There are currently no good indicators of which patients with cancer will respond or not to immunotherapy. Novel computational analysis of computed tomography scans (CT) (i.e. radiomics) provides ...information about the tumour-infiltrating CD8 and predict response to immunotherapy. We aim to validate in an external cohort the VHIO CT-radiomics signature and to develop a combined radiomics-clinical signature that predicts the response to immune checkpoint inhibitors in patients with advanced solid tumours.
The VHIO CT-radiomics signature was developed in a population of 115 consecutive patients treated with immune checkpoint inhibitors (programmed-death protein 1 PD-1 or programmed-death ligand 1 PD-L1 inhibitors) monotherapy in phase I clinical trials (Cohort 1). The external validation included 62 consecutive patients with urinary bladder cancer treated with anti-PD-1 or PD-L1 monotherapy (Cohort 2). From the baseline CT, a target lesion per patient was delineated. Radiomics variables of first-order, shape, and texture were extracted. An elastic-net model combining radiomics and clinical features was implemented. The association between the radiomics score and changes in tumour shrinkage was assessed using Mann-Whitney analysis.
In the Cohort 1 the CT-radiomics signature associates with response (area under the curve AUC of 0.81, p-value=2.74x10-5 and 0.72, p=0.001 in the training and internal validation sets, respectively). In the external validation set (Cohort 2), the CT-radiomics signature predicts a response with an AUC of and 0.76 (p=0.001). The model combining radiomics and clinical features has an AUC of 0.84 (p-value=5.04x10-9) for response prediction. Tumour homogeneity, hypodensity and spherical shape together with high lymphocytes and albumin and low neutrophils, corresponding to a high clinical-radiomics signature score, are indicators of tumour response. A higher CT-radiomics signature score is associated with a larger tumour shrinkage (p<0.05).
CT-radiomics signature at baseline predicts the response to immune checkpoint inhibitors. Integrating radiomics and clinical data improved the response prediction capacity.
The authors.
This study was supported by the Banco Bilbao Vizcaya Argentaria and Fundacio La Caixa. RPL is supported by a Prostate Cancer Foundation Young Investigator award.
J. Martín Liberal: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pierre Fabre; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bristol-Myers Squibb. R. Morales Barrera: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Sanofi Aventis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Merck Sharp & Dohme; Advisory / Consultancy, Speaker Bureau / Expert testimony: Asofarm; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Astellas; Travel / Accommodation / Expenses: Pharmacyclics; Travel / Accommodation / Expenses: Clovis Oncology; Travel / Accommodation / Expenses: Lilly. E. Elez: Travel / Accommodation / Expenses: Merck; Travel / Accommodation / Expenses: Sanofi; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Servier and Amge ; Research grant / Funding (self): Merck. E. Felip: Honoraria (self): AbbVie; Honoraria (self): AstraZeneca; Honoraria (self): Blue Print Medicines; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Celgene; Honoraria (self): Eli Lilly; Honoraria (self): Guardant Health; Honoraria (self): Janssen; Honoraria (self): Medscape; Honoraria (self): Merck KGaA; Honoraria (self): MSD; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Takeda; Honoraria (self): Touchtime. J. Tabernero: Advisory / Consultancy: Array Biopharma; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Bayer; Advisory / Consultancy: BeiGene; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Chugai; Advisory / Consultancy: Genentech, Inc; Advisory / Consultancy: Genmab A/S; Advisory / Consultancy: Halozyme; Advisory / Consultancy: Imugene Limited; Advisory / Consultancy: Inflection Biosciences Limited; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Kura Oncology; Advisory / Consultancy: Lilly; Advisory / Consultancy: MSD; Advisory / Consultancy: Menarini; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Merus; Advisory / Consultancy: Molecular Partners; Advisory / Consultancy: Novartis; Advisory / Consultancy: Peptomyc; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Pharmacyclics; Advisory / Consultancy: ProteoDesign SL; Advisory / Consultancy: F. Hoffmann-La Roche Ltd; Advisory / Consultancy: Sanofi; Advisory / Consultancy: SeaGen; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: Servier; Advisory / Consultancy: Symphogen; Advisory / Consultancy: Taiho; Advisory / Consultancy: VCN Biosciences; Advisory / Consultancy: Biocartis; Advisory / Consultancy: Foundation Medicine; Advisory / Consultancy: HalioDX SAS. R. Dienstmann: Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Symphogen; Speaker Bureau / Expert testimony: Ipsen; Speaker Bureau / Expert testimony: Amgen; Speaker Bureau / Expert testimony: Sanofi; Speaker Bureau / Expert testimony: MSD; Speaker Bureau / Expert testimony: Servier; Research grant / Funding (self): Merck. All other authors have declared no conflicts of interest.
Abstract Background The available prognostic models for overall survival (OS) in patients with metastatic urothelial carcinoma (UC) have been derived from clinical trial populations of ...cisplatin-treated patients. Objective To develop a new model based on real-world patients. Design, setting, and participants Individual patient-level data from 29 centers were collected, including metastatic UC and first-line cisplatin- or carboplatin-based chemotherapy administered between January 2006 and January 2011. Intervention First-line, platinum-based, combination chemotherapy. Outcome measurements and statistical analysis The population was randomly split into a development and a validation cohort. Generalized boosted regression modelling was used to screen out irrelevant variables and address multivariable analyses. Two nomograms were built to estimate OS probability, the first based on baseline factors and platinum agent, the second incorporating objective response (OR). The performance of the above nomograms and that of other available models was assessed. We plotted decision curves to evaluate the clinical usefulness of the two nomograms. Results and limitations A total of 1020 patients were analyzed (development: 687, validation: 333). In a platinum-stratified Cox model, significant variables for OS were performance status ( p < 0.001), white blood cell count ( p = 0.013), body mass index ( p = 0.003), ethnicity ( p = 0.012), lung, liver, or bone metastases ( p < 0.001), and prior perioperative chemotherapy ( p = 0.012). The c-index was 0.660. The distribution of the nomogram scores was associated with OR ( p < 0.001), and incorporating OR into the model further improved the c-index in the validation cohort (0.670). Conclusions We developed and validated two nomograms for OS to be used before and after completion of first-line chemotherapy for metastatic UC. Patient summary We proposed two models for estimating overall survival of patients with metastatic urothelial carcinoma receiving first-line, platinum-based chemotherapy. These nomograms have been developed on real-world patients who were treated outside of clinical trials and may be used irrespective of the chemotherapeutic platinum agent used.
Background: Hematological side effects are not generally expected due to radiotherapy involving limited radiation fields; however, patients with squamous cell carcinoma of the head and neck (SCCH&N) ...receiving radiation therapy frequently have chronic intraoral infections. Xerostomia has been implicated as a cause of it, but local or systemic immune alterations are not usually considered.
Methods: With the purpose of evaluating the impact of radiotherapy treatment to different anatomic sites on immune function, 70 patients were evaluated during and after radiotherapy: 50 cases with SCCH&N, 10 with squamous cell carcinoma of the uterine cervix (SCCUC) and 10 patients with central nervous system tumors (CNS). We analyzed lymphocyte counts and T-cell subsets, and over time, their association with the presence of intracellular infections and disease-free survival.
Results: Severe lymphopenia was observed in patients with SCCUC and SCCH&N by the fifth week of treatment. Patients with CNS tumors developed mild lymphopenia. In patients with SCCH&N and UC, lower counts were seen in B cells and total T lymphocyte counts including both CD4
+ and CD8
+ cell subsets. The patients with SCCUC recovered lymphocyte counts by the 24th month but T-cell subsets lagged behind. None of the SCCH&N patients had fully recovered by 60 months of follow-up. Recurrence correlates with low lymphocyte counts.
Discussion: This work highlights the vulnerability of the head and neck area to the impact of radiotherapy as a reservoir of lymphoid cells. The possibility of recovery as a consequence of thymopoiesis and/or peripheral clonal expansion may limit the antigen-specific recognition of relevant tumor or microbial antigens and cause significant and prolonged immune alterations that may impact long-term survival.
Purpose
To evaluate the efficacy and toxicity of docetaxel regimen as second-line after failure of a platinum-based chemotherapy.
Methods
Between May 2005 and June 2008, we retrospectively analyzed ...the data of 22 patients who had evidence of disease progression after one prior platinum-based regimen for metastatic urothelial carcinoma. Patients were treated with two different docetaxel dose schedules: (1) docetaxel 60 mg/m
2
every 21 days for unfit patients or (2) docetaxel 75 mg/m
2
every 21 days for fit patients.
Results
Median number of docetaxel cycles was three. Overall disease control rate was 18 %. Of the 22 patients, no patient achieved complete or partial response and four patients had stable disease. Median progression-free survival was 1.67 months and median overall survival was 3.12 months. Neutropenia was the most common adverse event.
Conclusions
This study identifies that docetaxel as second-line chemotherapy has low activity and was associated with significant toxicity.
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