Real-world prospective analysis of treatment patterns in durvalumab maintenance after chemoradiotherapy in unresectable,locally advanced NSCLC patients

Investigational New Drugs - The aim of this prospective study is to evaluate the clinical use and real-world efficacy of durvalumab maintenance treatment after chemoradiotherapy (CRT) in...     

Prognostic role of patient gender in limited-disease small-cell lung cancer treated with chemoradiotherapy

Background

Previous studies have demonstrated that female gender could be a prognostic factor in limited-disease (LD) small-cell lung cancer (SCLC), but the correlation between patient gender and survival parameters remains unclear.

Patients and methods

Data from 179 LD SCLC patients treated with definitive chemoradiotherapy (CRT) were reviewed. Influence of patient gender on time to progression (TTP), local control (LC), brain metastasis-free (BMFS), distant metastasis-free (DMFS) and overall survival (OS) was analysed.

Results

Definitive CRT was completed by 179 (110 men/69 women) patients. Of these, 68 (38%; 34 men/34 women) patients were treated in concurrent and 111 (62%; 76 men/35 women) in sequential mode. Prophylactic cranial irradiation (PCI) was subsequently applied in 70 (39%; 36 men/34 women) patients with partial or complete response after CRT. Median OS was 20 (95% confidence interval [CI] 10–22) and 14 (95% CI 10–18) months in female and male patients, respectively (p = 0.021). In subgroups defined by remission status (complete and partial response) after CRT, an OS benefit for females compared to males was also detected. There was no correlation between patient gender and TTP, LC or DMFS, and no difference in OS in the female and male subgroups treated with PCI. The incidence of metachronous brain metastases (BMs) in the male and female subgroups differed significantly (40/110 men vs. 18/69 women, p = 0.03). Also, mean BMFS was significantly longer in women (p = 0.023). Patient gender also significantly correlated with OS on multivariate analysis after adjustment for other prognostic factors (p = 0.04, HR 1.38, 95% CI 1.08–1.92).

Conclusion

In this heterogeneous LD SCLC patient cohort treated with definitive CRT, female gender was significantly associated with longer BMFS and OS, as well as with a lower incidence of metachronous brain failure.

     

How much primary tumor metabolic volume reduction is required to improve outcome in stage III NSCLC after chemoradiotherapy? A single-centre experience

Purpose

We analysed a correlation between pre- to post-treatment primary tumour metabolic volume (PT-MV) reduction on 18F-FDG-PET/CT and survival in non-small cell lung cancer (NSCLC) patients treated with chemoradiotherapy (CRT).

Methods

Sixty consecutive patients with NSCLC stage IIIA-B (UICC 7th edition), treated with chemoradiotherapy, who underwent 18F-FDG-PET/CT at the same institution before and 6 weeks after treatment, were analysed. Different metabolic response values were investigated on their correlation with survival parameters: complete response (100% PT-MV reduction); major response (80–99% PT-MV reduction); moderate response (50–79% PT-MV reduction); minor response (1–49% PT-MV reduction) and non-response (no change or increase in uptake).

Results

From 60 patients, 52 (87%) had repeat PET/CT scans 6 weeks after completion of CRT. Complete metabolic response (CR) was reached in ten (17%), whereas major and moderate metabolic responses occurred in 16 (27%) and 15 (25%) patients, respectively. Four patients (7%) had minor metabolic response. Non-response was documented in seven patients (12%). Median overall survival (MS) for the entire cohort was 17 months (95% CI: 11.9–22.1 months). MS according to the different metabolic response values was as follows: 34 months (95% CI: 0–84.1); 22 months (95% CI: 14.2–29.8); 12 months (95% CI: 0.4–23.6); 11 months (95% CI: 0.2–21.8) and 17 months in patients with complete, major, moderate, minor and non-response (95% CI: 6.7–27.3), respectively (p?=?0.008).On multivariate analysis, significant predictors of survival included ECOG performance status (p?=?0.035, HR 0.49, 95% CI: 0.25–0.95) as well as complete and major metabolic response as a continuous variable with PT-MV reduction of at least 80% (p?=?0.021, HR 0.36, 95% CI: 0.15–0.86). Moderate metabolic response did not correlate with improved outcome (p?=?0.522).

Conclusions

In this homogeneous locally-advanced NSCLC single-centre patient cohort, a PT-MV reduction of at least 80% (complete and major metabolic response) following CRT was necessary to significantly improve patient outcome.

     

Analysis of primary tumor metabolic volume during chemoradiotherapy in locally advanced non-small cell lung cancer

Purpose

Positron emission tomography with 2?deoxy-2-[fluorine-18] fluoro-d-glucose integrated with computed tomography (18F-FDG-PET/CT) has an established role in the initial diagnosis and staging of lung cancer. However, a prognostic value of PET/CT during multimodality treatment has not yet been fully clarified. This study evaluated the role of primary tumor metabolic volume (PT-MV) changes on PET/CT before, during, and after chemoradiotherapy (CRT).

Methods

A total of 65 patients with non-small-cell lung cancer (NSCLC) UICC stage IIIA/B (TNM 7th Edition) were treated with definitive chemoradiotherapy (sequential or concurrent setting). PET/CT was acquired before the start, at the end of the third week, and 6 weeks following CRT.

Results

Median overall survival (OS) for the entire cohort was 16 months (95% confidence interval [CI]: 12–20). In all, 60 (92.3%) patients were eligible for pre-treatment (pre-PT-MV), 28 (43%) for mid-treatment (mid-PT-MV), and 53 (81.5%) for post-treatment (post-PT-MV) volume analysis. Patients with pre-PT-MV >63?cm³ had worse OS (p < 0.0001). A reduction from mid-PT-MV to post-PT-MV of >15% improved OS (p = 0.001). In addition, patients with post-PT-MV > 25?cm³ had significantly worse outcome (p = 0.001). On multivariate analysis, performance status (p = 0.002, hazard ratio [HR] 0.007; 95% CI 0.00–0.158), pre-PT-MV1 < 63?cm³ (p = 0.027, HR 3.98; 95% CI 1.17–13.49), post-PT-MV < 25?cm³ (p = 0.013, HR 11.90; 95% CI 1.70–83.27), and a reduction from mid-PT-MV to post-PT-MV > 15% (p = 0.004, HR 0.25; 95% CI 0.02–0.31) correlated with improved OS.

Conclusions

Our results demonstrated that pre- and post-treatment PT-MV, as well as an at least 15% reduction in mid- to post-PT-MV, significantly correlates with OS in patients with inoperable locally advanced NSCLC.

     

Central nervous system relapse continues to be a therapeutic challenge in extensive disease small-cell lung cancer patients with initial symptomatic brain metastases and good response to chemoradiotherapy

A summary is presented of four case studies of extensive disease small-cell lung cancer patients with initial symptomatic brain metastases, who were initially successfully treated with concurrent chemoradiotherapy of the neurocranium followed by consolidation chemotherapy and thoracic chemoradiotherapy, but shortly after the initial treatment developed a sequence of central nervous system relapses despite second-line therapy. Symptoms of the effect on the central nervous system dominated the course of the cancer disease, whereas the primary tumor mass remained in complete remission in all four patients until the end of the follow-up period.     

Comparison of prostate positioning guided by three-dimensional transperineal ultrasound and cone beam CT

Objective

The accuracy of a transperineal three-dimensional ultrasound system (3DUS) was assessed for prostate positioning and compared to fiducial- and bone-based positioning in kV cone beam computed tomography (CBCT) during definitive radiotherapy of prostate cancer.

Methods

Each of the 7 patients had three fiducial markers implanted into the prostate before treatment. Prostate positioning was simultaneously measured by 3DUS and CBCT before each fraction. In total, 177 pairs of 3DUS and CBCT scans were collected. Bone-match and seed-match were performed for each CBCT. Using seed-match as a reference, the accuracy of 3DUS and bone-match was evaluated. Systematic and random errors as well as optimal setup margins were calculated for 3DUS and bone-match.

Results

The discrepancy between 3DUS and seed-match in CBCT (average ± standard deviation) was 0.0 ± 1.7?mm laterally, 0.2 ± 2.0?mm longitudinally, and 0.3 ± 1.7?mm vertically. Using seed-match as a reference, systematic errors for 3DUS were 1.2?mm, 1.1?mm, and 0.9?mm; and random errors were 1.4?mm, 1.8?mm, and 1.6?mm, on lateral, longitudinal, and vertical axes, respectively. By analogy, the difference of bone-match to seed-match was 0.1 ± 1.1?mm laterally, 1.3 ± 3.8?mm longitudinally, and 1.3 ± 4.5?mm vertically. Systematic errors were 0.5?mm, 2.2?mm, and 2.6?mm; and random errors were 1.0?mm, 3.1?mm, and 3.9?mm on lateral, longitudinal, and vertical axes, respectively. The accuracy of 3DUS was significantly higher than that of bone-match on longitudinal and vertical axes, but not on the lateral axis.

Conclusion

Image-guided radiotherapy of prostate cancer based on transperineal 3DUS was feasible, with overall small discrepancy to seed-match in CBCT in this retrospective study. Compared to bone-match, transperineal 3DUS achieved higher accuracy on longitudinal and vertical axes.