Neoadjuvant anthracycline-based (5-FEC) or anthracycline-free (docetaxel/carboplatin) chemotherapy plus trastuzumab and pertuzmab in HER2 + BC patients according to their TOP2A: a multicentre, open-label, non-randomized phase II trial.

PURPOSE: Previous studies have reported the benefit of dual HER2-targeting combined to neoadjuvant chemotherapy in HER2-amplified breast cancer (HER2 + BC). Moreover, besides the cardiac toxicity following their association to Trastuzumab, anthracyclines chemotherapy may not profit all patients. The NeoTOP study was designed to evaluate the complementary action of Trastuzumab and Pertuzumab, and the relevance of an anthracycline-based regimen according to TOP2A amplification status. METHODS: Open-label, multicentre, phase II study. Eligible patients were aged ≥ 18 with untreated, operable, histologically confirmed HER2 + BC. After centralized review of TOP2A status, TOP2A-amplified (TOP2A+) patients received FEC100 for 3 cycles then 3 cycles of Trastuzumab (8 mg/kg then 6 mg/kg), Pertuzumab (840 mg/kg then 420 mg/kg), and Docetaxel (75mg/m2 then 100mg/m2). TOP2A-not amplified (TOP2A-) patients received 6 cycles of Docetaxel (75mg/m2) and Carboplatin (target AUC 6 mg/ml/min) plus Trastuzumab and Pertuzumab. Primary endpoint was pathological Complete Response (pCR) using Chevallier's classification. Secondary endpoints included pCR (Sataloff), Progression-Free Survival (PFS), Overall Survival (OS), and toxicity. RESULTS: Out of 74 patients, 41 and 33 were allocated to the TOP2A + and TOP2A- groups respectively. pCR rates (Chevallier) were 74.4% (95%CI: 58.9-85.4) vs. 71.9% (95%CI: 54.6-84.4) in the TOP2A + vs. TOP2A- groups. pCR rates (Sataloff), 5-year PFS and OS were 70.6% (95%CI: 53.8-83.2) vs. 61.5% (95%CI: 42.5-77.6), 82.4% (95%CI: 62.2-93.6) vs. 100% (95%CI: 74.1-100), and 90% (95%CI: 69.8-98.3) vs. 100% (95%CI: 74.1-100). Toxicity profile was consistent with previous reports. CONCLUSION: Our results showed high pCR rates with Trastuzumab and Pertuzumab associated to chemotherapy. They were similar in TOP2A + and TOP2A- groups and the current role of neoadjuvant anthracycline-based chemotherapy remains questioned. TRIAL REGISTRATION NUMBER: NCT02339532 (registered on 14/12/14).

RFID trial: localization of non-palpable breast lesions using radiofrequency identification tags or wire.

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.

Prediction of residual disease using circulating DNA detection after potentiated radiotherapy for locally advanced head and neck cancer (NeckTAR): a study protocol for a prospective, multicentre trial.

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 15th, 2022.

Body Mass Index, Sarcopenia, and Their Variations in Predicting Outcomes for Patients Treated with Nivolumab for Metastatic Renal Cell Carcinoma.

INTRODUCTION: The advent of immune checkpoint inhibitors (ICIs) such as nivolumab has enabled outcomes for metastatic renal cell carcinoma (mRCC) to be improved. However, only around 25% of patients respond to these therapies without being able to formally identify them. Data on relevant predictive markers are still lacking. The obesity paradox has been shown as a relevant prognostic marker in mRCC with better outcomes for obese patients. Nevertheless, the impact of weight variation and the presence of sarcopenia during ICI treatment is not known for now. METHODS: In a retrospective study, weight and its variations were collected at first day of ICI and at 6 weeks of treatment. Scanographic imagery was used to define the skeletal muscle index (SMI) as a reflect of sarcopenia. The impact of these parameters as predictive and prognostic factors for mRCC with nivolumab was evaluated. RESULTS: A higher body mass index (BMI) at baseline was significantly associated with response at the first scan (p = 0.036). Longer overall survival (OS) was observed for patients with a weight gain compared to the group with weight loss (p = 0.00028). Median OS for sarcopenic patients was 17.2 months and 31.6 months for the non-sarcopenic group of patients, but there was no statistical difference. CONCLUSION: This trial showed that a higher BMI and weight gain during nivolumab treatment were good predictive markers for outcomes in mRCC with nivolumab. Sarcopenia and variations in SMI could thus be of interest, but further studies are required.

Preoperative stereotactic radiosurgery for brain metastases: the STEP study protocol for a multicentre, prospective, phase-II trial.

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.

Predictive factors of toxicity of TPF induction chemotherapy for locally advanced head and neck cancers.

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.

A decrease in brown adipose tissue activity is associated with weight gain during chemotherapy in early breast cancer patients.

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 18F-FDG uptake intensity (SUVmax) 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 18F-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 18F-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.

Continuous Wound Infiltration With Ropivacaine After Mastectomy: A Randomized Controlled Trial.

BACKGROUND: To evaluate the efficacy of continuous wound infiltration with ropivacaine to reduce acute postoperative pain in patients undergoing mastectomy for carcinoma of the breast. MATERIALS AND METHODS: A randomized, double-blind, placebo-controlled trial was conducted. One hundred fifty patients were randomly assigned to receive continuous ropivacaine (0.2%) (group A, n = 74) or saline solution (0.9%) (group B, n = 76) at 10 mL/h for 48 h through a multilumen catheter placed during the surgical procedure. Postoperative morphine consumption and visual analog scale (VAS) pain scores were recorded. A quality of life score (Quality of life questionnaire Core 30) and a VAS score were obtained at 1, 3, and 6 mo after surgery. RESULTS: The difference in mean morphine consumption between the two groups was close to significance during the first 48 h postsurgery (P = 0.056; 10.8 ± 16.5 versus 4.8 ± 10.4 mg). At day 1, patients in the ropivacaine-infusion group had lower morphine consumption than the control group (P = 0.0026). The link between local ropivacaine infiltration and a decrease in mean postoperative VAS scores reached significance for the first 24 h postsurgery (P = 0.039). No significant difference was found between the two arms for VAS pain scores (P = 0.36) or for quality of life (overall QLQ-C30 score, P = 0.09) at 1, 3, or 6 mo. CONCLUSIONS: Continuous wound infiltration with ropivacaine is efficacious in reducing postoperative pain. Quality of life and chronic pain at 1, 3, and 6 mo were not improved by ropivacaine wound infiltration.

Quality of life for older patients with cancer: a review of the evidence supporting melatonin use.

PURPOSE: The proportion of older populations living with cancer is on the increase. Maintaining or improving their quality of life (QoL) has become an important goal in the treatment of cancer and has become an endpoint in clinical trials. Melatonin regulates a wide variety of physiological functions and is involved in the initiation of sleep and the improvement of QoL. With age, the secretion of melatonin decreases and could lead to a deterioration in QoL. METHODS: Literature searches were conducted using the PubMed database. The search terms and derivatives of "metastatic cancer", "older patients", "quality of life" and "melatonin" were used. Titles and abstracts were screened to identify whether studies were relevant for full-text screening. RESULTS: There is major concern about the symptoms older cancer patients encounter during treatment because they can impact their QoL. Melatonin supplementation presents several benefits for older patients: improvement in survival, decrease in symptoms induced by cancer and cancer treatment, and also improvements in quality of life. CONCLUSION: It therefore seems appropriate to study the impact of melatonin supplementation during cytotoxic therapy on QoL among elderly patients with metastatic cancer. The use of melatonin as a therapeutic strategy seems particularly suitable for elderly patients, a population known to secrete significantly less melatonin. However, to date, no studies have been conducted in this population.

Treatment-Induced Cardiotoxicity in Breast Cancer: A Review of the Interest of Practicing a Physical Activity.

Physical activity is known to prevent the occurrence of cancer and decrease the risk of breast cancer. At diagnosis of breast cancer, fewer than half of the patients reach the international recommendation for physical activity. However, breast cancer patients, and particularly HER2+ breast cancer patients, are exposed to treatment-induced cardiotoxicity because of a side effect of 2 molecules used in standard therapy to treat these tumors, i.e., anthracycline and trastuzumab. Cardiotoxicity can sometimes lead to discontinuation of the treatment and even to the development of cardiovascular diseases. Exercise is known to protect the cardiovascular system in the healthy population. Consequently, being physically active during treatment appears to be a way to prevent the negative impact of cancer treatment on the heart in this population. In particular, aerobic exercising could have a protective effect against treatment-induced cardiotoxicity. A supervised physical activity program seems to be the best way for breast cancer patients to be active during treatment. However, there is very little information, and in particular a lack of guidelines, on exercising available to patients. The interventional trials that have been conducted on this topic are very heterogeneous and no standard recommendations have been made available for cancer patients thus far. An effective physical activity program needs to take each patient's barriers and motivations into account in order to encourage the practice of physical activity throughout treatment. To ensure the success of the program, it is essential to facilitate adherence and especially maintain motivation. Further studies are needed to determine what practice guidelines oncologists should give their patients.

Prospective Study on Body Composition, Energy Balance and Biological Factors Changes in Post-menopausal Women with Breast Cancer Receiving Adjuvant Chemotherapy Including Taxanes.

In breast cancer patients, weight and fat mass changes observed after chemotherapy have been related to poor prognosis but some recent works using modern chemotherapy failed to find this correlation with weight gain. In this study, the extent of changes in weight and body composition (DEXA, impedance) was characterized until six months after current chemotherapy, in 50 post-menopausal women with breast cancer. The evolution of factors contributing to the energy balance and some biological factors were also described. During chemotherapy, 20% of women lost weight due to both fat (-13.1% ± 10.3) and lean soft tissue mass loss (-3.6% ± 4.6). Twenty percent of women gained weight. No significant fat mass gain was observed in these women but significant water gain was highlighted. Six months later, women who gained weight presented a gain in fat mass (15.4% ± 19.0), especially in the abdominal region. Age and initial BMI were negatively correlated with fat mass in multivariate analyzes (r = 0.486, P = 0.0030). No significant variation of the glucose homeostasis, triglycerides, and HDL-Cholesterol was found six months after chemotherapy. These results do not suggest major adverse metabolic disturbances six months after modern chemotherapy and only a mild fat mass gain was observed in women who gained weight.

Preoperative stereotactic radiotherapy for the management of brain metastases.

Traditionally, postoperative whole-brain radiation therapy (WBRT) has been used for resected brain metastases, reducing local and intracerebral relapses. However, WBRT is associated with cognitive deterioration. Postoperative stereotactic radiotherapy (SRT) has emerged due to its neurocognitive preservation benefits. Despite its advantages, postoperative SRT has several drawbacks, including difficulties in target volume delineation, increased risk of radionecrosis (RN) and leptomeningeal disease (LMD), and prolonged treatment duration. Preoperative SRT has been proposed as a potential alternative, offering promising results in retrospective studies. Retrospective studies have suggested that preoperative SRT could achieve high local control rates with fewer LMD and RN rates compared to postoperative SRT. However, preoperative SRT is primarily based on retrospective data, and no phase 2/3 trials have been published to date. Ongoing clinical trials are expected to provide further insights into the efficacy and safety of preoperative SRT, addressing key questions regarding fractionation, dose, and timing relative to surgery.

Non-invasive intracranial pressure monitoring for high-grade gliomas patients treated with radiotherapy: results of the GMaPIC trial.

Introduction: Patients with high-grade gliomas are at risk of developing increased intracranial hypertension (ICHT) in relation to the increase in volume of their tumor. ICP change cannot be measured by invasive method but can be estimated by using routine clinical signs, in combination with a standard imaging method, magnetic resonance imaging (MRI). A non-invasive monitoring of ICP could be of interest in high-grade glioma, in particular after radiotherapy treatment with as major side effect a cerebral oedema. Patients and Methods: This prospective clinical study aimed to compare the ICP changes (estimated by a non-invasive method based upon distortion product otoacoustic emissions (DPOAE) monitoring) with volume changes observed on MRI in patients with high-grade gliomas treated with radiotherapy. DPOAE measurements were performed one month after the end of radiotherapy and then every 3 months for one year. At each visit, the patient also underwent MRI as well as an evaluation of clinical signs. Results: The variation in the estimate of intracranial pressure readout measured at each follow-up visit (in absolute value with respect to the baseline measurements) was significantly associated with the variation of T2/FLAIR volume (n=125; p<0.001) with a cut off value of change ICP readout of 40.2 degrees (e.i. an estimated change of 16 mm Hg). Discussion: The GMaPIC trial confirm the hypothesis that the ICP change estimated by DPOAEs measurement using a non-invasive medical device is correlated with the change of the tumor or edema in high grade glioma after radiotherapy. The device could thus become an easy-to-use and non-invasive intracranial pressure monitoring tool for these patients. Clinical Trial Registration: Clinicaltrials.gov, identifier (NCT02520492).

A phase-II study based on dose adjustment according to UGT1A1 polymorphism: is irinotecan underdosed in first-line FOLFIRI regimen for mCRC?

PURPOSE: Irinotecan has considerable importance in the treatment of metastatic colorectal cancer (mCRC). UDP-glucoronyltransferase (UGT) 1A1 is responsible for the inactivation of SN-38, a metabolite of irinotecan. Depending on UGT1A1 polymorphism, the activity of the UGT enzyme can be reduced leading to more frequent occurrence of adverse events related to irinotecan. The present study aimed to assess the safety and efficacy of different doses of irinotecan adjusted according to UGT1A1 polymorphism. METHODS: Thirty-four patients treated with FOLFIRI as first-line treatment for mCRC were included in this study. The irinotecan dosage was adapted on the basis of UGT1A1 polymorphisms: *1/*1 (370 mg/m2); *1/*28 (310 mg/m2), and *28/*28 (180 mg/m2). The incidence of grades 3 and 4 toxicities (neutropenia, febrile neutropenia, and diarrhoea) was recorded. Response was assessed according to the RECIST 1.1 criteria. RESULTS: On the basis of UGT1A1 genotyping, 20 patients were *1/*1 (58.8%), 12 were *1/*28 (35.3%) and 2 were *28/*28 (5.9%). Seven patients experienced at least one severe toxicity, i.e., 21% of the population, amounting to eleven adverse events. Concerning the response rate, 15 patients (44%) had partial or complete response. CONCLUSION: This study demonstrates that mCRC patients treated with FOLFIRI can tolerate a higher dose of irinotecan than the standard dose, i.e., > 180 mg/m2, on the basis of their UGT1A1 genotype, without increased toxicities. TRIAL REGISTRATION: NCT01963182 (registered on 16/10/2013, Clermont-Ferrand, France).

Pembrolizumab as a novel therapeutic option for patients with refractory thymic epithelial tumor: A case report.

BACKGROUND: Thymic epithelial carcinomas are rare and have a poor prognosis. Treatment of thymic epithelial carcinoma is multimodal and includes surgery, post-operative radiation therapy, adjuvant and neoadjuvant chemotherapy, or exclusive chemotherapy based on disease resectability. However, there is currently no standard treatment regimen for metastatic and recurrent thymic carcinoma. CASE SUMMARY: A 45-year-old Caucasian male, with no past medical history, presented with hepatalgia and a cervical mass. A computed tomography (CT) scan showed multiple suspect lesions in the lungs, liver, and anterior mediastinum associated with mediastinal and cervical adenopathy. CT-guided percutaneous biopsies of the liver lesions and anterior mediastinal mass were performed, confirming the histopathology of thymic epithelial carcinoma. Management consisted of several chemotherapy regimens and radiation therapy, administered between April 2016 and December 2018. The patient achieved complete metabolic response. Fluorodeoxyglucose positron emission tomography/CT performed in June 2019 showed disease relapse, with reappearance of a large hypermetabolic hepatic mass and involvement of mediastinal and axillary lymph nodes. Intravenous pembrolizumab (200 mg, every 3 wk) was administered after two prior systemic therapies. The patient's response to treatment was last documented on March 5, 2020. CONCLUSION: Pembrolizumab was successful in treatment of a patient with programmed death-ligand 1-negative metastatic thymic carcinoma, pretreated with chemotherapy.

Sister Mary Joseph Nodules: A Case Report about a Rare Location of Skin Metastasis.

Umbilical skin metastases (or Sister Mary Joseph nodules) are rare. Their presence typically indicates the late manifestation of deep-seated abdominopelvic malignancy. They occur mainly in gynecological cancers, and gastrointestinal cancers in men. The most common histology is adenocarcinoma (∼75% of cases), but it can also rarely be squamous cell or undifferentiated carcinoma. These metastases can be present at diagnosis or appear at disease recurrence, and are associated with a very poor prognosis with an average survival of 11 months. We report the clinical case of a 58-year-old man with metastatic pancreatic adenocarcinoma and umbilical cutaneous metastasis after receiving first-line chemotherapy. The diagnosis was established upon liver biopsy in July 2019, after the patient presented with a complaint of transfixing abdominal pain. The first-line treatment consisted of six cycles of modified FOLFIRINOX chemotherapy. However, in November 2019, computed tomography (CT) scan showed disease progression. Second-line treatment with gemcitabine (Gemzar®) led to a 16% decrease in target lesions. During the fourth cycle, three periumbilical indurated nodules appeared. After six cycles, skin infiltration had increased, and the patient reported his abdominal pain had intensified. Reassessment by CT scan showed an increase in both hepatic and peritoneal disease progression. Third-line treatment with FOLFIRI, started on April 15, 2020, could not control the disease, leading to greater induration and subcutaneous infiltration, which were responsible for the increased pain and ultimate death. Umbilical skin metastases are rare, and they are associated with advanced metastatic disease and a very poor prognosis. Cases reporting Sister Mary Joseph nodules are needed to better understand the conditions and mechanisms of their appearance and dissemination.

Eosinophil counts as a relevant prognostic marker for response to nivolumab in the management of renal cell carcinoma: a retrospective study.

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.

Adapted Physical Activity for Breast Cancer Patients Treated with Neoadjuvant Chemotherapy and Trastuzumab Against HER2 (APACAN2): A Protocol for a Feasibility Study.

BACKGROUND: The standard care for HER2-positive breast cancer is chemotherapy plus a HER2-directed therapy. This can lead to treatment-induced cardiotoxicity. On the other hand, the practice of physical activity is known to improve cardiac function; thus HER2-positive breast cancer patients could draw particular benefit from physical activity during treatment. However, at the time of diagnosis for breast cancer, the majority of patients are insufficiently active according to physical activity recommendations of World Health Organisation, and it is difficult to remain or become active during the treatment. There is a lack of data in the literature on the optimal program to propose to patients to encourage them to be active during treatment. The aim of our study is to assess the feasibility of a home-based physical activity program during neoadjuvant chemotherapy and trastuzumab for HER2-positive breast cancer. METHODS: The APACAN2 study is a single-centre, non-randomized interventional trial. Patients with HER2-positive breast cancer treated with anthracycline-based neoadjuvant chemotherapy and trastuzumab are eligible for enrolment. The supervised home-based physical activity program takes place during neoadjuvant chemotherapy (NACT). It combines aerobic and strengthening exercises. The primary endpoint is the proportion of patients reaching the international physical activity recommendations, i.e. 150 minutes of moderate-intensity activity per week at the end of NACT. The study started in April 2018 and seventy patients are expected to be recruited. DISCUSSION: In the literature, the majority of studies on practice of physical activity in breast cancer focus on adjuvant chemotherapy or on the period after the end of treatment. To the best of our knowledge, the APACAN2 study is the first to evaluate a home-based physical activity program during neoadjuvant chemotherapy for HER2-positive breast cancer. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT02963363, registered on July 11, 2016. Identifier with the French National Agency for the Safety of Medicines and Health Products N°ID RCB 2016-A01344-47, registered in August 2016. Protocol: version 8, 24 February 2021.

XENOBREAST Trial: A prospective study of xenografts establishment from surgical specimens of patients with triple negative or luminal b breast cancer.

Introduction: Patient-derived xenografts (PDX) can be used to explore tumour pathophysiology and could be useful to better understand therapeutic response in breast cancer. PDX from mammary tumours are usually made from metastatic tumours. Thus, PDX from primitive mammary tumours or after neoadjuvant treatment are still rare. This study aims to assess the feasibility to establish xenografts from tumour samples of patients with triple negative or luminal B breast cancer in neoadjuvant, adjuvant or metastatic setting. Methods: XENOBREAST is a single-centre and prospective study. This feasibility pilot trial aims to produce xenografts from tumour samples of patients with triple negative or luminal B breast cancer. Patient enrolment is expected to take 3 years: 85 patients will be enrolled and followed for 28 months. Additional blood samples will be taken as part of the study. Surgical specimens from post-NAC surgery, primary surgery or surgical excision of the metastases will be collected to establish PDX. Histomolecular characteristics of the established PDX will be investigated and compared with the initial histomolecular profile of the collected tumours to ensure that they are well-established. Ethics and dissemination: XENOBREAST belongs to category 2 interventional research on the human person. This study has been approved by the Sud Méditerranée IV - Montpellier ethics committee. It is conducted notably in accordance with the Declaration of Helsinki and General Data Protection Regulation (GDPR). Study data and findings will be published in peer-reviewed medical journals. We also plan to present the study and all data at national congresses and conferences. Registration: ClinicalTrials.gov ID NCT04133077; registered on October 21, 2019.

Impact of Chemotherapy-induced Menopause in Women of Childbearing Age With Non-metastatic Breast Cancer - Preliminary Results From the MENOCOR Study.

BACKGROUND: Young patients with breast cancer treated with chemotherapy can experience ovarian failure, which can lead to chemotherapy-induced menopause (CIM) impacting the quality of life (QoL). A prospective study was set out to evaluate the impact of CIM on QoL in women of childbearing age with non-metastatic breast cancer, and this article reports results of the interim analysis conducted to evaluate feasibility and to see preliminary results. PATIENTS AND METHODS: A total of 58 women (age, 18-46 years) with newly diagnosed breast cancer and treated with chemotherapy were eligible. QoL was assessed by self-administered questionnaires (Quality of Life Questionnaire-Core 30 [QLQ-C30], Quality of Life Questionnaire-Breast 23 [QLQ-BR23], and Kupperman index) and hormonal variations (anti-Müllerian hormone [AMH], follicle-stimulating hormone, and estradiol) were explored. We compared patients with ≥ 12 months amenorrhea (CIM) (n = 41) to patients with < 12 months of amenorrhea (non-CIM) (n = 17). RESULTS: A good inclusion rate (approximately 4/month) and sufficient data enabled us to perform this analysis. QLQ-C30 failed to show any difference between CIM and non-CIM patients (P = .5). In contrast, at 6 months post-chemotherapy, CIM patients tended to have lower QoL as shown by QLQ-BR23 (P = .16) and more severe climacteric symptoms (P = .01). Regarding hormonal variations, AMH pre-treatment level was higher in non-CIM patients (P = .0032). We also noted that CIM patients were older (P = .00013), had shorter menstruation cycle (P = .082), and experienced faster amenorrhea (P = .088). CONCLUSIONS: The study is technically feasible, and our preliminary results underline that age in association with pre-treatment AMH level could be helpful to predict ovarian function. QLQ-BR23 seemed to be stronger, more precise, and appropriate to evaluate QoL changes in patients with breast cancer than the QLQ-C30.