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

Association between Severe SARS-CoV-2 Infection and Severe Acute Pancreatitis in Pregnancy and Postpartum

Introduction: SARS-CoV-2 infection (COVID-19) affects the respiratory system but is not limited to it. The gastrointestinal symptoms are polymorphic, including diarrhea, vomiting, abdominal pain, and even acute pancreatitis (AP). Pregnant women are more vulnerable to SARS-CoV-2 infection and have a higher risk of severe outcomes of COVID-19. Case report: We present a case report of a 31-year-old primigravid patient at 30 weeks of gestation, unvaccinated, with a medical history of thrombophilia, chronic nephropathy of unknown origin, hypertension, and optic neuropathy with left eye hemianopsia. She was diagnosed with moderate-to-severe COVID-19 and respiratory failure, with indication for cesarean section. Postpartum, she developed severe acute pancreatitis, complicated by peripancreatic and supradiaphragmatic abscesses. After 3 months of hospitalization and eight surgical interventions, the patient was discharged. A short mini-review of the literature is introduced. Conclusion: Pregnant women with cardiovascular comorbidities are prone to severe complications of SARS-CoV-2 infection. Clinicians should be aware of the association of SARS-CoV-2 and AP in pregnant women

The Connection between MicroRNAs and Oral Cancer Pathogenesis: Emerging Biomarkers in Oral Cancer Management

Oral cancer is a common human malignancy that still maintains an elevated mortality rate despite scientific progress. Tumorigenesis is driven by altered gene expression patterns of proto-oncogenes and tumor-suppressor genes. MicroRNAs, a class of short non-coding RNAs involved in gene regulation, seem to play important roles in oral cancer development, progression, and tumor microenvironment modulation. As properties of microRNAs render them stable in diverse liquid biopsies, together with their differential expression signature in cancer cells, these features place microRNAs at the top of promising biomarkers for diagnostic and prognostic values. In this review, we highlight eight expression levels and functions of the most relevant microRNAs involved in oral cancer development, progression, and microenvironment sustainability. Furthermore, we emphasize the potential of using these small RNA species as non-invasive biomarkers for the early detection of oral cancerous lesions. Conclusively, we highlight the perspectives and limitations of microRNAs as novel diagnostic tools, as well as therapeutic models

Chimeric Antigen Receptor T-Cells for the Treatment of B-Cell Acute Lymphoblastic Leukemia

Chimeric antigen receptor (CAR) T-cell technology has seen a rapid development over the last decade mostly due to the potential that these cells may have in treating malignant diseases. It is a generally accepted principle that very few therapeutic compounds deliver a clinical response without treatment-related toxicity, and studies have shown that CAR T-cells are not an exception to this rule. While large multinational drug companies are currently investigating the potential role of CAR T-cells in hematological oncology, the potential of such cellular therapies are being recognized worldwide as they are expected to expand in the patient to support the establishment of the immune memory, provide a continuous surveillance to prevent and/or treat a relapse, and keep the targeted malignant cell subpopulation in check. In this article, we present the possible advantages of using CAR T-cells in treating acute lymphoblastic leukemia, presenting the technology and the current knowledge in their preclinical and early clinical trial use. Thus, this article first presents the main present-day knowledge on the standard of care for acute lymphoblastic leukemia. Afterward, current knowledge is presented about the use of CAR T-cells in cancer immunotherapy, describing their design, the molecular constructs, and the preclinical data on murine models to properly explain the background for their clinical use. Last, but certainly not least, this article presents the use of CAR T-cells for the immunotherapy of B-cell acute lymphoblastic leukemia, describing both their potential clinical advantages and the possible side effects

Intracranial Treatment in Melanoma Patients with Brain Metastasis Is Associated with Improved Survival in the Era of Immunotherapy and Anti-BRAF Therapy

Metastatic melanoma patients are at high risk of brain metastases (BM). Although intracranial control is a prognostic factor for survival, impact of local (intracranial) treatment (LT), surgery and/or radiotherapy (stereotactic or whole brain) in the era of novel therapies remains unknown. We evaluated BM incidence in melanoma patients receiving immune checkpoint inhibitors (ICI) or anti-BRAF therapy and identified prognostic factors for overall survival (OS). Clinical data and treatment patterns were retrospectively collected from all patients treated for newly diagnosed locally advanced or metastatic melanoma between May 2014 and December 2017 with available BRAF mutation status and receiving systemic therapy. Prognostic factors for OS were analyzed with univariable and multivariable survival analyses. BMs occurred in 106 of 250 eligible patients (42.4%), 64 of whom received LT. Median OS in patients with BM was 7.8 months (95% CI [5.4–10.4]). In multivariable analyses, LT was significantly correlated with improved OS (HR 0.21, p < 0.01). Median OS was 17.3 months (95% CI [8.3–22.3]) versus 3.6 months (95% CI [1.4–4.8]) in patients with or without LT. LT correlates with improved OS in melanoma patients with BM in the era of ICI and anti-BRAF therapy. The use of LT should be addressed at diagnosis of BM while introducing systemic treatment

Helical Tomotherapy for Inoperable Breast Cancer: A New Promising Tool

Background. We investigated the feasibility of helical tomotherapy (HT) for inoperable large breast tumors, after failing to achieve adequate treatment planning with conformal radiation techniques. Material and Methods. Five consecutive patients with locally advanced breast cancer (LABC) were treated by preoperative HT. All patients received up-front chemotherapy before HT. Irradiated volumes included breast and nodal areas (45–50 Gy) in 4 patients. One patient received a simultaneous integrated boost (55 Gy) to gross tumor volume (GTV) without lymph node irradiation. Acute toxicity was assessed with Common Toxicity Criteria for Adverse Events v.4. Patients were evaluated for surgery at the end of treatment. Results. Patients were staged IIB to IIIC (according to the AJCC staging system 2010). HT was associated in 4 patients with concomitant chemotherapy (5-fluorouracil and vinorelbine). Two patients were scored with grade 3 skin toxicity (had not completed HT) and one with grade 3 febrile neutropenia. One patient stopped HT with grade 2 skin toxicity. All patients were able to undergo mastectomy at a median interval of 43 days (31–52) from HT. Pathological partial response was seen in all patients. Conclusions. HT is feasible with acceptable toxicity profiles, potentially increased by chemotherapy. These preliminary results prompt us to consider a phase II study

Nomogram to predict rectal toxicity following prostate cancer radiotherapy.

To identify predictors of acute and late rectal toxicity following prostate cancer radiotherapy (RT), while integrating the potential impact of RT technique, dose escalation, and moderate hypofractionation, thus enabling us to generate a nomogram for individual prediction.In total, 972 patients underwent RT for localized prostate cancer, to a total dose of 70 Gy or 80 Gy, using two different fractionations (2 Gy or 2.5 Gy/day), by means of several RT techniques (3D conformal RT [3DCRT], intensity-modulated RT [IMRT], or image-guided RT [IGRT]). Multivariate analyses were performed to identify predictors of acute and late rectal toxicity. A nomogram was generated based on the logistic regression model used to predict the 3-year rectal toxicity risk, with its accuracy assessed by dividing the cohort into training and validation subgroups.Mean follow-up for the entire cohort was 62 months, ranging from 6 to 235. The rate of acute Grade ≥2 rectal toxicity was 22.2%, decreasing when combining IMRT and IGRT, compared to 3DCRT (RR = 0.4, 95%CI: 0.3-0.6, p<0.01). The 5-year Grade ≥2 risks for rectal bleeding, urgency/tenesmus, diarrhea, and fecal incontinence were 9.9%, 4.5%, 2.8%, and 0.4%, respectively. The 3-year Grade ≥2 risk for overall rectal toxicity increased with total dose (p<0.01, RR = 1.1, 95%CI: 1.0-1.1) and dose per fraction (2Gy vs. 2.5Gy) (p = 0.03, RR = 3.3, 95%CI: 1.1-10.0), and decreased when combining IMRT and IGRT (RR = 0.50, 95% CI: 0.3-0.8, p<0.01). Based on these three parameters, a nomogram was generated.Dose escalation and moderate hypofractionation increase late rectal toxicity. IMRT combined with IGRT markedly decreases acute and late rectal toxicity. Performing combined IMRT and IGRT can thus be envisaged for dose escalation and moderate hypofractionation. Our nomogram predicts the 3-year rectal toxicity risk by integrating total dose, fraction dose, and RT technique