Enhanced liver fibrosis score is stable after withdrawal in patients with heavy alcohol consumption: A pilot study.

BACKGROUND: Enhanced liver fibrosis (ELF) score is an accurate, noninvasive test for assessing the severity of liver fibrosis in chronic liver disease, including alcohol-related liver disease. However, whether the ELF score changes during alcohol withdrawal is unknown. This pilot study assessed changes in the ELF score during withdrawal in patients with a history of excessive alcohol intake. METHODS: In this prospective study, ELF was performed on day 0 (D0, at the beginning of hospitalization), at day 7 (D7, on discharge from hospital), and at follow-up visits on days 30 (D30) and 90 (D90). Transient elastography (TE) was also assessed on days 4 (D4) and D30. RESULTS: The study included 35 patients (71% male) with a mean alcohol intake of 139 g/day. On D30 and D90, 8 and 13 patients had resumed alcohol consumption (mean intake of 90 and 80 g/day, respectively). In patients who remained abstinent, the mean ELF score was 8.93 on D0, 9.14 on D30 (p = 0.32), and 9.27 on D90 (p = 0.14). In patients who resumed alcohol, mean ELF score was 9.7 on D0, 10.05 on D30 (p = 0.09), and 9.71 on D90 (p = 0.12). ELF score was comparable over the first months after withdrawal, although there was a slight increase in the first week (mean ELF score increased from 9.24 on D0 to 9.74 on D7, p < 0.001). Mean TE value was 7.9 kPa on D4 and 8.1 kPa on D30 (p = 0.84) in patients who resumed alcohol consumption, and 8.3 and 7.5 kPa (p = 0.03) on D4 and D30, respectively, in abstinent patients. CONCLUSION: The ELF score is stable during the first months after withdrawal and thus appears to be a useful tool to assess liver fibrosis or cirrhosis in this setting. Nevertheless, because in the first week there is a transient increase in ELF score, caution in interpretation is warranted.

Molecular and nutritional markers in head and neck cancer.

PURPOSE OF REVIEW: There is still a need of biomarkers in the induction and neoadjuvant settings for squamous cell carcinoma of the head and neck (SCCHN). The objective of this concise review article is to give an overview on both predictive and prognostic biomarkers potentially useful for the management of SCCHN. RECENT FINDINGS: Human papilloma virus (HPV) positivity translated by the presence of the protein indicator p16 is synonymous of favorable prognosis SCCHN. However, there is some disparity for disease evolution among p16 positive SCCHN. A lack of correlation between immunohistochemistry (IHC) and precise quantification of active epidermal growth factor receptors (EGFRs) may explain the absence of link between EGFR expression performed by IHC and response to EGFR targeting therapies reported in SCCHN. Circulating tumor cells (CTCs) have the property to share the main somatic mutations and genetic rearrangements with the primary tumors. A particular potential interest lies on the possibility to predict patient outcome based on a single-CTC analysis. SUMMARY: This short review indicates that key biological marker reflecting disease outcome is not yet emerging for a clinical use in SCCHN. Hopes can be put into the so-called liquid biopsies incorporating circulating tumor cells and circulating tumor DNA.

Very accelerated partial breast irradiation in 1 or 2 days: Late toxicity and early oncological outcome of the GEC-ESTRO VAPBI cohort.

PURPOSE: To analyze late toxicity after very accelerated partial breast irradiation (VAPBI) for low-risk breast cancer. MATERIALS: Methods: In this retrospective, observational, international multicenter study (HDH F20220713143949), patients with low-risk breast cancer underwent lumpectomy + vAPBI (high-dose rate multicatheter interstitial brachytherapy-MIBT). VAPBI was performed with 4(4x6.2 Gy/2d), 3(3x7.45 Gy/2d) or 1 fraction (1x16Gy or 1x18Gy/1d). Primary endpoint was late toxicity. Secondary endpoints were cumulative incidence of breast cancer local relapse (LR) and distant metastatic relapse (DMR) and specific (SS) and overall (OS) survivals. Prognostic factors for late toxicity were analyzed. RESULTS: From 01/2012 to 06/2022, 516 pts with early breast cancer were enrolled. Median follow-up was 44 months [95 %CI 39-46]. Median age was 71 years [40-100]. Median tumor size was 12 mm [1-35]. VAPBI delivered 1, 3 and 4 fractions for 205pts (39.7 %), 167pts (32.4 %) and 144pts (28 %) respectively. 221 late toxicity events were observed in 168pts (32.6 %) (Fibrosis, dyschromia, pain and telangiectasia). Grade 2 and 3 late toxicities were observed in 7.2 and 0.6 % respectively (no G4) with no difference between 1 and ≥ 2 treatment days. CTV > 50 cc (p = 0.007) and V150 > 40 % (p = 0.027) were prognostic factors for G ≥ 2 late toxicity. Four-year cumulative incidence rates of LR and DMR were 2 % [95 %CI 0-3] and 1 % [95 %CI 0-2] respectively. CONCLUSIONS: VAPBI based on 1 or ≥ 2 days of MIBT represents an attractive de-escalation of irradiation approach for low-risk breast cancer. Late toxicity profile appears acceptable while early oncological outcome shows encouraging local control. Longer follow-up is warranted in order to confirm these preliminary results.

Short course radiotherapy versus radiochemotherapy for locally advanced rectal cancers in the elderly (UNICANCER PRODIGE 42/GERICO 12 study): Quality of life and comprehensive geriatric assessment.

BACKGROUND: The results of the PRODIGE 42/GERICO 12 study showed that short course radiotherapy had a better tolerance profile than radiochemotherapy, with comparable oncological results. We have included Quality of Life analyses and oncogeriatric evaluations in this study. PATIENTS AND METHODS: In all, 101 patients ≥75 years of age with resectable T3-T4 rectal adenocarcinoma less than 12 cm from the anal margin received short course radiotherapy (5X5 Gy in one week) or radiochemotherapy (50 Gy, 2 y/f and capecitabine 800 mg/m2, 5 days/week) with delayed surgery (7 weeks ± 1) in both groups. The Quality of Life analyses (EORTC QLQ C-30 et ELD14) were conducted upon inclusion, pre-operatively, at 3, 6 and 12 months post-op, together with the oncogeriatric evaluations, including an evaluation of the IADL and ADL scores, walking speed, GDS15, MMSE, MNA. RESULTS: We did not highlight any statistical difference for the global EORTC QLQ-C30 score; several factors are statistically in favor of the short course radiotherapy group at 3 months post-op (cognitive functions, fatigue, appetite). In the case of the ELD14 score, the disease burden is perceived as more negative at 3, 6 and 12 months postop in the radiochemotherapy group. The IADL score deteriorated in 44.8 % of the radiochemotherapy group and 14.8 % of the radiotherapy group (p = 0.032); similarly, the GDS15 depression score was better preserved in the short course radiotherapy group (p = 0.05). An analysis of the other scores: ADL, walking speed, MNA, MMSE did not highlight any statistical difference. CONCLUSION: Short course radiotherapy achieves better results in terms of Quality of Life and preservation of autonomy in patients aged ≥75 treated for locally advanced rectal cancer.

Artificial Intelligence and Anticancer Drug Development-Keep a Cool Head.

Artificial intelligence (AI) is progressively spreading through the world of health, particularly in the field of oncology. AI offers new, exciting perspectives in drug development as toxicity and efficacy can be predicted from computer-designed active molecular structures. AI-based in silico clinical trials are still at their inception in oncology but their wider use is eagerly awaited as they should markedly reduce durations and costs. Health authorities cannot neglect this new paradigm in drug development and should take the requisite measures to include AI as a new pillar in conducting clinical research in oncology.

Salvage brachytherapy for second ipsilateral breast tumor event: Relating dosimetric analysis to late side effects.

PURPOSE: For second ipsilateral breast tumor event (2ndIBTE), conservative treatment (CT) involving wide local excision plus accelerated partial breast reirradiation (APBrI) is increasingly used as an alternative to mastectomy. This study investigates the impact of APBrI technique and multicatheter interstitial high dose-rate brachytherapy (MIB) dosimetry parameters on toxicity and survival in patients with 2ndIBTE. MATERIALS-METHODS: Data from patients with 2ndIBTE treated with CT, were analyzed. Inclusion criteria specified 2ndIBTE occurring at least one year after 1st CT for primary breast cancer. Treatment details and dosimetry parameters were recorded. Primary endpoint was late toxicity. Secondary endpoints were late toxicity prognostic factors analysis and oncological outcome. RESULTS: From 07/2005 and 07/2023, 201 patients (pts) received 2nd CT. With a median follow-up of 49.6 months (44.9-59.5), tumor size was less than 2 cm (88.1%), with estrogen receptor positive (92.7%). Patients were low (63.7%) or intermediate (29.8%) GEC-ESTRO APBI risk classification. Late toxicities were observed in 34.8% (G1 52.3%, G2 40.7%). Cutaneous fibrosis was the most common toxicity. Cosmetic outcomes were excellent in 64.1%. Dosimetry analysis revealed positive correlations between complications and absolute volumes of CTV, V100, V150, and V200. Volumes requiring higher needle number and lower DNR resulted in fewer complications. 5-year disease-free and overall survival were 88% and 95% respectively. CONCLUSION: Second CT for 2ndIBTE showed favorable oncological outcomes and survival rates. Complications were correlated with specific dosimetric parameters, emphasizing the importance of tailored treatment planning. This study provides valuable insights in risk stratification and MIB optimization for APBrI.

Randomized phase II study of preoperative afatinib in untreated head and neck cancers: predictive and pharmacodynamic biomarkers of activity.

There is no strong and reliable predictive biomarker in head and neck squamous cell carcinoma (HNSCC) for EGFR inhibitors. We aimed to identify predictive and pharmacodynamic biomarkers of efficacy of afatinib, a pan-HER tyrosine kinase inhibitor, in a window-of-opportunity trial (NCT01415674). Multi-omics analyses were carried out on pre-treatment biopsy and surgical specimen for biological assessment of afatinib activity. Sixty-one treatment-naïve and operable HNSCC patients were randomised to afatinib 40 mg/day for 21-28 days versus no treatment. Afatinib produced a high rate of metabolic response. Responders had a higher expression of pERK1/2 (P = 0.02) and lower expressions of pHER4 (P = 0.03) and pRB1 (P = 0.002) in pre-treatment biopsy compared to non-responders. At the cellular level, responders displayed an enrichment of tumor-infiltrating B cells under afatinib (P = 0.02). At the molecular level, NF-kappa B signaling was over-represented among upregulated genes in non-responders (P < 0.001; FDR = 0.01). Although exploratory, phosphoproteomics-based biomarkers deserve further investigations as predictors of afatinib efficacy.

Information and oncosexological management in breast cancer patients.

OBJECTIVES: Breast cancer treatment is a particularly high-risk situation for the deterioration of sexual health, leading to an alteration in body image and physical deteriorations such as vaginal trophicity. The aim of this study was to evaluate the information received by patients concerning this alteration of their sexual health in relation to their treatment, and to identify their expectations and needs in terms of oncosexual management. STUDY DESIGN: A bicentric qualitative retrospective study was conducted, involving women aged 18 to 80, treated for breast cancer by total or partial mastectomy after 2014 and having had a follow-up consultation between July and December 2019. Data were collected using medical files and a de-identified questionnaire sent by post or e-mail after obtaining consent. The main outcome measures were the proportion of patients who received informations about oncosexology and those who felt impact on their sexual health. RESULTS: Of the 274 patients included in the study, 60% said they had received no information about the sexological side effects of their disease or treatment. Of these, 62.5% dared not talk about it during consultation. Patients were keen to receive oncosexological advice or treatment from a specialized nurse or doctor. In 76.1% of cases, patients declared that they had been sexually active in the year prior to their cancer diagnosis, compared with 54.94% after treatment. They reported a loss of femininity in 24% of cases, and 40.5% had no sexual desire. CONCLUSION: Women treated for breast cancer report a lasting alteration in their body image and sexual activity. Information on the impact of the disease and its treatment on sexual health is inadequate, even though patients are keen to receive specialized care with professional sexology consultations. The impact of breast cancer on sexual health should systematically explained to the patients, especially as treatment options exist and can be offered.

Survival analysis of patient groups defined by unsupervised machine learning clustering methods based on patient metabolomic data.

Purpose: Meta-analyses failed to accurately identify patients with non-metastatic breast cancer who are likely to benefit from chemotherapy, and metabolomics could provide new answers. In our previous published work, patients were clustered using five different unsupervised machine learning (ML) methods resulting in the identification of three clusters with distinct clinical and simulated survival data. The objective of this study was to evaluate the survival outcomes, with extended follow-up, using the same 5 different methods of unsupervised machine learning. Experimental design: Forty-nine patients, diagnosed between 2013 and 2016, with non-metastatic BC were included retrospectively. Median follow-up was extended to 85.8 months. 449 metabolites were extracted from tumor resection samples by combined Liquid chromatography-mass spectrometry (LC-MS). Survival analyses were reported grouping together Cluster 1 and 2 versus cluster 3. Bootstrap optimization was applied. Results: PCA k-means, K-sparse and Spectral clustering were the most effective methods to predict 2-year progression-free survival with bootstrap optimization (PFSb); as bootstrap example, with PCA k-means method, PFSb were 94% for cluster 1&2 versus 82% for cluster 3 (p = 0.01). PCA k-means method performed best, with higher reproducibility (mean HR=2 (95%CI [1.4-2.7]); probability of p ≤ 0.05 85%). Cancer-specific survival (CSS) and overall survival (OS) analyses highlighted a discrepancy between the 5 ML unsupervised methods. Conclusion: Our study is a proof-of-principle that it is possible to use unsupervised ML methods on metabolomic data to predict PFS survival outcomes, with the best performance for PCA k-means. A larger population study is needed to draw conclusions from CSS and OS analyses.

Prognostic impact of post-treatment FDG PET/CT in anal canal cancer: A prospective study.

BACKGROUND AND PURPOSE: The aim of our prospective study was to assess the prognostic value of 18F-FDG PET/CT performed two months post treatment for anal canal neoplasm. POPULATION AND METHODS: Consecutive patients with histologically proved anal cancer, with 18F-FDG PET/CT pre and two months post treatment were included. Patients were not previously treated for this neoplasm and then received radiotherapy ± chemotherapy. Clinical and pathologic data were collected and for 18F-FDG PET/CT visual and quantitative analysis (standardized uptake value, metabolic volume) were performed; response was classified according to EORTC and PERCIST criteria. The results were assessed for disease free survival and local recurrence free survival using the log-Rank test RESULTS: From December 2014 to September 2019, 94 consecutive patients were screened and 78 were included in this study. Median follow-up was 51 months. Two months post treatment, 37 patients (47.4%) had a complete radiological response according to both EORTC and PERCIST criteria, 66 patients (84.6%) had a clinical complete response. For disease free survival, the prognostic value of complete response was statistically significant (p=0.02) with 18F-FDG PET/CT and with clinical examination (p<0.001). For local recurrence free survival, the prognostic value with 18F-FDG PET/CT was lower (p=0.04) than clinical examination (p < 0.007). CONCLUSION: While clinical examination remains the gold standard for post treatment evaluation in anal cancer, 18F-FDG PET/CT has a statistically significant prognostic value. These two assessments could be combined to improve early evaluation.

Second Conservative Treatment for Local Recurrence Breast Cancer: A GEC-ESTRO Oncological Outcome and Prognostic Factor Analysis.

PURPOSE: For second ipsilateral breast tumor event (2nd IBTE), second conservative treatment (2nd CT) combining lumpectomy plus accelerated partial breast reirradiation (APBrI) represents a curative option. The aim of this study was to analyze oncological prognostic factors for patients with a 2nd IBTE treated with 2nd CT. METHODS AND MATERIALS: An analysis of clinical practices was conducted across 7 academic hospitals/cancer centers in 6 European countries based on the GEC-ESTRO database. Patients presenting a 2nd IBTE occurring after conservative surgery (lumpectomy + axillary evaluation) and irradiation performed for the primary tumor underwent a 2nd CT with brachytherapy-based APBrI. The main outcome was 5-year cumulative incidence (CI) rate of second local relapse. All analyzed patients were classified according to risk groups for Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) accelerated partial breast irradiation (APBI) and molecular classification and time interval between first and second breast surgery (TIS1S2). Finally, we combined GEC-ESTRO APBI, molecular, and TIS1S2 risk groups, leading to the definition of a new score (named TAM: score based on the combination of time interval [T] between first and second surgery and APBI [A] and molecular [M] classifications) specifically designed for 2nd IBTE oncological outcome analysis. RESULTS: From July 1994 to January 2021, a total of 508 patients received a 2nd CT. At the time of 2nd IBTE, median age was 64.6 years (range, 56.2-72.6). With a median follow-up of 60.9 months (56.2-72.6), the 5-year second local relapse CI rate was 4% (95% confidence interval [95% CI], 2%-6%). The 5-year distant metastasis disease CI rate was 7% (95% CI, 4%-10%). Five-year disease-free and overall survival rates were 89% (95% CI, 86%-93%) and 91% (95% CI, 88%-94%), respectively. In multivariate analysis, TAM score was an independent prognostic factor for all the oncological items (P < .001) except disease-specific survival (P = .07) and overall survival (P = .09). The grade ≥3 late toxicity rate was 12.1%. CONCLUSIONS: This analysis of 2nd CT combining lumpectomy with APBrI for 2nd IBTE confirmed the excellent oncological results obtained after 2nd CT. Furthermore, the GEC-ESTRO TAM score appears to be an important prognostic factor, assisting patients and physicians in the decision-making process.

Development and External Validation of a PET Radiomic Model for Prognostication of Head and Neck Cancer.

AIM: To build and externally validate an [18F]FDG PET radiomic model to predict overall survival in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Two multicentre datasets of patients with operable HNSCC treated with preoperative afatinib who underwent a baseline and evaluation [18F]FDG PET/CT scan were included (EORTC: n = 20, Unicancer: n = 34). Tumours were delineated, and radiomic features were extracted. Each cohort served once as a training and once as an external validation set for the prediction of overall survival. Supervised feature selection was performed using variable hunting with variable importance, selecting the top two features. A Cox proportional hazards regression model using selected radiomic features and clinical characteristics was fitted on the training dataset and validated in the external validation set. Model performances are expressed by the concordance index (C-index). RESULTS: In both models, the radiomic model surpassed the clinical model with validation C-indices of 0.69 and 0.79 vs. 0.60 and 0.67, respectively. The model that combined the radiomic features and clinical variables performed best, with validation C-indices of 0.71 and 0.82. CONCLUSION: Although assessed in two small but independent cohorts, an [18F]FDG-PET radiomic signature based on the evaluation scan seems promising for the prediction of overall survival for HNSSC treated with preoperative afatinib. The robustness and clinical applicability of this radiomic signature should be assessed in a larger cohort.

Validation of RUBY for Breast Cancer Knowledge Extraction From a Large French Electronic Medical Record System.

PURPOSE: RUBY is a tool for extracting clinical data on breast cancer from French medical records on the basis of named entity recognition models combined with keyword extraction and postprocessing rules. Although initial results showed a high precision of the system in extracting clinical information from surgery, pathology, and biopsy reports (≥92.7%) and good precision in extracting data from consultation reports (81.8%), its validation is needed before its use in routine practice. METHODS: In this work, we analyzed RUBY's performance compared with the manual entry and we evaluated the generalizability of the approach on different sets of reports collected on a span of 40 years. RESULTS: RUBY performed similarly or better than the manual entry for 15 of 27 variables. It showed similar performances when structuring newer reports but failed to extract entities for which changes in terminology appeared. Finally, our tool could automatically structure 15,990 reports in 77 minutes. CONCLUSION: RUBY can automate the data entry process of a set of variables and reduce its burden, but a continuous evaluation of the format and structure of the reports and a subsequent update of the system is necessary to ensure its robustness.

Metabolomic Signatures of Scarff-Bloom-Richardson (SBR) Grade in Non-Metastatic Breast Cancer.

PURPOSE: Identification of metabolomic biomarkers of high SBR grade in non-metastatic breast cancer. METHODS: This retrospective bicentric metabolomic analysis included a training set (n = 51) and a validation set (n = 49) of breast cancer tumors, all classified as high-grade (grade III) or low-grade (grade I-II). Metabolomes of tissue samples were studied by liquid chromatography coupled with mass spectrometry. RESULTS: A molecular signature of the top 12 metabolites was identified from a database of 602 frequently predicted metabolites. Partial least squares discriminant analyses showed that accuracies were 0.81 and 0.82, the R2 scores were 0.57 and 0.55, and the Q2 scores were 0.44431 and 0.40147 for the training set and validation set, respectively; areas under the curve for the Receiver Operating Characteristic Curve were 0.882 and 0.886. The most relevant metabolite was diacetylspermine. Metabolite set enrichment analyses and metabolic pathway analyses highlighted the tryptophan metabolism pathway, but the concentration of individual metabolites varied between tumor samples. CONCLUSIONS: This study indicates that high-grade invasive tumors are related to diacetylspermine and tryptophan metabolism, both involved in the inhibition of the immune response. Targeting these pathways could restore anti-tumor immunity and have a synergistic effect with immunotherapy. Recent studies could not demonstrate the effectiveness of this strategy, but the use of theragnostic metabolomic signatures should allow better selection of patients.

Added value of [18F]FDOPA PET to the management of high-grade glioma patients after their initial treatment: a prospective multicentre study.

BACKGROUND: Diagnostic value of 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine ([18F]FDOPA) PET in patients with suspected recurrent gliomas is recognised. We conducted a multicentre prospective study to assess its added value in the practical management of patients suspected of recurrence of high grade gliomas (HGG). METHODS: Patients with a proven HGG (WHO grade III and IV) were referred to the multidisciplinary neuro-oncology board (MNOB) during their follow-up after initial standard of care treatment and when MRI findings were not fully conclusive. Each case was discussed in 2 steps. For step 1, a diagnosis and a management proposal were made only based on the clinical and the MRI data. For step 2, the same process was repeated taking the [18F]FDOPA PET results into consideration. A level of confidence for the decisions was assigned to each step. Changes in diagnosis and management induced by [18F]FDOPA PET information were measured. When unchanged, the difference in the confidence of the decisions were assessed. The diagnostic performances of each step were measured. RESULTS: 107 patients underwent a total of 138 MNOB assessments. The proposed diagnosis changed between step 1 and step 2 in 37 cases (26.8%) and the proposed management changed in 31 cases (22.5%). When the management did not change, the confidence in the MNOB final decision was increased in 87 cases (81.3%). Step 1 had a sensitivity, specificity and accuracy of 83%, 58% and 66% and step 2, 86%, 64% and 71% respectively. CONCLUSION: [18F]FDOPA PET adds significant information for the follow-up of HGG patients in clinical practice. When MRI findings are not straightforward, it can change the management for more than 20% of the patients and increases the confidence level of the multidisciplinary board decisions.

Breast Cancer and SARS-Cov2: Lessons from a Pandemic.

BACKGROUND/AIM: The COVID-19 pandemic introduced drastic containment measures, which had a direct impact on breast cancer management. During the first wave, a delay in care and a decrease in new consultation numbers was observed. It would be interesting to study the resulting long-term consequences on breast cancer presentation and time to first treatment. PATIENTS AND METHODS: This retrospective cohort study was conducted at the surgery Department of the Anti-Cancer Center of Nice, France. Two periods of 6 months were compared: a pandemic period from June to December 2020 (after the end of the first wave), and a control period one year earlier. The primary endpoint was to measure the time to care access. The patients and cancer characteristics and the management type were also compared. RESULTS: A total of 268 patients underwent diagnosis for breast cancer in each period. The time from biopsy to consultation was shortened after the containment was lifted (16 days vs. 18 days, p=0.024). The time between first consultation and treatment was unchanged between the two periods. The tumor size was larger in the pandemic period (21 mm vs. 18 mm, p=0.028). The clinical presentation was different: 59.8% of patients consulted for a palpable mass in the pandemic period, vs. 49.6% in the control period (p=0.023). There was no significant change in therapeutic management. The use of genomic testing was significantly increased. The number of breast cancer cases diagnosed decreased by 30% during the first COVID-19 lockdown. Even though a rebound was expected after the first wave, the number of consultations for breast cancer remained constant. This finding shows the fragility of screening adherence. CONCLUSION: It is necessary to reinforce education in the face of crises that may be repeated. Management of breast cancer did not change, which is a reassuring aspect regarding the care pathway in anticancer centers.

Application of machine learning methods to guide patient management by predicting the risk of malignancy of Bethesda III-V thyroid nodules.

OBJECTIVE: Indeterminate thyroid nodules (ITN) are common and often lead to (sometimes unnecessary) diagnostic surgery. We aimed to evaluate the performance of two machine learning methods (ML), based on routinely available features to predict the risk of malignancy (RM) of ITN. DESIGN: Multi-centric diagnostic retrospective cohort study conducted between 2010 and 2020. METHODS: Adult patients who underwent surgery for at least one Bethesda III-V thyroid nodule (TN) with fully available medical records were included. Of the 7917 records reviewed, eligibility criteria were met in 1288 patients with 1335 TN. Patients were divided into training (940 TN) and validation cohort (395 TN). The diagnostic performance of a multivariate logistic regression model (LR) and its nomogram, and a random forest model (RF) in predicting the nature and RM of a TN were evaluated. All available clinical, biological, ultrasound, and cytological data of the patients were collected and used to construct the two algorithms. RESULTS: There were 253 (19%), 693 (52%), and 389 (29%) TN classified as Bethesda III, IV, and V, respectively, with an overall RM of 35%. Both cohorts were well-balanced for baseline characteristics. Both models were validated on the validation cohort, with performances in terms of specificity, sensitivity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve of 90%, 57.3%, 73.4%, 81.4%, 84% (CI95%: 78.5%-89.5%) for the LR model, and 87.6%, 54.7%, 68.1%, 80%, 82.6% (CI95%: 77.4%-87.9%) for the RF model, respectively. CONCLUSIONS: Our ML models performed well in predicting the nature of Bethesda III-V TN. In addition, our freely available online nomogram helped to refine the RM, identifying low-risk TN that may benefit from surveillance in up to a third of ITN, and thus may reduce the number of unnecessary surgeries.

Abigene, a Prospective, Multicentric Study of Abiraterone Acetate Pharmacogenetics in Metastatic Castration-Resistant Prostate Cancer.

Abiraterone acetate (AA) is the first-in-class of drugs belonging to the second-generation of agents inhibiting androgen neosynthesis in advanced prostate cancer. A cumulative experience attests that germinal gene polymorphisms may play a role in the prediction of anticancer agent pharmacodynamics variability. In the present prospective, multicentric study, gene polymorphisms of CYP17A1 (AA direct target) and the androgen transporter genes SLCO2B1 and SLCO1B3 (potential modulators of AA activity) were confronted with AA pharmacodynamics (treatment response and toxicity) in a group of 137 advanced prostate cancer patients treated in the first line by AA. The median follow-up was 56.3 months (95% CI [52.5-61]). From multivariate analysis, rs2486758 C/C (CYP17A1) and PSA (≥10 ng/mL) were associated with a shorter 3-year biological PFS (HR = 4.05, IC95% [1.46-11.22]; p = 0.007 and HR = 2.08, IC95% [1.31-3.30]; p = 0.002, respectively). From a multivariate analysis, the rs743572 (CYP17A1) and performance status were independently associated with significant toxicity (OR = 3.78 (IC95% [1.42-9.75]; p = 0.006 and OR = 4.54; IC95% [1.46-13.61]; p = 0.007, respectively). Host genome characteristics may help to predict AA treatment efficacy and identify patients at risk for toxicity.

Docetaxel-Cisplatin-Fluorouracil Induction Chemotherapy for Larynx Preservation in Patients with Locally Advanced Hypopharyngeal Cancer: Predictive Factors of Oncologic and Functional Outcomes.

BACKGROUND: The aims of this study were to evaluate the clinical outcomes and their predictive factors in locally advanced hypopharyngeal cancer (HC) patients included in a docetaxel-cisplatin-fluorouracil induction chemotherapy (ICT)-based larynx preservation (LP) program. METHODS: Between 2005 and 2021, 82 patients with a locally advanced resectable HC who received ICT in an LP program were included in this retrospective study. The predictors of oncologic and swallowing outcomes were determined in univariate and multivariate analyses. RESULTS: The three- and five-year overall survival (OS) rates were 67 and 54%, respectively. The T4 tumor stage was the only predictive factor of poor response to ICT (p = 0.03). In multivariate analysis, a T stage = 4 (p = 0.02), an ICT cycle number < 3 (p = 0.003) and the absence of a response to ICT (p = 0.03) were significantly associated with worse OS. A low body mass index before therapy (p = 0.003) and enteral nutrition during therapy (p = 0.005) were significantly associated with severity of dysphagia 6 months after treatment. CONCLUSIONS: The T stage, number of ICT cycles performed and response to ICT are the main predictors of oncologic outcomes. Patients with T4 HC are poor candidates for LP and should be referred to immediate radical surgery.

Salvage vs. Primary Total Laryngectomy in Patients with Locally Advanced Laryngeal or Hypopharyngeal Carcinoma: Oncologic Outcomes and Their Predictive Factors.

BACKGROUND: The aims of this study were to compare the survival outcomes of salvage vs. primary total laryngectomy (TL) in patients with locally advanced laryngeal or hypopharyngeal carcinoma and to determine their predictive factors. METHODS: Overall (OS), cause-specific (CSS) and recurrence-free survival (RFS) of primary vs. salvage TL were compared in univariate and multivariate analysis taking into account other potential predictive factors (tumor site, tumor stage, comorbidity level etc.). RESULTS: A total of 234 patients were included in this study. Five-year OS was 53% and 25% for the primary and salvage TL groups, respectively. Multivariate analysis confirmed the independent negative impact of salvage TL on OS (p = 0.0008), CSS (p < 0.0001) and RFS (p < 0.0001). Hypopharyngeal tumor site, ASA score ≥ 3, N-stage ≥ 2a and positive surgical margins were the main other predictors of oncologic outcomes. CONCLUSIONS: Salvage TL is associated with significantly worse survival rates than primary TL highlighting the need for careful selection of patients who are candidates for larynx preservation. The predictive factors of survival outcomes identified here should be considered in the therapeutic decision-making, especially in the setting of salvage TL, given the poor prognosis of these patients.