Radiation dose is significantly associated with overall survival in patients with stage III non-small cell lung cancer treated with combined radiation and chemotherapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18074-18074
Author(s):  
L. Wang ◽  
L. Zhao ◽  
J. Hayman ◽  
G. Kalemkerian ◽  
F. Kong
Keyword(s):  
Lung Cancer ◽  
Prognostic Factor ◽  
Radiation Dose ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Risk Of Death ◽  
Stage Iii Nsclc

18074 Background: Radiation dose is an independent prognostic factor for survival in patients with early stage non-small cell lung cancer (NSCLC). We hypothesized that radiation dose is also a significant independent factor associated with survival in patients with stage III disease treated with combined radiation and chemotherapy. Methods: This is an Institutional Review Board approved retrospective study. Eligible subjects included those with stage III NSCLC registered in the radiation oncology database at University of Michigan Hospital between January 1992 and July 2004. Radiation was given using 3-dimensional conformal technique with doses ranging from 30 to 102.9 Gy, corresponding to a bioequivalent dose (BED) of 39 to 124.5Gy. Median age was 65 years (range, 36–89). There were 80 males and 67 females. Median follow-up was 13.0 months (range, 2.7–145.9). Results: For patients treated with radiation alone (n=40), sequential chemoradiation (n=42), and concurrent chemoradiation (n=65), median survival was 8.6 (95% CI: 5.7–11.5), 12.8 (95% CI: 9.5–16.0) and 15.4 (95% CI: 12.7–18.0) months, respectively (P =0 .011). Multivariate Cox-regression analysis showed that BED (HR=0.96, 95% CI: 0.95–0.97, P<0.001) and administration of chemotherapy (HR=0.44, 95% CI: 0.28–0.70, P=0.001) were independent prognostic factors associated with the risk of death. T stage was marginally significant (P=0.065). Age, gender and N stage were not independent factors (P>0.05). To isolate the BED effect, multivariate analysis was performed separately in patients treated with and without chemotherapy: the hazard ratios of BED for the risk of death were 0.97 (95% CI: 0.95–0.99, P=0 .013) and 0.95 (95% CI: 0.93–0.98, P=0.001), respectively. BED also remained a significant independent prognostic factor in patients treated with chemotherapy and radiation in the dose range of 60–66 Gy (HR=0.91, 95% CI: 0.84–0.99, P=0.041). Conclusions: Radiation dose is significantly associated with survival in patients with stage III NSCLC treated with combined radiation and chemotherapy. No significant financial relationships to disclose.

scholarly journals 244 Genomic determinants of response to chemoradiation and durvalumab consolidation for stage III non-small cell lung cancer

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A263-A263
Author(s):  
Matthew Guo ◽  
Joseph Murray ◽  
Paola Ghanem ◽  
Khinh Ranh Voong ◽  
Russell Hales ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Molecular Profiling ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Definitive Chemoradiation ◽  
Stage Iii Nsclc

BackgroundDurvalumab consolidation after chemoradiation for unresectable stage III non-small cell lung cancer (NSCLC) improves overall survival. However, up to 25% of patients progress within 18 months following durvalumab consolidation. Little is known regarding the genomic determinants of response to therapy.1 2MethodsWe retrospectively reviewed medical records of 76 patients with stage III NSCLC who received definitive chemoradiation and durvalumab consolidation between 2015–2020 at a large tertiary academic center. Tumor characteristics, molecular profiling, and clinical outcomes including response, progression-free survival (PFS), and overall survival (OS) were documented in an IRB-approved database. Outcomes were assessed by molecular alterations identified from diagnostic biopsy samples using Kaplan-Meier analysis.ResultsOf 76 patients with stage III NSCLC treated with definitive chemoradiation and durvalumab consolidation, 74 were evaluable for PFS and OS. Median age at diagnosis was 66.5 years and 43% were women (n=32). Histology included adenocarcinoma (55%, n=41) and squamous cell carcinoma (32%, n=24). Median follow-up time was 23.0 months from start of durvalumab. The cohort’s median PFS was 15.9 months with 36 patients having documented radiographic progression. Overall survival for the cohort was 32.0 months with 28 deaths. Molecular profiling was performed at time of diagnosis in 35 patients (47%), of which 30 had adenocarcinoma histology. 18 patients had KRAS mutations including KRAS p.G12C (n=8), which were mutually exclusive with 8 patients who had other clinically targetable alterations (EGFR mutations n=1, ALK fusion n=1, RET fusion n=1, MET exon 14 skipping mutation n=1, or ERBB2 mutation n=4). Three patients had non-targetable mutations (BRAF non-p.V600E, STK11, KEAP1) and the remaining six patients lacked an identifiable alteration. There was no significant difference in PFS (p=0.92 by log-rank) or OS (p=0.36 by log-rank) between patients with KRAS mutations, other targetable alterations, non-targetable mutations, or those without molecular profiling. Within patients with KRAS mutations, there was no significant difference in PFS (p=0.33 by log-rank) or OS (p=0.69 by log-rank) when comparing KRAS p.G12C to non-p.G12C mutations.ConclusionsOur study of real-world cohort of patients with stage III NSCLC examined genomic determinants of response to treatment with definitive chemoradiation and durvalumab. Results from this retrospective study suggest that patients with KRAS-mutated tumors derive similar benefit from therapy than patients with other targetable, non-targetable or no identifiable genomic alterations. Future directions for this cohort include analysis of post-progression therapy, subgroup analysis comparing genomic alterations to patterns of progression, and examination of molecular signatures of patients with progression.ReferencesAntonia SJ, Villegas A, Daniel D, et al. Durvalumab after chemoradiotherapy in stage III non–small-cell lung cancer. N Engl J Med 2017;377(20):1919–1929. doi:10.1056/NEJMoa1709937Faivre-Finn C, Vicente D, Kurata T, et al. Four-year survival with durvalumab after chemoradiotherapy in stage III NSCLC—an update from the PACIFIC trial. Journal of Thoracic Oncology 2021;16(5):860–867. doi:10.1016/j.jtho.2020.12.015Ethics ApprovalThis retrospective chart review study has obtained ethics approval from the Institutional Review Board at the Johns Hopkins School of Medicine (number: IRB00232313).

scholarly journals Efficacy and cost of high-frequency IGRT in elderly stage III non-small-cell lung cancer patients

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0252053
Author(s):  
Samuel P. Heilbroner ◽  
Eric P. Xanthopoulos ◽  
Donna Buono ◽  
Daniel Carrier ◽  
Ben Y. Durkee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
High Frequency ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Free Survival ◽  
Stage Iii Nsclc ◽  
The Impact

Background High-frequency image-guided radiotherapy (hfIGRT) is ubiquitous but its benefits are unproven. We examined the cost effectiveness of hfIGRT in stage III non-small-cell lung cancer (NSCLC). Methods We selected stage III NSCLC patients ≥66 years old who received definitive radiation therapy from the Surveillance, Epidemiology, and End-Results-Medicare database. Patients were stratified by use of hfIGRT using Medicare claims. Predictors for hfIGRT were calculated using a logistic model. The impact of hfIGRT on lung toxicity free survival (LTFS), esophageal toxicity free survival (ETFS), cancer-specific survival (CSS), overall survival (OS), and cost of treatment was calculated using Cox regressions, propensity score matching, and bootstrap methods. Results Of the 4,430 patients in our cohort, 963 (22%) received hfIGRT and 3,468 (78%) did not. By 2011, 49% of patients were receiving hfIGRT. Predictors of hfIGRT use included treatment with intensity-modulated radiotherapy (IMRT) (OR = 7.5, p < 0.01), recent diagnosis (OR = 51 in 2011 versus 2006, p < 0.01), and residence in regions where the Medicare intermediary allowed IMRT (OR = 1.50, p < 0.01). hfIGRT had no impact on LTFS (HR 0.97; 95% CI 0.86–1.09), ETFS (HR 1.05; 95% CI 0.93–1.18), CSS (HR 0.94; 95% CI 0.84–1.04), or OS (HR 0.95; 95% CI 0.87–1.04). Mean radiotherapy and total medical costs six months after diagnosis were $17,330 versus $15,024 (p < 0.01) and $71,569 versus $69,693 (p = 0.49), respectively. Conclusion hfIGRT did not affect clinical outcomes in elderly patients with stage III NSCLC but did increase radiation cost. hfIGRT deserves further scrutiny through a randomized controlled trial.

scholarly journals Identification of Potential Prognostic and Predictive Immunological Biomarkers in Patients with Stage I and Stage III Non-Small Cell Lung Cancer (NSCLC): A Prospective Exploratory Study

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6259
Author(s):  
Rianne D. W. Vaes ◽  
Kobe Reynders ◽  
Jenny Sprooten ◽  
Kathleen T. Nevola ◽  
Kasper M. A. Rouschop ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Exploratory Study ◽  
Predictive Biomarkers ◽  
Small Cell ◽  
Stage I ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Stage Iii Nsclc

Radiotherapy (RT) and chemotherapy can induce immune responses, but not much is known regarding treatment-induced immune changes in patients. This exploratory study aimed to identify potential prognostic and predictive immune-related proteins associated with progression-free survival (PFS) in patients with non-small cell lung cancer (NSCLC). In this prospective study, patients with stage I NSCLC treated with stereotactic body radiation therapy (n = 26) and patients with stage III NSCLC treated with concurrent chemoradiotherapy (n = 18) were included. Blood samples were collected before (v1), during (v2), and after RT (v3). In patients with stage I NSCLC, CD244 (HR: 10.2, 95% CI: 1.8–57.4) was identified as a negative prognostic biomarker. In patients with stage III NSCLC, CR2 and IFNGR2 were identified as positive prognostic biomarkers (CR2, HR: 0.00, 95% CI: 0.00–0.12; IFNGR2, HR: 0.04, 95% CI: 0.00–0.46). In addition, analysis of the treatment-induced changes of circulating protein levels over time (Δv2/v3−v1) also identified CXCL10 and IL-10 as negative predictive biomarkers (CXCL10, HR: 3.86, 95% CI: 1.0–14.7; IL-10, HR: 16.92 (2.74–104.36)), although serum-induced interferon (IFN) response was a positive prognostic. In conclusion, we identified several circulating immunogenic proteins that are correlated with PFS in patients with stage I and stage III NSCLC before and during treatment.

Role of T0 status in overall survival for unresectable stage III non-small cell lung cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9026-9026
Author(s):  
Takefumi Komiya ◽  
Emily Powell ◽  
Charles Vu ◽  
Achuta Kumar Guddati
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Survival Rate ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Unresectable Stage ◽  
Stage Iii Nsclc

9026 Background: Occult (T0) primary non-small cell lung cancer (NSCLC) with mediastinal involvement is a known but rare clinical condition. Its prognosis has not been evaluated well in the literature. Methods: Using National Cancer Database (NCDB), cases diagnosed between 2004 and 2016 with unresectable clinical stage III NSCLC with N2 or N3 involvement were selected and assigned to T0 or T1-4 group according to AJCC staging version 6th or 7th. Clinical demographics including use of chemotherapy/immunotherapy in first course of treatment were collected. As validation, independent data using Surveillance, Epidemiology, and End Results Program (SEER) was analyzed accordingly. Survival analyses were conducted using Kaplan-Meier and log-rank tests. Results: A total of 458 and 84,263 cases met criteria for unresectable, N2/N3 stage III NSCLC with T0 and T1-4 status, respectively. T0 status was associated with younger age, recent diagnosis, adenocarcinoma histology, N3, and use of chemotherapy. Overall survival (OS) was improved in T0 over T1-4 group (p < 0.0001) with a five-year survival rate of 30.5% and 12.7%, respectively, with a validation with multivariate proportional hazard models. Propensity score matching analyses using all 458 patients in each group demonstrated a significant difference in OS (p < 0.0001). The difference was also significant in a subset of those who have undergone chemoradiation (p < 0.0001). Independent analysis using SEER data confirmed its superior survival of T0 over T1-4 with a five-year survival rate of 35.3% and 13.5%, respectively. Conclusions: Both NCDB and SEER analyses demonstrated better survival of T0 than T1-4 counterpart in the setting of unresectable stage III NSCLC, irrespective of chemotherapy status. This group may require a distinct assignment to new staging group after further investigation.

scholarly journals Management of Stage III Non–Small-Cell Lung Cancer: ASCO Guideline

2021 ◽  
Author(s):  
Megan E. Daly ◽  
Navneet Singh ◽  
Nofisat Ismaila ◽  
Mara B. Antonoff ◽  
Douglas A. Arenberg ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Literature Search ◽  
Expert Panel ◽  
Small Cell ◽  
Stage Iii ◽  
Evidence Based ◽  
Small Cell Lung ◽  
Stage Iii Nsclc

PURPOSE To provide evidence-based recommendations to practicing clinicians on management of patients with stage III non–small-cell lung cancer (NSCLC). METHODS An Expert Panel of medical oncology, thoracic surgery, radiation oncology, pulmonary oncology, community oncology, research methodology, and advocacy experts was convened to conduct a literature search, which included systematic reviews, meta-analyses, and randomized controlled trials published from 1990 through 2021. Outcomes of interest included survival, disease-free or recurrence-free survival, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS The literature search identified 127 relevant studies to inform the evidence base for this guideline. RECOMMENDATIONS Evidence-based recommendations were developed to address evaluation and staging workup of patients with suspected stage III NSCLC, surgical management, neoadjuvant and adjuvant approaches, and management of patients with unresectable stage III NSCLC. Additional information is available at www.asco.org/thoracic-cancer-guidelines .

scholarly journals Conservative treatment of stage III lung cancer using chemoradiotherapy in hypofractionation mode, case report

2020 ◽  
pp. 271-276
Author(s):  
N. V. Marinichenko ◽  
K. K. Laktionov ◽  
A. V. Nazarenko ◽  
T. N. Borisova ◽  
M. S. Ardzinba ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Case Report ◽  
Radiation Dose ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Locally Advanced ◽  
Small Cell ◽  
Stage Iii ◽  
Small Cell Lung ◽  
Post Radiation

Lung cancer is a leader in the world in terms of morbidity and mortality. Moreover, the number of patients with locally advanced forms of non-small cell lung cancer exceeds 30% of all newly diagnosed cases. The standard of treatment for patients with inoperable stage III lung cancer is chemoradiotherapy. Currently, ways to increase the effectiveness of chemoradiotherapy are being considered, in particular, local escalation of the radiation dose to the tumor, which allows personalizing approaches in the treatment of this category of patients. One of the most common complications of chemoradiotherapy is post-radiation pulmonitis, which requires timely diagnosis and treatment with glucocorticosteroids in severe cases. We present a case report of a patient with locally advanced non-small cell lung cancer who received treatment as part of simultaneous chemoradiotherapy in the hypofraction mode, complicated by post-radiation pulmonitis. Successful treatment of complications led to the restoration of the general condition of the patient; during the follow-up examination, a complete response to the specific treatment was recorded. Thus, a promising method of treating patients with inoperable stage III non-small cell lung cancer is the option of simultaneous chemoradiotherapy with local escalation of the radiation dose to the tumor, while being wary of complications such as pulmonitis, allows for timely diagnosis and treatment of the condition.

scholarly journals Long-Term Results of NRG Oncology RTOG 0617: Standard- Versus High-Dose Chemoradiotherapy With or Without Cetuximab for Unresectable Stage III Non–Small-Cell Lung Cancer

2020 ◽  
Vol 38 (7) ◽  
pp. 706-714 ◽  
Author(s):  
Jeffrey D. Bradley ◽  
Chen Hu ◽  
Ritsuko R. Komaki ◽  
Gregory A. Masters ◽  
George R. Blumenschein ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Radiation Dose ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Concurrent Chemotherapy ◽  
Small Cell ◽  
Stage Iii ◽  
High Dose ◽  
Small Cell Lung ◽  
Grade 3

PURPOSE RTOG 0617 compared standard-dose (SD; 60 Gy) versus high-dose (HD; 74 Gy) radiation with concurrent chemotherapy and determined the efficacy of cetuximab for stage III non–small-cell lung cancer (NSCLC). METHODS The study used a 2 × 2 factorial design with radiation dose as 1 factor and cetuximab as the other, with a primary end point of overall survival (OS). RESULTS Median follow-up was 5.1 years. There were 3 grade 5 adverse events (AEs) in the SD arm and 9 in the HD arm. Treatment-related grade ≥3 dysphagia and esophagitis occurred in 3.2% and 5.0% of patients in the SD arm v 12.1% and 17.4% in the HD arm, respectively ( P = .0005 and < .0001). There was no difference in pulmonary toxicity, with grade ≥3 AEs in 20.6% and 19.3%. Median OS was 28.7 v 20.3 months ( P = .0072) in the SD and HD arms, respectively, 5-year OS and progression-free survival (PFS) rates were 32.1% and 23% and 18.3% and 13% ( P = .055), respectively. Factors associated with improved OS on multivariable analysis were standard radiation dose, tumor location, institution accrual volume, esophagitis/dysphagia, planning target volume and heart V5. The use of cetuximab conferred no survival benefit at the expense of increased toxicity. The prior signal of benefit in patients with higher H scores was no longer apparent. The progression rate within 1 month of treatment completion in the SD arm was 4.6%. For comparison purposes, the resultant 2-year OS and PFS rates allowing for that dropout rate were 59.6% and 30.7%, respectively, in the SD arms. CONCLUSION A 60-Gy radiation dose with concurrent chemotherapy should remain the standard of care, with the OS rate being among the highest reported in the literature for stage III NSCLC. Cetuximab had no effect on OS. The 2-year OS rates in the control arm are similar to the PACIFIC trial.

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