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.

Impact of virtual surgical planning and three-dimensional modeling on time to surgery in mandibular reconstruction by free fibula flap.

PURPOSE: Mandible reconstruction using a free fibula flap (FFF) is preferably performed with virtual surgical planning (VSP) to potentially improve functional and aesthetic outcomes. However, VSP is time-consuming. This study aims to assess the impact of VSP on time to surgery (TS). MATERIALS AND METHODS: All patients who underwent FFF for oral cavity cancer between 2007 and 2020 were included. Time to surgery (from the date of the first consultation to the surgery date) was compared between patients without VSP and with VSP. In our department, VSP and 3D modeling were performed by an external engineering laboratory. RESULTS: One hundred sixty-five patients were included retrospectively. VSP was utilized for 90 patients (55%). The mean time to surgery was 31 ± 16 days for patients undergoing conventional surgery without VSP and 44 ± 19 days for patients with VSP (p < 0.001). No clinical or tumoral characteristic were associated with a TS extended, except for the utilization of VSP (p < 0.001). By constituting groups of 25 consecutive patients, there is no difference in TS between the groups. CONCLUSION: The use of VSP significantly increased the time to surgery in our study, unrelated to clinical differences or year of surgery. This delay may have an impact on oncologic outcomes, so it should be considered in the care organization for each patient. Implementing new procedures to reduce this difference is warranted.

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.

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.

The safety and efficacy of total mesorectal excision (TME) surgery following dose-escalation: Surgical outcomes from the organ preservation in early rectal adenocarcinoma (OPERA) trial, a European multicentre phase 3 randomised trial (NCT02505750).

AIM: Nonsurgical treatment with chemoradiotherapy for rectal cancer is gaining interest as it avoids total mesorectal excision (TME) surgery and stoma. The OPERA trial aims to evaluate whether dose escalation with contact X-ray brachytherapy (CXB) boost improves organ preservation compared to external beam radiotherapy (EBRT) boost. It has been suggested that dose escalation adversely affects surgical outcomes and therefore we report outcomes following TME in OPERA at 36 months. METHODS: OPERA is a European multicentre phase 3 trial (NCT02505750) which randomises patients with cT2-3a-b, cN0-1, M0 to EBCRT (45 Gy in 25 fractions over 5 weeks with oral capecitabine 825 mg/m2 ) followed by EBRT boost (9 Gy in 5 fractions over 5 days) versus EBCRT followed by CXB boost (90 Gy in 3 fractions over 4 weeks). Patients were assessed at 14, 20 and 24 weeks from the start of treatment. Watch and wait management was adopted for patients who achieved a clinical complete response (cCR) at 24 weeks following treatment. Either local excision (LE) or TME surgery was offered for residual disease or local regrowth, according to patient and surgeon preference. Surgical morbidity and mortality were recorded prospectively. RESULTS: Between July 2015 and June 2020, 148 patients were randomised of which 141 were evaluable in March 2022. At median follow-up of 38.2 months (range: 34.2-42.5), surgery was performed for 66 (47%) patients. A total of 27 (20%) patients had local excision and 39 (29%) had TME surgery, 22/39 (56%) underwent anterior resection and 17/39 (44%) underwent abdominoperineal excision of the rectum. The R0 resection rate was 87%. There were no deaths, and six patients (15%) had Clavien-Dindo IIIb complications. Whilst there was a statistically significant decrease in the TME rate following CXB boost (HR 0.38, 95% CI: 0.19-0.74, p = 0.00419) there was no difference in surgical outcomes between patients who received EBRT and CXB boost. CONCLUSION: Dose escalation can facilitate nonsurgical treatment for cT2-3 rectal cancer patients who are fit but wish to avoid TME surgery and stoma. If TME surgery is required, then it can be performed safely and effectively.

Safety and efficacy of two-drug combination in elderly patients with locally advanced non-small cell lung cancer and validation of the Charlson Index as a predictor of survival.

Background: The best platinum-based chemotherapy regimen remains to be determined in elderly patients treated with definitive chemoradiotherapy for advanced non-small cell lung cancer (NSCLC). Predictive indexes for toxicity and survival are also needed to give the safest and most effective treatment for this population. Methods: This is a retrospective cohort study. Patients with histologically confirmed stage IIIA, IIIB or IIIC NSCLC over 70 years of age, treated with radiotherapy and chemotherapy, were included. Patients from two cancer centers treated between 12/2006 and 08/2019 were included in the data analysis. Results: Fifty-eight patients were enrolled in the study. The median age was 76.6 years [interquartile range (IQR): 71.6-83.4]. Thirty-nine patients were treated with concomitant chemoradiotherapy and 19 with a sequential strategy. The chemotherapy regimen consisted in a combination of platinum and taxanes. At a median follow-up of 52 months (IQR: 7-69), the 2-year progression-free survival (PFS) and overall survival (OS) were 35.5% and 66.9%, respectively. Male sex and a high Charlson index were identified as independent prognostic factors for worse OS. Acute grade 3-5 toxicities occurred in 34.4% of patients, including 1 grade 5 toxicity, and grade 3-4 late toxicities occurred in 17.2% of patients. In the whole cohort a high Charlson index was the only predictive factor for a higher risk of grade 3-5 acute toxicities (statistical trend in the concurrent cohort, P=0.06). Conclusions: The Charlson index correlated with toxicity and survival in elderly patients treated with chemoradiotherapy in locally advanced NSCLC. The addition of taxanes to platinum chemotherapy was safe in the present study and warrants further exploration.

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.

Comparison of outcome after stereotactic ablative radiotherapy of patients with metachronous lung versus primary lung cancer.

BACKGROUND: Early-stage lung cancer, primarily treated with surgery, often occur in poor surgical candidates (impaired respiratory function, prior thoracic surgery, severe comorbidities). Stereotactic ablative radiotherapy (SABR) is a non-invasive alternative that provides comparable local control. This technique is particularly relevant for surgically resectable metachronous lung cancer, in patients unable to undergo surgery.. The objective of this study is to evaluate the clinical outcome of patients treated with SABR for stage I metachronous lung cancer (MLC) versus stage I primary lung cancer (PLC). PATIENTS AND METHODS: 137 patients treated with SABR for stage I non-small cell lung cancer were retrospectively reviewed, of which 28 (20.4%) were MLC and 109 (79.6%) were PLC. Cohorts were evaluated for differences in overall survival (OS), progression-free survival (PFS), metastasis-free survival, local control (LC), and toxicity. RESULTS: After SABR, patients treated for MLC have comparable median age (76.6 vs 78.6, p = 0.2), 3-year LC (83.6% vs. 72.6%, p = 0.2), PFS (68.7% vs. 50.9%, p = 0.9), and OS (78.6% vs. 52.1%, p = 0.9) as PLC, along with similar rates of total (54.1% vs. 42.9%, p = 0.6) and grade 3 + toxicity (3.7% vs. 3.6%, p = 0.9). Previous treatment of MLC patients was either surgery (21/28, 75%) or SABR (7/28, 25%). The median follow-up was 53 months. CONCLUSION: SABR is a safe and effective approach for localized metachronous lung cancer.

Comparative Performance of Four Staging Classifications to Select «High-Risk¼ Head and Neck Cutaneous Squamous Cell Carcinomas.

BACKGROUND: Many classifications exist to select patients with "high-risk" head and neck cutaneous squamous cell carcinoma (HNCSCC). OBJECTIVE: To compare the performance of the Brigham and Women's Hospital (BWH) classification with the performance of the American Joint Committee on Cancer 8th Edition (AJCC8), the Union for International Cancer Control 8th Edition (UICC8), and the National Comprehensive Cancer Network (NCCN) classifications. METHODS: In this single-center retrospective study, HNCSCC resected in a tertiary care center were classified as "low-risk" or "high-risk" tumors according to the four classifications. Rates of local recurrence (LR), lymph node recurrence (NR), and disease-specific death (DSD) were collected. The performance of each classification was then calculated in terms of homogeneity, monotonicity, and discrimination and compared. RESULTS: Two hundred and seventeen HNCSCC from 160 patients, with a mean age of 80 years, were included. For predicting the risk of any poor outcome and risk of NR, the BWH classification had the best specificity and positive predictive value. However, its concordance index was not significantly higher than that of the AJCC8 and UICC8 classifications. The NCCN classification was the least discriminant. CONCLUSIONS AND RELEVANCE: This study suggests that the BWH classification is the most appropriate for predicting the risk of poor outcomes in patients with HNCSCC when compared with the NCCN, UICC8, and AJCC8 classifications.

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.

Enteral Nutrition during Radiotherapy for Oropharyngeal Cancers: Prevalence and Prognostic Factors Based on HPV Status (A GETTEC Study).

Nutritional support during radiotherapy is crucial to tolerating and completing oropharyngeal squamous cell carcinoma (OPSCC) treatment. The impact of HPV status on nutritional support is debated. The objective was to evaluate the rate of Reactive Feeding Tube (RFT) use and determine its prognostic factors during definitive radiotherapy for OPSCC. All OPSCC patients treated from 2009 to 2014 were included in this multicentric retrospective study. The impact of tumor p16 status on the risk of RFT was assessed through multivariate analyses. Among the 543 patients, 103 patients required an RFT (19.0%). The use of RFT differed between centers (5% to 32.4%). In multivariate analysis, only tongue base involvement and concurrent chemotherapy were significantly associated with RFT (OR = 2.18 and 3.7, respectively). Tongue base involvement and concomitant chemotherapy were prognostic factors for RFT. HPV status was not a prognostic factor for enteral nutrition during radiotherapy for OPSCC.

Post-therapeutic surveillance of HPV-driven oropharyngeal cancers: are we ready to change our practices?

PURPOSE: Although HPV-positive and negative oropharyngeal cancers are two distinct diseases, Post-Therapeutic Surveillance (PTS) modalities are similar. Adjusting PTS strategies to HPV status will represent a massive practice change that raises the issue of its acceptability, by both physicians and patients. METHODS: Two distinct surveys were designed and submitted, respectively, to HPV-positive patients and physicians (surgeons, radiation and medical oncologists) involved in head and neck cancer treatment. RESULTS: 133 patients and 90 physicians have participated to the study. Most patients were reluctant to embrace new PTS options (remote consultations, nurse consultations and smart phone applications). However, 84% of patients would be favorable to use HPV Circulating DNA (HPV Ct DNA) measurement to guide surveillance modalities. 57% of physicians acknowledged that our current PTS strategy is improvable and most of them would accept the use of new monitoring options from the third year of follow-up. 87% of physicians would be interested to participate to a trial comparing the current PTS strategy to a new approach, where monitoring modalities (number of visits, imaging prescription) would depend on HPV Ct DNA level. CONCLUSIONS: Patients and physicians are aware that PTS modalities should depend on HPV status. Their adhesion is a prerequisite to any potential changes. Strategies based on HPV Ct DNA measurement should be assessed within a randomized clinical trial.

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.

Association between progression-free survival and overall survival in women receiving first-line treatment for metastatic breast cancer: evidence from the ESME real-world database.

BACKGROUND: Overall survival (OS) is the gold standard endpoint to assess treatment efficacy in cancer clinical trials. In metastatic breast cancer (mBC), progression-free survival (PFS) is commonly used as an intermediate endpoint. Evidence remains scarce regarding the degree of association between PFS and OS. Our study aimed to describe the individual-level association between real-world PFS (rwPFS) and OS according to first-line treatment in female patients with mBC managed in real-world setting for each BC subtype (defined by status for both hormone-receptor [HR] expression and HER2 protein expression/gene amplification). METHODS: We extracted data from the ESME mBC database (NCT03275311) which gathers deidentified data from consecutive patients managed in 18 French Comprehensive Cancer Centers. Adult women diagnosed with mBC between 2008 and 2017 were included. Endpoints (PFS, OS) were described using the Kaplan-Meier method. Individual-level associations between rwPFS and OS were estimated using the Spearman's correlation coefficient. Analyses were conducted by tumor subtype. RESULTS: 20,033 women were eligible. Median age was 60.0 years. Median follow-up duration was 62.3 months. Median rwPFS ranged from 6.0 months (95% CI 5.8-6.2) for HR-/HER2 - subtype to 13.3 months (36% CI 12.7-14.3) for HR + /HER2 + subtype. Correlation coefficients were highly variable across subtypes and first-line (L1) treatments. Among patients with HR - /HER2 - mBC, correlation coefficients ranged from 0.73 to 0.81, suggesting a strong rwPFS/OS association. For HR + /HER2 + mBC patients, the individual-level associations were weak to strong with coefficients ranging from 0.33 to 0.43 for monotherapy and from 0.67 to 0.78 for combined therapies. CONCLUSIONS: Our study provides comprehensive information on individual-level association between rwPFS and OS for L1 treatments in mBC women managed in real-life practice. Our results could be used as a basis for future research dedicated to surrogate endpoint candidates.

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.

Neoadjuvant chemoradiotherapy with radiation dose escalation with contact x-ray brachytherapy boost or external beam radiotherapy boost for organ preservation in early cT2-cT3 rectal adenocarcinoma (OPERA): a phase 3, randomised controlled trial.

BACKGROUND: Organ preservation after reaching clinical complete response on neoadjuvant therapy is gaining interest for rectal cancers, although the role of radiation dose escalation is still not known. We aimed to determine whether a contact x-ray brachytherapy boost, following or preceding neoadjuvant chemoradiotherapy, increases the probability of 3-year organ preservation for patients with early rectal cancers. METHODS: OPERA was a multicentre, open-label, phase 3 randomised controlled trial done at 17 cancer centres that included operable patients, aged 18 years or older, with cT2, cT3a, or cT3b adenocarcinoma of low-mid rectum, tumours of less than 5 cm in diameter, and cN0 or cN1 smaller than 8 mm. All patients received neoadjuvant chemoradiotherapy and 45 Gy external beam radiotherapy in 25 fractions over 5 weeks with concurrent oral capecitabine (825 mg/m2 twice a day). Patients were randomly assigned (1:1) to receive a boost of external beam radiotherapy at 9 Gy in five fractions (group A) or a boost with contact x-ray brachytherapy (90 Gy in three fractions; group B). Randomisation was done centrally using an independent web-based system and stratified by trial centre, tumour classification (cT2 vs cT3a or cT3b), tumour distance from rectum (<6 cm from anal verge vs ≥6 cm), and tumour diameter (<3 cm vs ≥3 cm). Treatment in group B was stratified by tumour diameter, with the contact x-ray brachytherapy boost given before neoadjuvant chemoradiotherapy in patients with tumours smaller than 3 cm. The primary outcome was organ preservation at 3 years, analysed in the modified intention-to-treat population. This study was registered with ClinicalTrials.gov, NCT02505750, and is ongoing. FINDINGS: Between June 14, 2015, and June 26, 2020, 148 patients were assessed for eligibility and were randomly assigned to group A (n=74) or group B (n=74). Seven patients withdrew their consent (five in group A and two in group B). 141 patients were included in the primary efficacy analysis, including 69 assigned to group A (29 with tumours <3 cm in diameter and 40 with tumours ≥3 cm) and 72 assigned to group B (32 with tumours <3 cm and 40 with tumours ≥3 cm). After a median follow-up of 38·2 months (IQR 34·2-42·5), the 3-year organ preservation rate was 59% (95% CI 48-72) in group A versus 81% (72-91) in group B (hazard ratio [HR] 0·36, 95% CI 0·19-0·70; p=0·0026). For patients with tumours less than 3 cm in diameter, 3-year organ preservation rates were 63% (95% CI 47-84) in group A versus 97% (91-100) in group B (HR 0·07, 95% CI 0·01-0·57; p=0·012). For patients with tumours of 3 cm or larger, 3-year organ preservation rates were 55% (95% CI 41-74) in group A versus 68% (54-85) in group B (HR 0·54, 95% CI 0·26-1·10; p=0·11). 21 (30%) patients in group A and 30 (42%) in group B had an early grade 2-3 adverse event (p=1·0). The most common early grade 2-3 adverse events were proctitis (four [6%] in group A, nine [13%] in group B) and radiation dermatitis (seven [10%] in group A, two [3%] in group B). The main late side-effect was grade 1-2 rectal bleeding due to telangiectasia, which was more frequent in group B (37 [63%] of 59) than in group A (five [12%] of 43; p<0·0001) and subsided after 3 years. INTERPRETATION: Neoadjuvant chemoradiotherapy with a contact x-ray brachytherapy boost significantly improved the 3-year organ preservation rate, particularly for patients with tumours smaller than 3 cm who were treated with contact x-ray brachytherapy first, compared with neoadjuvant chemoradiotherapy with a boost via external beam radiotherapy. This approach could be discussed and offered to operable patients with early cT2-cT3 disease who are keen to avoid surgery and seek organ preservation. FUNDING: The French Programme Hospitalier de Recherche Cinique.

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.

Outcomes following brachytherapy boost for intermediate- and high-risk prostate cancer: A retrospective bicenter study by the SFRO brachytherapy group.

INTRODUCTION: Radiotherapy dose escalation improves biochemical control in intermediate- or high-risk prostate cancer. Brachytherapy boost was shown to further improve biochemical control compared to radiotherapy alone in three randomized trials. The SFRO brachytherapy group sought to evaluate the efficacy and toxicity of BT-boost for intermediate and high-risk prostate cancer in real life, and to determine prognostic factors for efficacy and toxicity. MATERIAL AND METHOD: A retrospective study was conducted, including all patients with intermediate- or high-risk prostate cancer treated with a combination of external beam radiotherapy (EBRT) and high dose-rate brachytherapy boost (HDR-BB), from 2006 until December 2019 at two centers. Patient characteristics, initial disease, treatment and follow-up were collected. RESULTS: 709 patients from two centers were analyzed given a short follow-up in the other centers. Out of those, 277 were intermediate risk (170 favorable and 107 unfavorable) and 432 were high risk. The median EBRT and HDR-BB doses were 46 Gy (35-50) and 14 Gy (10-20). After a median follow-up of 62 months, biochemical control at 5 years was 87.5 % for the overall population, 91 % and 85 % for intermediate- and high-risk cancers, respectively. At 5 years, biochemical and clinical relapse-free survival, metastasis-free survival and local control rates were 83 %, 90 % and 97 % respectively. 5-years overall survival was 94 %. Late grade 2 or higher GU or GI toxicity was found in 36 patients (5 %) and 9 patients (1.3 %). CONCLUSION: This bicenter analysis shows the efficacy and tolerability of HDR-BB as a complement to external radiotherapy. Further improvements such as combination with new hormonal agents or new brachytherapy-radiotherapy fractionation regimens are warranted to improve further the outcomes and therapeutic ratio.