Explore the vast range of titles available.

Background Despite standard treatments including chemoradiotherapy with temozolomide (TMZ) (STUPP protocol), the prognosis of glioblastoma patients remains poor. AGuIX nanoparticles have a high radiosensitizing potential, a selective and long-lasting accumulation in tumors and a rapid renal elimination. Their therapeutic effect has been proven in vivo on several tumor models, including glioblastoma with a potential synergetic effect when combined with TMZ based chemoradiotherapy, and they are currently evaluated in 4 ongoing Phase Ib and II clinical trials in 4 indications (brain metastases, lung, pancreatic and cervix cancers) (> 100 patients received AGuIX). Thus, they could offer new perspectives for patients with newly diagnosed glioblastoma. The aim of this study is to determine the recommended dose of AGuIX as a radiosensitizer in combination with radiotherapy and TMZ during the concurrent radio-chemotherapy period for phase II (RP2D) and to estimate the efficacy of the combination. Methods NANO-GBM is a multicenter, phase I/II, randomized, open-label, non-comparative, therapeutic trial. According to a dose escalation scheme driven by a TITE-CRM design, 3 dose levels of AGuIX (50, 75 and 100 mg/kg) will be tested in phase I added to standard concomitant radio-chemotherapy. Patients with grade IV glioblastoma, not operated or partially operated, with a KPS ≥ 70% will be eligible for the study. The primary endpoints are i) for phase I, the RP2D of AGuIX, with DLT defined as any grade 3–4 NCI-CTCAE toxicity and ii) for phase II, the 6-month progression-free survival rate. The pharmacokinetics, distribution of nanoparticles, tolerance of the combination, neurological status, overall survival (median, 6-month and 12-month rates), response to treatment, and progression-free survival (median and 12-month rates) will be assessed as secondary objectives. Maximum sixty-six patients are expected to be recruited in the study from 6 sites. Discussion The use of AGuIX nanoparticles could allow to overpass the radioresistance to the reference treatment of newly diagnosed glioblastomas that have the poorest prognosis (incomplete resection or biopsy only). Trial registration Clinicaltrials.gov: NCT04881032 , registered on April 30, 2021. Identifier with the French National Agency for the Safety of Medicines and Health Products (ANSM): N°Eudra CT 2020-004552-15. Protocol: version 3, 23 May 2022.

Background Most breast cancers are detected at an early stage in which case conservative surgery is indicated. An accurate preoperative localization technique is essential for conservative surgery of non-palpable breast lesions. Currently, the gold standard technique is wire localization (WL). However, this technique has well-known drawbacks. Several wire-free techniques have been developed to overcome these drawbacks; one technique is localisation by Radiofrequency Identification (RFID). The purpose of this clinical trial was to assess the superiority of RFID tags (HOLOGIC) in terms of patient satisfaction, over wire localization of non-palpable breast lesions. Methods This was a single-centre, prospective, controlled and non-interventional trial. Patients were followed from their inclusion at the time of the preoperative consultation to the postoperative consultation, one month after surgery. Data on anxiety and satisfaction was collected from patients and clinicians using questionnaires, and clinical data was collected from the medical files. The primary outcome was the patients’ satisfaction scores, assessed using a visual analogue scale. Results Eighty patients were sequentially enrolled in two groups: the wire group ( n  = 40) and the RFID group ( n  = 40). One patient from the RFID group was excluded from the analysis because of a substantial migration during deployment. On a 10-point Visual Analogue Scale, the patients’ median satisfaction score was 9.8 (IQR = 1.32) for the wire group and 10 (IQR = 0.07) for the RFID group ( p  < 0.001). A reduction in pain between device insertion and surgery was observed in the RFID group ( p  = 0.009). The median placement time was shorter in the RFID group (15 min, IQR = 6) than in the wire group (20 min, IQR = 30) ( p  = 0.01). Conclusion Our results show a statistically significant difference in median patient satisfaction score with the localization of non-palpable breast cancer lesions using RFID tags compared to the use of the WL. Although our results did not show clinically significant outcomes in terms of satisfaction, RFID tags are a reliable alternative to WL and simplify the organization of patients’ healthcare trajectories. Trial registration ClinicalTrials.gov ID; NCT04750889 registered on February 11, 2021. https://clinicaltrials.gov/ct2/show/NCT04750889?term=rfid&draw=2&rank=1

Background The rate of toxic deaths related to induction chemotherapy in the treatment of locally advanced head and neck cancers is unacceptable and calls into question this therapeutic strategy, which is however highly effective in terms of rate and speed of response. The purpose of the study was to investigate predictive factors of toxicity of induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (TPF) in locally advanced head and neck cancers (LAHNC). Methods Between June 2009 and December 2017, 113 patients treated consecutively with TPF were included retrospectively. Patients were receiving induction chemotherapy for either an inoperable cancer or laryngeal preservation. For inoperable cancer, induction chemotherapy was proposed to patients presenting either a large tumor with strong symptoms (dyspnea, dysphagia, pain) or a tumor with rapid progression. Risk factors were chosen among the initial patient and tumour characteristics and chemotherapy modalities. Results Eighty-nine patients (79%) were male; the median age was 58 years [32–71]. Sixty-nine (61%) patients were treated for inoperable cancer and 44 (39%) for laryngeal preservation. 45% had stage IVa cancer, 28% stage III and 25% stage IVb. Sixty percent of patients had a partial response after TPF, 22% had a complete response, 12% were stable, 5% were progressing, and 1% had a discordant response. Thirty-four patients (30%) received enteral feeding during induction chemotherapy with TPF. The possibility of oral feeding without a tube was predictive of a better response ( p  = 0.003). Seven (6%) patients died during TPF. There was an increased risk of death with preexisting liver dysfunction (liver dysmorphia on imaging or decrease prothrombin rate) ( p  = 0.032). There was an increased risk of grade ≥ 3 infection if an enteral feeding occurred during the period of induction chemotherapy (p = 0.03). Conclusions TPF induction chemotherapy had an 82% objective response rate with 6% toxic deaths. Nutritional status and the presence of hepatic dysfunction are significant risk factors to be taken into account in therapeutic decisions.

Background Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in women. Approximately 50% of breast cancers are discovered at an early stage in patients for whom conservative surgery is indicated. Intraoperative localization of non-palpable breast lesions is generally accomplished using a hook wire to mark the area of concern under ultrasound or stereotactic localization. But this technique has several drawbacks (painful, stressful…). We propose the use of a wire-free breast lesion system using miniature radiofrequency identification (RFID) tags. This technique could improve patient comfort and surgical comfort for surgeons. We therefore propose a study to assess the interest of introducing the RFID localization technique at the Jean PERRIN comprehensive cancer center. Methods This is a single-center prospective trial designed to assess the interest in introducing the RFID localization technique at the Jean Perrin center. It aims to show the superiority of the RFID technique in terms of patient tolerance compared to the gold-standard (hook wire). A sequential inclusion in time will be performed: 20 inclusions in the gold-standard group, then 20 patients in the RFID group before repeating the inclusion scheme. Any patient requiring preoperative localization will receive a senology consultation. The RFID tag will be placed during this consultation. The hook wire localization will be done the day before the surgery. Patients will fill out a Hospital Anxiety and Depression scale (HAD) questionnaire at the time of inclusion. They will then fill out a satisfaction questionnaire in 2 steps: during the placement of the device (RFID tag or hook wire) or during the postoperative consultation at 1 month. Radiologists and surgeons will fill out a questionnaire to evaluate the localization technique, respectively after the localization and surgery procedures. Discussion The RFID study is the first study in France which specifically assesses the interest of the RFID localization in terms of patients comfort. Patient comfort is one of the key elements to take into consideration when managing patients in oncology and new technologies such as RFID tags could improve it. Trial registration ClinicalTrials.gov ID; NCT04750889 registered on February 11, 2021.

Background A decrease in thermogenesis is suspected to be implicated in the energy expenditure reduction during breast cancer treatment. This study aimed to investigate the impact of chemotherapy on the metabolic activity of brown adipose tissue (BAT) and the link with weight variation. Methods This was an ancillary analysis of a multicentre trial involving 109 HER2+ breast cancer patients treated with neoadjuvant chemotherapy. A centralised review of 18 F-FDG uptake intensity (SUV max ) in specific BAT regions (cervical and supraclavicular) was conducted on two PET-CT scans for each patient (before and after the first course of chemotherapy). Results Overall, after one course of chemotherapy a significant decrease of 4.4% in 18 F-FDG-uptake intensity was observed. It was not correlated to initial BMI, age or season. During chemotherapy, 10.1% ( n  = 11) of the patients lost weight (− 7.7 kg ± 3.8 kg; ie, − 9.4% ± 3.7%) and 29.4% ( n  = 32) gained weight (+ 5.1 kg ± 1.7 kg; ie, + 8.5% ± 2.6%). Among these subgroups, only the patients who had gained weight underwent a significant decrease (13.42%) in 18 F-FDG uptake intensity ( p  = 0.042). Conclusion This study is the first to highlight in a large cohort of patients the negative impact of chemotherapy on brown adipose tissue activity. Weight gain during chemotherapy could thus potentially be explained in part by a decrease in brown adipose tissue activity.

Background Over the past twenty years, the post-cancer rehabilitation has been developed, usually in a hospital setting. Although this allows better care organization and improved security, it is perceived as stressful and restrictive by the “cancer survivor”. Therefore, the transfer of benefits to everyday life is more difficult, or even uncertain. Staying in a thermal resort seemed to offer a good compromise: the security and structure of centralized reception in a thermal resort for treatment and medical supervision, and accommodation in a hotel with full dietary board. It combines institutional quality and security with the freedom of real life and the dynamics of a group formed under innovative conditions. This rehabilitation procedure was tested with the program PACThe (Program of Accompanying women after breast Cancer treatment completion in Thermal resorts) which was evaluated at one year in a randomized controlled trial involving 251 patients [ 1 ] and at five years in another study [ 2 ]. The results shown a significative improvement in many areas such as quality of life, functional abilities and sleep. The aim of this study is therefore to confirm the benefits of the PACThe program at six months for breast cancer women in complete remission in real-life conditions. Methods The project PACThe Real-Life conditions is an observational trial in which 400 breast cancer women in complete remission will be sent to a 3 week thermal “post-cancer rehabilitation” program. Primary objective is to assess the quality of life until 12 months. The outcome will be measured with the self-questionnaire SF-36 [ 3 ] at five timepoints (inclusion visit, end of thermal resort, 6 months post-cure, 12 months post-cure and 18 months post-cure). The duration of patient participation in the study will therefore be 18 months. The main analysis will consist of comparing the SF-36 global score at 6 months with the baseline. Discussion This study aims to investigate the improvements in quality of life of 3 weeks stay at thermal resort for breast cancer women in complete remission. The comprehensive overview of the program PACThe will likely contribute to enhancing thermal therapy post-cancer rehabilitation in this population in real life conditions. Trial registration The PACThe Real-Life conditions trial is a prospective observational study registered at the ANSM registry (2022-A00171-42) on March 1, 2022. This study has been registered on ClinicalTrials.gov: NCT05433077. Protocol: version 4, 22 December 2022.

Background While well-characterised on its molecular base, non-small cell lung cancer (NSCLC) and its interaction with local microbiota remains scarcely explored. Moreover, current studies vary in source of lung microbiota, from bronchoalveolar lavage fluid (BAL) to tissue, introducing potentially differing results. Therefore, the objective of this study was to provide detailed characterisation of the oral and multi-source lung microbiota of direct interest in lung cancer research. Since lung tumours in lower lobes (LL) have been associated with decreased survival, characteristics of the microbiota in upper (UL) and lower tumour lobes have also been examined. Methods Using 16S rRNA gene sequencing technology, we analysed microbiota in saliva, BAL (obtained directly on excised lobe), non-malignant, peritumoural and tumour tissue from 18 NSCLC patients eligible for surgical treatment. Detailed taxonomy, diversity and core members were provided for each microbiota, with analysis of differential abundance on all taxonomical levels (zero-inflated binomial general linear model with Benjamini-Hochberg correction), between samples and lobe locations. Results Diversity and differential abundance analysis showed clear separation of oral and lung microbiota, but more importantly, of BAL and lung tissue microbiota. Phylum Proteobacteria dominated tissue samples, while Firmicutes was more abundant in BAL and saliva (with class Clostridia and Bacilli , respectively). However, all samples showed increased abundance of phylum Firmicutes in LL, with decrease in Proteobacteria . Also, clades Actinobacteria and Flavobacteriia showed inverse abundance between BAL and extratumoural tissues depending on the lobe location. While tumour microbiota seemed the least affected by location, peritumoural tissue showed the highest susceptibility with markedly increased similarity to BAL microbiota in UL. Differences between the three lung tissues were however very limited. Conclusions Our results confirm that BAL harbours unique lung microbiota and emphasise the importance of the sample choice for lung microbiota analysis. Further, limited differences between the tissues indicate that different local tumour-related factors, such as tumour type, stage or associated immunity, might be the ones responsible for microbiota-shaping effect. Finally, the “shift” towards Firmicutes in LL might be a sign of increased pathogenicity, as suggested in similar malignancies, and connected to worse prognosis of the LL tumours. Trial registration ClinicalTrials.gov ID: NCT03068663 . Registered February 27, 2017.

Background Sensitive and reproducible detection of residual disease after treatment is a major challenge for patients with locally advanced head and neck cancer. Indeed, the current imaging techniques are not always reliable enough to determine the presence of residual disease. The aim of the NeckTAR trial is to assess the ability of circulating DNA (cDNA), both tumoral and viral, at three months post-treatment, to predict residual disease, at the time of the neck dissection, among patients with partial cervical lymph node response on PET-CT, after potentiated radiotherapy. Methods This will be an interventional, multicentre, single-arm, open-label, prospective study. A blood sample will be screened for cDNA before potentiated radiotherapy and after 3 months if adenomegaly persists on the CT scan 3 months after the end of treatment. Patients will be enrolled in 4 sites in France. Evaluable patients, i.e. those with presence of cDNA at inclusion, an indication for neck dissection, and a blood sample at M3, will be followed for 30 months. Thirty-two evaluable patients are expected to be recruited in the study. Discussion The decision to perform neck dissection in case of persistent cervical adenopathy after radio-chemotherapy for locally advanced head and neck cancer is not always straightforward. Although studies have shown that circulating tumour DNA is detectable in a large proportion of patients with head and neck cancer, enabling the monitoring of response, the current data is insufficient to allow routine use of this marker. Our study could lead to better identification of patients who do not have residual lymph node disease in order to avoid neck dissection and preserve their quality-of-life while maintaining their prospects of survival. Trial registration Clinicaltrials.gov: NCT05710679, registered on 02/02/2023, https://clinicaltrials.gov/ct2/show/ . Identifier with the French National Agency for the Safety of Medicines and Health Products (ANSM): N°ID RCB 2022-A01668-35, registered on July 15 th , 2022.

Background Despite improvements in the management of renal cell carcinomas (RCC) with the advent of immunotherapy, only a few patients respond to these treatments. Predictors of response to nivolumab are currently being investigated but are still lacking. Aim of the study To evaluate eosinophil levels and their variations during treatment as an accurate biomarker for outcome in metastatic RCC treated with nivolumab. Methods A retrospective analysis was carried out for patients with metastatic RCC treated with nivolumab. Absolute eosinophil counts, their variation, and relative change were evaluated at six weeks. Relative eosinophil change was categorized in three groups (≥10%‐decrease, no change, ≥10%‐increase). Univariable and multivariable analyses were performed to determine whether eosinophils and their variations were prognostic markers for response at the first scan evaluation, progression‐free survival, and overall survival. Results Sixty‐five patients aged on average 66 years, 68% men, and 77% with good or intermediate International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk group were included. The median follow‐up was 16.6 months. Median overall survival (OS) was not reached for good prognosis and was 22.5 and 6.5 months for intermediate and poor prognosis, respectively. An increase in eosinophils and relative eosinophil change at six weeks of nivolumab was associated with a good response to immunotherapy (p = 0.012 and p = 0.024 respectively). In the group of patients with a 10%‐decrease in relative change, PFS reduced significantly compared to the other groups (p = 0.0044 with the 10%‐increase group and p = 0.03 with the no‐change group). This relative increase was independent of IMDC risks factors for better OS (HR = 3.3 [1.45–7.4]; p = 0.004). The eosinophil baseline level was not associated with response to treatment. Conclusion Eosinophil levels and relative eosinophil change at 6 weeks might be good prognostic markers for response to nivolumab for metastatic RCC, and were associated with better PFS and OS. Despite improvements in the management of renal cell carcinomas (RCC) with the advent of immunotherapy, only a few patients respond to these treatments. Predictors of response to nivolumab are currently being investigated but are still lacking. Eosinophil levels and relative eosinophil change at 6 weeks might be good prognostic markers for response to nivolumab for metastatic RCC and were associated with better PFS and OS.

Background Surgery is an important therapeutic option for brain metastases. Currently, postoperative stereotactic radiosurgery (SRT) leads to 6-month and 1-year local control estimated at 70 and 62% respectively. However, there is an increased risk of radio-necrosis and leptomeningeal relapse. Preoperative SRT might be an alternative, providing local control remains at least equivalent. It is an innovative concept that could enable the stereotactic benefits to be retained with advantages over post-operative SRT. Methods STEP has been designed as a national, multicentre, open-label, prospective, non-randomized, phase-II trial. Seventeen patients are expected to be recruited in the study from 7 sites and they will be followed for 12 months. Patients with more than 4 distinct brain metastases, including one with a surgical indication, and an indication for SRT and surgery, are eligible for enrolment. The primary objective of the trial is to assess 6-month local control after preoperative SRT. The secondary objectives include the assessment of local control, radio-necrosis, overall survival, toxicities, leptomeningeal relapse, distant control, cognitive function, and quality of life. The experimental design is based on a Flemming plan. Discussion There is very little data available in the literature on preoperative SRT: there have only been 3 American single or two-centre retrospective studies. STEP is the first prospective trial on preoperative SRT in Europe. Compared to postoperative stereotactic radiotherapy, preoperative stereotactic radiotherapy will enable reduction in the irradiated volume, leptomeningeal relapse and the total duration of the combined treatment (from 4 to 6 weeks to a few days). Trial registration number Clinicaltrials.gov: NCT04503772 , registered on August 07, 2020. Identifier with the French National Agency for the Safety of Medicines and Health Products (ANSM): N°ID RCB 2020-A00403–36, registered in February 2020. Protocol: version 4, 07 December 2020.