Brain metastases from breast cancer: prognostic significance of HER-2 overexpression, effect of trastuzumab and cause of death

<p>Abstract</p> <p>Background</p> <p>To access the prognostic significance of HER-2 overexpression, the effect of trastuzumab and the cause of death in patients with brain metastases (BM) from breast cancer (BC).</p> <p>Methods</p> <p>We analyzed the outcome of 130 patients with BM from BC who received whole-brain radiotherapy (WBRT) (without surgery or radiosurgery) between January 1998 and April 2006. Demographic data, tumor characteristics, and treatments were prospectively recorded. The impact of HER-2 overexpression and trastuzumab-based therapy on overall survival (OS) and the cause of death were evaluated.</p> <p>Results</p> <p>The median follow-up for the whole population was 6.25 months (mean: 9.15; range: 0.23-53). The median survival time and 1-year survival rates after BM diagnosis were 7.43 months and 35.8% (95% CI: 28-45.7) respectively. The median survival time for HER-2 negative patients (n = 78), HER-2 positive patients not treated with trastuzumab (n = 20) and HER-2 positive patients treated with trastuzumab (n = 32) were 5.9 months, 5.6 months and 19.53 months, respectively. The 1-year survival rates were 26.1%, 29.2% and 62.6% respectively, (p < 0.004). Among the 18 HER-2 positive patients treated with trastuzumab who died, 11 (61%) apparently succumbed from CNS progression, in the face of stable or responsive non-CNS disease. Trastuzumab-based therapy was associated with a 51% reduction in the risk of death (multiadjusted hazard ratio: 0.49; 95% CI, 0.29-0.83).</p> <p>Conclusions</p> <p>In our experience, trastuzumab-based therapy for HER-overexpressing tumors was associated with improved survival in BM BC patients. This subgroup of patients may benefit from innovative approaches, in order to obtain better intra cerebral control.</p

Radiation therapy of anal canal carcinoma

La radio(chimio)thérapie correspond au traitement de référence des carcinomes épidermoïdes du canal anal localisés qui représentent la majorité des cas. Elle a pour objectif d’obtenir une stérilisation tumorale définitive tout en conservant un sphincter anal fonctionnel. Cet article a pour objectif de préciser les indications et les modalités de la radiothérapie pelvienne dans cette situation. Il sera également question des nouvelles modalités d’irradiation (Radiothérapie Conformationnelle avec Modulation d’Intensité ; Tomothérapie hélicoïdale et irradiation avec modulation d’intensité volumétrique par Arc thérapie) qui permettent à la fois une meilleure définition des volumes cibles et une meilleure protection des organes à risque (intestin grêle, recto-sigmoïde, vessie, organes génitaux notamment). Cette dernière réduit la toxicité induite, ce qui permet d’envisager une réduction de la durée totale du traitement (réduction de la durée de la pause thérapeutique entre les 2 séquences de radiothérapie, voire suppression de cette pause avec traitement continu). La réduction de la toxicité devrait également permettre d’augmenter la dose totale délivrée dans le volume cible. L’intérêt d’une telle stratégie mérite d’être évalué.Radio(chemo)therapy is the standard treatment of localized epidermoid carcinomas of the anal canal, which represent the majority of cases. The aim of treatment is to obtain tumor sterilization while preserving functional anal sphincter. This article concerns the indications and the modalities of radiotherapy in this situation, with special attention to the new available radiation techniques (conformational static field intensity modulated radiotherapy; helicoidal tomotherapy; volumetric modulated arc therapy). These developments mainly allow to reduce the dose to normal tissues and organs at risk thereby minimizing the risk of toxicity. The reduction of the induced morbidity should allow to shorten the classical 2 to 6 weeks gap period between the two sequences of radiotherapy and therefore the total duration of treatment. It also should allow dose escalation to the tumor volume potentially leading to improved locoregional control

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

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LE HAVRE-BU Centrale (763512101) / SudocSudocFranceF

Effectiveness of radiotherapy to prevent recurrence of heterotopic ossification in patients with spinal cord injury and traumatic head injury: A retrospective case-controlled study

International audienceObjective: To evaluate recurrence and early postoperative complications (sepsis) following surgical excision combined with radiotherapy for troublesome hip heterotopic ossification in patients with spinal cord injury and traumatic brain injury. Design: Retrospective case-control study. Setting: Data relating to patients with spinal cord injury or traumatic brain injury who underwent surgical excision of hip heterotopic ossification were retrieved from the BANKHO database. Case patients underwent excision + radiotherapy, and controls underwent excision only. Control patients were matched to case patients according to sex and age (± 4 years). Participants: Data from 19 case patients and 76 controls were analysed. Main outcome measure: The primary end-point was recurrence of heterotopic ossification. Secondary endpoints were postoperative complications and, more specifically, sepsis that required surgical revision. Results: There was no difference between the odds ratios (OR) for recurrence for each group (OR case group = 0.63, OR spinal cord injury subgroup = 0.45 and OR head injury subgroup = 1.04). The rate of sepsis requiring surgical revision was significantly higher in the case group (p < 0.05). Conclusion: Based on the results of this case-control study, we suggest that radiotherapy should not be combined with surgery in patients with troublesome hip heterotopic ossification undergoing excision. Radiotherapy does not appear to prevent recurrence and, moreover, it is associated with an increased risk of postoperative sepsis

Mutational analysis of anal cancers demonstrates frequent PIK3CA mutations associated with poor outcome after salvage abdominoperineal resection

International audienceBackground: A better understanding of the molecular profile of anal squamous cell carcinomas (ASCCs) is necessary to consider new therapeutic approaches, and the identification of prognostic and predictive factors for response to treatment. Methods: We retrospectively analysed tumours from ASCC patients for mutational analysis of KRAS, NRAS, HRAS, BRAF, PIK3CA, MET, TP53 and FBXW7 genes by HRM and Sanger sequencing analysis. Results: Specimens from 148 patients were analysed: 96 treatment-naive tumours and 52 recurrences after initial radiotherapy (RT) or chemoradiotherapy (CRT). Mutations of KRAS, PIK3CA, FBXW7 and TP53 genes were present in 3 (2.0%), 30 (20.3%), 9 (6.1%) and 7 tumours (4.7%), respectively. The distribution of the mutations was similar between treatment-naive tumours and recurrences, except for TP53 mutations being more frequent in recurrences (P = 0.0005). In patients treated with abdominoperineal resection (APR) after relapse (n = 38, median follow-up of 18.2 years), overall survival (OS) was significantly correlated with HPV16 status (P = 0.048), gender (P = 0.045) and PIK3CA mutation (P = 0.037). The PIK3CA status retained its prognostic significance in Cox multivariate regression analysis (P = 0.025). Conclusions: Our study identified PIK3CA mutation as an independent prognostic factor in patients who underwent APR for ASCC recurrence, suggesting a potential benefit from adjuvant treatment and the evaluation of targeted therapies with PI3K/Akt/mTor inhibitors in PIK3CA-mutated patients

Expert consensus statement on venovenous extracorporeal membrane oxygenation ECMO for COVID-19 severe ARDS: an international Delphi study

Abstract Background The high-quality evidence on managing COVID-19 patients requiring extracorporeal membrane oxygenation (ECMO) support is insufficient. Furthermore, there is little consensus on allocating ECMO resources when scarce. The paucity of evidence and the need for guidance on controversial topics required an international expert consensus statement to understand the role of ECMO in COVID-19 better. Twenty-two international ECMO experts worldwide work together to interpret the most recent findings of the evolving published research, statement formulation, and voting to achieve consensus. Objectives To guide the next generation of ECMO practitioners during future pandemics on tackling controversial topics pertaining to using ECMO for patients with COVID-19-related severe ARDS. Methods The scientific committee was assembled of five chairpersons with more than 5 years of ECMO experience and a critical care background. Their roles were modifying and restructuring the panel’s questions and, assisting with statement formulation in addition to expert composition and literature review. Experts are identified based on their clinical experience with ECMO (minimum of 5 years) and previous academic activity on a global scale, with a focus on diversity in gender, geography, area of expertise, and level of seniority. We used the modified Delphi technique rounds and the nominal group technique (NGT) through three face-to-face meetings and the voting on the statement was conducted anonymously. The entire process was planned to be carried out in five phases: identifying the gap of knowledge, validation, statement formulation, voting, and drafting, respectively. Results In phase I, the scientific committee obtained 52 questions on controversial topics in ECMO for COVID-19, further reviewed for duplication and redundancy in phase II, resulting in nine domains with 32 questions with a validation rate exceeding 75% (Fig. 1). In phase III, 25 questions were used to formulate 14 statements, and six questions achieved no consensus on the statements. In phase IV, two voting rounds resulted in 14 statements that reached a consensus are included in four domains which are: patient selection, ECMO clinical management, operational and logistics management, and ethics. Conclusion Three years after the onset of COVID-19, our understanding of the role of ECMO has evolved. However, it is incomplete. Tota14 statements achieved consensus; included in four domains discussing patient selection, clinical ECMO management, operational and logistic ECMO management and ethics to guide next-generation ECMO providers during future pandemic situations