scholarly journals Planning target volume as a predictor of disease progression in inoperable stage III non-small cell lung cancer patients treated with chemoradiotherapy and concurrent and/or sequential immune checkpoint inhibition

2021 ◽  
Author(s):  
Julian Taugner ◽  
Lukas Käsmann ◽  
Monika Karin ◽  
Chukwuka Eze ◽  
Benedikt Flörsch ◽  
...  
Keyword(s):  
Planning Target Volume ◽  
Immune Checkpoint ◽  
Target Volume ◽  
Continuous Variable ◽  
Stage Iii ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Platinum Based Chemotherapy ◽  
Stage Iii Nsclc ◽  
Nsclc Patients

SummaryBackground. The present study evaluates outcome after chemoradiotherapy (CRT) with concurrent and/or sequential Programmed Cell Death 1 (PD-1) or Ligand 1 (PD-L1) immune checkpoint inhibition (CPI) for inoperable stage III NSCLC patients depending on planning target volume (PTV). Method and patients. Prospective data of thirty-three consecutive patients with inoperable stage III NSCLC treated with CRT and sequential durvalumab (67%, 22 patients) or concurrent and sequential nivolumab (33%, 11 patients) were analyzed. Different PTV cut offs and PTV as a continuous variable were evaluated for their association with progression-free (PFS), local–regional progression-free (LRPFS), extracranial distant metastasis-free (eMFS) and brain-metastasis free-survival (BMFS). Results. All patients were treated with conventionally fractionated thoracic radiotherapy (TRT); 93% to a total dose of at least 60 Gy, 97% of patients received two cycles of concurrent platinum-based chemotherapy. Median follow-up for the entire cohort was 19.9 (range: 6.0–42.4) months; median overall survival (OS), LRFS, BMFS and eMFS were not reached. Median PFS was 22.8 (95% CI: 10.7–34.8) months. Patients with PTV ≥ 900ccm had a significantly shorter PFS (6.9 vs 22.8 months, p = 0.020) and eMFS (8.1 months vs. not reached, p = 0.003). Furthermore, patients with PTV ≥ 900ccm and stage IIIC disease (UICC-TNM Classification 8th Edition) achieved a very poor outcome with a median PFS and eMFS of 3.6 vs 22.8 months (p < 0.001) and 3.6 months vs. not reached (p = 0.001), respectively. PTV as a continuous variable also had a significant impact on eMFS (p = 0.048). However, no significant association of different PTV cut-offs or PTV as a continuous variable with LRPFS and BMFS could be shown. The multivariate analysis that was performed for PTV ≥ 900ccm and age (≥ 65 years), gender (male), histology (non-ACC) as well as T- and N-stage (T4, N3) as covariates also revealed PTV ≥ 900ccm as the only factor that had a significant correlation with PFS (HR: 5.383 (95% CI:1.263–22.942, p = 0.023)). Conclusion. In this prospective analysis of inoperable stage III NSCLC patients treated with definitive CRT combined with concurrent and/or sequential CPI, significantly shorter PFS and eMFS were observed in patients with initial PTV ≥ 900ccm.

Association of planning target volume with disease progression in inoperable stage III non-small cell lung cancer patients treated with chemoradiotherapy and concurrent and/or sequential immune checkpoint inhibition.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20557-e20557
Author(s):  
Julian Taugner ◽  
Monika Karin ◽  
Lukas Käsmann ◽  
Chukwuka Eze ◽  
Julian Guggenberger ◽  
...  
Keyword(s):  
Planning Target Volume ◽  
Progression Free Survival ◽  
Target Volume ◽  
Continuous Variable ◽  
Stage Iii ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Free Survival ◽  
Stage Iii Nsclc ◽  
Nsclc Patients

e20557 Background: The present study evaluates outcome after chemoradiotherapy (CRT) with concurrent and/or sequential Programmed Cell Death 1 (PD-1) or Ligand 1 (PD-L1) immune checkpoint inhibition (CPI) for inoperable stage III NSCLC patients depending on planning target volume (PTV). Methods: Prospective data of thirty-nine consecutive patients with inoperable stage III NSCLC who completed CRT with sequential durvalumab (72%, 28 patients) or concurrent and sequential nivolumab (28%, 11 patients) were analyzed. Different cut offs for PTV as well as PTV as a continuous variable were evaluated for association with progression-free survival (PFS) and extracranial metastasis-free survival (eMFS). Results: All patients were treated with conventionally fractionated TRT to a total dose of at least 60 Gy (range: 60-63.6Gy), 97% (27 patients) received two cycles of concurrent platinum-based chemotherapy. Median follow-up for the entire cohort was 23.2 (range: 6.0-42.6) months; median overall survival (OS) and eMFS were not reached. Median Progression-free survival (PFS) was 22.8 (95% CI: 10.3-35.2) months. Age (65 years), gender and UICC stage had no significant impact on PFS. There was no significant difference between durvalumab and nivolumab patients. Patients with PTV ≥ 900ccm had a significantly shorter PFS (11.77 vs 26.3 months, p = 0.049) and eMFS (11.7 months vs not reached, p = 0.019). Furthermore, patients with PTV ≥ 900ccm and stage IIIC disease (TNM 8th Ed.) achieved a dismal median PFS of only 3.6 months (vs. 26.3 months p < 0.001). PTV as a continuous variable showed a trend for association with PFS (p = 0.064) and was a significant negative prognosticator for eMFS (p = 0.030; HR: 4.065; 95%CI: 1.148-14.397). Conclusions: PTV has a significant impact on the PFS and eMFS after CRT combined with concurrent and/or sequential CPI in inoperable stage III NSCLC. Patients with PTV ≥ 900ccm had a significantly shorter PFS and eMFS.

PO-1195 Residual MTV after chemoradiotherapy ± immune checkpoint inhibition for inoperable stage III NSCLC

2021 ◽  
Vol 161 ◽  
pp. S991
Author(s):  
J. Taugner ◽  
M. Unterrainer ◽  
L. Käsmann ◽  
C. Eze ◽  
W. Kunz ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Stage Iii ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Stage Iii Nsclc

scholarly journals Differential role of residual metabolic tumor volume in inoperable stage III NSCLC after chemoradiotherapy ± immune checkpoint inhibition

2021 ◽  
Author(s):  
Marcus Unterrainer ◽  
Julian Taugner ◽  
Lukas Käsmann ◽  
Amanda Tufman ◽  
Niels Reinmuth ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Tumor Volume ◽  
Metabolic Tumor Volume ◽  
Stage Iii ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Pet Ct ◽  
Stage Iii Nsclc ◽  
Fdg Pet Ct ◽  
Nsclc Patients

Abstract Background The PET-derived metabolic tumor volume (MTV) is an independent prognosticator in non-small cell lung cancer (NSCLC) patients. We analyzed the prognostic value of residual MTV (rMTV) after completion of chemoradiotherapy (CRT) in inoperable stage III NSCLC patients with and without immune checkpoint inhibition (ICI). Methods Fifty-six inoperable stage III NSCLC patients (16 female, median 65.0 years) underwent 18F-FDG PET/CT after completion of standard CRT. rMTV was delineated on 18F-FDG PET/CT using a standard threshold (liver SUVmean + 2 × standard deviation). 21/56 patients underwent additional ICI (CRT-IO, 21/56 patients) thereafter. Patients were divided in volumetric subgroups using median split dichotomization (MTV ≤ 4.3 ml vs. > 4.3 ml). rMTV, clinical features, and ICI-application were correlated with clinical outcome parameters (progression-free survival (PFS), local PFS (LPFS), and overall survival (OS). Results Overall, median follow-up was 52.0 months. Smaller rMTV was associated with longer median PFS (29.3 vs. 10.5 months, p = 0.015), LPFS (49.9 vs. 13.5 months, p = 0.001), and OS (63.0 vs. 23.0 months, p = 0.003). CRT-IO patients compared to CRT patients showed significantly longer median PFS (29.3 vs. 11.2 months, p = 0.034), LPFS (median not reached vs. 14.0 months, p = 0.016), and OS (median not reached vs. 25.2 months, p = 0.007). In the CRT subgroup, smaller rMTV was associated with longer median PFS (33.5 vs. 8.6 months, p = 0.001), LPFS (49.9 vs. 10.1 months, p = 0.001), and OS (63.0 vs. 16.3 months, p = 0.004). In the CRT-IO subgroup, neither PFS, LPFS, nor OS were associated with MTV (p > 0.05 each). The findings were confirmed in subsequent multivariate analyses. Conclusion In stage III NSCLC, smaller rMTV is highly associated with superior clinical outcome, especially in patients undergoing CRT without ICI. Patients with CRT-IO show significantly improved outcome compared to CRT patients. Of note, clinical outcome in CRT-IO patients is independent of residual MTV. Hence, even patients with large rMTV might profit from ICI despite extensive tumor load.

Prognostic impact of inflammatory profiling during and after multimodal treatment for stage III NSCLC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20559-e20559
Author(s):  
Lukas Käsmann ◽  
Natalia Christina Cabeza-Boeddinghaus ◽  
Julian Taugner ◽  
Chukwuka Eze ◽  
Thomas Philipp Hofer ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Immune Checkpoint ◽  
Multimodal Treatment ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
Stage Iii ◽  
Prognostic Impact ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Stage Iii Nsclc

e20559 Background: Immune cells have a broad impact on tumor initiation, growth, and progression, and many of these effects are mediated by proinflammatory cytokines. The prognostic impact of dynamic changes of inflammatory cytokines in non-operable stage III NSCLC patients treated with (chemo)-radiotherapy ± immune checkpoint inhibition is unknown. In a prospective analysis, pro-inflammatory cytokines including interleukin 2, 6, and 8 from peripheral blood samples were evaluated 5-10 days before treatment start (T1), on the last day of thoracic radiotherapy (T2), and 3 weeks after radiation (T3) for their impact on overall survival (OS) and progression-free survival (PFS). Methods: Twenty patients, 85% male, at a median age of 65.5 (range 33-77) years were prospectively enrolled in this study. Eighteen (90%) patients received platinum-based concurrent chemoradiotherapy (CRT); seven (35%) patients additional concurrent and/or sequential immune checkpoint inhibition (four patients nivolumab and three durvalumab); patients treated with nivolumab received induction chemotherapy. Thoracic irradiation (TRT) was applied in all patients with a median cumulative dose in equivalent 2Gy fractions (EQD2) of 64Gy (range: 52-65Gy). Results: Median follow-up achieved 25 (range 14-30) months, median OS was not reached and median PFS was 11.8 (95%CI 5.2-18.4) months. To analyze pre-treatment data, median values were used as cut-off for dichotomization. Higher IL6 levels (≥9.75pg/ml) before irradiation (T1) were associated with impaired OS (median 11 months vs. not reached; p < 0.001) and PFS (median 7.0 months vs. not reached; p = 0.041). Higher IL8 levels (≥4.62pg/ml) were also associated with shorter OS (median 16 months vs. not reached; p = 0.009) and PFS (median 7 months vs. not reached p = 0.040). Patients with a decline of ≥10% of IL8 level between T1 and T2 had a significantly shorter PFS (11.8 months vs. not reached; p = 0.028). Conclusions: High proinflammatory cytokine levels were significantly associated with deterioration of outcome regarding OS and PFS in patients enrolled in multimodal treatment for stage III NSCLC. A decline of ≥10% of IL8 level during TRT was associated with impaired PFS.

Combined modality therapy with carboplatin, irinotecan and radiation therapy followed by consolidation docetaxel for patients with stage III NSCLC

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17088-17088
Author(s):  
L. E. Raez ◽  
E. Roman ◽  
L. Negret ◽  
C. Takita ◽  
C. Lobo ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Planning Target Volume ◽  
Primary Tumor ◽  
Radiation Pneumonitis ◽  
Combined Modality Therapy ◽  
Active Role ◽  
Target Volume ◽  
Nodal Metastasis ◽  
Stage Iii ◽  
Stage Iii Nsclc

17088 Background: Irinotecan (I) has an active role and potential as a radiosensitizing agent in patients with NSCLC. SWOG 9504 established the concept of “consolidation” chemotherapy with 3 cycles of docetaxel (D) after chemo/radiation (CRXT). We evaluated the efficacy and safety of administering weekly doses of carboplatin/irinotecan (CI) concomitantly with radiation therapy followed by D chemotherapy for patients (pts) with stages IIIA/B NSCLC. Methods: We have enrolled 23 pts, treatment included: C: (AUC = 2) and I: 30 mg/m2, weekly concomitant with radiation therapy, and D: 75 mg/m2 every 3 weeks for 3 times after CRXT was finished. The daily administered dose of radiation was 1.8 Gy, 5 days a week for 5 weeks, 25 fractions, (45 Gy) to the primary tumor and mediastinum (primary planning target volume: PPTV. After 45 Gy, the primary tumor and involved nodal metastasis (secondary planning target volume: SPTV) was boosted at 2 Gy per day to 18 Gy in 9 fractions. The total dose given was 63 Gy in 35 fractions over seven weeks. Evaluation of response has been done with RECIST criteria. Results: Median age is 55 years (range: 42–78), 18 (78%) of the pts are female, 17 (74%) are white, 13 (57%) are Hispanic, and 14 (65%) had an ECOG 1. Most common histologies are poorly differentiated and squamous cell carcinomas: 14 pts (61%), and half of the pts are stage IIIB. 111 weeks of CI and 39 cycles of D have been administered and we have documented 22 grade 3/4 adverse events (AE) among them: 4 pts pneumonia (17%), 3 pts radiation pneumonitis (13%), 2 pts: dehydration o neutropenia o dyspnea (9%) and 1 pt with diarrhea, nausea and vomiting (4.5%). No grade 4 neutropenia, esophagitis or diarrhea was reported. 12 severe AE were reported including: 2 pts with pneumonia (9%), 2 pts with dehydration (9%), and 2 pts with radiation pneumonitis (9%) requiring hospitalization. The rest of SAE were unrelated to therapy. Data for response is available in 18 pts. A partial response was seen in 10 pts (56%), and stable disease in 6 pts (33%). 2 pts are ineligible for response. Median survival (and PFS) has not been reached and it will be presented in the meeting. Conclusions: CI administered with radiation therapy and followed by D is safe and efficacious in the treatment of stage III NSCLC. [Table: see text]

scholarly journals Outlook into the future of front-line immune checkpoint inhibition in metastatic urothelial carcinoma

2021 ◽  
Vol 13 ◽  
pp. 175628722110047
Author(s):  
Jason R. Brown ◽  
Spencer Krane ◽  
Jorge Garcia ◽  
Pedro C. Barata
Keyword(s):  
Immune Checkpoint ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Front Line ◽  
Programmed Death Ligand 1 ◽  
Future Studies ◽  
Programmed Death ◽  
Platinum Based Chemotherapy ◽  
Metastatic Urothelial Carcinoma ◽  
Positive Results

Immune checkpoint inhibition has been approved for front-line treatment of metastatic bladder cancer in patients who are cisplatin-ineligible and demonstrate programmed death-ligand 1 (PD-L1) positivity. This approval followed the positive results of IMvigor210 and KEYNOTE-052 studies. Immunotherapy has also demonstrated efficacy as maintenance therapy patients for patients who initially respond to platinum-based chemotherapy. Other studies have investigated combinations of immunotherapy with chemotherapy, combinations between immunotherapies, and immunotherapy with novel agents. Although these combinations have demonstrated promise, further investigation is necessary to optimize the patients who would benefit from these approaches. Biomarkers beyond PD-L1 scoring can help predict response and resistance to immune checkpoint inhibition and will be integral to future studies.

scholarly journals Association of Planning Target Volume with Patient Outcome in Inoperable Stage III NSCLC Treated with Chemoradiotherapy: A Comprehensive Single-Center Analysis

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3035
Author(s):  
Monika Karin ◽  
Julian Taugner ◽  
Lukas Käsmann ◽  
Chukwuka Eze ◽  
Olarn Roengvoraphoj ◽  
...  
Keyword(s):  
Overall Survival ◽  
Planning Target Volume ◽  
Tnm Classification ◽  
Univariate Analysis ◽  
Target Volume ◽  
Stage Iii ◽  
Exact Matching ◽  
Safety Margins ◽  
Stage Iii Nsclc ◽  
The Impact

Inoperable stage III non-small cell lung cancer (NSCLC) represents a highly heterogeneous patient cohort. Multimodal treatment approaches including radiotherapy have been the new standard of care, with promising outcomes. The planning target volume (PTV), including the primary tumor, involved lymph node stations and safety margins, can vary widely. In order to evaluate the impact of the PTV for overall survival (OS), progression-free survival (PFS) and loco-regional control, we analyzed retrospective and prospective data of 122 consecutive patients with inoperable stage III NSCLC treated with CRT. The majority of patients (93%) received a total dose ≥ 60 Gy and 92% of all patients were treated with concurrent or sequential chemotherapy. Median follow-up for the entire cohort was 41.2 (range: 3.7–108.4) months; median overall survival (OS) reached 20.9 (95% CI: 14.5–27.3) months. PTVs from 500 to 800 ccm were evaluated for their association with survival in a univariate analysis. In a multivariate analysis including age, gender, total radiation dose and histology, PTV ≥ 700 ccm remained a significant prognosticator of OS (HR: 1.705, 95% CI: 1.071–2.714, p = 0.025). After propensity score matching (PSM) analysis with exact matching for Union internationale contre le cancer (UICC) TNM Classification (7th ed.)T- and N-stage, patients with PTV < 700 ccm reached a median PFS and OS of 11.6 (95% CI: 7.3–15.9) and 34.5 (95% CI: 25.6–43.4) months vs. 6.2 (95% CI: 3.1–9.3) (p = 0.057) and 12.7 (95% CI: 8.5–16.9) (p < 0.001) months in patients with PTV ≥ 700 ccm, respectively. Inoperable stage III NSCLC patients with PTV ≥ 700 ccm had significantly detrimental outcomes after conventionally fractionated CRT. PTV should be considered as a stratification factor in multimodal clinical trials for inoperable stage III NSCLC.

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