Early prediction of tumour-response to radiotherapy in NSCLC patients

2021 ◽  
Author(s):  
Lameck Mbangula Amugongo ◽  
Eliana Vasquez Osorio ◽  
Andrew Frederick Green ◽  
David Cobben ◽  
Marcel van Herk ◽  
...  
Keyword(s):  
Tumour Response ◽  
Early Prediction ◽  
Nsclc Patients

PO-1569: Early prediction of tumour-response to radiotherapy in NSCLC patients.

2020 ◽  
Vol 152 ◽  
pp. S850
Author(s):  
L.M. Amugongo ◽  
E. Vasquez Osorio ◽  
A. Green ◽  
D. Cobben ◽  
M. Van Herk ◽  
...  
Keyword(s):  
Tumour Response ◽  
Early Prediction ◽  
Nsclc Patients

scholarly journals POS0293 TRheuMa REGISTRY PROVIDES FIRST EVIDENCE OF DIFFERENT COURSE OF RHEUMATIC IMMUNE-RELATED ADVERSE EVENTS AND TUMOUR RESPONSE RATES DEPENDING ON THE TUMOUR ENTITY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 372.3-372
Author(s):  
L. Diekmann ◽  
L. Daniello ◽  
J. Kunz ◽  
J. Leipe ◽  
H. M. Lorenz ◽  
...  
Keyword(s):  
Tumour Response ◽  
Research Support ◽  
Grant Funding ◽  
Real World Data ◽  
Underlying Malignancy ◽  
Tumour Entity ◽  
Melanoma Patients ◽  
Funding Institution ◽  
Nsclc Patients ◽  
Research Grant

Background:Rheumatic immune-related adverse events (irAE) are associated with a better tumour response to immune checkpoint inhibitors (ICI). In contrast to other irAEs, their potentially chronic course may require long-term immunosuppressive treatment.Objectives:Our registry-based study analyses real-world data on the characteristics and outcome of rheumatic irAEs and underlying malignancy. Herein, we present first evidence that these parameters and the optimal clinical management may differ depending on the tumour entity.Methods:The TRheuMa registry is a prospective long-term observational study of a patient cohort suffering from rheumatic side effects of cancer therapies with focus on ICI. It is part of the MalheuR project initiated in July 2018 at the University Hospital Heidelberg to explore interrelations of malignancies and RMDs.Results:64 patients were recruited due to a rheumatic irAE under ICI treatment (nivolumab n=30, pembrolizumab n=33, ipilimumab n=12, PD-L1i n=5, ipi/nivo n=10) with a follow-up of up to 30 months. Of these, 47% had NSCLC and 41% melanoma. In local cohorts of patients receiving ICI, 4% of NSCLC (n total=888) and 13% of melanoma (n total=195) developed a rheumatic irAE. 7% of NSCLC and 23% of melanoma patients experienced a flare of a pre-existing RMD. De novo irAE mostly resembled phenotypes of spondyloarthritis both in NSCLC (43%) as well as in melanoma patients (33%). CRP levels were increased in 83% of NSCLC and 71% of melanoma patients. Almost all irAE patients showed autoantibody negativity and signs of inflammation in ultrasound examination (96%). Comparison of best responses to treatment in patients with and without rheumatic irAE in melanoma and without any irAE in NSCLC patients were as following: Complete remission (CR) in 48% vs. 4% of melanoma patients and partial remission (PR) in 68% vs. 41% of NSCLC patients. In accordance with our severity-based treatment algorithm, 25% of the melanoma patients in CR and 16% of the NSCLC patients in PR needed add-on DMARDs for sufficient irAE-treatment. ICI-treatment was discontinued in 7 cases (17% NSCLC, 8% melanoma)Conclusion:Prospective real-world data from the TRheuMa-registry provide first evidence that rheumatic irAE have distinct characteristics depending on the underlying malignancy. Oncological outcome was better with rheumatic irAE than in their absence and this effect was more pronounced in melanoma patients despite a larger use of immunosuppressants for irAE-treatment.Disclosure of Interests:Leonore Diekmann: None declared, Lea Daniello: None declared, Julia Kunz: None declared, Jan Leipe Consultant of: Pfizer; Novartis; Honoraria (self), Abbvie; Astra Zeneca; BMS; Celgene; Hospira; Janssen-Cilag; Gilead; LEO Pharma; Lilly; MSD; Roche; Sanofi; UCB., Grant/research support from: Research grant/Funding (self): Pfizer; Novartis; Honoraria (self), Hanns-Martin Lorenz Consultant of: Abbvie; BMS; MSD; Pfizer; Celgene; Roche; Chugai; Medac; GSK; Honoraria (self), Novartis; UCB; Janssen-Cilag; Astra Zeneca; Lilly, Grant/research support from: Research grant/Funding (institution): Abbvie; BMS; MSD; Pfizer; Celgene; Roche; Chugai; Medac; GSK; Honoraria (self), Research grant/Funding (institution), Novartis; UCB; Janssen-Cilag; Astra Zeneca; Lilly; Research grant/Funding (institution): Baxter; SOBI; Biogen; Actelion; Mundipharma; Bayer Vital; Octapharm; Sanofi; Hexal; Thermo Fischer; Shire., Jessica Hassel Consultant of: MDS; Honoraria (self): Roche; Novartis; Pierre Fabre., Grant/research support from: BMS; Honoraria (self), Karin Jordan Consultant of: Advisory/Consultancy: Amgen; Merck; MSD; Riemser; Helsinn; Tesaro; Kreussler; Voluntis; Pfizer; Pomme-med; Hexal., Petros Christopoulos Consultant of: advisory board/lecture fees from AstraZeneca, Boehringer Ingelheim, Chugai, Novartis, Pfizer, Roche, Takeda., Grant/research support from: research funding from AstraZeneca, Novartis, Roche, Takeda, Karolina Benesova Grant/research support from: Foundations and Awards” commission of the University of Heidelberg: University of Heidelberg; AbbVie; Novartis; Rheumaliga Baden-Württemberg e.V

scholarly journals Early Prediction of Response to Tyrosine Kinase Inhibitors by Quantification of EGFR Mutations in Plasma of NSCLC Patients

2015 ◽  
Vol 10 (10) ◽  
pp. 1437-1443 ◽  
Author(s):  
Antonio Marchetti ◽  
John F. Palma ◽  
Lara Felicioni ◽  
Tommaso M. De Pas ◽  
Rita Chiari ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Egfr Mutations ◽  
Early Prediction ◽  
Prediction Of Response ◽  
Nsclc Patients

scholarly journals Early prediction of pathologic response to neoadjuvant treatment of breast cancer: use of a cell-loss metric based on serum thymidine kinase 1 and tumour volume

2019 ◽  
Author(s):  
Bernhard Tribukait ◽  
Jonas Bergh ◽  
Thomas Hatschek
Keyword(s):  
Breast Cancer ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Tumour Response ◽  
Cell Loss ◽  
Tumour Volume ◽  
Tumour Cells ◽  
Early Prediction ◽  
Cytotoxic Treatment ◽  
A Cell

Abstract Background After neoadjuvant chemotherapy of breast cancer pathologic complete response (pCR) indicates a favourable prognosis. Among non-selected patients, pCR is, however, achieved in only 10-30%. Early evaluation of tumour response to treatment would facilitate individualized therapy, with ineffective chemotherapy interrupted or changed. The methodology for this purpose is still limited. Tumour imaging and analysis of macromolecules, released from disrupted tumour cells are principle alternatives.Objective To investigate whether a metric of cell-loss, defined as the ratio between serum concentration of thymidine kinase1 (sTK1) (ng x ml -1 ) and tumour volume (cm 3 ), can be used in the early prediction of pathologic response.Methods 104 women with localized breast cancer received neoadjuvant epirubicin/docetaxel in 6 cycles, supplemented with bevacizumab in cycles 3-6. The cell-loss metric was established at baseline (n=104), prior to cycle 2 (n=57) and 48h after cycle 2 (n=104). The performance of the metric was evaluated by association with pathologic tumour response at surgery ̴ 16 weeks later.Results Means for the three points of the metric were 0.007, 0.084 and 0.107 units. For each individual, the baseline value was subtracted from the 48-h value and patients were grouped into quartiles. Means of these were: 0.002, 0.011, 0.030 and 0.357 units. The cell-loss metric was associated with the pCR in the quartiles: 11%, 11%, 23% and 46% (p=0.01). In the 80 patients with remaining tumour, pathologic tumour size was inversely related to the metric (p=0.002). In the subgroup of 57 patients, data obtained prior to the 2nd cycle indicated a higher predictive value than the data obtained 48h after this treatment.Conclusion A cell-loss metric, established by combining serum levels of TK1, released from disrupted tumour cells, and tumour volume, reveal tumour response early during neoadjuvant treatment. The metric appears to reflect a tumour property that differ greatly between patients and determines the sensitivity to cytotoxic treatment. The findings point to the significance of cell loss for the growth rate of tumours. The metric should be considered in personalized oncology and in the evaluation of new therapeutic modalities.

Excision repair cross complementation group 1 (ERCC-1) gene polymorphisms and response to nivolumab in advanced non-small cell lung cancer (NSCLC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3032-3032 ◽  
Author(s):  
Marco M. Aiello ◽  
Paolo Giovanni Vigneri ◽  
Paolo Bruzzi ◽  
Francesco Verderame ◽  
Sabrina Paratore ◽  
...  
Keyword(s):  
Genetic Instability ◽  
Excision Repair ◽  
Tumour Response ◽  
Stage Iiib ◽  
Disease Stage ◽  
Clinical Activity ◽  
Nucleotide Polymorphisms ◽  
Wild Type ◽  
Cell Reactivity ◽  
Nsclc Patients

3032 Background: Anti PD1 antibodies showed significant clinical activity in different cancer types. Recently, it was observed that cancers with higher somatic mutation burden, as tumors with genome instability due to DNA repair defects, develop more elevated anti PD1 induced neoantigen specific T cell reactivity which results into increased susceptibility to PD1 blockade. We hypothesize that NSCLC pts with single nucleotide polymorphisms (SNPs) of the ERCC-1 gene, a key enzyme of DNA nucleotide excision repair pathway, may be more responsive to PD-1 blockade due to their genetic instability. Methods: We evaluated the rs11615 and rs3212986 ERCC1 SNPs by pyrosequencing analysis on tumor DNA of stage IIIb-IV previously treated NSCLC patients receiving Nivolumab (Nivo) 3 mg/kg q2w. To be eligible for this study, pts had to have a complete record of clinical and radiological parameters. Objective tumour response was assessed according to RECIST 1.1 criteria. Results: Between Jul 2015 and Jan 2016, 45 NSCLC pts received Nivo. Pts characteristics were as follows: M/F = 37/8; median age (range) = 64 (38-80); ECOG PS, 0/1/2 = 33/9/3; Stage IIIb/IV = 8/37; sqNSCLC/non sq NSCLC = 11/34; current-former smokers/non-smokers = 40/5; EGFR status, mutant/wildtype/unknown = 4/35/6; median cycles (range) = 12 (1-28). Only two pts presented the rs11615 SNP. 16 pts were positive for the rs3212986 SNP. ORR for all pts was 26.6% (95% CI, 10 to 47). The ORR was significantly higher in NSCLC pts positive for the rs3212986 SNP than for wild-type NSCLC patients (62.5% vs. 6.9%. p = 0.0001). For all pts median PFS was 4.3 mos (95% CI, 1.2 to 7.4)and median OS not-reached. Among pts positive for the rs3212986 SNP, median PFS and OS were 8.2 mos and not-reached respectively. In contrast wild-type patients presented a median PFS of 3.1 mos (HR = 0.21 95% CI, 0.07 to 0.57; p = 0.02) and a median OS of 6.5 mos (HR = 0,403 95% CI = 0,131-1,237 p = 0.11). Multivariate analyses confirmed the effect of rs3212986 SNP after adjustment for age, PS, sex and disease stage for PFS. Conclusions: This study suggests that genetic instability due to tumor ERCC1 SNPs in advanced NSCLC pts may be of value to predict clinical benefit from Nivo.

scholarly journals Early prediction of pathologic response to neoadjuvant treatment of breast cancer: use of a cell-loss metric based on serum thymidine kinase 1 and tumour volume

2020 ◽  
Author(s):  
Bernhard Tribukait
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Treatment ◽  
Tumour Response ◽  
Cell Loss ◽  
Tumour Volume ◽  
Pathologic Response ◽  
Tumour Cells ◽  
Early Prediction ◽  
Cytotoxic Treatment ◽  
A Cell

Abstract Background: After neoadjuvant chemotherapy of breast cancer pathologic complete response (pCR) indicates a favorable prognosis. Among non-selected patients, pCR is, however, achieved in only 10-30%. Early evaluation of tumour response to treatment would facilitate individualized therapy, with ineffective chemotherapy interrupted or changed. The methodology for this purpose is still limited. Tumour imaging and analysis of macromolecules, released from disrupted tumour cells, are principal alternatives. Objective: To investigate whether a metric of cell-loss, defined as the ratio between serum concentration of thymidine kinase1 (sTK1, ng x ml-1) and tumour volume, can be used for early prediction of pathologic response. Methods: 104 women with localized breast cancer received neoadjuvant epirubicin/docetaxel in 6 cycles, supplemented with bevacizumab in cycles 3-6. The cell-loss metric was established at baseline (n=104), 48h after cycle 2 (n=104) and prior to cycle 2 (n=57). The performance of the metric was evaluated by association with pathologic tumour response at surgery 4 months later. Results: Treatment caused a rise in sTK1, a reduction in tumour volume and a marked increase in the cell-loss metric. Patients were subdivided into quartiles according to the baseline cell-loss metric. For these groups, baseline means were 0.0016, 0.0042, 0.0062, 0.0178 units. After subtraction of baselines, means for the quartiles 48h after treatment 2 were 0.002, 0.011, 0.030 and 0.357 units. pCR was achieved in 24/104, their distribution in the quartiles (11%, 11%, 23% and 46%) differed significantly (p=0.01). In 80 patients with remaining tumour, tumour size was inversely related to the metric (p=0.002). In 57 patients studied before treatment 2, positive and negative predictive values of the metric were 77.8% and 83.3%, compared to 40.5% and 88.7% 48h after treatment 2. Conclusion: A cell-loss metric, based on serum levels of TK1, released from disrupted tumour cells, and tumour volume, reveal tumour response early during neoadjuvant treatment. The metric reflect tumour properties that differ greatly between patients and determine the sensitivity to cytotoxic treatment. The findings point to the significance of cell loss for tumour growth rate. The metric should be considered in personalized oncology and in the evaluation of new therapeutic modalities.

PO-0900: Evaluating tumour response of NSCLC patients with FDG-PET: potential for treatment individualisation

2014 ◽  
Vol 111 ◽  
pp. S105
Author(s):  
I. Toma-Dasu ◽  
J. Uhrdin ◽  
A. Dasu ◽  
S. Carvalho ◽  
W. Van Elmpt ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Tumour Response ◽  
Nsclc Patients

scholarly journals Early prediction of pathologic response to neoadjuvant treatment of breast cancer: use of a cell-loss metric based on serum thymidine kinase 1 and tumour volume

2020 ◽  
Author(s):  
Bernhard Tribukait
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Treatment ◽  
Tumour Response ◽  
Cell Loss ◽  
Tumour Volume ◽  
Tumour Cells ◽  
Early Prediction ◽  
Predictive Values ◽  
Cytotoxic Treatment ◽  
A Cell

Abstract Background: After neoadjuvant chemotherapy of breast cancer pathologic complete response (pCR) indicates a favorable prognosis. Among non-selected patients, pCR is, however, achieved in only 10-30%. Early evaluation of tumour response to treatment would facilitate individualized therapy, with ineffective chemotherapy interrupted or changed. The methodology for this purpose is still limited. Tumour imaging and analysis of macromolecules, released from disrupted tumour cells, are principal alternatives.Objective: To investigate whether a metric of cell-loss, defined as the ratio between serum concentration of thymidine kinase1 (sTK1, ng x ml-1) and tumour volume, can be used for early prediction of pathologic response.Methods: 104 women with localized breast cancer received neoadjuvant epirubicin/docetaxel in 6 cycles, supplemented with bevacizumab in cycles 3-6. The cell-loss metric was established at baseline (n=104), 48h after cycle 2 (n=104) and prior to cycle 2 (n=57). The performance of the metric was evaluated by association with pathologic tumour response at surgery 4 months later.Results: Treatment caused a rise in sTK1, a reduction in tumour volume and a marked increase in the cell-loss metric. Patients were subdivided into quartiles according to the baseline cell-loss metric. For these groups, baseline means were 0.0016, 0.0042, 0.0062, 0.0178 units. After subtraction of baselines, means for the quartiles 48h after treatment 2 were 0.002, 0.011, 0.030 and 0.357 units. pCR was achieved in 24/104, their distribution in the quartiles (11%, 11%, 23% and 46%) differed significantly (p=0.01). In 80 patients with remaining tumour, tumour size was inversely related to the metric (p=0.002). In 57 patients studied before treatment 2, positive and negative predictive values of the metric were 77.8% and 83.3%, compared to 40.5% and 88.7% 48h after treatment 2.Conclusion: A cell-loss metric, based on serum levels of TK1, released from disrupted tumour cells, and tumour volume, reveal tumour response early during neoadjuvant treatment. The metric reflect tumour properties that differ greatly between patients and determine the sensitivity to cytotoxic treatment. The findings point to the significance of cell loss for tumour growth rate. The metric should be considered in personalized oncology and in the evaluation of new therapeutic modalities.Trial registration: PROMIX (Clinical Trials.gov NCT000957125).https://clinicaltrials.gov/ct2/show/NCT00957125

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