No influence of sarcopenia on survival of ovarian cancer patients in a prospective validation study.

OBJECTIVE: Decrease in skeletal muscle index (SMI) during neoadjuvant chemotherapy (NACT) has been associated with worse outcome in patients with advanced ovarian cancer. To validate these findings, we tested if a decrease in SMI was a prognostic factor for a homogenous cohort of patients who received NACT in the randomized phase 3 OVHIPEC-trial. METHODS: CT-scans were performed at baseline and after two cycles of neoadjuvant chemotherapy in stage III ovarian cancer patients. The SMI (skeletal muscle area in cm2 divided by body surface area in m2) was calculated using SliceOMatic software. The difference in SMI between both CT-scans (ΔSMI) was calculated. Cox-regression analyses were performed to analyze the independent effect of a difference in SMI (ΔSMI) on outcome. Log-rank tests were performed to plot recurrence-free (RFS) and overall survival (OS). The mean number of adverse events per patient were compared between groups using t-tests. RESULTS: Paired CT-scans were available for 212 out of 245 patients (87%). Thirty-four of 74 patients (58%) in the group with a decrease in ΔSMI and 73 of 138 of the patients (53%) in the group with stable/increase in ΔSMI had died. Median RFS and OS did not differ significantly (p = 0.297 and p = 0.764) between groups. Patients with a decrease in SMI experienced more pre-operative adverse events, and more grade 3-4 adverse events. CONCLUSION: Decreased SMI during neoadjuvant chemotherapy was not associated with worse outcome in patients with stage III ovarian cancer included in the OVHIPEC-trial. However, a strong association between decreasing SMI and adverse events was found.

Trastuzumab versus observation for HER2 nonamplified early breast cancer with circulating tumor cells (EORTC 90091-10093, BIG 1-12, Treat CTC): a randomized phase II trial.

Background: Trastuzumab improves the outcome of women with HER2 positive breast cancer. We aimed to assess whether trastuzumab decreases the detection rate of circulating tumor cells (CTCs) in women with high risk, HER2 nonamplified, early breast cancer. Patients and methods: The EORTC 90091-10093 BIG 1-12 Treat CTC is a phase II trial, conducted in 70 hospitals and 6 CTC laboratories across 5 European countries. Patients with centrally confirmed HER2 nonamplified breast cancer and ≥1 centrally confirmed CTC per 15 ml of blood by CellSearch® following surgery and (neo)adjuvant chemotherapy were randomized (1 : 1) to 6 cycles of trastuzumab intravenously versus 18 weeks of observation. Randomization was stratified for center, locally confirmed estrogen receptor status and adjuvant versus neoadjuvant chemotherapy. The primary end point was rate of detection of ≥1 CTC per 15 ml of blood at week 18. Secondary end points were invasive disease-free survival (iDFS) and cardiac safety. Results: Between 30 April 2013 and 17 October 2016, 1317 patients were screened; 95 (7.2%) had detectable CTC(s), and 63 (4.8%) were randomized to trastuzumab (n = 31) or observation (n = 32). Fifty-eight patients were assessable for the primary end point, 29 in each arm. In 9 of the 58 patients, CTC(s) were still detected at week 18 : 5 in the trastuzumab and 4 in the observation arm (one-sided Fisher's exact test, P = 0.765). An Independent Data Monitoring Committee recommended stopping further accrual for futility for the primary end point. Median follow-up at database lock was 13 months (IQR 4-16.5). The 1-year iDFS was 93.8% (95% CI 77.3-98.4) in the observation versus 84.8% (95% CI 63.4-94.2) in the trastuzumab arm. No grade 2-4 cardiac events were observed in the trastuzumab arm. Conclusion: Trastuzumab does not decrease the detection rate of CTCs in HER2 nonamplified, nonmetastatic breast cancer.

Pictilisib PI3Kinase inhibitor (a phosphatidylinositol 3-kinase [PI3K] inhibitor) plus paclitaxel for the treatment of hormone receptor-positive, HER2-negative, locally recurrent, or metastatic breast cancer: interim analysis of the multicentre, placebo-controlled, phase II randomised PEGGY study.

BACKGROUND: Approximately 40% of hormone receptor-positive, HER2-negative breast cancers (BCs) are associated with activating mutations of the phosphatidylinositol 3-kinase (PI3K) pathway. Pictilisib, a potent and highly specific class I pan-PI3K inhibitor, demonstrated preclinical activity in BC cell lines and may potentiate the effect of taxanes, benefiting patients with or without aberrant activation of the PI3K pathway. PEGGY (NCT01740336), a randomised, placebo-controlled phase II trial, examined whether pictilisib augments the anti-tumour activity of paclitaxel in patients with hormone receptor-positive, HER2-negative locally recurrent or metastatic BC (mBC). We report results from the protocol-specified interim analysis. PATIENTS AND METHODS: One hundred and eighty-three eligible patients were randomised (1:1) to receive paclitaxel (90 mg/m2 weekly for 3 weeks in every 28-day cycle) with either 260 mg pictilisib or placebo (daily on days 1-5 every week). The primary end point was progression-free survival (PFS) in the intention-to-treat (ITT) population and patients with PIK3CA-mutated tumours. Secondary end points included overall response rate (ORR), duration of response, and safety. RESULTS: In the ITT population, the median PFS was 8.2 months with pictilisib (n = 91) versus 7.8 months with placebo (n = 92) [hazard ratio (HR) for progression or death, 0.95; 95% confidence interval (CI) 0.62-1.46; P = 0.83]. In patients with PIK3CA-mutated tumours, the median PFS was 7.3 months for pictilisib (n = 32) versus 5.8 months with placebo (n = 30) (HR, 1.06; 95% CI 0.52-2.12; P = 0.88). ORR was similar between treatment arms. The safety profile of pictilisib was consistent with previous reports, with no new safety signals. Proportions of patients with grade ≥3 adverse events (AEs), serious AEs, and dose reductions/discontinuations due to AEs were higher with pictilisib. CONCLUSIONS: PEGGY did not meet its primary end point, revealing no significant benefit from adding pictilisib to paclitaxel for patients with hormone receptor-positive, HER2-negative locally recurrent or mBC. CLINICAL TRIAL NUMBER: NCT01740336.

Prognostic and predictive effects of primary versus secondary platinum resistance for bevacizumab treatment for platinum-resistant ovarian cancer in the AURELIA trial.

BACKGROUND: Progression-free survival (PFS), objective response rate (ORR), and patient-reported outcomes (PROs) were significantly improved by adding bevacizumab to chemotherapy for platinum-resistant ovarian cancer (PROC) in the phase III AURELIA trial. We explored treatment outcomes according to primary platinum resistance (PPR) versus secondary platinum resistance (SPR). PATIENTS AND METHODS: Patients were categorized as PPR (disease progression <6 months after completing first-line platinum therapy) or SPR (progression ≥6 months after first platinum but <6 months after second). The exploratory Cox and logistic regression analyses correlated PFS, ORR, overall survival (OS), and PROs with the time to development of platinum resistance. RESULTS: Baseline characteristics were similar in patients with PPR (n = 262; 73%) and SPR (n = 99; 27%), although ascites were more common in the PPR subgroup. In bevacizumab-treated patients (n = 179), SPR was associated with improved PFS (median 10.2 versus 5.6 months in PPR patients; P < 0.001) and OS (median 22.2 versus 13.7 months, respectively; P < 0.001) but not PROs (22% versus 22% with improved abdominal/gastrointestinal symptoms at week 8/9). In multivariate analyses, SPR remained an independent prognostic factor for better PFS [adjusted hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.25-0.67; P < 0.001] and OS (HR 0.49, 95% CI 0.30-0.80; P = 0.005) in bevacizumab-treated patients, but was not statistically significant for either end point in the chemotherapy-alone subgroup. The magnitude of PFS benefit from bevacizumab appeared greater in SPR than PPR patients (HR 0.30 versus 0.55, respectively; interaction P = 0.07) with a similar direction of effect for OS (interaction P = 0.18). CONCLUSIONS: In bevacizumab-treated patients, PFS and OS were more favorable in SPR than PPR patients with equally improved PROs. The PFS and OS benefit from combining bevacizumab with chemotherapy was more pronounced in SPR than PPR PROC. PPR versus SPR should be a stratification factor in future trials evaluating anti-angiogenic therapy for PROC.

Neoadjuvant treatment with docetaxel plus lapatinib, trastuzumab, or both followed by an anthracycline-based chemotherapy in HER2-positive breast cancer: results of the randomised phase II EORTC 10054 study.

BACKGROUND: Neoadjuvant trials conducted using a double HER2 blockade with lapatinib and trastuzumab, combined with different paclitaxel-containing chemotherapy regimens, have shown high pathological complete response (pCR) rates, but at the cost of important toxicity. We hypothesised that this toxicity might be due to a specific interaction between paclitaxel and lapatinib. This trial assesses the toxicity and activity of the combination of docetaxel with lapatinib and trastuzumab. PATIENTS AND METHODS: Patients with stage IIA to IIIC HER2-positive breast cancer received six cycles of chemotherapy (three cycles of docetaxel followed by three cycles of fluorouracil, epirubicin, cyclophosphamide). They were randomised 1 : 1 : 1 to receive during the first three cycles either lapatinib (1000 mg orally daily), trastuzumab (4 mg/kg loading dose followed by 2 mg/kg weekly), or trastuzumab + lapatinib at the same dose. The primary end point was pCR rate defined as ypT0/is. Secondary end points included safety and toxicity. pCR rate defined as ypT0/is ypN0 was assessed as an exploratory analysis. In June 2012, arm A was closed for futility based on the results from other studies. RESULTS: From October 2010 to January 2013, 128 patients were included in 14 centres. The percentage of the 122 assessable patients with pCR in the breast, and pCR in the breast and nodes, was numerically highest in the lapatinib + trastuzumab group (60% and 56%, respectively), intermediate in the trastuzumab group (52% and 52%), and lowest in the lapatinib group (46% and 36%). Frequency (%) of the most common grade 3-4 toxicities in the lapatinib /trastuzumab/lapatinib + trastuzumab arms were: febrile neutropenia 23/15/10, diarrhoea 9/2/18, infection (other) 9/4/8, and hepatic toxicity 0/2/8. CONCLUSIONS: This study demonstrates a numerically modest pCR rate increase with double anti-HER2 blockade plus chemotherapy, but suggests that the use of docetaxel rather than paclitaxel may not reduce toxicity. CLINICALTRIALSGOV: NCT00450892.

Desmoid tumour of the breast: case report and review of the literature.

Fibromatosis or desmoid tumour of the breast is an extremely rare, locally aggressive tumour with a tendency to relapse. Nevertheless these tumours do not have metastatic potential. Early recognition and wide local excision of the tumour is the treatment of choice. We present a case of a desmoid tumour of the breast in a 67-year-old woman and provide a review of the literature.

Assessment of potential process quality indicators for systemic treatment of breast cancer in Belgium: a population-based study.

BACKGROUND: Quality indicators (QIs) for the management of breast cancer (BC) have been published in Europe and internationally. In Belgium, a task force was established to select measurable process indicators of systemic treatment for BC, focusing on appropriateness of delivered care. The objective of this study was to evaluate the results of the selected QIs, both nationally and among individual centres. PATIENTS AND METHODS: Female Belgian residents with unilateral primary invasive BC diagnosed between 2010 and 2014 were selected from the Belgian Cancer Registry database. The national number enabled linkage with the national reimbursement database, which contains information on all reimbursed medical procedures. A total of 12 process indicators were measured on the population and hospital level. Intercentre variability was assessed by median results and interquartile ranges. RESULTS: A total of 48 872 patients were included in the study. QIs concerning specific BC subtypes only applied to patients diagnosed in 2014 (n = 9855). Clinical stage (cStage) I patients (n = 17 116) were staged with positron emission tomography/computed tomography. Among patients who were pT1aN0 human epidermal growth factor receptor 2 (HER2) positive (n = 47), 25.5% (n = 12) received adjuvant trastuzumab. Among patients with de novo metastatic luminal A/B-like HER2-negative BC (n = 295), 17.3% (n = 51) received upfront chemotherapy. (Neo)adjuvant chemotherapy was administered in 52.4% (n = 12 592) of operated women with cStage I-III, in 37.0% (n = 1270) of operated women with cStage I-III luminal A/B-like HER2-negative BC, and in 19.1% of operated women with cStage I luminal A/B-like HER2-negative BC. In the population of operated patients with cStage I-III, of those younger than 70 years that started adjuvant endocrine therapy (n = 3591), 81.7% (n = 2932) continued treatment for ≥4.5 years. Among patients in cStage I-III older than 70 years (n = 8544), 19.0% (n = 1622) received (neo)adjuvant chemotherapy, whereas among patients with cStage I-III luminal A/B-like HER2-negative BC (n = 1388), 13.0% (n = 181) received (neo)adjuvant chemotherapy. In patients with cStage I-II luminal A/B-like HER2-negative BC older than 70 years (n = 1477), 11.6% (n = 171) were not operated and received upfront endocrine treatment. CONCLUSION: Well-considered QIs using population-based data can evaluate quality of care and expose disparities among treatment centres. Their use in daily practice should be implemented in all centres treating BC.

Multicenter phase II randomized trial evaluating antiangiogenic therapy with sunitinib as consolidation after objective response to taxane chemotherapy in women with HER2-negative metastatic breast cancer.

The aim of this study is to test the hypothesis that antiangiogenic treatment with sunitinib consolidation can prolong remissions induced by taxane-based chemotherapy in women with metastatic breast cancer. The method involves a two-arm open-label (2:1 randomization) multicenter, randomized phase II trial evaluating the efficacy of sunitinib (arm A) versus no therapy (arm B) in patients with HER-2-negative metastatic breast cancer who achieved an objective response to taxane-based chemotherapy. The results of this study indicates that the primary endpoint of progression-free survival (PFS) > or =5 months was achieved in 10 of 36 patients (28%) in arm A and 4 of 19 patients (21%) in arm B. The median PFS was 2.8 and 3.1 months, respectively. A protocol amendment to the sunitinib dosing schedule was made because 53% (17/32) of patients treated at a starting dose of 50 mg (4 weeks on/2 weeks off) required dose reduction. Changing the starting dose to sunitinib 37.5 mg continuously resulted in dose reductions in 44% (7/16) of patients. Grades III-IV toxicity occurred in 69% of patients in arm A (fatigue 31%, musculoskeletal pain 11%, neutropenia and thrombopenia 8%) and 11% in arm B. The proof-of-principle study does not confirm the hypothesis that sunitinib consolidation therapy can lead to a predefined clinically relevant proportion of patients with PFS of > or =5 months after an objective response to taxanes. Furthermore, toxicity was significant.

Perforated jejunal diverticulitis: a rare presentation of acute abdomen.

Jejunal diverticulosis is a rare clinical finding with possible serious complications. A case of acute abdomen due to a perforated jejunal diverticulum is discussed, followed by a literature review concerning aetiology, symptoms, complications, diagnosis and treatment is provided.

Treatment algorithm in patients with ovarian cancer.

Most ovarian cancer patients are diagnosed only at advanced stages when survival outcomes are worse, andwhen therapeutic decisions might prove challenging. The fundamental treatment for women with ovarian cancerincludes debulking surgery whenever possible and appropriate systemic therapy (chemotherapy, targeted andantiangiogenic agents). In the last few years, knowledge about histological and molecular characteristics of ovariancancer subtypes and stages has increased considerably. This has enabled the development and improvement ofseveral options for the diagnosis and treatment of ovarian cancer in a patient-tailored approach. Accordingly,therapeutic decisions are guided by the characteristics of the patient and the tumour, especially the molecularfeatures of the cancer subtype and disease stage. Particularly relevant are the advances in early genetic testing ofgermline and somatic mutations involved in DNA repair, and the clinical development of targeted agents. In orderto implement the best individual medical strategies, in this article, we present an algorithm of treatment options,including recently developed targeted agents, for primary and recurrent ovarian cancer patients in Belgium.

Lesion detection on a combined "All-in-One" window compared to conventional window settings in thoracic oncology chest CT examinations.

PURPOSE: The purpose of this study was to investigate if lesion detection using a single "All-in-One" (AIO) window was non-inferior to lesion detection on conventional window settings in thoracic oncology chest computed tomography (CT) examinations. MATERIALS AND METHODS: In a retrospective study, 50 consecutive chest CT examinations of 50 patients (31 men, 19 women; mean age 64±10 [SD] years, range: 35-82 years) containing 417 lesions, were reviewed by 6 radiologists, subdivided into 2 groups of 3 radiologists each, with similar levels of expertise in each group (senior staff member, junior staff member and radiology resident). All examinations were reviewed in conventional or AIO window settings by one of the groups. A 'lesion' was defined as any abnormality seen on the chest CT examination, including both benign and malignant lesions, findings in chest and upper abdomen, and measurable and non-measurable disease. Lesions were listed as 'missed' when they were not seen by at least two out of three observers. F-tests were used to evaluate the significance of the variables of interest within a mixed model framework and kappa statistics to report interobserver agreement. RESULTS: On a reader level, 54/417 lesions (12.9%) were not detected by the senior staff member reading the studies in conventional window settings and 45/417 (10.8%) by the senior staff member reading the AIO images. For the junior staff member and radiology resident this was respectively 55/417 (13.2%) and 67/417 (16.1%) for the conventional window settings and 43/417 (10.3%) and 61/417 (14.6%) for the AIO window. On a lesion level, 68/417 (16.3%) were defined as 'missed' lesions (lesions not detected by at least 2 readers): 21/68 (30.9%) on the AIO-window, 30/68 (44.1%) on conventional views and 17/68 (25.0%) on both views. The use of the AIO window did not result in an increase of missed lesions (P>0.99). Interobserver agreement in both groups was similar (P=0.46). Regarding lesions that were categorized as 'missed' on the AIO window or on conventional window settings, there was no effect of location (chest or upper abdomen) (P=0.35), window (P=0.97) and organ (P=0.98). CONCLUSIONS: A single AIO-window is non-inferior to multiple conventional window settings for lesion detection on chest CT examinations in thoracic oncology patients.

The effect of adjuvant chemotherapy on symptom burden and quality of life over time; a preliminary prospective observational study using individual data of patients aged ≥70 with early stage invasive breast cancer.

OBJECTIVES: We aim to assess short and long term effects of chemotherapy on patient-reported quality of life (QOL) and patient versus clinician symptom reporting in older patients with breast cancer adjusted for tumour and aging parameters. MATERIAL AND METHODS: In this prospective, multicentre, non-interventional, observational study, women aged ≥70years were enrolled after surgery and assigned to a TC chemotherapy (docetaxel and cyclophosphamide) group or a control group depending on their planned adjuvant treatment. Longitudinal multivariate models were used to assess the statistical and minimal clinically important difference (MCID) in the impact of TC chemotherapy over time on QOL and symptom burden adjusted for baseline aging and tumour parameters. Statistical significance was set at 5% and MCID at 10 points. RESULTS: In total, 57 patients were enrolled in the chemotherapy and 52 patients in the control group. Within the chemotherapy group, clinical deterioration was reported at 3months for Fatigue (17.73), Dyspnoea (17.05), Diarrhoea (12.06) and Appetite Loss (17.05) scores (all p<0.001). However, the scores had returned to baseline (or even better for Role Functioning) at year 1. No clinical deterioration was reported in the control group. Symptom scores as reported by patients were significantly (p<0.05) higher than those reported by the clinicians, even more so for Fatigue, Dyspnoea, and Pain. CONCLUSION: Our results show that symptom burden and diminished QOL in an older breast cancer population receiving adjuvant TC chemotherapy are short-lived and disappear after a while with no long-term differences compared to a similar population not receiving chemotherapy.

Anal tenesmus caused by seminal vesicle cyst.

Congenital cysts of the seminal vesicles with ipsilateral renal aplasia or dysplasia are rare but have been well described in the literature. We report the first case where anal tenesmus was the only presenting symptom. Another unique feature was the combination of this anomaly with a duplication of the inferior vena cava.

Recurrences after highly selective vagotomy in refractory and non-refractory duodenal ulcer disease.

The recurrence rate after highly selective vagotomy was evaluated in patients with chronic duodenal ulcer disease presenting non-refractory (64 cases) or refractory ulcers (41 cases) followed for 1 to 8 years postoperatively. Refractoriness was considered when an ulcer remained symptomatic and was not healed at endoscopy after 8 weeks (3 cases) or 12 weeks (30 cases) of appropriate treatment with cimetidine, or when it recurred during maintenance therapy and did not heal after adapted treatment (8 cases). The cumulative 5 year-recurrence rate was 28.7% in refractory ulcers, in contrast with 9.3% in non-refractory ulcers (p less than 0.05). The early and constantly increased risk of recurrences in the refractory ulcer group could not be explained by factors related to surgeon or technique, nor by differing patient characteristics, including sex, age at the first ulcer episode, duration of the preoperative ulcer disease, familial ulcer history, prior ulcer complications, use or abuse of anti-inflammatory drugs, caffeine or alcohol, smoking habits and occupational state. It is concluded that highly selective vagotomy can not be considered a surgical procedure of choice in patients with refractory duodenal ulcers as there are valuable alternatives.

Gastric pseudolymphoma.

The observation of a gastric pseudolymphoma is presented. Diagnostic, pathologic and therapeutic implications of this uncommon condition are discussed.

[Primary torsion of the greater omentum as a cause of acute abdomen]. / Primaire torsie van het omentum majus als oorzaak van een acuut abdomen.

The authors report one case of primary torsion of the greater omentum. The presenting symptoms are similar to those of an acute appendicitis. Diagnosis is rarely considered before laparotomy. The presence of sero-sanguineous peritoneal fluid should lead to careful exploration of the omentum, with resection of the involved segment.

Large adrenal pseudocyst.

Cystic lesions of the adrenal gland are rare entities. Pseudocysts account for 40% of all cystic tumors of the adrenal glands, and are a consequence of hemorrhage and degeneration. Clinical signs are aspecific. On US and CT, a well defined large mass with cystic appearance is found. Thickening and irregularity of the cystic wall areas of different attenuation values within the cyst and central calcifications are due to hemorrhage. The more complex pseudocysts should be distinguished from cystic degeneration in adrenal malignancy and from cystic hypernephroma in the renal upper pole.

Desmoid tumours of the abdominal wall.

Desmoid tumours of the anterior abdominal wall are benign neoplasms arising from musculo-aponeurotic tissues. Desmoid tumours tend to be locally infiltrative resulting in a high local recurrence following surgical resection only. From 1980 to 1989, 10 patients with desmoid tumours of the anterior abdominal wall were treated. Two patients had only surgical resection, six patients received adjuvant radiation therapy after surgical resection and two patients had medical and/or chemotherapeutic treatment. At the time of analysis, all six patients with adjuvant radiation therapy after a microscopically incomplete resection showed no evidence of disease. Radiation therapy in adequate doses can achieve local tumour control after microscopically incomplete resection of a desmoid tumour of the anterior abdominal wall.

Perioperative complications in corrective facial orthopedic surgery: a 5-year retrospective study.

PURPOSE: Frequency and severity of complications have a profound impact on referral patterns for facial orthopedic surgery. Therefore, a retrospective study was undertaken to determine the incidence of such problems in a large series of patients, with the intent to use these data to make possible changes in the perioperative protocol used in our clinic. PATIENTS AND METHODS: The files of all patients operated on between 1992 and 1996 were studied. These comprised 1,108 patients with 1,872 osteotomy procedures. The following parameters were descriptively analyzed: airway obstruction, hemorrhage, hematoma, infection, neurosensory disturbances, unfavorable fractures, malposition of condyles and nasal septum, and vascularization problems. RESULTS: The most frequent complication was impairment of trigeminal nerve function. In 31.5% of the mandibular base osteotomies, 43.6% of the combined mandibular base and chin osteotomies, and 13% of the chin osteotomies, lip sensibility was decreased immediately postoperatively. After 1 year, this number was reduced to approximately 5%. The function of 17 lingual nerves and 45 infraorbital nerves was temporarily impaired. A wound infection was next in frequency. Fifty-three infections (mandible-to-maxilla ratio, 2.5:1) were treated with drainage under local anesthesia and antibiotic therapy. Loss of part or all of an osteotomized segment did not occur. Other complications were rare and/or temporary. CONCLUSIONS: The most frequent complication was impairment of inferior alveolar nerve function. Life-threatening complications were not encountered. The frequency of infections (<5%) requires further consideration regarding ways to reduce the incidence.