Neratinib + fulvestrant + trastuzumab for HR-positive, HER2-negative, HER2-mutant metastatic breast cancer: outcomes and biomarker analysis from the SUMMIT trial.

BACKGROUND: HER2 mutations are targetable alterations in patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC). In the SUMMIT basket study, patients with HER2-mutant MBC received neratinib monotherapy, neratinib + fulvestrant, or neratinib + fulvestrant + trastuzumab (N + F + T). We report results from 71 patients with HR+, HER2-mutant MBC, including 21 (seven in each arm) from a randomized substudy of fulvestrant versus fulvestrant + trastuzumab (F + T) versus N + F + T. PATIENTS AND METHODS: Patients with HR+ HER2-negative MBC with activating HER2 mutation(s) and prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy received N + F + T (oral neratinib 240 mg/day with loperamide prophylaxis, intramuscular fulvestrant 500 mg on days 1, 15, and 29 of cycle 1 then q4w, intravenous trastuzumab 8 mg/kg then 6 mg/kg q3w) or F + T or fulvestrant alone. Those whose disease progressed on F + T or fulvestrant could cross-over to N + F + T. Efficacy endpoints included investigator-assessed objective response rate (ORR), clinical benefit rate (RECIST v1.1), duration of response, and progression-free survival (PFS). Plasma and/or formalin-fixed paraffin-embedded tissue samples were collected at baseline; plasma was collected during and at end of treatment. Extracted DNA was analyzed by next-generation sequencing. RESULTS: ORR for 57 N + F + T-treated patients was 39% [95% confidence interval (CI) 26% to 52%); median PFS was 8.3 months (95% CI 6.0-15.1 months). No responses occurred in fulvestrant- or F + T-treated patients; responses in patients crossing over to N + F + T supported the requirement for neratinib in the triplet. Responses were observed in patients with ductal and lobular histology, 1 or ≥1 HER2 mutations, and co-occurring HER3 mutations. Longitudinal circulating tumor DNA sequencing revealed acquisition of additional HER2 alterations, and mutations in genes including PIK3CA, enabling further precision targeting and possible re-response. CONCLUSIONS: The benefit of N + F + T for HR+ HER2-mutant MBC after progression on CDK4/6is is clinically meaningful and, based on this study, N + F + T has been included in the National Comprehensive Cancer Network treatment guidelines. SUMMIT has improved our understanding of the translational implications of targeting HER2 mutations with neratinib-based therapy.

Veliparib monotherapy following carboplatin/paclitaxel plus veliparib combination therapy in patients with germline BRCA-associated advanced breast cancer: results of exploratory analyses from the phase III BROCADE3 trial.

BACKGROUND: In the BROCADE3 trial, addition of the poly(ADP-ribose) polymerase inhibitor, veliparib, to carboplatin/paclitaxel improved progression-free survival (PFS) (hazard ratio 0.71, 95% confidence interval 0.57-0.88; P = 0.002) in patients with advanced human epidermal growth factor receptor 2-negative, germline BRCA1/2-mutated breast cancer. A subset of patients discontinued both carboplatin and paclitaxel before progression and continued on veliparib/placebo maintenance monotherapy until progression. Analyses in this patient subgroup are reported. PATIENTS AND METHODS: Patients were randomized 2 : 1 to veliparib plus carboplatin/paclitaxel or placebo plus carboplatin/paclitaxel. Veliparib (120 mg twice daily) or placebo was given on days -2 to 5, carboplatin (area under the curve 6 mg/ml) on day 1, and paclitaxel (80 mg/m2) on days 1, 8, and 15 of 21-day cycles. Patients who discontinued both carboplatin and paclitaxel before progression received blinded study drug monotherapy at an increased dose of 300-400 mg twice daily continuously. PFS was the primary endpoint. Exploratory analyses were carried out in the subgroup of patients who received blinded study drug as monotherapy. A time-varying Cox model including data from all patients was also used to evaluate treatment effect in the combination and monotherapy phases. RESULTS: A total of 136 of 337 patients randomized to veliparib plus carboplatin/paclitaxel and 58/172 patients randomized to placebo plus carboplatin/paclitaxel discontinued both carboplatin and paclitaxel before progression and continued on blinded veliparib or placebo monotherapy. In this blinded monotherapy subgroup, investigator-assessed median PFS from randomization was 25.7 months with veliparib versus 14.6 months with placebo. Hazard ratios from a time-varying Cox model favored veliparib during both combination therapy and monotherapy. Any-grade adverse events occurring in the monotherapy phase were primarily gastrointestinal. The most common grade ≥3 adverse events were neutropenia and anemia (4% each with veliparib; 5% and 2%, respectively, with placebo). CONCLUSIONS: Veliparib maintenance monotherapy had a tolerable safety profile and may extend PFS following combination chemotherapy.

Current and future diagnostic and treatment strategies for patients with invasive lobular breast cancer.

BACKGROUND: Invasive lobular breast cancer (ILC) is the second most common type of breast cancer after invasive breast cancer of no special type (NST), representing up to 15% of all breast cancers. DESIGN: Latest data on ILC are presented, focusing on diagnosis, molecular make-up according to the European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets (ESCAT) guidelines, treatment in the early and metastatic setting and ILC-focused clinical trials. RESULTS: At the imaging level, magnetic resonance imaging-based and novel positron emission tomography/computed tomography-based techniques can overcome the limitations of currently used imaging techniques for diagnosing ILC. At the pathology level, E-cadherin immunohistochemistry could help improving inter-pathologist agreement. The majority of patients with ILC do not seem to benefit as much from (neo-)adjuvant chemotherapy as patients with NST, although chemotherapy might be required in a subset of high-risk patients. No differences in treatment efficacy are seen for anti-human epidermal growth factor receptor 2 (HER2) therapies in the adjuvant setting and cyclin-dependent kinases 4 and 6 inhibitors in the metastatic setting. The clinical utility of the commercially available prognostic gene expression-based tests is unclear for patients with ILC. Several ESCAT alterations differ in frequency between ILC and NST. Germline BRCA1 and PALB2 alterations are less frequent in patients with ILC, while germline CDH1 (gene coding for E-cadherin) alterations are more frequent in patients with ILC. Somatic HER2 mutations are more frequent in ILC, especially in metastases (15% ILC versus 5% NST). A high tumour mutational burden, relevant for immune checkpoint inhibition, is more frequent in ILC metastases (16%) than in NST metastases (5%). Tumours with somatic inactivating CDH1 mutations may be vulnerable for treatment with ROS1 inhibitors, a concept currently investigated in early and metastatic ILC. CONCLUSION: ILC is a unique malignancy based on its pathological and biological features leading to differences in diagnosis as well as in treatment response, resistance and targets as compared to NST.

Preventing taxane-related peripheral neuropathy, pain and nail toxicity: a prospective self-controlled trial comparing hilotherapy with frozen gloves in early breast cancer.

PURPOSE: The prevention of taxane-related toxicities at the extremities is highly important for patients' treatment and quality-of-life. Several studies endorse hand/foot-cooling using frozen gloves as a prophylactic intervention. Unlike frozen gloves, hilotherapy produces cooling at a constant temperature. Comparative data with frozen gloves are unavailable. METHODS: This prospective self-controlled study explores the efficacy of hilotherapy at the right hand and foot compared to frozen gloves at the left in patients with early breast cancer treated with weekly paclitaxel 80 mg/m2 or three-weekly docetaxel 75 mg/m2. Patient-reported outcomes were collected at baseline, 6, 12, 18 and 24 weeks after the start of treatment. Primary and secondary endpoints were the incidence of any-grade and ≥ grade 2 side-effects (peripheral neuropathy, pain and nail toxicities), and perceived comfort of both interventions. RESULTS: Sixty-two patients participated. The incidence of any-grade side-effects was similar on both sides, 85.5% with hilotherapy and 90.3% with frozen gloves (p = 1.000). The incidence of ≥ grade 2 side-effects at the extremities was significantly lower with hilotherapy: 43.6% compared to 61.3% with frozen gloves (p = 0.013). Perceived comfort was significantly better for hilotherapy than for frozen gloves (p < 0.0001). CONCLUSIONS: Compared to frozen gloves, continuous cooling of hands and feet using hilotherapy produces better prevention of ≥ grade 2 patient-reported side-effects at the extremities (peripheral neuropathy, pain and nail toxicities). Perceived comfort was significantly better for hilotherapy. From a clinical and patient perspective, hilotherapy is a better alternative for preventing clinically significant taxane-related side-effects.

Scalp cooling in breast cancer patients treated with docetaxel-cyclophosphamide: patient- and nurse-reported results.

PURPOSE: Recent evidence supports the efficacy of scalp cooling in preventing chemotherapy-induced alopecia in breast cancer treatments. However, efficacy largely varies between treatment regimens. The aim of this study was to explore the patient- and nurse-reported results of scalp cooling in terms of hair loss and need for a wig/head cover in patients with breast cancer treated with 3-weekly docetaxel 75 mg/m2- cyclophosphamide 600 mg/m2. METHODS: We studied nurse-reported efficacy as noted in the electronic patient files of 85 patients treated with docetaxel 75 mg/m2- cyclophosphamide 600 mg/m2 between 1/1/2017 and 1/1/2020. Sixty-nine of them also self-reported on their scalp cooling results up to one year after adjuvant chemotherapy in a retrospective way. RESULTS: Nurse- and patient-reported data showed that scalp cooling was successful (i.e., hair loss < 50%) in 47.1 and 44.9% of patients, respectively, and 55% of patients were (very) satisfied with the result of scalp cooling. Scalp cooling was perceived as (very) uncomfortable in 36.2% of patients. Regarding hair status one year after treatment, 47 patients (55.3%) reported no changes compared to their hair status before treatment. CONCLUSIONS: Scalp cooling is successful in preventing severe chemotherapy-induced alopecia in almost half of the patients with breast cancer treated with docetaxel 75 mg/m2- cyclophosphamide 600 mg/m2. Better understanding of the success rate of scalp cooling enables correct patient information and decision-making support.

Efficacy of anti-HER2 therapy in metastatic breast cancer by discordance of HER2 expression between primary and metastatic breast cancer.

PURPOSE: In stage IV breast cancer, the efficacy of human epidermal growth factor receptor 2 (HER2) targeted therapies in cases with discordance in HER2 expression between primary and metastatic site is not well known. We studied progression free (PFS) and overall survival (OS) by HER2 concordance when treating women with taxane-trastuzumab (± pertuzumab) in first or second line and trastuzumab-emtansine (T-DM1) or capecitabine-lapatinib in later lines. PATIENTS AND METHODS: Retrospective monocentric study including all breast cancer patients receiving trastuzumab between January 2002 and September 2017 at the University Hospital in Leuven; we selected metastatic patients with an available HER2 status in primary and metastatic site. The Kaplan-Meier method was used for estimating PFS/OS and log-rank test for analyzing between group differences. A Cox model is used for testing difference between groups while correcting for Pertuzumab. Multivariable Cox regression is used to model overall survival as a function group, correcting for possible confounders. RESULTS: We included 74 patients; 46 had an unchanged HER2 status (positive/positive), 9 lost HER2 (positive/negative), while 19 acquired HER2 amplification (negative/positive). 25 out of 28 cases with a discordant HER2 status were positive for ER and/or PgR in the primary site. HER2 positive/negative cases had a significantly lower PFS for taxane-trastuzumab-(pertuzumab) (PFS = 5.5 months), compared to HER2 positive/positive (PFS 9 months, p = 0.01) and HER2 negative/positive (PFS 14 months, p = 0.01) patients. PFS for later line T-DM1 (n = 30) was significantly higher for the HER2 positive/positive group (PFS 6.0 months) than for the discordant groups HER2 negative/positive (PFS 1.0 month, p = 0.04) and HER2 positive/negative (PFS 1.5 month, p = 0.01). After correcting for possible confounders, the HER2 positive/negative group had a significantly worse OS compared to HER2 positive/positive (HR 0.19, 95% CI 0.08-0.44) and negative/positive (HR 0.15, 95% 0.06-0.38). CONCLUSION: Conversion of HER2 status was seen in 28 out of 74 cases and was mostly observed in hormone receptor-positive tumors. In contrast to patients with HER2 loss, patients with a positive conversion of HER2 status derived substantial benefit from first line treatment with taxane-trastuzumab-(pertuzumab). This study highlights the importance of re-biopsying the metastatic lesion and changing treatment according to the last HER2 result.

Intra-arterial Mitomycin C infusion in a large cohort of advanced liver metastatic breast cancer patients: safety, efficacy and factors influencing survival.

PURPOSE: The aim of this study was to determine the safety and efficacy of Mitomycin C (MMC) infusion in a large cohort of advanced liver metastatic breast cancer patients (LMBC) and to determine factors influencing overall survival (OS). METHODS: We retrospectively analysed LMBC patients, treated with MMC infusion between 2000 and 2017. Hepatic response was measured with baseline CT scans and first available CT scan after MMC infusion by RECIST 1.1 criteria. Adverse events were registered by the CTCAE version 5.0. OS and hepatic progression free survival (hPFS) were evaluated using Kaplan-Meier estimates. After univariable analysis, a stepwise forward multivariable (MV) prediction analysis was developed to select independent pre-treatment factors associated with OS. RESULTS: We included 176 patients with a total of 599 MMC infusions, mostly heavily pre-treated patients with a median time from diagnosis of MBC to MMC infusion of 36.9 months. RECIST evaluation of liver lesions (n = 132) showed a partial response rate of 15%, stable disease of 43% and progressive disease in 17%. Adverse events grade 3 and 4 were reported in 17.5%. Median PFS was 5.5 months and median OS was 7.8 months. Significant independent baseline predictors of worse OS included number of prior systemic chemotherapy lines, prior liver ablation, higher liver tumour burden and elevated levels of bilirubin and ALT. CONCLUSION: MMC infusion is safe and effective in advanced LMBC patients. An increased number of prior therapies, a higher liver tumour burden and elevated levels of bilirubin and ALT were associated with a worse OS.

Determining clinically important differences in health-related quality of life in older patients with cancer undergoing chemotherapy or surgery.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Adherence to geriatric assessment-based recommendations in older patients with cancer: a multicenter prospective cohort study in Belgium.

Background: 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. Patient and methods: 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. Results: From November 2012 till February 2015, G8 screening was carried out 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 12 384 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. Conclusions: 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 are frequently applied in the multidisciplinary approach of older patients with cancer.

Palbociclib in highly pretreated metastatic ER-positive HER2-negative breast cancer.

PURPOSE: We aimed to investigate the role of palbociclib, a first-in-class cyclin-dependent kinase 4 and 6 inhibitor, in postmenopausal women with highly pretreated endocrine therapy-resistant metastatic breast cancer (MBC). METHODS: Between 28 September 2015 and 14 March 2017, a compassionate use program was established in the University Hospitals Leuven in which 82 postmenopausal women with estrogen receptor-positive, HER2-negative MBC were included after at least four lines of systemic treatment. The efficacy and safety analysis was performed in 82 patients who had received at least one dose of palbociclib and who had at least 6-month follow-up at the data cut-off point. The primary objective was the evaluation of efficacy of the combination of palbociclib and endocrine therapy with clinical benefit as primary endpoint, defined as the absence of progressive disease and being on treatment for at least 6 months. Secondary objectives were the evaluation of toxicity and the identification of potential predictors for clinical benefit. RESULTS: The median age of the patients was 67.1 years (range 34.8-85.9) at the time of inclusion. The average duration of treatment was 5.6 months (range 1-19), with a median progression-free survival of 3.17 (95% CI 2.76-4.70) months. At the data cut-off point, 10 patients were still on treatment with palbociclib. In this highly pretreated setting, 34 patients experienced no progressive disease within 6 months, resulting in an overall clinical benefit rate (CBR) of 41.5%. 20.7% (17/82) showed stable disease for ≥ 9 months and 13.4% for ≥ 12 months. None of the investigated predicting factors were significantly associated with clinical benefit at 6 months. For 43.9% of the patients, treatment delay or dose reduction was indicated. CONCLUSIONS: Palbociclib in combination with endocrine therapy shows an unexpectedly high CBR and favorable safety profile in heavily pretreated endocrine-resistant estrogen receptor-positive, HER2-negative MBC patients.

Breast cancer subtype and survival by parity and time since last birth.

BACKGROUND: Pregnancy affects breast cancer risk but how it affects the subtype and prognosis remain controversial. We studied the effect of parity and time since last birth on breast cancer subtype and outcome. PATIENTS AND METHODS: We conducted a retrospective multivariate cohort study including all premenopausal women with early breast cancer aged ≤ 50 years (N = 1306) at diagnosis at the University Hospitals Leuven (Jan. 2000-Dec. 2009). Primary study endpoints were the breast cancer subtype, disease-free survival, and distant disease-free survival by parity and time since last birth. Statistical methods used were baseline-category logits models and Cox proportional hazard models. Multivariable models were used to correct for possible confounders. RESULTS: Breast cancer subtypes did not differ between nulliparous (N = 266) and parous women (N = 1040) but subtypes differed significantly in parous women by time since last birth (p < 0.001). Tumors within 5 years of last birth were proportionally more likely triple negative and HER-2 like, even when corrected for age at diagnosis. After a mean follow-up period of 10 years, parous women had a better disease-free survival compared to nulliparous women (HR 0.733; CI 0.560-0.961; p = 0.025, HR 0.738; CI 0.559-0.974; p = 0.032 before and after correction for known prognostic factors, respectively). In parous women, a longer time since last birth was correlated with a longer disease-free survival compared to patients with a recent pregnancy (HR 0.976; CI 0.957-0.996; p = 0.018). However, after correction, this association completely disappeared (HR 1.010; CI 0.982-1.040; p = 0.480). CONCLUSION: We observed a better disease-free survival for parous than nulliparous women. The influence of recent birth on disease-free survival is probably due to tumor and patient characteristics, as recent birth is associated with more aggressive subtypes.

Body mass index, age at breast cancer diagnosis, and breast cancer subtype: a cross-sectional study.

PURPOSE: Evidence suggests that premenopausal obesity decreases and postmenopausal obesity increases breast cancer risk. Because it is not well known whether this is subtype dependent, we studied the association between body mass index (BMI) and age at breast cancer diagnosis, or the probability of being diagnosed with a specific breast cancer phenotype, by menopausal status. METHODS: All patients with non-metastatic operable breast cancer from the University Hospital Leuven diagnosed between January 1, 2000 and December 31, 2013 were included (n = 7020) in this cross-sectional study. Linear models and logistic regression were used for statistical analysis. Allowing correction for age-related BMI-increase, we used the age-adjusted BMI score which equals the difference between a patient's BMI score and the population-average BMI score corresponding to the patient's age category. RESULTS: The quadratic relationship between the age-adjusted BMI and age at breast cancer diagnosis (p = 0.0207) interacted with menopausal status (p < 0.0001); increased age at breast cancer diagnosis was observed with above-average BMI scores in postmenopausal women, and with below-average BMI scores in premenopausal women. BMI was linearly related to the probabilities of Luminal B and HER2-like breast cancer phenotypes, but only in postmenopausal women. The relative changes in probabilities between both these subtypes mirrored each other. CONCLUSION: BMI associates differently before and after menopause with age at breast cancer diagnosis and with the probability that breast cancer belongs to a certain phenotype. The opposite effect of increasing BMI on relative frequencies of Luminal B and HER2-like breast cancers suggests a common origin.

Incidence of medication-related osteonecrosis of the jaw in patients treated with both bone resorption inhibitors and vascular endothelial growth factor receptor tyrosine kinase inhibitors.

BACKGROUND: Several case reports and small case series have suggested a higher incidence of medication-related osteonecrosis of the jaw (MRONJ) in patients treated concomitantly with bone resorption inhibitors (BRIs) and vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs), as compared to patients treated with BRIs alone. We aimed to assess ONJ-incidence in patients exposed concomitantly to BRIs and VEGFR-TKIs. PATIENTS AND METHODS: We reviewed the records of all patients who received VEGFR-TKIs concomitantly with BRIs. Patients, who were treated with BRIs without VEGFR-TKI, served as a control group. Endpoints of the study were total MRONJ-incidence, MRONJ-incidence during the first and second year of exposure, and time-to-ONJ-incidence. RESULTS: Ninety patients were treated concomitantly with BRIs and VEGFR-TKIs with a median BRI-exposure of 5.0 months. Total MRONJ-incidence was 11.1%. During the first year of BRI-exposure (with a median concomitant exposure of 4.0 months), 6 out of 90 patients (6.7%) developed a MRONJ, compared to 1.1% in the control group (odds ratio 5.9; 95%CI 2.0-18.0; p = 0.0035). In Kaplan-Meier estimates, time-to-ONJ-incidence was significantly shorter in patients treated with BRIs and VEGFR-TKIs compared to BRIs alone (hazard ratio 9.5; 95%CI 3.1-29.6; p < 0.0001). MRONJs occurred earlier in patients treated concomitantly compared to patients treated with BRIs only (after a median exposure of 4.5 and 25.0 months, respectively; p = 0.0033). CONCLUSION: With a global MRONJ-incidence of 11%, patients receiving concomitant treatment with VEGFR-TKIs and BRIs have a five to ten times higher risk for development of MRONJ compared to patients treated with BRIs alone.

Postoperative complications in individuals aged 70 and over undergoing elective surgery for colorectal cancer.

AIM: This study aims to describe the nature, incidence, severity and outcomes of in-hospital postoperative complications (POCs) in older patients undergoing elective surgery for colorectal cancer. METHOD: Patients ≥ 70 years old were identified from a prospectively collected database (2009-2015) focusing on the implementation of geriatric screening and assessment in patients with cancer. Medical and surgical POCs were retrieved retrospectively from the medical records, and the severity of the POCs was graded by the Clavien-Dindo (CD) grading system. The following outcomes were analysed comparing patients with and without CD ≥ 2 and CD ≥ 3 POCs: length of stay (LOS), transfer to the intensive care unit, 30-day readmission rates, 30-day and 1-year mortality. RESULTS: In the 190 patients included, medical POCs (40.5%) were more frequent than surgical POCs (17.9%), and 37.9% experienced CD ≥ 2 POCs. The most common medical POCs were infections (26.8%), transient confusion or altered mental function (12.1%), cardiac arrhythmia (4.7%), and ileus/gastroparesis/prolonged recovery of transit (4.7%). The most common surgical POCs were surgical site infections (12.1%), wound dehiscence/bleeding (4.7%), anastomotic leak (3.7%) and surgical site bleeding (3.7%). The reoperation rate was 7.9%. CD ≥ 2 POCs led to 11 intensive care unit admissions and increased median postoperative LOS by 114% (P < 0.0001 for both), but did not significantly alter 30-day readmission and 30-day and 1-year mortality rates. CD ≥ 3 POCs increased LOS by 162% (P < 0.0001) and showed an increased 1-year mortality (P = 0.07). CONCLUSION: This study shows that in-hospital medical and surgical complications after surgery for colorectal cancer in patients ≥ 70 years old are frequent and that complications lead to less favourable outcomes.

Geriatric Assessment and Functional Decline in Older Patients with Lung Cancer.

PURPOSE: Older patients with lung cancer are a heterogeneous population making treatment decisions complex. This study aims to evaluate the value of geriatric assessment (GA) as well as the evolution of functional status (FS) in older patients with lung cancer, and to identify predictors associated with functional decline and overall survival (OS). METHODS: At baseline, GA was performed in patients ≥70 years with newly diagnosed lung cancer. FS measured by activities of daily living (ADL) and instrumental activities of daily living (IADL) was reassessed at follow-up to define functional decline and OS was collected. Predictors for functional decline and OS were determined. RESULTS: Two hundred and forty-five patients were included in this study. At baseline, GA deficiencies were present in all domains and ADL and IADL were impaired in 51 and 63% of patients, respectively. At follow-up, functional decline in ADL was observed in 23% and in IADL in 45% of patients. In multivariable analysis, radiotherapy was predictive for ADL decline. No other predictors for ADL or IADL decline were identified. Stage and baseline performance status were predictive for OS. CONCLUSIONS: Older patients with lung cancer present with multiple deficiencies covering all geriatric domains. During treatment, functional decline is observed in almost half of the patients. None of the specific domains of the GA were predictive for functional decline or survival, probably because of the high impact of the aggressiveness of this tumor type leading to a poor prognosis.

Relationship between prolactin, breast cancer risk, and antipsychotics in patients with schizophrenia: a critical review.

OBJECTIVE: A recent meta-analysis showed that breast cancer probably is more common in female patients with schizophrenia than in the general population (effect size = 1.25, P < 0.05). Increasing experimental and epidemiological data have alerted researchers to the influence of prolactin (PRL) in mammary carcinogenesis. We therefore investigated the possible relationship between antipsychotic-induced hyperprolactinemia (HPRL) and breast cancer risk in female patients with schizophrenia. METHOD: A literature search (1950 until January 2015), using the MEDLINE database, was conducted for English-language published clinical trials to identify and synthesize data of the current state of knowledge concerning breast cancer risk (factors) in women with schizophrenia and its (their) relationship between HPRL and antipsychotic medication. RESULTS: Although an increasing body of evidence supports the involvement of PRL in breast carcinogenesis, results of human prospective studies are limited, equivocal, and correlative (with risk ratios ranging from 0.70 to 1.9 for premenopausal women and from 0.76 to 2.03 for postmenopausal women). Moreover, these studies equally do not take into account the local production of PRL in breast epithelium, although amplification or overexpression of the local autocrine/paracrine PRL loop may be a more important mechanism in tumorigenesis. Until now, there is also no conclusive evidence that antipsychotic medication can increase the risk of breast malignancy and mortality. CONCLUSION: Other breast risk factors than PRL, such as nulliparity, obesity, diabetes mellitus, and unhealthy lifestyle behaviours (alcohol dependence, smoking, low physical activity), probably are of greater relevance in individual breast cancer cases within the population of female patients with schizophrenia.

Dealing with chemotherapy-related symptoms at home: a qualitative study in adult patients with cancer.

Given that chemotherapy treatments are done mostly in an outpatient setting, patients with cancer must deal with treatment-related symptoms mainly at home. Evidence suggests that they often feel left alone or unprepared to do so. This qualitative study explores how patients deal with chemotherapy-related symptoms in their home, which factors and ideas influence their self-management and what role professional caregivers play. One-off, semi-structured interviews were held with 28 adult patients with cancer being treated with chemotherapy. Using a Grounded Theory approach, we cyclically collected and analysed data to come to a thorough understanding of the major conceptual themes and their interconnections. Dealing with chemotherapy-related symptoms involves a process of experiencing and learning how side effects unfold over time and how to deal with them. Patients express very personal symptom experiences and symptom-management styles, which are shaped by personal factors (e.g. coping with cancer and cancer treatment, perceived level of control) and environmental factors (e.g. professionals' attitude, information resources). Improving symptom self-management support requires active exploration of the personal symptom experience and symptom-management style. Professional care should be tailored to the patient's perspective and should address personal and environmental determinants of their behaviour.

Renal effects of molecular targeted therapies in oncology: a review by the Cancer and the Kidney International Network (C-KIN).

A number of cancer therapy agents are cleared by the kidney and may affect renal function, including cytotoxic chemotherapy agents, molecular targeted therapies, analgesics, antibiotics, radiopharmaceuticals and radiation therapy, and bone-targeted therapies. Many of these agents can be nephrotoxic, including targeted cancer therapies. The incidence, severity, and pattern of renal toxicities may vary according to the respective target of the drug. Here, we review the renal effects associated with a selection of currenty approved targeted cancer therapies, directed to vascular endothelial growth factor or VEGF receptor(s) (VEGF/VEGFR), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor2 (HER2), BRAF, anaplastic lymphoma kinase (ALK), programmed cell death protein-1 or its ligand (PD-1/PDL-1), receptor activator of nuclear factor kappa-B ligand (RANKL), and mammalian target of rapamycin (mTOR). The early diagnosis and prompt treatment of these renal alterations are essential in the daily practice where molecular targeted therapies have a definitive role in the armamentarium used in many cancers.

Screening tools for multidimensional health problems warranting a geriatric assessment in older cancer patients: an update on SIOG recommendations†.

BACKGROUND: Screening tools are proposed to identify those older cancer patients in need of geriatric assessment (GA) and multidisciplinary approach. We aimed to update the International Society of Geriatric Oncology (SIOG) 2005 recommendations on the use of screening tools. MATERIALS AND METHODS: SIOG composed a task group to review, interpret and discuss evidence on the use of screening tools in older cancer patients. A systematic review was carried out and discussed by an expert panel, leading to a consensus statement on their use. RESULTS: Forty-four studies reporting on the use of 17 different screening tools in older cancer patients were identified. The tools most studied in older cancer patients are G8, Flemish version of the Triage Risk Screening Tool (fTRST) and Vulnerable Elders Survey-13 (VES-13). Across all studies, the highest sensitivity was observed for: G8, fTRST, Oncogeriatric screen, Study of Osteoporotic Fractures, Eastern Cooperative Oncology Group-Performance Status, Senior Adult Oncology Program (SAOP) 2 screening and Gerhematolim. In 11 direct comparisons for detecting problems on a full GA, the G8 was more or equally sensitive than other instruments in all six comparisons, whereas results were mixed for the VES-13 in seven comparisons. In addition, different tools have demonstrated associations with outcome measures, including G8 and VES-13. CONCLUSIONS: Screening tools do not replace GA but are recommended in a busy practice in order to identify those patients in need of full GA. If abnormal, screening should be followed by GA and guided multidisciplinary interventions. Several tools are available with different performance for various parameters (including sensitivity for addressing the need for further GA). Further research should focus on the ability of screening tools to build clinical pathways and to predict different outcome parameters.