Haematological biomarkers of pathological response on neo-adjuvant chemo-immunotherapy treatment for resectable stage IIIA non-small cell lung cancer (NSCLC) patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20026-e20026
Author(s):  
Raquel Laza Briviesca ◽  
Alberto Cruz Bermudez ◽  
Miguel Barquin ◽  
Ernest Nadal ◽  
Amelia Insa ◽  
...  
Keyword(s):  
Adjuvant Treatment ◽  
Complete Blood Count ◽  
Locally Advanced ◽  
Pathological Response ◽  
Stage Iiia ◽  
Lymphocyte Ratio ◽  
Incomplete Response ◽  
Advanced Stages ◽  
Nsclc Patients ◽  
Viable Tumour

e20026 Background: PD1/PDL1 treatments have become the main therapy in advanced stages of NSCLC due to its significant increase in overall survival (OS), but recently, combination with chemotherapy in locally advanced stages is showing promising results. Many studies have described the neutrophil-to-lymphocyte ratio (NLR) and platelets-to-lymphocyte ratio (PLR) as indicator of systemic inflammation, that could be use as biomarker of response to immunotherapy. In our study, we described the effect of neoadjuvant chemo-immunotherapy in Complete Blood Count (CBC) parameters and evaluated their relationship with pathological responses. Methods: Immune cell populations of 46 resectable stage IIIA NSCLC patients treated with neo-adjuvant chemo-immunotherapy from NADIM clinical trial were analysed. Samples were extracted before initiating the neo-adjuvant treatment with nivolumab plus carboplatin and at the third cycle before patients underwent surgery. We classified patients in 3 subgroups of pathological response assessed in the resection specimen: complete response (pCR), mayor response (< 10% viable tumour) and incomplete response (> 10% viable tumour). Wilcoxon and Mann-Whitney U statistic test were used to evaluated differences between pre and post treatment and between pathological responses groups respectively. Results: From 46 patients, 5 patients did not undergo surgery, so they were excluded from the analysis. Absolute numbers (x103cells/µl) of CBC were significantly reduced after neo-adjuvant treatment in patients, leucocytes (8.80 vs 6.64), Eosinophil (0.22 vs 0.15), Monocytes (0.72 vs 0.62), Neutrophils (5.53 vs 3.53), Haemoglobin (35.82 vs 29.68), Platelets (292.44 vs 227.22), NLR (2.73 vs 1.71) and PLR (143.34 vs 115.85) except Lymphocytes (2.22 vs 2.25) and Basophils (0.06 vs 0.05). Moreover, when the analysis was done by subgroups of pathological responses, PLR variation was significantly different between pCR and incomplete response (-21.33 vs -76.98) whereas NLR and the rest of the immune populations were no different between subgroups. Conclusions: In our study, NLR is not associated to chemo-immune neo-adjuvant treatment response. Nevertheless, in our cohort a higher decrease on PLR post neo-adjuvant treatment is associated to an incomplete pathological response.

Cisplatin(P)-including triplets versus P-free doublets in the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC): SICOG 0101 randomized trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7103-7103 ◽  
Author(s):  
P. Comella ◽  
S. Palmeri ◽  
G. De Cataldis ◽  
G. Filippelli ◽  
R. Cioffi ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Locally Advanced ◽  
Stage Iv ◽  
Standard Of Care ◽  
Rank Test ◽  
Stage Iiia ◽  
Log Rank Test ◽  
Grade 3 ◽  
Metastatic Sites ◽  
Nsclc Patients

7103 Background: We previously reported that triplets with P-gemcitabine (G) plus vinorelbine (V) (PGV) or paclitaxel (T) (PGT) prolonged the survival (S) of advanced NSCLC patients (pts) in comparison with P-based doublets (PG or PV). Aims of the present study were: (1) to compare (log-rank test) the S of P-based triplets vs P-free doublets, and (2) to compare (Fisher test) safety and response rate (RR) of T- and V-regimens. Methods: A 2x2 factorial design was adopted. Pts aged ≤ 70 years, with PS (ECOG) < 2, inoperable stage IIIA, IIIB, or IV NSCLC were randomly treated with: GV = G 1,000 mg/m2 + V 25 mg/m2 on day (D) 1 and 8; GT = G 1,000 mg/m2 + T 125 mg/m2 on D 1 and 8; PGV = P 50 mg/m2 on D 1 and 8 + GV; PGT = P 50 mg/m2 on D 1 and 8 + GT. In all arms, cycles were repeated Q 3 weeks. Only responder pts after 3 cycles received further chemotherapy (CT). Thoracic RT was delivered after CT to pts with intra-thoracic disease. 330 events were required to have a 90% power to demonstrate (two-sided P < 0.05) a 30% reduction of hazard of death. Results: From April 2001 to December 2005, 431 pts were recruited in the 4 arms. Characteristics in % were well balanced in P-based triplets and P-free doublets: males, 84/91; PS 0, 25/23; squamous cell carcinoma, 38/42; weight loss, 22/29; stage IV, 66/65; CNS metastases, 5/8; ≥ 2 metastatic sites, 29/30. So far, 411 pts were assessed for response: RR of triplets vs doublets was 88/204 (43%) vs 68/207 (33%) (P = 0.020), and of T-based vs V-based regimens was 40% vs 36% (P = 0.218). To date, 313 deaths were registered: median and 1-year S were 10.6 mo. and 41% for pts treated with triplets, and 10.4 mo. and 39% for pts treated with doublets (P = 0.786). Over initial 3 courses, occurrence of grade ≥ 3 toxicity (T vs V, % pts) was: neutropenia, 18% vs 30% (P < 0.004); febrile neutropenia, 4% vs 7%; platelets, 7% vs 12% (P = 0.056); anemia, 5% vs 7%; vomiting, 1% vs 2%; diarrhea, 6% vs 3%; stomatitis, 3% vs 0.5%. Grade ≥ 2 neurotoxicity occurred in 1% of both groups. Conclusions: Activity was significantly higher with P-based triplets, but they did not affect the OS. T-based regimens were equally active and less toxic than V-based regimens. Therefore, the GT regimen may represent a new standard of care for advanced NSCLC pts. No significant financial relationships to disclose.

A fractionated schedule of oral vinorelbine (NVBo) with cisplatin (CDDP) concomitantly with radiotherapy (RT) after induction chemotherapy (CT) in locally advanced (LA) non-small cell lung cancer (NSCLC): Safety and efficacy results of a phase II trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7539-7539
Author(s):  
D. Lerouge ◽  
R. Gervais ◽  
E. Dansin ◽  
C. Dujon ◽  
C. Chouaid ◽  
...  
Keyword(s):  
Disease Control ◽  
Therapeutic Option ◽  
Locally Advanced ◽  
Oral Formulation ◽  
Fixed Dose ◽  
Time To Progression ◽  
Stage Iiia ◽  
Oral Vinorelbine ◽  
Nsclc Patients

7539 Background: NVB+CDDP as induction and concomitant regimen with RT is a recognized treatment in LA NSCLC (Vokes, J Clin Oncol. 2002). The oral formulation of NVB may simplify the administration and a new fractionated schedule may further improve the results during CT-RT. Methods: Non operable stage IIIA-IIIB NSCLC patients (pts) received an induction CT of 2 cycles of NVBiv 25 mg/m2 + CDDP 80 mg/m2 on D1 and NVBo 60mg/m2 on D8 every 3 weeks. Non progressive pts received 2 additional cycles of fixed dose NVBo of 20 mg on D1, D3 and D5, + CDDP 80 mg/m2 on D1 every 3 weeks, combined with a conformal RT at 66 Gy. Results: Between October 05 and May 08, 70 pts were enrolled (68 evaluable for the safety, 64 for response) : 28% stage IIIA, 72% IIIB; 44 % squamous, 30 % adenocarcinoma; 85% male; median age 61 years (range 41;73); median KPS 90%. After induction CT, OR was 42% (PR), Disease Control (DC) = 87%. 4 pts were down-staged and underwent surgery. After CT-RT completion, OR was 55% (CR = 7%), DC = 88%. Main Toxicities (G3–4, % of pts) were: neutropenia (19%), N/V (1%), radic pneumopathy (1%), anorexia (7%). Oesophagitis was recorded in 42% of pts with no G3–4 : G1 (26%), G2 (16%). Conclusions: This new schedule provides a disease control in 88% of pts with 55% OR. Given the optimal tolerance profile of this fractionated administration of NVBo+CDDP, 72% of pts could complete the planned treatment. Furthermore, NVBo taken at home at D3 and D5 reduces the organizational constraints linked to CT-RT. This new scheme offers a well tolerated and efficient therapeutic option in the treatment of non operable IIIA-IIIB NSCLC. Further follow-up is required in order to assess time to progression and survival. [Table: see text]

Management of locally advanced non-small cell lung cancer (NSCLC) at a community hospital: A retrospective analysis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e17506-e17506
Author(s):  
Laura Jane Spranklin ◽  
Jon Willis Heflin ◽  
Alejandro R. Calvo
Keyword(s):  
Performance Status ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Relative Survival ◽  
Concurrent Chemoradiation ◽  
Poor Performance Status ◽  
Stage Iiia ◽  
Unresectable Stage ◽  
Iiia Nsclc ◽  
Nsclc Patients

e17506 Background: The optimal management of stage IIIA NSCLC has not been clearly defined. Much of this controversy is due to the heterogenity of this group. The current standard for unresectable stage IIIA disease is concurrent chemoradiotherapy. In patients with resectable stage IIIA disease however, neoadjuvant treatment followed by surgery provides better outcomes but not a significant survival benefit. Our study analyzed the management of stage IIIA NSCLC patients diagnosed at Kettering Health Network (KHN) and the observed 5-year survival as compared to the current NCCN guidelines and national 5-year relative and observed survival using the SEER database and National Cancer Database statistics. Methods: This retrospective study included all patients treated at KHN for Stage IIIA NSCLC from January 2004 to December 2009. 117 cases were analyzed, 53% female and 47% male. 42% were squamous cell, 28% adenocarcinoma, and the final 30% accounting for the remaining histology. 20 patients were not candidates for therapy due to poor performance status or comorbidity. 37 of the 97 patients under active treatment underwent resection at some point during treatment and 60 patients were deemed unresectable. Results: 68% of individuals with unresectable NSCLC received definitive concurrent chemoradiation, 32% received chemotherapy alone. In regards to resectable stage IIIA, 25% were treated with neoadjuvant therapy. 54% received postoperative therapy. 21% were treated with surgery alone due to multiple factors. The observed 5-year survival was 12.2% as compared to 10% nationally. The SEER data 5-year relative survival from 2001 to 2007 for stage IIIA NSCLC is 14%. Conclusions: In this heterogenous group of patients, treatment provided at KHN was individualized and followed national trends. The majority of unresectable stage IIIA NSCLC patients at KHN received the standard approach of concurrent chemoradiation. In terms of resectable stage IIIA NSCLC, approximately 25% were treated with either neoadjuvant chemotherapy or chemoradiotherapy. Overall, the 5-year survival rate for stage IIIA NSCLC at KHN is comparable to other community hospitals however slightly lower than the national average.

scholarly journals P2.04-10 Biomarkers of Pathological Response on Neo-Adjuvant Chemo-Immunotherapy Treatment for Resectable Stage IIIA NSCLC Patients

2019 ◽  
Vol 14 (10) ◽  
pp. S711
Author(s):  
R. Laza-Briviesca ◽  
A. Cruz-Bermudez ◽  
M. Casarrubios ◽  
E. Nadal ◽  
A. Insa ◽  
...  
Keyword(s):  
Pathological Response ◽  
Stage Iiia ◽  
Iiia Nsclc ◽  
Nsclc Patients

Peripheral blood T-cell receptor immune repertoire characterization of resectable stage IIIA non-small cell lung cancer patients receiving neo-adjuvant chemo-immunotherapy treatment from NADIM study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9041-9041
Author(s):  
Alberto Cruz Bermudez ◽  
Marta Casarrubios ◽  
Raquel Laza Briviesca ◽  
Belen Sierra-Rodero ◽  
Miguel Barquin ◽  
...  
Keyword(s):  
T Cell Receptor ◽  
Peripheral Blood ◽  
Cell Receptor ◽  
Pathological Response ◽  
Stage Iiia ◽  
Immune Repertoire ◽  
Tcr Repertoire ◽  
Response Groups ◽  
Viable Tumour

9041 Background: Characterization of the peripheral blood T-cell receptor (TCR) repertoire has become a novel approach to predict the clinical benefit to anti-PD1/PDL1 therapy. However, there is lack of knowledge about the clinical relevance of TCR repertoire in terms of pathological response and clinical outcomes (PFS and OS) in chemo-immunotherapy. To answer this question we have analysed samples from the NADIM study (NCT03081689), in which resectable stage IIIA NSCLC patients were treated with neoadjuvant chemo-immunotherapy with Nivolumab. Methods: Using ION Torrent-based next-generation sequencing we have analysed TCR repertoire of peripheral blood from 30 patients receiving chemo-immunotherapy. Using 25ng of total RNA from PBMCs, clonal convergence, evenness and diversity were calculated at diagnosis (pre-treatment) and after 3 cycles of Nivolumab plus carboplatin (post-treatment). Regarding pathological responses, patients were classified in 3 groups: complete response (pCR) (0% viable tumour at the resection specimen), mayor response (pMR) ( < 10% viable tumour) and incomplete response (pIR) ( > 10% of viable tumour). At data analysis, PFS and OS median follow-up times were longer than 20 months. Results: No statistically significant differences in TCR repertoire in terms of evenness (p = 0,373), diversity (p = 0,691) or convergence (p = 0,054) between pre- and post-neoadjuvant treatment were observed. Similarly, no significant differences were observed in these metrics between pathological response groups. However, a detailed analysis of the clones showed that the percentage of frequent clones (greater than 0.1%) that increase after neoadjuvant therapy does show differences between the different pathological response groups (pIR vs pMR), being elevated in patients who presented responses greater than 90% (p = 0.0385). Regarding the clinical benefit, having this parameter higher than the median (43,90% in this cohort) is associated with a higher PFS (p = 0.0490) and OS (p = 0.078) using KM Log-rank test. Conclusions: Evenness, Diversity and Convergence derived from immune repertoire analysis do not appear to be clinically useful in the context of neoadjuvant chemo-immunotherapy in lung cancer. However, the detailed analysis of the clones seems promising. The increase of the most frequent clones after treatment seems to be associated to different clinical variables such as pathological response and PFS in these patients. Clinical trial information: NCT03081689.

scholarly journals Blood biomarkers associated to complete pathological response on NSCLC patients treated with neoadjuvant chemoimmunotherapy included in NADIM clinical trial

2021 ◽  
Vol 11 (7) ◽  
Author(s):  
Raquel Laza‐Briviesca ◽  
Alberto Cruz‐Bermúdez ◽  
Ernest Nadal ◽  
Amelia Insa ◽  
María del Rosario García‐Campelo ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Pathological Response ◽  
Blood Biomarkers ◽  
Complete Pathological Response ◽  
Nsclc Patients

scholarly journals Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio and Their Role as Predictors of Disease Severity of Coronavirus Disease 2019 (COVID-19)

2021 ◽  
Author(s):  
Rohit Jain ◽  
Arun Gopal ◽  
Basant Kumar Pathak ◽  
Sourya Sourabh Mohakuda ◽  
TVSVGK Tilak ◽  
...  
Keyword(s):  
Disease Severity ◽  
Complete Blood Count ◽  
Wide Spectrum ◽  
Statistical Significance ◽  
Severe Disease ◽  
Neutrophil To Lymphocyte Ratio ◽  
Screening Tools ◽  
Platelet To Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Time Of Admission

Abstract Context Due to the wide spectrum of clinical illness in coronavirus disease 2019 (COVID-19) patients, it is important to stratify patients into severe and nonsevere categories. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been evaluated rapidly by a few studies worldwide for its association with severe disease, but practically none have been conducted in the Indian population. This study was undertaken to examine the role of NLR and PLR in predicting severe disease in Indian patients. Objectives The objective was to study the association of NLR and PLR observed at the time of admission with maximum disease severity during hospitalization and to study their role in predicting disease severity. Material and Methods A total of 229 COVID-19 patients were admitted at the center during the study period. After applying inclusion and exclusion criteria, 191 patients were included in the study. The demographic, clinical, and laboratory (complete blood count, NLR, and PLR) data of all patients were obtained at the time of admission. Maximum disease severity of all patients was assessed during hospitalization. Statistical Analysis Chi-square and Mann–Whitney U tests were used to assess statistical significance. Receiver operating characteristic curve (ROC) was plotted for NLR and PLR to estimate the cutoff values and sensitivity and specificity using Youden’s index for predicting severe disease. Logistic regression analysis was used to estimate the odds ratios (OR) and 95% confidence intervals. Results Mean NLR and PLR were significantly higher in severe patients (NLR = 7.41; PLR = 204) compared with nonsevere patients (NLR = 3.30; PLR = 121). ROC analysis showed that NLR, in comparison to PLR, had a higher area under the curve (AUC) of 0.779, with a larger OR of 1.237 and cutoff of 4.1, and showed 69% sensitivity and 78% specificity in predicting severe disease. Cut off for PLR was 115.3, which showed 79% sensitivity and 62% specificity in predicting severe disease. Conclusion NLR and PLR, both showing acceptable AUCs, can be used as screening tools to predict disease severity. However, NLR was a better predictor of disease severity.

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