Search

Geriatric screening and geriatric assessment (GS/GA) have proven their benefits in the care for older patients with cancer. However, less is known about the predictive value of GS/GA for outcomes. To research this, clinical data on GS/GA can be enriched with population-based data. In this article we describe the methods and feasibility of data linkage, and first clinical outcomes (GS/GA results and overall survival). A large cohort study consisting of patients aged ≥70 years with a new cancer diagnosis was established using linked data from clinical and population-based databases. Clinical data were derived from a previous prospective study where older patients with cancer were screened with G8, followed by GA in case of an abnormal result (GS/GA study; 2009-2015). These data were linked to cancer registration data from the Belgian Cancer Registry (BCR), reimbursement data of the health insurance companies (InterMutualistic Agency, IMA), and hospital discharge data (Technical Cell, TCT). Cox regression analyses were conducted to evaluate the prognostic value of the G8 geriatric screening tool. Of the 8067 eligible patients with a new cancer diagnosis, linkage of data from the GS/GA study and data from the BCR was successful for 93.7%, resulting in a cohort of 7556 patients available for the current analysis. Further linkage with the IMA and TCT database resulted in a cohort of 7314 patients (96.8%). Based on G8 geriatric screening, 67.9% of the patients had a geriatric risk profile. Malnutrition and functional dependence were the most common GA-identified risk factors. An abnormal baseline G8 score (≤14/17) was associated with lower overall survival (adjusted HR [aHR] = 1.62 [1.50-1.75], p < 0.001). Linking clinical and population-based databases for older patients with cancer has shown to be feasible. The GS/GA results at cancer diagnosis demonstrate the vulnerability of this population and the G8 score showed prognostic value for overall survival. The established

Recurrent respiratory papillomatosis (RRP) is a currently incurable benign neoplasm caused by human papilloma virus (HPV) infection. It usually reduces voice, respiratory, and general quality of life, and is sometimes life-threatening. Patients usually need repeated operations. The use of adjuvant bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor A, has been described in several case reports, with a good efficacy and safety profile. We report the cases of five patients with aggressive RRP who were treated with adjuvant systemic bevacizumab in a single Belgian tertiary center. A complete response was achieved in four patients after a median of 4.5 months, and a partial response in one. In all cases, the number of surgeries was drastically reduced, and quality of life improved. Toxicity was easily managed. Systemic bevacizumab seems to be an effective and safe adjuvant treatment for aggressive RRP.

Adrenocortical carcinoma is a rare and aggressive tumour. The only curative treatment is surgery with negative margins. In most series, the average lesion size ranges from 5.5 to 15 cm. We report the case of a 27-year-old female with hyperandrogenism and Cushing syndrome due to a right adrenocortical carcinoma of 19.7 cm. The tumour abutting on liver and vena cava and the presence two nodules in liver required extensive surgery including a right posterior sectionectomy and an en bloc resection of the adrenal mass together with the right kidney and the gallbladder. The vena cava was also resected with a reconstruction using a pericardial patch since it was invaded on its border. Pathological examination confirmed an adrenocortical carcinoma, with tumour invasion of vessels, tumour capsule, vena cava and two metastases in the liver (pT4N0M1). All margins were negative. Three months after surgery, two lung nodules, cardio-phrenic and internal mammary adenomegalies were noticed on a PET/CT scan, justifying the initiation of chemotherapy, alongside with mitotane. After a 10-month follow-up, CT scan was stable excepted for a lung nodule growing from 4 to 7 mm. Targeted stereotaxic radiotherapy was then administered. Twenty-two months after surgery, the patient has improved considerably and all signs of hyperandrogenism and Cushing syndrome have resolved. This case of adrenocortical carcinoma illustrates one of the largest tumours among those reported. It demonstrates the feasibility and effectiveness of a multimodal approach in its treatment even if it is giant and at high risk.

This phase 1 postapproval study assessed the effect of the mitogen-activated protein kinase kinase enzyme 1/enzyme 2 inhibitor trametinib (2 mg once daily, repeat dosing) on the pharmacokinetics of combined oral contraceptives (COCs) containing norethindrone (NE; 1 mg daily) and ethinyl estradiol (EE; 0.035 mg daily) in 19 female patients with solid tumors. Compared with NE/EE administered without trametinib, NE/EE administered with steady-state trametinib was associated with a clinically nonrelevant 20% increase in NE exposure (area under the curve [AUC]) and no effect on EE exposure (geometric mean ratio [geo-mean] of NE/EE + trametinib to NE/EE [90%CI]: NE AUC calculated to the end of a dosing interval at steady-state [AUC ] 1.20 [1.02-1.41]; NE AUC from time zero to the last measurable concentration sampling time [AUC ] 1.2 [0.999-1.45]; EE AUC 1.06 [0.923-1.22]; EE AUC 1.05 [0.883-1.25]). Maximum serum concentration (C ) of NE increased by 13% and C of EE decreased by 8.5% when dosed with steady-state trametinib compared with COCs administered alone (geo-mean ratio [90%CI]: NE C 1.13 [0.933-1.36]; EE C 0.915 [0.803-1.04]). These results indicate that repeat-dose trametinib does not lower exposure to NE or EE and, hence, is unlikely to impact the contraceptive efficacy of COCs. The pharmacokinetic parameters of trametinib and its metabolite M5 were consistent with historic data of trametinib alone. Coadministration of trametinib and COCs was generally well tolerated in this study, with observed safety signals consistent with the known safety profile of trametinib and no new reported safety events. Overall, the findings indicate that hormonal COCs can be coadministered in female patients who receive trametinib monotherapy without compromising the contraceptive efficacy.

Biomarkers for cyclin-dependent kinase 4/6 inhibitors, such as palbociclib, for patients with hormone receptor-positive/HER2-negative metastatic breast cancer are lacking. Thymidine kinase is a proliferation marker downstream of the cyclin-dependent kinase 4/6 pathway. We prospectively investigated the prognostic role of serum thymidine kinase activity (sTKa), in patients treated with Palbociclib + fulvestrant. PYTHIA was a phase II, single-arm, multicentre, trial that enrolled 124 post-menopausal women with endocrine-resistant hormone receptor-positive/HER2-negative metastatic breast cancer. Serum samples were collected pre-treatment (pre-trt; n = 122), at day 15 of cycle 1 (D15; n = 108), during the one week-off palbociclib before initiating cycle 2 (D28; n = 108) and at end of treatment (n = 76). sTKa was determined centrally using Divitum®, a refined ELISA-based assay with a limit of detection of 20 Divitum Units (Du)/L. The primary study endpoint was progression-free survival, assessed for its association with pre- and on-treatment sTKa. Data from 122 women were analysed. Pre-treatment sTKa was not associated with clinical characteristics and moderately correlated with tissue Ki-67. Palbociclib + fulvestrant markedly suppressed sTKa levels at D15, with 83% of patients recording levels below limit of detection. At D28, sTKa showed a rebound in 60% of patients. At each timepoint, higher sTKa was associated with shorter progression-free survival (each p < 0.001), with the strongest effect at D15. STKa is an independent prognostic biomarker in patients treated with palbociclib. High pre-treatment sTKa and its incomplete suppression during treatment may identify patients with poorer prognosis and primary resistance. This warrants validation in prospective comparative trials. CLINICALTRIALS. NCT02536742; EudraCT 2014-005387-15.

Retrospective studies reported that preoperative oxaliplatin-based chemotherapy increased pathological response (PR) in patients resected for colorectal liver metastases (CRLM). This multicenter prospective randomized (1/1) phase II trial evaluated PR on resected CRLM after preoperative mFOLFOX6 (arm A) or FOLFIRI (arm B) + bevacizumab. The primary endpoint was the major pathological response rate (MPRR), defined as the percentage of patients presenting CRLMs with mean tumor regression grade (TRG) < 3. Secondary endpoints included safety, progression-free survival (PFS) and overall survival (OS). Out of 65 patients, 57 patients (28 and 29 in arm A/B) were resected for CRLM (one patient with lung metastases). Clinical and treatment characteristics were similar in both arms. One-month postoperative complications were 39.3%/31.0% in arm A/B (p = 0.585). MPRR and complete PR were 32.1%/20.7% (p = 0.379)

Sacituzumab govitecan (SG) is an antibody-drug conjugate composed of an anti-Trop-2 antibody coupled to SN-38 via a proprietary hydrolyzable linker. In the ASCENT study, SG improved survival versus single-agent treatment of physician's choice (TPC) in pre-treated metastatic triple-negative breast cancer (mTNBC). Hormone/HER2 receptor changes are common, particularly at relapse/metastasis. This subanalysis assessed outcomes in patients who did/did not have TNBC at initial diagnosis, before enrollment. TNBC diagnosis was only required at study entry. Patients with mTNBC refractory/relapsing after ≥ 2 prior chemotherapies were randomized 1:1 to receive SG or TPC. Primary endpoint was progression-free survival (PFS) in patients without brain metastases. Overall, 70/235 (30%) and 76/233 (33%) patients who received SG and TPC, respectively, did not have TNBC at initial diagnosis. Clinical benefit with SG versus TPC was observed in this subset. Median PFS was 4.6 versus 2.3 months (HR 0.48; 95% CI 0.32-0.72), median overall survival was 12.4 versus 6.7 months (HR 0.44; 95% CI 0.30-0.64), and objective response rate (ORR) was 31% versus 4%; those who also received prior CDK4/6 inhibitors had ORRs of 21% versus 5%. Efficacy and safety for patients with TNBC at initial diagnosis were generally similar to those who did not present with TNBC at initial diagnosis. Patients without TNBC at initial diagnosis had improved clinical outcomes and a manageable safety profile with SG, supporting SG as a treatment option for mTNBC regardless of subtype at initial diagnosis. Subtype reassessment in advanced breast cancer allows for optimal treatment. Clinical trial registration number NCT02574455, registered October 12, 2015.

Patients with pretreated estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer have poor prognosis. Elacestrant is a novel, oral selective ER degrader that demonstrated activity in early studies. This randomized, open-label, phase III trial enrolled patients with ER-positive/HER2-negative advanced breast cancer who had one-two lines of endocrine therapy, required pretreatment with a cyclin-dependent kinase 4/6 inhibitor, and ≤ 1 chemotherapy. Patients were randomly assigned to elacestrant 400 mg orally once daily or standard-of-care (SOC) endocrine monotherapy. Primary end points were progression-free survival (PFS) by blinded independent central review in all patients and patients with detectable mutations. Patients were randomly assigned to elacestrant (n = 239) or SOC (n = 238). mutation was detected in 47.8% of patients, and 43.4% received two prior endocrine therapies. PFS was prolonged in all patients (hazard ratio = 0.70; 95% CI, 0.55 to 0.88; = .002) and patients with mutation (hazard ratio = 0.55; 95% CI, 0.39 to 0.77; = .0005). Treatment-related grade 3/4 adverse events occurred in 7.2% receiving elacestrant and 3.1% receiving SOC. Treatment-related adverse events leading to treatment discontinuations were 3.4% in the elacestrant arm versus 0.9% in SOC. Nausea of any grade occurred in 35.0% receiving elacestrant and 18.8% receiving SOC (grade 3/4, 2.5% and 0.9%, respectively). Elacestrant is the first oral selective ER degrader demonstrating a significant PFS improvement versus SOC both in the overall population and in patients with mutations with manageable safety in a phase III trial for patients with ER-positive/HER2-negative advanced breast cancer.

The Quality Assurance project for stage III non-small cell lung cancer radiotherapy ProCaLung performed a multicentric two-step exercise evaluating mediastinal nodal Target Volume Definition and Delineation (TVD) variability and the opportunity for standardization. The TVD variability before and after providing detailed guidelines and the value of qualitative contour reviewing before applying quantitative measures were investigated. The case of a patient with stage III NSCLC and involved mediastinal lymph nodes was used as a basis for this study. Twenty-two radiation oncologists from nineteen centers in Belgium and Luxembourg participated in at least one of two phases of the project (before and after introduction of ProCaLung contouring guidelines). The resulting thirty-three mediastinal nodal GTV and CTV contours were then evaluated using a qualitative-before-quantitative (QBQ) approach. First, a qualitative analysis was performed, evaluating adherence to most recent guidelines. From this, a list of observed deviations was created and these were used to evaluate contour conformity. The second analysis was quantitative, using overlap and surface distance measures to compare contours within qualitative groups and between phases. A 'most robust' reference volume for these analyses was created using the STAPLE-algorithm and an averaging method. Five GTV and seven CTV qualitative groups were identified. Second step contours were more often in higher-conformity groups (p = 0.012 for GTV and p = 0.024 for CTV). Median Residual Mean Square Distances improved from 2.34 mm to 1.36 mm for GTV (p = 0.01) and from 4.53 mm to 1.58 mm for CTV (p < 0.0001). Median Dice coefficients increased from 0.81 to 0.84 for GTV (p = 0.07) and from 0.82 to 0.89 for CTV (p ≤ 0.001). Using HC-contours only to generate references translated in more robust quantitative evaluations. Variability of mediastinal nodal TVD was reduced after providing the ProCaLung consensus guidelines. A qualitative r

Invasive lobular carcinoma (ILC) is the most common histologic subtype of breast cancer after invasive ductal carcinoma (i.e., no special type [NST]). ILC differs from NST in clinical presentation, site-specific metastases and response to conventional therapies. Loss of E-cadherin protein expression, due to alterations in its encoding gene is the most frequent oncogenic event in ILC. Synthetic lethality approaches have shown promising antitumor effects of ROS1 inhibitors in models of E-cadherin-defective breast cancer in studies and provide the rationale for testing their clinical activity in patients with ILC. Entrectinib is a tyrosine kinase inhibitor targeting TRK, ROS1 and ALK tyrosine kinases. Here, the authors present ROSALINE (NCT04551495), a phase II study testing neoadjuvant entrectinib and endocrine therapy in women with estrogen receptor-positive, HER2-negative early ILC.

Older patients are at higher risk of chemotherapy-induced toxicity, raising interest in less toxic anti-HER2 regimens for older persons with HER2-positive (HER2+) metastatic breast cancer (MBC). This phase II study randomized (1:1) patients with HER2+ MBC, aged 70+ or frail 60+, to first line chemotherapy with metronomic oral cyclophosphamide (M) + Trastuzumab (T) and Pertuzumab (P) or TP alone. T-DM1 was offered in case of progression. In total, 39 and 41 patients were randomized to TP and TPM arm respectively. Median follow-up is 54.0 months. 24-month PFS was 18.7% (95% CI 8.2-32.4) and 28.7% (95% CI 15.8-43.0), respectively. A total of 49 (61.3%) patients died of whom 37 (75.5%) from disease progression; number of deaths per arm was 27 (69.2%) for TP and 22 (53.7%) for TPM. There was no significant difference in OS between the two arms (median OS TP vs TPM: 32.1 vs 37.5 months, p 0.25). Among the 40 patients who have started T-DM1 after disease progression on TP/TPM, PFS rate at 6 months after start of T-DM1 was 43.6% (95% CI: 27.7-58.5) and grade 3 or higher AE occurred in 18 pts (45%). Metronomic chemotherapy-based dual blockade (TPM), followed by T-DM1 after progression, provides an active and relatively well tolerated treatment option in an older/frail HER2+ MBC population, with a median survival of over 3 years. Nevertheless, the majority of this older/frail population died from breast cancer, highlighting the need for well tolerated and efficacious treatments in these patients.

While circulating tumour (ct)DNA is an indicator of minimal residual disease and negative prognostic factor in stage II-III colon cancer, no study has ever analysed the value of this biomarker in colon cancer patients treated with neoadjuvant chemotherapy. We sought to fill this gap by using prospectively collected plasma samples from 80 stage III colon cancer patients, receiving one cycle of neoadjuvant FOLFOX followed by surgery +/- adjuvant FOLFOX in the PePiTA trial. Samples were collected at baseline, 2 weeks and surgery. NPY and WIF1 were selected as universal methylation markers for ctDNA, and analysed with ddPCR technology. ROC curves were applied for cut-off points, and outcome measures included 5-year disease-free survival (DFS) and 6-year overall survival (OS). After a median follow-up of 52.5 months, baseline circulating-free (cf) DNA was an independent prognostic factor for DFS (HR 3.35, 95% CI: 1.15-9.77, = .03), and a trend towards a similar association was observed for relative cfDNA changes between baseline and surgery (HR 2.57, 95% CI: 0.94-7.05, = .07). Among 60 ctDNA assessable patients, 25 (42%) had detectable ctDNA at baseline. While detection of ctDNA at any pre-operative timepoint was not associated with outcome, patients with ctDNA increase (change of the worst trending methylation marker ≥11%, or mean ctDNA change of NPY and WIF1 ≥ 0%) between baseline and surgery showed a trend towards worse 5-year DFS (HR 3.66, 95% CI: 0.81-16.44, = .09). This is the first study of ctDNA in the neoadjuvant setting of early-stage colon cancer. Results are hypothesis-generating and should be confirmed in larger series.

Glioblastoma (GBM) is the most common and aggressive primary brain tumor. Despite recent advances in therapy modalities, the overall survival of GBM patients remains poor. GBM diagnosis relies on neuroimaging techniques. However, confirmation via histopathological and molecular analysis is necessary. Given the intrinsic limitations of such techniques, liquid biopsy (mainly via blood samples) emerged as a non-invasive and easy-to-implement alternative that could aid in both the diagnosis and the follow-up of GBM patients. Cancer cells release tumoral content into the bloodstream, such as circulating tumor DNA, circulating microRNAs, circulating tumor cells,extracellular vesicles, or circulating nucleosomes: all these could serve as a marker of GBM. In this narrative review, we discuss the current knowledge, the advantages, and the disadvantages of each circulating biomarker so far proposed.

We report the case of a 50-year old women with an oncological history of metastatic breast carcinoma who underwent lung stereotactic body radiation therapy (SBRT) of 60Gy in 8 fractions for a left upper lobe metastatic lesion. Seven months later, she complains about hoarseness and weakness of voice. Tumoral relapse and other frequent etiologies were excluded. The diagnosis of radiation induced left recurrent laryngeal nerve paralysis causing left vocal cord paralysis (VCP) was made. The symptomatology did not improve till the disease progression and death of the patient 29 months after SBRT. VCP after lung SBRT is a rare adverse event that has not yet been well described in the medical literature.

Peripheral T cell lymphoma (PTCL) is a heterogeneous group of hematological cancers arising from the malignant transformation of mature T cells. In a cohort of 28 PTCL cases, we identified recurrent overexpression of MYCN, a member of the MYC family of oncogenic transcription factors. Approximately half of all PTCL cases was characterized by a MYC expression signature. Inducible expression of MYCN in lymphoid cells in a mouse model caused T cell lymphoma that recapitulated human PTCL with a MYC expression signature. Integration of mouse and human expression data identified EZH2 as a key downstream target of MYCN. Remarkably, EZH2 was found to be an essential co-factor for the transcriptional activation of the MYCN-driven gene expression program, which was independent of methyltransferase activity, but dependent on phosphorylation by CDK1. MYCN-driven T cell lymphoma was sensitive to EZH2 degradation or CDK1 inhibition, which displayed synergy with FDA-approved HDAC inhibitors.

The exact impact of chemotherapy on the immune system of older patients with breast cancer is not well known. A longitudinal study was performed investigating the evolution of the blood immune profile during and after chemotherapy in this population. The study included 39 patients receiving adjuvant chemotherapy (chemotherapy group, CTG) and 32 patients receiving only hormone therapy (control group, CG). A 10-gene panel associated with immunosenescence was measured in peripheral blood mononuclear cells (PBMC) before (T1), at 3 months (T2) and at 12 months (T3) after initiation of adjuvant therapy. Nutrition status was assessed by using a mini nutritional assessment scale. Linear mixed model analyses were performed for trajectory evolution, with or without adjusting for age, tumor stage, breast cancer phenotype, and/or corresponding baseline gene levels. Six genes relating to T cell activation (CD28, CD27, CD86, LCK, GRAP, LRRN3), and two genes relating to oxidative stress (PRDX6, HMOX1) exhibited a significant group-by-time effect, even after adjusting covariates(p≤ 0.01). In CTG, the T cell activation genes substantially declined from T1 to T2 and bounced back to a level higher than baseline at T3 (p<0.03), which was not observed in CG (p>0.26). Patients with malnutrition detected at T1 experienced more pronounced perturbation regarding CD27, LCK, CD69, VAMP5, and LRRN3 (p<0.05). Chemotherapy leads to transient perturbation of immune-related gene expression and potentially stimulates immunity in the long term. Well-nourished patients experience less impact of chemotherapy on immune-related gene expression profiles.

Solid cancer is an independent prognostic factor for poor outcome with COVID-19. As guidelines for patient management in that setting depend on retrospective efforts, we here present the first analyses of a nationwide database of patients with cancer hospitalized with COVID-19 in Belgium, with a focus on changes in anticancer treatment plans at the time of SARS-CoV-2 infection. Nineteen Belgian hospitals identified all patients with a history of solid cancer hospitalized with COVID-19 between March 2020 and February 2021. Demographic, cancer-specific and COVID-specific data were pseudonymously entered into a central Belgian Society of Medical Oncology (BSMO)-COVID database. The association between survival and primary cancer type was analyzed through multivariate multinomial logistic regression. Group comparisons for categorical variables were carried out through a Chi-square test. A total of 928 patients were registered in the database; most of them were aged ≥70 years (61.0%) and with poor performance scores [57.2% Eastern Cooperative Oncology Group (ECOG) ≥2]. Thirty-day COVID-related mortality was 19.8%. In multivariate analysis, a trend was seen for higher mortality in patients with lung cancer (27.6% versus 20.8%, P = 0.062) and lower mortality for patients with breast cancer (13.0% versus 23.3%, P = 0.052) compared with other tumour types. Non-curative treatment was associated with higher 30-day COVID-related mortality rates compared with curative or no active treatment (25.8% versus 14.3% versus 21.9%, respectively, P < 0.001). In 33% of patients under active treatment, the therapeutic plan was changed due to COVID-19 diagnosis, most frequently involving delays/interruptions in systemic treatments (18.6%). Thirty-day COVID-related mortality was not significantly different between patients with and without treatment modifications (21.4% versus 20.5%). Interruption in anticancer treatments at the time of SARS-CoV-2 infection was not associated with a reduction

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. 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. 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

This study evaluated the effect of lipegfilgrastim, a glycopegylated granulocyte-colony stimulating factor, used as primary (PP) or secondary prophylaxis (SP) on chemotherapy (CT) treatment modifications, as well as the incidence of CT-induced neutropenic events in adult patients receiving cytotoxic CT with or without biological therapy (BT) for solid and hematological tumors, in routine clinical practice. Other objectives were to characterize the population of lipegfilgrastim-treated cancer patients and safety assessment. : This phase 4, prospective, observational study was conducted at 15 centers from Belgium and Luxembourg, between 2015 and 2017. : Of 139 patients, 82.7% had breast cancer and 54.7% were treated with dose-dense regimens. Most received lipegfilgrastim as PP (82.0%) and were at high-risk of febrile neutropenia (FN) (68.3%). FN and grade III/IV neutropenia were reported for 7.9% and 22.3% patients. Among 123 evaluated patients, CT/BT dose modifications were recorded for 33.3% (PP) and 52.4% (SP) of patients receiving lipegfilgrastim; dose reductions, followed by dose delays, were more frequent than omissions. Among 45 patients with dose modifications, FN was reported for 8.8% and 9.1% patients and grade IV neutropenia for 17.6% and 18.2% of patients when lipegfilgrastim was applied for PP and SP, respectively. Adverse events related to lipegfilgrastim occurred for 55 (39.6%) patients; bone pain and back pain were more frequent. Lipegfilgrastim-related serious adverse events were reported for 9 (6.5%) patients. : Use of lipegfilgrastim in real-world settings resulted in limited CT dose modifications and low incidences of neutropenic events, with no new safety concerns arising.

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)adj

Eccrine porocarcinoma is a rare malignant cutaneous tumor with high rates of extracutaneous spread, and its diagnosis and management can be quite challenging. This is a case of an 82-year-old woman presenting with an asymptomatic and chronic pubic skin lesion for whom the work-up required many investigations and procedures to confirm the diagnosis of metastatic eccrine porocarcinoma. Indeed, the patient underwent a wide local excision of the skin lesion, imaging with an FDG-PET scan, a colonoscopy, and two inguinal node dissections. As illustrated in this case, surgery should always be considered to achieve disease remission. Other treatments such as chemotherapy and radiotherapy have also been reported in the literature without clear standard guidelines.

PURPOSE: CXCR1, one of the receptors for CXCL8, has been identified as a druggable target on breast cancer cancer stem cells (CSC). Reparixin (R), an investigational oral inhibitor of CXCR1, was safely administered to metastatic breast cancer patients in combination with paclitaxel (P) and appeared to reduce CSC in a window-of-opportunity trial in operable breast cancer. The fRida trial (NCT02370238) evaluated the addition of R to weekly as first-line therapy for metastatic (m) TNBC. SUBJECTS AND METHODS: Subjects with untreated mTNBC were randomized 1:1 to R or placebo days 1-21 in combination with weekly P 80 mg/m2 on days 1, 8, 15 of 28-day cycles. The primary endpoint was PFS by central review. RESULTS: 123 subjects were randomized (62 to R + P and 61 to placebo + P). PFS was not different between the 2 groups (median 5.5 and 5.6 months for R + P and placebo + P, respectively; HR 1.13, p = 0.5996). ALDH+ and CD24-/CD44+ CSC centrally evaluated by IHC were found in 16 and 34 of the 54 subjects who provided a metastatic tissue biopsy at study entry. Serious adverse events (21.3 and 20% of subjects) and grade ≥ 3 adverse reactions (ADR) (9.1 and 6.3% of all ADRs) occurred at similar frequency in both groups. CONCLUSION: fRida is the first randomized, double-blind clinical trial of a CSC-targeting agent in combination with chemotherapy in breast cancer. The primary endpoint of prolonged PFS was not met.

Immune-related adverse events including cardiac toxicity are increasingly described in patients receiving immune checkpoint inhibitors. We described a malignant pericardial effusion complicated by a cardiac tamponade in an advanced non-small cell lung cancer patient who had received five infusions of atezolizumab, a PDL-1 monoclonal antibody, in combination with cabozantinib. The definitive diagnosis was quickly made by cytology examination showing typical cell abnormalities and high fluorescence cell information provided by the hematology analyzer. The administration of atezolizumab and cabozantinib was temporarily discontinued due to cardiogenic hepatic failure following cardiac tamponade. After the re-initiation of the treatment, pericardial effusion relapsed. In this patient, the analysis of the pericardial fluid led to the final diagnosis of pericardial tumor progression. This was afterwards confirmed by the finding of proliferating intrapericardial tissue by computed tomography scan and ultrasound. This report emphasizes the value of cytology analysis performed in a hematology laboratory as an accurate and immediate tool for malignancy detection in pericardial effusions.

Regorafenib is a standard treatment for refractory metastatic colorectal cancer (mCRC). In view of the toxicity burden, significant research efforts have been made to increase the therapeutic ratio of this multikinase inhibitor. Predictive factors for treatment-related adverse events (TRAEs), however, are still lacking. We assessed the association between a number of baseline clinical, laboratory and imaging parameters and the occurrence of TRAEs in 136 patients who had received regorafenib (160 mg/day, 3-weeks-on/1-week-off) in a prospective phase II clinical trial. Grade ≥ 2 TRAEs during the first cycle of treatment (84% vs. 60%, P = .002) and grade ≥ 3 TRAEs throughout the whole treatment (71% vs. 53%, P = .035) occurred more frequently in females, with sex being the only independent predictive factor of early and any-time toxicity (OR 3.4; 95% CI: 1.2-11.1, P = .02 and OR 2.1; 95% CI: 1.0-4.4, P = .045, respectively). Fatigue, anorexia, hypertension, and rash were reported significantly more frequently by females than males (P < .04). Females were also more likely to suffer early (19% vs. 5%, P = .014) and any-time serious AEs (28% vs. 9%, P = .005), and to require early dose modifications (55% vs. 37%, P = .055). This is the first study showing an association between sex and TRAEs during regorafenib treatment for mCRC. If confirmed in larger, independent series, these results could pave the way for the implementation of personalized regorafenib dosing strategies with the potential to optimize oncological outcomes while reducing toxicity and preserving quality of life.

In the cerebrospinal fluid (CSF), the demonstration of malignant cells by cytological examination is currently the gold standard for the diagnosis of leptomeningeal carcinomatosis (LC). However, a positive cytology is observed in only 50-60% of patients with LC and highly dependent on pre-analytical factors. The hematology laboratory could provide an immediate and accurate diagnosis, but diagnostic sensitivity is not always optimized once the sample is received. We hereby report a 49-year-old woman with a 3-year grade III invasive ductal carcinoma who was admitted to the emergency department due to headaches, nausea, and vomiting. The CSF revealed pleocytosis with suspicious high fluorescent cells on the hematology analyzer concomitantly with biochemical alterations. Cytomorphological examination confirmed tumor cells, thus diagnosing a leptomeningeal metastasis of her breast cancer. The patient was eventually transferred to palliative care. Cytological examination is a valuable tool for a rapid diagnosis of LC if diagnostic performance is optimized. In addition to repeated CSF collections with a sufficient volume (5-10 mL), this could be reached by processing the CSF as soon as possible, taking into account the fluorescence information from the analyzer, proceeding systematically to microscopic examination even with normal CSF white blood cell count, and providing quality improvement of the staff to identify malignant cells.

Trastuzumab emtansine (T-DM1) is indicated as second-line treatment for human epidermal growth factor receptor 2 (HER2)-positive metastatic or unresectable locally advanced breast cancer, after progression on trastuzumab and a taxane-based chemotherapy. We wished to determine if the line of treatment in which T-DM1 is administered has an impact on progression-free survival (PFS) and in particular, if prior treatment with capecitabine/lapatinib or pertuzumab modifies PFS of further treatment with T-DM1. We performed a multicenter retrospective study in 3 Belgian institutions. We evaluated PFS with T-DM1 in patients treated for HER2 positive metastatic or locally advanced unresectable breast cancer between January 1, 2009 and December 31, 2016. We included 51 patients. The median PFS was 9.01 months. The line of treatment in which T-DM1 (1st line, 2nd line, 3rd line or 4+ lines) was administered had no influence on PFS (hazard ratio 0.979, CI95: 0.835-1.143). There was no significant difference in PFS whether or not patients had received prior treatment with capecitabine/lapatinib (9.17 vs 5.56 months, p-value 0.875). But, patients who received pertuzumab before T-DM1 tended to exhibit a shorter PFS (3.55 months for T-DM1 after pertuzumab vs 9.50 months for T-DM1 without pretreatment with pertuzumab), even if this difference was not statistically significant (p-value 0.144). Unlike with conventional chemotherapy, the line of treatment in which T-DM1 is administered does not influence PFS in our cohort of patients with advanced HER2-positive breast cancer.

Inoperable malignant intestinal obstruction (IMIO) is a severe complication in patients with cancer, usually gastrointestinal or gynecologic in origin. For patients with IMIO, there is a need to relieve symptoms and limit nasogastric tube (NGT) use. Previous studies have suggested the efficacy of somatostatin analogues in relieving obstruction-related symptoms, such as nausea, vomiting, and pain. The purpose of this study was to assess the efficacy of lanreotide autogel 120 mg (LAN 120 mg) in the management of symptoms resulting from IMIO in patients with advanced cancer. This single-arm, multicenter study enrolled 52 patients mostly with advanced gastrointestinal or ovarian malignant tumors (35 patients with NGT and 17 patients without NGT). Patients received 1 deep subcutaneous injection of LAN 120 mg. Evaluations were performed on days 7, 14, and 28. The primary end point was the percentage of responding patients before or at day 7. Response was defined as ≤2 vomiting episodes per day (for patients without NGT at baseline) or no vomiting recurrence (after NGT removal) during at least 3 consecutive days at any time point between treatment and day 7. Responders at day 28 were offered a second LAN 120 mg injection and followed up until day 56. The proportion of responders in the intention-to-treat population was 24 of 52 (46.2%), which was significantly greater than the reference proportion of 30% (P = 0.0055). Patients without NGT had a higher response (88.2%) than patients with NGT (25.7%) and had a steady trend for clinical improvement that led to sustainable responses. Median time to response was 9 days for the overall population, 3 days for patients without NGT, and 14 days for patients with NGT (P < 0.0001). Our study is the first to use long-acting LAN 120 mg in patients with IMIO and suggests an effect in controlling clinical symptoms in patients with and without NGT at baseline. The safety profile of LAN 120 mg was similar to that reported in other indicati

Chemotherapy has represented the main treatment option for patients with advanced triple-negative breast cancer for a long time. However, due to our better understanding of tumour biology, recent clinical trials led to a change in the treatment paradigm of this disease, identifying clinically relevant subgroups with different therapeutic options. Both clinical and biological factors have become relevant and need to be considered in the treatment decision algorithm of this heterogeneous disease.

BACKGROUND: Smoking cessation after a cancer diagnosis is associated with improved overall survival. Few studies have reported oncologists' cessation practice patterns, but differences between the curative and palliative settings have not been described. We aimed to study the oncologist's perceptions on patients' tobacco use, current practices and barriers to providing smoking cessation support, while distinguishing between treatment with curative (C) and palliative (P) intent. METHODS: In 2019, an online 34-item survey was sent to approximately 6235 oncologists from 16 European countries. Responses were descriptively reported and compared by treatment setting. RESULTS: Responses from 544 oncologists were included. Oncologists appeared to favour addressing tobacco in the curative setting more than in the palliative setting. Oncologists believe that continued smoking impacts treatment outcomes (C: 94%, P: 74%) and that cessation support should be standard cancer care (C: 95%, P: 63%). Most routinely assess tobacco use (C: 93%, P: 78%) and advise patients to stop using tobacco (C: 88%, P: 54%), but only 24% (P)-39% (C) routinely discuss medication options, and only 18% (P)-31% (C) provide cessation support. Hesitation to remove a pleasurable habit (C: 13%, P: 43%) and disbelieve on smoking affecting outcomes (C: 3%, P: 14%) were disparate barriers between the curative and palliative settings (p < 0.001), but dominant barriers of time, resources, education and patient resistance were similar between settings. CONCLUSION: Oncologists appear to favour addressing tobacco use more in the curative setting; however, they discuss medication options and/or provide cessation support in a minority of cases. All patients who report current smoking should have access to evidence-based smoking cessation support, also patients treated with palliative intent given their increasing survival.

PURPOSE: Low-grade serous ovarian carcinomas (LGSOCs) have historically low chemotherapy responses. Alterations affecting the MAPK pathway, most commonly KRAS/BRAF, are present in 30%-60% of LGSOCs. The purpose of this study was to evaluate binimetinib, a potent MEK1/2 inhibitor with demonstrated activity across multiple cancers, in LGSOC. METHODS: This was a 2:1 randomized study of binimetinib (45 mg twice daily) versus physician's choice chemotherapy (PCC). Eligible patients had recurrent measurable LGSOC after ≥ 1 prior platinum-based chemotherapy but ≤ 3 prior chemotherapy lines. The primary end point was progression-free survival (PFS) by blinded independent central review (BICR); additional assessments included overall survival (OS), overall response rate (ORR), duration of response (DOR), clinical-benefit rate, biomarkers, and safety. RESULTS: A total of 303 patients were randomly assigned to an arm of the study at the time of interim analysis (January 20, 2016). Median PFS by BICR was 9.1 months (95% CI, 7.3 to 11.3) for binimetinib and 10.6 months (95% CI, 9.2 to 14.5) for PCC (hazard ratio,1.21; 95%CI, 0.79 to 1.86), resulting in early study closure according to a prespecified futility boundary after 341 patients had enrolled. Secondary efficacy end points were similar in the two groups: ORR 16% (complete response [CR]/partial responses[PRs], 32) versus 13% (CR/PRs, 13); median DOR, 8.1 months (range, 0.03 to ≥ 12.0 months) versus 6.7 months (0.03 to ≥ 9.7 months); and median OS, 25.3 versus 20.8 months for binimetinib and PCC, respectively. Safety results were consistent with the known safety profile of binimetinib; the most common grade ≥ 3 event was increased blood creatine kinase level (26%). Post hoc analysis suggests a possible association between KRAS mutation and response to binimetinib. Results from an updated analysis (n = 341; January 2019) were consistent. CONCLUSION: Although the MEK Inhibitor in Low-Grade Serous Ovarian Cancer Study did not m

BACKGROUND: Patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) progressing on platinum-based chemotherapy have poor prognoses and limited therapeutic options. Programmed cell death-1 (PD-1) and its ligand 1 (PD-L1) are frequently upregulated in HNSCC. The international, multi-institutional, single-arm, phase II HAWK study (NCT02207530) evaluated durvalumab monotherapy, an anti-PD-L1 monoclonal antibody, in PD-L1-high patients with platinum-refractory R/M HNSCC. PATIENTS AND METHODS: Immunotherapy-naïve patients with confirmed PD-L1-high tumour cell expression (defined as patients with ≥25% of tumour cells expressing PD-L1 [TC ≥ 25%] using the VENTANA PD-L1 [SP263] Assay) received durvalumab 10 mg/kg intravenously every 2 weeks for up to 12 months. The primary end-point was objective response rate; secondary end-points included progression-free survival (PFS) and overall survival (OS). RESULTS: Among evaluable patients (n = 111), objective response rate was 16.2% (95% confidence interval [CI], 9.9-24.4); 29.4% (95% CI, 15.1-47.5) for human papillomavirus (HPV)-positive patients and 10.9% (95% CI, 4.5-21.3) for HPV-negative patients. Median PFS and OS for treated patients (n = 112) was 2.1 months (95% CI, 1.9-3.7) and 7.1 months (95% CI, 4.9-9.9); PFS and OS at 12 months were 14.6% (95% CI, 8.5-22.1) and 33.6% (95% CI, 24.8-42.7). Treatment-related adverse events were 57.1% (any grade) and 8.0% (grade ≥3); none led to death. At data cut-off, 24.1% of patients remained on treatment or in follow-up. CONCLUSION: Durvalumab demonstrated antitumour activity with acceptable safety in PD-L1-high patients with R/M HNSCC, supporting its ongoing evaluation in phase III trials in first- and second-line settings. In an ad hoc analysis, HPV-positive patients had a numerically higher response rate and survival than HPV-negative patients.

Lung large-cell neuroendocrine carcinoma (L-LCNEC) is a rare subset of lung carcinoma associated with poor overall survival. Due to its rarity, little has been established about its optimal treatment in the advanced stage. We report the case of a 41-year-old woman diagnosed with an unresectable locally advanced L-LCNEC who presented an impressive tumor response to immunotherapy with nivolumab after non-curative thoracic radiotherapy. Salvage surgery was then performed, and pathologic analysis of the resected piece revealed the absence of residual viable tumor cells. Based on this case report, we discuss the literature regarding the efficacy of inhibitors of programmed death-1 protein (PD-1) in L-LCNEC and their use in association with radiotherapy and in the neoadjuvant setting.

BACKGROUND: Radiation-associated-dysphagia is a serious side effect of radiotherapy (RT) for head and neck cancer (HNC). METHODS: Seventy-six patients had a weekly prospective follow-up from baseline until one week post-RT. Combined mixed model analysis (n = 43) determined the evolution of self-perceived swallowing function, isometric tongue strength (MIP), tongue strength (TS) during swallowing (Pswal), and quality of life (QoL) in these patients during RT. RESULTS: Swallowing deteriorated from the third week on, resulting in an increase of tube dependency from 10% at baseline toward 31% post-RT. Both MIP and Pswal are reduced, with anterior MIP decreasing in 29% of patients and posterior MIP in 17%. Pswal decreases for saliva and a bolus swallow. All QoL subscales except "sleep" were affected during RT. CONCLUSIONS: Self-perceived swallowing function, TS and QoL decrease during RT for HNC. Current findings highlight the need for early monitoring of these parameters.

BACKGROUND: Immunotherapeutic approaches have revolutionized oncological practice but are less evaluated in gynecological malignancies. PD-1/PD-L1 blockade in gynecological cancers showed objective responses in 13-17% of patients. This could be due to immunosuppressive effects exerted by gynecological tumors on the microenvironment and an altered tumor vasculature. In other malignancies, combining checkpoint blockade with radiation delivers benefit that is believed to be due to the abscopal effect. Addition of immune modulation agents has also shown to enhance immune checkpoint blockade efficacy. Therefore we designed a regimen consisting of PD-1 blockade combined with radiation, and different immune/environmental-targeting compounds: repurposed drugs, metronomic chemotherapy and a food supplement. We hypothesize that these will synergistically modulate the tumor microenvironment and induce and sustain an anti-tumor immune response, resulting in tumor regression. METHODS: PRIMMO is a multi-center, open-label, non-randomized, 3-cohort phase 2 study with safety run-in in patients with recurrent/refractory cervical carcinoma, endometrial carcinoma or uterine sarcoma. Treatment consists of daily intake of vitamin D, lansoprazole, aspirin, cyclophosphamide and curcumin, starting 2 weeks before the first pembrolizumab dose. Pembrolizumab is administered 3-weekly for a total of 6 cycles. Radiation (3 × 8 Gy) is given on days 1, 3 and 5 of the first pembrolizumab dose. The safety run-in consists of 6 patients. In total, 18 and 25 evaluable patients for cervical and endometrial carcinoma respectively are foreseen to enroll. No sample size is determined for uterine sarcoma due to its rarity. The primary objective is objective response rate at week 26 according to immune-related response criteria. Secondary objectives include safety, objective response rate at week 26 according to RECIST v1.1, best overall response, progression-free survival, overall survival and quality of li

OBJECTIVES: This study aims to investigate health-related quality of life (HRQOL) at baseline and at follow-up in older patients with cancer and to determine prognostic factors for HRQOL decline. METHODS: A prospective Belgian multicentre (n = 22) study was performed. Patients ≥70 years with a malignant tumor and abnormal G8 (≤14/17) screening tool were included. Patients underwent geriatric assessment (GA) and HRQOL evaluation with follow up at three months. Uni- and multivariate regression models were performed to determine factors associated (p < .05) with baseline HRQOL and HRQOL decline at follow-up. RESULTS: Results reflect data collected from 3673 patients. A multivariate analysis showed that younger patients, and those with poor Eastern Cooperative Oncology Group - Performance Status (ECOG-PS), specific tumor types (gastrointestinal, gynaecological and thorax) and higher stage had lower baseline HRQOL. In addition worse functional status and presence of pain, fatigue, depression and malnutrition were associated with lower baseline HRQOL. During treatment (n = 2972), improvement in HRQOL was observed in 1037 patients (35%) and a decline in 838 patients (28.2%). In multivariate analysis, stage and presence of baseline comorbidities, pain, fatigue or malnutrition were associated with HRQOL evolution. CONCLUSION: Baseline HRQOL in older patients with cancer and an abnormal G8 depends on tumor and age related parameters. During follow-up, HRQOL improved in one third of patients, indicating that they may benefit from cancer treatment while one quarter demonstrated a HRQOL decline for which prognostic factors were identified.

AIM: To evaluate the pCR rate and toxicity of the addition of weekly carboplatin (Cp) to paclitaxel (wP) and dose-dense (dd) epirubicin/cyclophosphamide (EC) in an open-label phase II study in TNBC patients. METHODS: Patients were included if they had stage II and III TNBC and received wP (80 mg/m2/week) concurrent with weekly Cp (AUC = 2) for 12 weeks, followed by bi-weekly epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) plus granulocyte colony-stimulating factor (G-CSF) for four cycles, followed by surgery. The primary endpoint was the rate of pCR [(ypT0/isypN0)]. Secondary endpoints included safety and drug delivery. RESULTS: Sixty-three eligible patients were included. Median age was 51 years (range 29-74); 88.9% had stage II disease, 46% were clinically node positive, and 77.8% had grade 3 tumors. Fifty-four percent achieved a pCR. Twelve percent missed two or more doses of wP, whereas at least two cycles of EC were missed in 9.5%. The rate of tolerance without delays or dose reductions is very low (16%). Sixty-two percent had G3/4 neutropenia. Febrile neutropenia occurred in 18 patients of which more than eighty percent occurred during EC despite primary prophylaxis with G-CSF. Thrombocytopenia grade 3/4 was noticed in 11 pts. Three patients developed grade 3 peripheral neuropathy. CONCLUSION: The addition of weekly carboplatin to neoadjuvant paclitaxel and dd EC leads to a pCR rate comparable to prior studies (54%). However, hematological toxicity and febrile neutropenia rate was unexpectedly high. Future investigations could focus on reversing the sequence, which may lead to better hematological tolerability.

BACKGROUND: Endocrine therapy-based neoadjuvant treatment for luminal breast cancer allows efficient testing of new combinations before surgery. The activation of the phosphatidylinositol-3-kinase (PI3K) pathway is a known mechanism of resistance to endocrine therapy. Taselisib is an oral, selective PI3K inhibitor with enhanced activity against PIK3CA-mutant cancer cells. The LORELEI trial tested whether taselisib in combination with letrozole would result in an increased proportion of objective responses and pathological complete responses. METHODS: In this multicentre, randomised, double-blind, parallel-cohort, placebo-controlled phase 2, study, we enrolled postmenopausal women (aged ≥18 years) with histologically confirmed, oestrogen receptor (ER)-positive, HER2-negative, stage I-III, operable breast cancer, from 85 hospitals in 22 countries worldwide. To be eligible, patients had have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1, adequate organ function, and had to have evaluable tumour tissue for PIK3CA genotyping. Patients were randomly assigned (1:1) by means of a permuted block algorithm (block size of four) via an interactive voice or web-based response system, to receive letrozole (2·5 mg/day orally, continuously) with either 4 mg of oral taselisib or placebo (on a 5 days-on, 2 days-off schedule) for 16 weeks, followed by surgery. Randomisation was stratified by tumour size and nodal status. Site staff, patients, and the sponsor were masked to treatment assignment. Coprimary endpoints were the proportion of patients who achieved an objective response by centrally assessed breast MRI and a locally assessed pathological complete response in the breast and axilla (ypT0/Tis, ypN0) at surgery in all randomly assigned patients and in patients with PIK3CA-mutant tumours. Analyses were done in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02273973, and is closed to accrual. FINDINGS: Between N

TMEM45A is a transmembrane protein involved in tumor progression and cancer resistance to chemotherapeutic agents in hypoxic condition. It is correlated to a low breast cancer patient overall survival. However, little is known about this protein, in particular the mechanisms by which TMEM45A modulates cancer cell chemosensitivity. In this work, the messenger RNA expression of TMEM45A was assessed in head and neck squamous cell carcinoma (HNSCC) and renal cell carcinoma (RCC) biopsies. TMEM45A was upregulated in patients diagnosed for head and neck or renal cancer. Then, the implication of this protein in cisplatin sensitivity was explored in SQD9 and RCC4 + pVHL cells. TMEM45A inactivation decreased cell proliferation and modulated cell responses to cisplatin. Indeed, TMEM45A inactivation increased the sensitivity of SQD9 cells to cisplatin, whereas it rendered RCC4 + pVHL cells resistant to this anticancer agent. Through RNA-sequencing analysis, we identified several deregulated pathways that indicated that the impact on cisplatin sensitivity may be associated to the inhibition of DNA damage repair and to UPR pathway activation. This study demonstrated, for the first time, an anti or a pro-apoptotic role of this protein depending on the cancer type and highlighted the role of TMEM45A in modulating patient responses to treatment.

Olaparib has shown significant clinical benefit as maintenance therapy in women with newly diagnosed advanced ovarian cancer with a mutation. The effect of combining maintenance olaparib and bevacizumab in patients regardless of mutation status is unknown. We conducted a randomized, double-blind, international phase 3 trial. Eligible patients had newly diagnosed, advanced, high-grade ovarian cancer and were having a response after first-line platinum-taxane chemotherapy plus bevacizumab. Patients were eligible regardless of surgical outcome or mutation status. Patients were randomly assigned in a 2:1 ratio to receive olaparib tablets (300 mg twice daily) or placebo for up to 24 months; all the patients received bevacizumab at a dose of 15 mg per kilogram of body weight every 3 weeks for up to 15 months in total. The primary end point was the time from randomization until investigator-assessed disease progression or death. Of the 806 patients who underwent randomization, 537 were assigned to receive olaparib and 269 to receive placebo. After a median follow-up of 22.9 months, the median progression-free survival was 22.1 months with olaparib plus bevacizumab and 16.6 months with placebo plus bevacizumab (hazard ratio for disease progression or death, 0.59; 95% confidence interval [CI], 0.49 to 0.72; P<0.001). The hazard ratio (olaparib group vs. placebo group) for disease progression or death was 0.33 (95% CI, 0.25 to 0.45) in patients with tumors positive for homologous-recombination deficiency (HRD), including tumors that had mutations (median progression-free survival, 37.2 vs. 17.7 months), and 0.43 (95% CI, 0.28 to 0.66) in patients with HRD-positive tumors that did not have mutations (median progression-free survival, 28.1 vs. 16.6 months). Adverse events were consistent with the established safety profiles of olaparib and bevacizumab. In patients with advanced ovarian cancer receiving first-line standard therapy including bevacizumab, the addition of maintenan

The incidence of thyroid cancer has increased markedly in recent decades, but has been stable in terms of mortality rates. For the most part, these cancers are treated with surgery, which may or may not be followed by radioactive iodine depending on the tumor subtype. Still, many of these cancers will recur and may be treated with radioactive iodine or another surgery. It is unclear what treatment is best for cases of locally advanced or metastatic thyroid cancer that are refractory to radioactive iodine. Chemotherapy has a very low response rate. However, in the past few years, several systemic therapies, primarily targeted, have emerged to improve the overall survival of these patients. Alternative treatments are also of interest, namely peptide receptor radionuclide therapy or immunotherapy.

Predictive biomarkers are eagerly awaited in advanced colorectal cancer (aCRC). Targeted sequencing performed on tumor and baseline plasma samples in 20 patients with aCRC treated with regorafenib identified 89 tumor-specific mutations of which ≥50% are also present in baseline plasma. Droplet digital PCR (ddPCR) assays were optimized to monitor circulating tumor DNA (ctDNA) levels in plasmatic samples collected throughout the treatment course and showed the importance of using the absolute value for ctDNA rather than the mutant/wild type ratio in monitoring the therapy outcome. High baseline cell free DNA (cfDNA) levels are associated with shorter overall survival (OS) (HR 7.38, P=0.001). An early increase (D14) in mutated copies/mL is associated with a significantly worse PFS (HR 6.12, P=0.008) and OS (HR 8.02, P=0.004). These data suggest a high prognostic value for early ctDNA level changes and support the use of blood-born genomic markers as a tool for treatment.

In the general older population, geriatric assessment (GA)-guided treatment plans can improve overall survival, quality of life and functional status (FS). In GA-related research in geriatric oncology, studies mainly focused on geriatric screening and GA but not on geriatric recommendations, interventions and follow-up. The aim of this study was to investigate the adherence to geriatric recommendations and subsequent actions undertaken in older patients with cancer. A prospective Belgian multicenter (N=22) cohort study included patients ≥70 years with a malignant tumor upon oncologic treatment decision. Patients with an abnormal result on the geriatric screening (G8 ≤14/17) underwent GA. Geriatric recommendations were formulated based on GA results. At follow-up the adherence to geriatric recommendations was documented including a description of actions undertaken. From 11-2012 till 2-2015, G8 screening was performed in 8451 patients, of which 5838 patients had an abnormal result. Geriatric recommendations data were available for 5631 patients. Geriatric recommendations were made for 4459 patients. Geriatric interventions data were available for 4167 patients. A total of 12384 geriatric recommendations were made. At least one different geriatric recommendation was implemented in 2874 patients. A dietician, social worker and geriatrician intervened most frequently for problems detected on the nutritional, social and functional domain. A total of 7569 actions were undertaken for a total of 5725 geriatric interventions, most frequently nutritional support and supplements, extended home care and psychological support. This large scale Belgian study focuses on the adherence to geriatric recommendations and subsequent actions undertaken and contributes to the optimal management of older patients with cancer. We identified the domains for which geriatric recommendations are most frequently made and adhered to, and which referrals to other health care workers and facilities

Despite the high incidence of metastatic breast cancer and its related mortality in the elderly population, our knowledge about optimal treatment for older patients with cancer is far from adequate. We aimed to evaluate the efficacy of dual anti-HER2 treatment with or without metronomic chemotherapy in older patients with HER2-positive metastatic breast cancer. We did a multicentre, open-label, randomised, phase 2 trial in 30 centres from eight countries in Europe, in patients with histologically proven, HER2-positive metastatic breast cancer, without previous chemotherapy for metastatic disease, who were 70 years or older, or 60 years or older with confirmed functional restrictions defined by protocol, and had a life expectancy of more than 12 weeks and a performance status according to WHO scale of 0-3. Eligible patients were randomly assigned (1:1) by an online randomisation system based on the minimisation method to receive metronomic oral cyclophosphamide 50 mg per day plus trastuzumab and pertuzumab, or trastuzumab and pertuzumab alone. Trastuzumab was given intravenously with a loading dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks. Pertuzumab was given intravenously with a loading dose of 840 mg, followed by 420 mg every 3 weeks. Patients were stratified by hormone receptor positivity, previous HER2 treatment, and baseline geriatric screening. The primary endpoint was investigator-assessed progression-free survival at 6 months as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A difference of 10% or greater between the two groups was sought. Efficacy analyses were by intention to treat; safety was assessed in all patients who received at least one dose of study treatment. In case of progression, all patients were offered trastuzumab emtansine. This trial is registered with ClinicalTrials.gov, number NCT01597414, and is completed. Between July 2, 2013, and May 10, 2016, 80 patients, of whom 56 (70%) had a potential frailty profile a

Les répercussions sexuelles du cancer et de ses traitements ont longtemps été considérées comme secondaires. Une prise de conscience relativement récente quant à l’importance de la dimension sexuelle du patient cancéreux s’est cependant largement développée. Ceci a entrainé un regain d’intérêt scientifique et la publication de lignes de conduites internationales. Dans cet article nous détaillons les principaux troubles sexuels rencontrés par les patients cancéreux, masculins et féminins. Parmi ceux-ci, chez la femme ce sont surtout diminution de la libido et dyspareunie qui sont le plus souvent observés. Chez l’homme, c’est la dysfonction érectile et la diminution de la libido qui constituent les problèmes majeurs. Ces troubles peuvent avoir des répercussions conséquentes sur la vie de couple. Nous décrivons également les effets secondaires des différents traitements anti-cancéreux sur la sphère sexuelle et enfin nous donnons quelques conseils et traitements non pharmacologiques pour leur prise en charge.

Using the EORTC Global Health Status (GHS) scale, we aimed to determine minimal clinically important differences (MCID) in health-related quality of life (HRQOL) changes for older cancer patients with a geriatric risk profile, as defined by the geriatric 8 (G8) health screening tool, undergoing treatment. Simultaneously, we assessed baseline patient characteristics prognostic for HRQOL changes. Our analysis included 1424 (G8 ≤ 14) older patients with cancer scheduled to receive chemotherapy (n = 683) or surgery (n = 741). Anchor-based methods, linking the GHS score to clinical indicators, were used to determine MCID between baseline and follow-up at 3 months. A threshold of 0.2 standard deviation (SD) was used to exclude MCID estimates too small for interpretation. Logistic regressions analysed baseline patient characteristics prognostic for HRQOL changes. The 15-item Geriatric Depression Scale (GDS15), Visual Analogue Scale (VAS) for Fatigue and ECOG Performance Status (PS) were selected as clinical anchors. In the surgery group, MCID estimates for improvement and deterioration were ECOG PS (5*, 11*), GDS15 (5*, 2) and VAS Fatigue (3, 9*). In the chemotherapy group, MCID estimates for improvement and deterioration were ECOG PS (8*, 7*), GDS15 (5, 4) and VAS Fatigue (5, 5*). Estimates with * were > 0.2 SD threshold. Patients experiencing pain or malnutrition (surgery group) or fatigue (chemotherapy group) at baseline showed a significantly stable or improved HRQOL (p < 0.05) after their treatment. The reported MCID for improvement and deterioration depended on the anchor used and treatment received. The estimates can be used to evaluate significant changes in HRQOL and to determine sample sizes in clinical trials.

To describe a rare pathology, the liposarcoma of the spermatic cord (LSC), and discuss its diagnosis and treatment.

BACKGROUND: Abiraterone acetate (AA) increases overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel. However, survival time varies substantially between individuals. Our goal was to identify prognostic factors that better estimate OS. MATERIALS AND METHODS: This is a retrospective multicentric analysis of 368 patients with mCRPC starting AA with prednisone after docetaxel. Cox proportional hazards statistics were applied. A multivariate model was constructed based on significant univariate predictors by using a manual stepwise forward and backward selection strategy. Model performance was determined by using receiver operating characteristic (ROC) curves. RESULTS: Univariate analysis identified 20 significant OS predictors. A multivariate model was constructed, based on 220 patients, incorporating 5 independent risk factors for decreased OS at the time of AA initiation: hemoglobin < 12 g/dL (hazard ratio [HR] 2.02), > 10 metastases (HR 1.80), ECOG performance status ≥ 2 (HR 1.88), radiographic progression (HR 1.50), and time since diagnosis < 90 months (HR 1.66, all P < .05). Patients were stratified into 3 groups: good (0-2 risk factors, median OS 22.6 months), intermediate (3 risk factors, median OS 13.9 months), and poor prognosis (4-5 risk factors, median OS 6.2 months). The area under the ROC curve based on the event "death by the time of median OS (13.3 months)" was 0.736 (95% confidence interval 0.670-0.803). CONCLUSION: We identified 5 readily available risk factors independently associated with decreased OS. The resulting model may be used for patient counseling in daily clinical practice, as well as patient stratification in clinical trials.

PURPOSE: To investigate the patterns of regional recurrences with emphasis on recurrences in the electively irradiated lymph node regions after dose de-escalation to 40Gy (EQD2Gy) in head and neck cancer. METHODS AND MATERIALS: Two hundred thirty-three patients treated with radio(chemo)therapy using 40Gy (EQD2Gy) to the elective lymph node regions were included. All regional recurrences were reconstructed and projected on the initial radiotherapy planning Computed Tomography studies to identify the localization of recurrence. Furthermore, patient and treatment characteristics were correlated with the regional recurrences to identify risk factors. RESULTS: The median follow-up in our study was 26months. Overall- and disease-specific survival at 2years were 71.2% (95% CI 65.3-77.1) and 64.2% (95% CI 59.2-69.3), respectively. Local, regional and distant control at 2years was 84.1% (95% CI 79.1-89.2), 89.2% (95% CI 84.3-94.1) and 83.2% (95% CI 76.3-90.1), respectively. Twenty-eight patients experienced a regional recurrence. Fourteen of these patients had a recurrence within the high dose volume (14 of 28). Nine had a recurrence in the electively irradiated lymph node regions (9 of 28) and 5 recurrences occurred outside the target volume. The actuarial rate of recurrence in the electively irradiated lymph node regions was 3.9% (95% CI 1.8-6.0) at 2years. No significant associations could be observed between recurrence in electively irradiated lymph node regions and age, gender, tumor site, stage, or the presence of human papillomavirus in oropharyngeal cancers. CONCLUSIONS: The actuarial rate of recurrence in the electively irradiated lymph node regions was 3.9% (95% CI 1.8-6.0) at 2years. This incidence is comparable to recurrence rates after standard dose of 50Gy, suggesting that lower doses to the elective neck do not result in higher regional recurrences.