Exclusion of non-Involved uterus from the target volume (EXIT-trial): An individualized treatment for locally advanced cervical cancer using modern radiotherapy and imaging techniques followed by completion surgery.

Background and purpose: Chemoradiotherapy followed by brachytherapy is the standard of care for locally advanced cervical cancer (LACC). In this study, we postulate that omitting an iconographical unaffected uterus (+12 mm distance from the tumour) from the treatment volume is safe and that no tumour will be found in the non-targeted uterus (NTU) leading to reduction of high-dose volumes of surrounding organs at risk (OARs). Material and Methods: In this single-arm phase 2 study, two sets of target volumes were delineated: one standard-volume (whole uterus) and an EXIT-volume (exclusion of non-tumour-bearing parts of the uterus with a minimum 12 mm margin from the tumour). All patients underwent chemoradiotherapy targeting the EXIT-volume, followed by completion hysterectomy. In 15 patients, a plan comparison between two treatment plans (PTV vs PTV_EXIT) was performed. The primary endpoint was the pathological absence of tumour involvement in the non-targeted uterus (NTU). Secondary endpoints included dosimetric impact of target volume reduction on OARs, acute and chronic toxicity, overall survival (OS), locoregional recurrence-free survival (LRFS), and progression-free survival (PFS). Results: In all 21 (FIGO stage I: 2; II: 14;III: 3; IV: 2) patients the NTU was pathologically negative. Ssignificant reductions in Dmean in bladder, sigmoid and rectum; V15Gy in sigmoid and rectum, V30Gy in bladder, sigmoid and rectum; V40Gy and V45Gy in bladder, bowel bag, sigmoid and rectum; V50Gy in rectum were achieved. Median follow-up was 54 months (range 7-79 months). Acute toxicity was mainly grade 2 and 5 % grade 3 urinary. The 3y- OS, PFS and LRFS were respectively 76,2%, 64,9% and 81 %. Conclusion: MRI-based exclusion of the non-tumour-bearing parts of the uterus at a minimum distance of 12 mm from the tumour out of the target volume in LACC can be done without risk of residual disease in the NTU, leading to a significant reduction of the volume of surrounding OARS treated to high doses.

Patient-reported outcomes and functional exercise capacity in a real-life setting in non-small cell lung cancer patients undergoing stereotactic body radiotherapy: the Lung PLUS study.

Introduction: To better understand the impact of stereotactic body radiotherapy (SBRT) and its treatment-related toxicity on early-stage non-small cell lung cancer (ES-NSCLC) patients, we conducted the Lung PLUS study in a real-world setting. Methods: This is a monocentric prospective longitudinal study up to 12 months post-treatment, evaluating clinician- and patient-reported toxicity (resp. CTCAE and PRO-CTCAE), health-related quality of life (HRQoL) (EORTC QLQ-C30 and LC-13), activities of daily living (HAQ-DI) and functional exercise capacity (6 Minute Walking Test (6MWT)). A mixed model approach was applied to analyze the data. Results: At baseline, clinicians and patients (n=51) reported mostly fatigue (63% vs 79%), cough (49% vs 75%) and dyspnea (65% vs 73%) of any grade. Dyspnea (p=.041) increased over time. Meaningful clinical improvements were particularly seen in pain, fatigue, and cough. Clinician reported clinically meaningful improvements and deteriorations over time in fatigue, cough, and dyspnea. Almost at every timepoint, more people reported deterioration to the clinician than improvement in aforementioned toxicities. Overall HRQoL (p=.014), physical (p=.011) and emotional (p<.001) functioning improved over time. At baseline, patients had a moderate daily functioning score and walked an average distance of 360 meters. No statistically significant differences were found in daily functioning and exercise capacity over time. Conclusion: Our study showed an increase in patient-reported toxicity and dyspnea, without impacting functional status, following SBRT. Overall HRQoL, physical and emotional functioning improved over time. Understanding the impact of treatment on patient-reported outcomes is crucial to identify the needs/problems of patients to enhance their HRQoL.

Completion surgery after intensity-modulated arc therapy for locally advanced cervical cancer: long-term follow-up and update on surgical outcome and oncologic results of a unique tertiary care single-center retrospective cohort.

BACKGROUND: Chemoradiotherapy (CRT) followed by brachytherapy (BT) is the standard treatment for locally advanced cervical cancer (LACC), but replacement of BT by surgery (CRT-S) could be an acceptable alternative. The main concern is the risk of operative morbidity. The aim is to report on therapeutic morbidity, OS, PC, and LC of CRT-S. METHODS: This was a single tertiary center retrospective cohort study in patients treated with CRT-S. A type II Wertheim hysterectomy was performed 6-8 weeks after CRT. Acute and chronic radiotherapy-related and surgical morbidity was classified according to the CTCAE v4.0. OS, and DFS, PC, and LC were calculated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazard models were performed to determine variables with a prognostic role. RESULTS: A total of 130 consecutive LACC patients were treated with CRT, and 119 underwent completion surgery. The median follow-up was 53 months. Five-year OS rate, local control, pelvic control, and 5-year DFS rate were 73%, 93%, 90%, and 74%, respectively. The 5-year OS rate was 92%/72%/67%/56% for FIGO (2009) stage I/II/III/IV, respectively. The five-year OS rate was 79% and 71% for adenocarcinoma and squamous cell carcinoma (p > 0.05), respectively. There was no intra- and perioperative mortality. Intraoperative and early postoperative complication rates were 7% and 20% (3% ≥ G3), respectively; they resolved within 3 months. The late postoperative complication rate was 9% (7% ≥ G3). Acute/late radiotherapy-related G3 side effects were 5%/3% for gastrointestinal and 3%/7% for genitourinary side effects. CONCLUSIONS: CRT-S is safe with an acceptable rate of complications for both the CRT and completion surgery and shows encouraging outcome data for stage III/IV and adenocarcinoma patients.

Atypical presentation of acute coronary syndrome (ACS): a case report.

CASE: A 45-year-old man presented at the emergency department (ED) with stomach pain since eight days. The patient was not worried about his symptoms and requested only pain relief. The emergency physician requested a consult of the gastroenterologist. Clinical examination was unremarkable. However, 12-lead ECG and ischemic markers were suggestive of acute coronary syndrome (ACS) which led to admission at the cardiology department. Despite delayed presentation, the patient was still referred for urgent coronary angiogram after receiving heparin, ticagrelor and acetylsalicylic acid because of persistent pain. An acute occlusion of the posterior descending artery was visualized and a percutaneous coronary intervention (PCI) with implantation of a drug-eluting stent was performed. DISCUSSION: Atypical presentation of ACS can range from non-chest pain to an epileptic seizure. Risk factors for atypical presentation include female gender, old age, comorbidities and severe mental illness. Troponin testing plays a central role when confronted with ACS but has only limited added-value with non-chest pain ACS. In cohort studies 1-2.2% of diagnosis of ACS is missed by emergency physicians. Possible explanations include atypical symptoms, non-diagnostic ECG and failure to interpret subtle ECG changes. ACS without chest pain frequently gets underdiagnosed and undertreated, which leads to more complications and a higher in-hospital mortality rate.

Late-life depression: issues for the general practitioner.

Late-life depression (LLD) is both a prevalent and life-threatening disorder, affecting up to 13.3% of the elderly population. LLD can be difficult to identify because patients mainly consult their general practitioner (GP) for somatic complaints. Moreover, patients may be hesitant to express the problem to their GP. Increased vigilance on the part of the GP can only benefit older people with depression. To recognize the risk of LLD, screening tools are provided in addition to treatment options for LLD. This review aims to provide the GP with guidance in recognizing and treating LLD. It tries to connect mainstream etiologies of LLD (e.g., vascular, inflammation, hypothalamo-pituitary-adrenal axis) with risk factors and current therapies. Therefore, we provide a basis to the GP for decision-making when choosing an appropriate therapy for LLD.

Swallow presyncope in an athletic patient caused by third-degree atrioventricular block.

Introduction Swallow syncope is a neurally mediated syncope. Multiple causes have been described in literature. A rare cause is arrhythmias. Only a limited amount of cases present the association of swallow syncope and third degree AV-block. Case presentation A 39-year-old man presented with episodes of presyncope while eating. Further medical history, physical examination, resting 12-lead ECG, cyclo-ergometry, transthoracic echocardiography and MRI of the heart were normal. 24 h Holter monitoring demonstrated high-grade third-degree atrioventricular (AV) block. The patient was scheduled for pacemaker implantation. Discussion Arrhythmia is a rare cause of swallow syncope. Reported arrhythmic causes are sinus bradycardia, sinoatrial block, atrioventricular block and complete atrial and ventricular asystole. Essential to the diagnosis is that (pre)syncope is preceded by swallowing and documentation of AV block on 24 h Holter monitoring. Treatment is guided by ESC guidelines which state that reflex syncope has a grade IIa recommendation for pacing, while current evidence suggests that asymptomatic vagally mediated AV block should not be treated until symptomatic.