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. 2022 Jul 16;17(1):126.
doi: 10.1186/s13014-022-02080-9.

Long-term survival of patients with central or > 7 cm T4 N0/1 M0 non-small-cell lung cancer treated with definitive concurrent radiochemotherapy in comparison to trimodality treatment

Nika Guberina  1 , Christoph Pöttgen  2 , Martin Schuler  3   4   5 , Maja Guberina  2 , Georgios Stamatis  6 , Till Plönes  6 , Martin Metzenmacher  3   4 , Dirk Theegarten  7 , Thomas Gauler  2 , Kaid Darwiche  8 , Clemens Aigner  5   6 , Wilfried E E Eberhardt  3   4 , Martin Stuschke  2   5
Affiliations

Long-term survival of patients with central or > 7 cm T4 N0/1 M0 non-small-cell lung cancer treated with definitive concurrent radiochemotherapy in comparison to trimodality treatment

Nika Guberina et al. Radiat Oncol. .

Abstract

Abstarct: BACKGROUND: To examine long-term-survival of cT4 cN0/1 cM0 non-small-cell lung carcinoma (NSCLC) patients undergoing definitive radiochemotherapy (ccRTx/CTx) in comparison to the trimodality treatment, neoadjuvant radiochemotherapy followed by surgery, at a high volume lung cancer center.

Methods: All consecutive patients with histopathologically confirmed NSCLC (cT4 cN0/1 cM0) with a curative-intent-to-treat ccRTx/CTx were included between 01.01.2001 and 01.07.2019. Mediastinal involvement was excluded by systematic EBUS-TBNA or mediastinoscopy. Following updated T4-stage-defining-criteria initial staging was reassessed by an expert-radiologist according to UICC-guidelines [8th edition]. Outcomes were compared with previously reported results from patients of the same institution with identical inclusion criteria, who had been treated with neoadjuvant radiochemotherapy and resection. Factors for treatment selection were documented. Endpoints were overall-survival (OS), progression-free-survival (PFS), and cumulative incidences of isolated loco-regional failures, distant metastases, secondary tumors as well as non-cancer deaths within the first year.

Results: Altogether 46 consecutive patients with histopathologically confirmed NSCLC cT4 cN0/1 cM0 [cN0 in 34 and cN1 in 12 cases] underwent ccRTx/CTx after induction chemotherapy (iCTx). Median follow-up was 133 months. OS-rates at 3-, 5-, and 7-years were 74.9%, 57.4%, and 57.4%, respectively. Absolute OS-rate of ccRTx/CTx at 5 years were within 10% of the trimodality treatment reference group (Log-Rank p = 0.184). The cumulative incidence of loco-regional relapse was higher after iCTx + ccRT/CTx (15.2% vs. 0% at 3 years, p = 0.0012, Gray's test) while non-cancer deaths in the first year were lower than in the trimodality reference group (0% vs 9.1%, p = 0.0360, Gray's test). None of the multiple recorded prognostic parameters were significantly associated with survival after iCTx + ccRT/CTx: Propensity score weighting for adjustment of prognostic factors between iCTx + ccRT/CTx and trimodality treatment did not change the results of the comparisons.

Conclusions: Patients with cT4 N0/1 M0 NSCLC have comparable OS with ccRTx/CTx and trimodality treatment. Loco-regional relapses were higher and non-cancer related deaths lower with ccRTx/CTx. Definitive radiochemotherapy is an adequate alternative for patients with an increased risk of surgery-related morbidity.

Keywords: Definitive radiochemotherapy; Non-small cell lung cancer; TNM-staging.

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Conflict of interest statement

PD Dr. med. N Guberina, PD Dr. med. M Guberina, Dr. med. M Metzenmacher, Prof. Dr. med. K Darwiche, PD Dr. med. T Ploenes, Prof. Dr. med. M Schuler, Prof. Dr. med. D Theegarten, Prof.. Dr. med. G. Stamatis, Prof. Dr. med. C Aigner: There are no relationships/conditions/circumstances that present a potential conflict of interest. All authors declare that they have no conflict of interest. Prof. Dr. med. C Pöttgen reports personal fees from Roche Pharma, personal fees from Boehringer Ingelheim, personal fees from Astra Zeneca, all outside the submitted work; .There are no relationships/conditions/circumstances that present a potential conflict of interest. PD Dr. med. W:E:E. Eberhardt reports honoraria (Advisory board function) from Astra Zeneca, BMS, Roche, MSD, Pfizer, Boehringer, Takeda, Eli Lilly, Bayer, Celgene Honoraria, and (educational lectures) from BMS, MSD Astra Zeneca, Roche, Novartis, Pfizer, Boehringer, Takeda, Abbvie, Celgene, Eli Lilly as well as (research grants) from Eli Lilly, BMS, and Astra Zeneca. The author declares that no competing interests exist. Dr med. T. Gauler reports advisory board/consultant function for Ipsen, No-vartis, BMS, Eisai and honoraria from BMS, Ipsen, Novartis, MSD, Eisai, Pfizer as well as traveling expenses from BMS, Ipsen, Novartis, MSD, Eisai, Pfizer and stocks from Bayer. Prof. Dr. med. M. Stuschke reports research grants contributed by AstraZeneca in 2019 and 2020. Professor Dr.med. M. Stuschke confirms that the above mentioned funding source was not involved in the study design or materials used, nor in the collection, analysis, and interpretation of data nor in the writing of the paper.

Figures

Fig. 1
Fig. 1
Overall survival of patients with T4 N0/1 M0 non-small cell lung cancer treated with definitive concurrent combination chemotherapy and radiotherapy (RCTx 1). For comparison, survival of NSCLC patients of the same TNM stage who received neoadjuvant radiochemotherapy and surgery were included (trimodal 2). The 95% confidence intervals for an inference at a single fixed time are shown as background areas of the same colour as the respective survivor functions. There were no significant differences between survival curves (p = 0.184, Log rank test)
Fig. 2
Fig. 2
Progression free survival of patients with T4 N0/1 M0 non-small cell lung cancer treated with definitive ccRTx/CTx (RCTx 1) in comparison to patients of the same TNM stage who underwent a trimodality treatment (trimodal 2) (p = 0.276, Log rank test)
Fig. 3
Fig. 3
Cumulative incidence function (CIF) for loco-regional recurrences as the first site of relapse for patients treated with definitive radiochemotherapy (RCTx 1) or neoadjuvant radiochemotherapy followed by surgery (trimodal 2). Concurrent risks were distant metastases or secondary cancers. The background areas of the same colour as the CIF represent the pointwise 95% confidence. Also moderate, the incidences of loco-regional recurrences were significantly higher after definitive radiochemotherapy in comparison to trimodality (p = 0.0012 Gray’s test)
Fig. 4
Fig. 4
Cumulative incidence function for distant metastases as the first site of relapse for patients treated with definitive radiochemotherapy (RCTx 1) or neoadjuvant radiochemotherapy followed by surgery (trimodal 2). Concurrent risks were local recurrences or secondary cancers. The incidences of distant metastases were not significantly different between definitive radiochemotherapy and the trimodality treatment regimen (p = 0.4983 Gray’s test)
Fig. 5
Fig. 5
Cumulative incidence function for secondary tumors revealed no significant intermodality difference between incidences of secondary malignanciesfor patients treated with definitive concurrent radiochemotherapy (RCTx 1) compared to those treated with neoadjuvant radiochemotherapy followed by surgery (trimodal 2) (p = 0.4352, Gray’s test)
Fig. 6
Fig. 6
Cumulative incidence function (CIF) for deaths without detected relapse of the NSCLC in the first year. Concurrent risks were deaths after a relapse. The cumulative incidence after surgery was higher indicating a higher post treatment morbidity within the first year for patients treated with definitive radiochemotherapy (RCTx 1) compared to those treated with neoadjuvant radiochemotherapy followed by surgery (trimodal 2) (p = 0.0360, Gray’s test)
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