Prognostic value of PD-L1 expression on tumor cells combined with CD8+ TIL density in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiotherapy.

BACKGROUND/AIM:mmune checkpoint inhibition (CPI) has an increasing impact in the multimodal treatment of locally advanced non-small cell lung cancer (LA-NSCLC). Increasing evidence suggests treatment outcome depending on tumor cell PD-L1 expression. The purpose of this retrospective study was to investigate the prognostic value of PD-L1 expression on tumor cells in combination with CD8+ tumor stroma-infiltrating lymphocyte (TIL) density in inoperable LA-NSCLC treated with concurrent chemoradiotherapy (CRT). PATIENTS AND METHOD:We retrospectively assessed clinical characteristics and initial tumor biopsy samples of 31 inoperable LA-NSCLC patients treated with concurrent CRT. Prognostic impact of tumor cell PD-L1 expression (0% versus ≥1%) and CD8+ TIL density (0-40% vs. 41-100%) for local control, progression-free (PFS) and overall survival (OS) as well as correlations with clinicopathological features were evaluated. RESULTS:Median OS was 14 months (range: 3-167 months). The OS rates at 1- and 2 years were 68 and 20%. Local control of the entire cohort at 1 and 2 years were 74 and 61%. Median PFS, 1-year and 2-year PFS were 13 ± 1.4 months, 58 and 19%. PD-L1 expression < 1% on tumor cells was associated with improved OS, PFS and local control in patients treated with concurrent CRT. Univariate analysis showed a trend towards improved OS and local control in patients with low CD8+ TIL density. Evaluation of Tumor Immunity in the MicroEnvironment (TIME) appears to be an independent prognostic factor for local control, PFS and OS. The longest and shortest OS were achieved in patients with type I (PD-L1neg/CD8low) and type IV (PD-L1pos/CD8low) tumors (median OS: 57 ± 37 vs. 10 ± 5 months, p = 0.05), respectively. CONCLUSION:Assessment of PD-L1 expression on tumor cells in combination with CD8+ TIL density can be a predictive biomarker in patients with inoperable LA-NSCLC treated with concurrent CRT

Pneumonitis in Irradiated Lungs After Nivolumab: A Brief Communication and Review of the Literature

Nivolumab is a feasible therapy option in patients with advanced non-small cell lung cancer (NSCLC) who progress on first-line treatment. However, there is limited information about an overlapping toxicity of PD-1 inhibitors when administered following thoracic radiotherapy (TRT). Three of 25 patients with advanced NSCLC were treated with palliative or curative intent. Nivolumab was initiated as second or third-line therapy after TRT for recurrent or progressive disease. All 3 patients developed grade 3 pneumonitis at some point during nivolumab therapy. Herein, we describe 3 cases of pneumonitis in patients with NSCLC started on nivolumab following TRT. Imaging analysis was strongly consistent with heterogenous lung parenchyma changes in the irradiated lung volume receiving a total dose of 15-20Gy. Pulmonary toxicity was manageable;however, interruption of immunotherapy was necessary

Effectiveness and tolerability of radiotherapy for patients with indolent non-Hodgkin's lymphoma: a monocenter analysis

To analyze the effectiveness and toxicities of radiotherapy in indolent non-Hodgkin's lymphoma (iNHL) patients treated in our institution. Patients with iNHL treated with radiotherapy between 1999 and 2016 were included. The primary endpoint was progression-free survival (PFS). Secondary endpoints were local control (LC), overall survival (OS) and toxicities. PFS, LC, and OS were analyzed using Kaplan-Meier method. Log-rank test was used to investigate the differences between subgroups. Cox proportional hazard model was used for univariate continuous analysis. Seventy-five patients were identified in our institutional database between 1999 and 2016. Fifty-eight (77.3%) had stage I after Ann-Arbor and 17 patients (22.7%) had stage II. The median follow-up was 87~months (95% CI 72-102~months). Median single dose per fraction was 2.0~Gy (range 1.5-2~Gy) and median total dose was 30.6~Gy (range 16-45~Gy). Radiotherapy was performed in 2D (n = 10; 13.3%), 3D (n = 63; 84.0%) and VMAT (n = 2; 2.7%) techniques, respectively. The median PFS was 14.0~years (95% CI 8.3-19.7~years). The estimated PFS after 5 and 10~years were 73.0% and 65.5% in Kaplan-Meier analysis, respectively. The 5- and 10-year LC were 94.9% and 92.3%, respectively. The 5- and 10-year OS were 88.6% and 73.9%. In univariate analyses of PFS, younger patients (≤ 60~years old) had significantly superior PFS to those older than 60~years old (5-year PFS 81.9% vs. 65.1%, p = 0.021). Dose escalation > 36.0~Gy had no prognostic influence in term of PFS (p = 0.425). Extranodal involvement, stage and histology had no prognostic impact on PFS. Depending on the site of lymphomas, the most common acute side effects were: dermatitis CTCAE° I-II (8.0%), xerostomia CTC° I (8.0%), cataract CTC° I (12.0%) and dry eyes CTC° I-II (14.6%). No adverse event CTC° III was reported. Most acute side effects recovered at 3 to 6~months after radiotherapy except for CTC° I cataract and xerostomia. Local Radiotherapy was highly effective for treatment of early stage iNHL with no serious side effects in our cohort. The most acute CTCAE° I-II side effects recovered 3 to 6~months later. Technique advances seem to have further improved effectiveness and tolerability of radiotherapy.Trial registration: Local ethics committee of Ludwig-Maximilian-University (LMU) Munich approved this retrospective analysis on the May 7th, 2019 (Nr. 19-137)

Moderate hypofractionated image-guided thoracic radiotherapy for locally advanced node-positive non-small cell lung cancer patients with very limited lung function: a case report

Patients with locally advanced lung cancer and very limited pulmonary function (forced expiratory volume in 1 second [FEV1] <= 1 L) have dismal prognosis and undergo palliative treatment or best supportive care. We describe two cases of locally advanced node-positive non-small cell lung cancer (NSCLC) patients with very limited lung function treated with induction chemotherapy and moderate hypofractionated image-guided radiotherapy (Hypo-IGRT). Hypo-IGRT was delivered to a total dose of 45 Gy to the primary tumor and involved lymph nodes. Planning was based on positron emission tomography-computed tomography (PET/CT) and four-dimensional computed tomography (4D-CT). Internal target volume (ITV) was defined as the overlap of gross tumor volume delineated on 10 phases of 4D-CT. ITV to planning target volume margin was 5 mm in all directions. Both patients showed good clinical and radiological response. No relevant toxicity was documented. Hypo-IGRT is feasible treatment option in locally advanced node-positive NSCLC patients with very limited lung function (FEV1 <= 1 L)

Evaluation of the role of remission status in a heterogeneous limited disease small-cell lung cancer patient cohort treated with definitive chemoradiotherapy

Background: The role of remission status in limited disease (LD) small-cell lung cancer (SCLC) patients treated with definitive chemoradiotherapy (CRT) remains to be finally clarified. Methods: Individual data from 184 patients treated with definitive CRT concurrently or sequentially were retrospectively reviewed. Kaplan-Meier analysis as well as univariate and multivariate Cox regression models were used to describe survival within patient subgroups defined by remission status. Results: 71 (39 %) patients were treated in the concurrent, 113 (61 %) in the sequential CRT mode. Prophylactic cranial irradiation (PCI) was applied in 71 (39 %) patients. 37 (20 %) patients developed local, while 89 (48 %) distant recurrence. 58 (32 %) patients developed metachronous brain metastases. Complete, partial remission and non-response (defined as stable and progressive disease) were documented in 65 (35 %), 77 (42 %), and 37 (20 %) patients, respectively. In complete responders median overall survival was 21.8 months (95CI: 18.6-25) versus 14.9 (95 % CI: 11.7-18.2) (p = 0.041, log-rank test) and 11.5 months (95 % CI: 8.9-15.0) (p < 0.001, log-rank test) in partial and non-responders, respectively. The same effect was documented for the time to progression and distant metastasis-free survival. In the multivariate analysis achievement of complete remission as a variable shows a trend for the prolonged time to progression (p = 0.1, HR 1.48) and distant metastasis-free survival (p = 0.06, HR 1.63) compared to partial responders and was highly significant compared to non-responders. Conclusion: In this treated heterogeneous LD SCLC patient cohort complete remission was associated with longer time to progression, distant metastasis-free and overall survival compared to the non-and especially partial responders

Evaluation of the role of remission status in a heterogeneous limited disease small-cell lung cancer patient cohort treated with definitive chemoradiotherapy

Background: The role of remission status in limited disease (LD) small-cell lung cancer (SCLC) patients treated with definitive chemoradiotherapy (CRT) remains to be finally clarified. Methods: Individual data from 184 patients treated with definitive CRT concurrently or sequentially were retrospectively reviewed. Kaplan-Meier analysis as well as univariate and multivariate Cox regression models were used to describe survival within patient subgroups defined by remission status. Results: 71 (39 %) patients were treated in the concurrent, 113 (61 %) in the sequential CRT mode. Prophylactic cranial irradiation (PCI) was applied in 71 (39 %) patients. 37 (20 %) patients developed local, while 89 (48 %) distant recurrence. 58 (32 %) patients developed metachronous brain metastases. Complete, partial remission and non-response (defined as stable and progressive disease) were documented in 65 (35 %), 77 (42 %), and 37 (20 %) patients, respectively. In complete responders median overall survival was 21.8 months (95CI: 18.6-25) versus 14.9 (95 % CI: 11.7-18.2) (p = 0.041, log-rank test) and 11.5 months (95 % CI: 8.9-15.0) (p < 0.001, log-rank test) in partial and non-responders, respectively. The same effect was documented for the time to progression and distant metastasis-free survival. In the multivariate analysis achievement of complete remission as a variable shows a trend for the prolonged time to progression (p = 0.1, HR 1.48) and distant metastasis-free survival (p = 0.06, HR 1.63) compared to partial responders and was highly significant compared to non-responders. Conclusion: In this treated heterogeneous LD SCLC patient cohort complete remission was associated with longer time to progression, distant metastasis-free and overall survival compared to the non-and especially partial responders

Concurrent Afatinib and Whole-Brain Radiotherapy in Exon 19-del-EGFR Mutant Lung Adenocarcinoma: A Case Report and Mini Review of the Literature

Leptomeningeal metastases (LM) are found in approximately 3.8% of non-small cell lung cancer cases with an increased incidence in adenocarcinoma, and approximately one-third of patients will present with concomitant brain metastases. We report the case of a 50-year-old male patient with stage IV exon 19-del-EGFR mutant lung adenocarcinoma who progressed on second-generation TKI therapy with manifestation of symptomatic simultaneous diffuse brain and LM. Whole-brain radiotherapy with concurrent afatinib resulted in an almost complete regression of neurological symptoms as well as good, durable radiological response. Furthermore, treatment was well tolerated with no relevant adverse effects