, 27 months vs. 16 months; 5-year OS, 30.4 % vs. 22.5 %; p = 0.012). The median PFS were 12 months in the CCT group and 9 months in the non-CCT group (p = 0.291). The survival advantages of CCT were significant for males (HR: 0.63; 95 % CI, 0.44 − 0.90), patients with age < 60 years (HR: 0.63; 95 % CI, 0.42 − 0.95), non-squamous histology (HR: 0.44; 95 % CI, 0.25 − 0.76), pretreatment KPS ≥ 80 (HR: 0.67; 95 % CI, 0.48 − 0.93), stage IIIb (HR: 0.64; 95 % CI, 0.43 − 0.95), stable disease (HR: 0.31; 95 % CI, 0.14 − 0.65) and radiotherapy dose ≥ 60 Gy (HR: 0.69; 95 % CI, 0.48 − 1.00). There was no significant difference between the CCT group and the non-CCT group regarding treatment-related toxicities.ConclusionsCCT might further prolong survival compared with CRT alone for LA-NSCLC without increasing treatment-related toxicities, especially for males, patients with age < 60 years, non-squamous histology, pretreatment KPS ≥ 80, stage IIIb, stable disease and radiotherapy dose ≥ 60 Gy. Large size prospective investigations that incorporate patient characteristics and treatment response are warranted to validate our findings.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1710-2) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 92%

Consolidation chemotherapy may improve survival for patients with locally advanced non-small-cell lung cancer receiving concurrent chemoradiotherapy - retrospective analysis of 203 cases

Li-pin

et al. 2015

BMC Cancer

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“…Since the lung represents the most RT sensitive tissue, this results in fatal complications. Among the many cytokines involved in this process, TGFβ is thought to play a pivotal role [26,27]. TGFβ is overexpressed at sites of injury, which contributes to delayed tissue fibrosis after radiation and chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…TGFβ is overexpressed at sites of injury, which contributes to delayed tissue fibrosis after radiation and chemotherapy. Various interventional therapies that aim to block TGFβ signaling or reduce decrease tissue levels of TGFβ have proven to be effective in reducing the development of fibrosis in the lung, liver, and intestines [26][27][28]. Reducing normal tissue injury by TGFβ inhibition is undoubtedly significant in RT dose-escalation for lung cancer and will increase tumor control probability.…”

Section: Discussionmentioning

confidence: 99%

“…Drugs such as gemcitabine, cisplatin, and docetaxel have been demonstrated to radiosensitize tumors in NSCLC [25]. Although these sensitizers increase the rates of local tumor control and in some cases overall survival [26], they are not specific for tumor cells, and can also increase radiation toxicity to normal tissues. This nonspecific mechanism of action is one of the major limiting factors of many radiation modulators.…”

Section: Discussionmentioning

confidence: 99%

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Biologically Augmenting Radiation Therapy by Inhibiting TGFβ in NSCLC from Molecular to Microenvironment

Pellicciotta

Barcellos-Hoff

2013

International Journal of Radiation Oncology*Biology*Physics

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Purpose To determine whether TGFβ inhibition increases the response to radiotherapy in human and mouse non-small cell lung carcinoma (NSCLC) cells in vitro and in vivo. Methods TGFβ mediated growth response and pathway activation were examined in human NSCLC NCI-H1299, NCI-H292, and A549 cell lines and murine Lewis lung cancer (LLC) cells. Cells were treated in vitro with LY364947, a small molecule inhibitor of the TGFβ type I receptor kinase, or with pan-isoform TGFβ neutralizing monoclonal antibody, 1D11, before radiation exposure. DNA damage response was measured by ATM or Trp53 protein phosphorylation, γH2AX foci formation or comet assay in irradiated cells. Radiation sensitivity was determined by clonogenic assay. Mice bearing LLC syngeneic subcutaneous tumors were treated with 5 fractions of 6 Gy and/or neutralizing or control antibody. Results NCI-H1299, A549 and LLC NSCLC cell lines pretreated with LY364947 prior to radiation exposure exhibited compromised DNA damage response indicated by decreased ATM and p53 phosphorylation, reduced γH2AX foci, and increased radiosensitivity. NCI-H292 cells were unresponsive. TGFβ signaling inhibition in irradiated LLC cells resulted in unresolved DNA damage. Subcutaneous LLC tumors in mice treated with TGFβ neutralizing antibody exhibited fewer γH2AX foci after irradiation and significantly greater tumor growth delay in combination with fractionated radiation. Conclusions TGFβ inhibition prior to radiation attenuated DNA damage recognition and increased radiosensitivity in most NSCLC in vitro and promoted radiation-induced tumor control in vivo. These data support the rationale for concurrent TGFβ inhibition and radiotherapy to provide therapeutic benefit in NSCLC.

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“…Established with numerous phase III randomized controlled trials and meta-analyses, concurrent chemoradiotherapy (C-CRT) has long been the standard of care for inoperable stage III non-small-cell lung cancers (NSCLC) [1–6]; even a well-accepted approach in select septuagenarians [7]. Conventionally fractionated doses ≥60 Gy had been considered acceptable, whilst the efficacy of safe escalation of the radiotherapy (RT) dose by preserving the critical organs at risk (OAR) continues to be debated [8–13].…”

Section: Introductionmentioning

confidence: 99%

Significance of overall concurrent chemoradiotherapy duration on survival outcomes of stage IIIB/C non-small-cell lung carcinoma patients: Analysis of 956 patients

et al. 2019

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Background To investigate the detrimental effects of prolonged overall radiotherapy duration (ORTD) on survival outcomes of stage IIIB/C NSCLC patients treated with concurrent chemoradiotherapy (C-CRT) Methods The study cohort consisted of 956 patients who underwent C-CRT for stage IIIB/C NSCLC. Primary endpoint was the association between the ORTD and overall survival (OS) with locoregional progression-free survival (LRPFS) and PFS comprising the secondary endpoints. Receiver operating characteristic (ROC) curve analysis was utilized for accessibility of the cut-off that interacts with survival outcomes. Multivariate Cox model was utilized to identify the independent associates of survival outcomes. Results The ROC curve analysis exhibited significance at 49 days of ORTD cut-off that dichotomized patients into ORTD<50 versus ORTD≥50 days groups for OS [area under the curve (AUC): 82.8%; sensitivity: 81.1%; specificity: 74.8%], LRPFS (AUC: 91.9%; sensitivity: 90.6%; specificity: 76.3%), and PFS (AUC: 76.1%; sensitivity: 72.4%; specificity: 68.2%), respectively. Accordingly, ORTD≥50 days group had significantly shorter median OS (P<0.001), LRPFS (P<0.001), and PFS (P<0.001); and 10-year actuarial locoregional control (P<0.001) and distant metastases-free (P<0.011) rates than the ORTD<50 days group. The ORTD retained its significant association with survival outcomes at multivariate analyses independent of the other favorable covariates (p<0.001, for OS, LRPFS, and PFS): Stage IIIB disease (versus IIIC), lymph node bulk <2 cm (versus ≥2 cm), and 2–3 chemotherapy cycles (versus 1). The higher sensitivity for LRPFS (90.6%) than PFS (72.4%) on ROC curve analysis suggested the prolonged ORTD-induced decrements in locoregional control rates as the major cause of the poor survival outcomes. Conclusions Longer ORTD beyond ≥50 days was associated with significantly poorer OS, LRPFS and PFS outcomes, where reduced locoregional control rates appeared to be the main causative.

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Outcomes of aggressive concurrent radiochemotherapy in highly selected septuagenarians with stage IIIB non-small cell lung carcinoma: Retrospective analysis of 89 patients

Cited by 13 publications

References 21 publications

Consolidation chemotherapy may improve survival for patients with locally advanced non-small-cell lung cancer receiving concurrent chemoradiotherapy - retrospective analysis of 203 cases

Consolidation chemotherapy may improve survival for patients with locally advanced non-small-cell lung cancer receiving concurrent chemoradiotherapy - retrospective analysis of 203 cases

Biologically Augmenting Radiation Therapy by Inhibiting TGFβ in NSCLC from Molecular to Microenvironment

Significance of overall concurrent chemoradiotherapy duration on survival outcomes of stage IIIB/C non-small-cell lung carcinoma patients: Analysis of 956 patients

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