Diabetes Alone should not be a Reason for Withholding Adjuvant Chemotherapy for Stage III Colon Cancer

Background: With increasing prevalence of diabetes mellitus and colon cancer, the number of patients suffering from both diseases is growing, and physicians are being faced with complicated treatment decisions. Objective: To investigate the association between diabetes and treatment/course of stage III colon cancer and the association between colon cancer and course of diabetes. Materials and Methods: Additional information was collected from the medical records of all patients with both stage III colon cancer and diabetes (n=201) and a random sample of stage III colon cancer patients without diabetes (n=206) in the area of the population-based Eindhoven Cancer Registry (1998–2007). Results: Colon cancer patients without diabetes were more likely to receive adjuvant chemotherapy compared with diabetic colon cancer patients (OR 1.8; 95% CI 1.2–2.7). After adjustment for age, this difference was borderline significant (OR 1.6; 95% CI 1.0–2.6). Diabetic patients did not have: significantly more side-effects from surgery or adjuvant chemotherapy; more recurrence from colon cancer; significantly shorter time interval until recurrence; or a poorer disease-free survival or overall survival. Age and withholding of adjuvant chemotherapy were most predictive of all-cause mortality. After colon cancer diagnosis, the dose of antiglycaemic medications was increased in 22% of diabetic patients, resulting in significantly lower glycaemic indexes than before colon cancer diagnosis. Conclusions: Since diabetic patients did not have more side-effects of adjuvant chemotherapy, and adjuvant chemotherapy had a positive effect on survival for both patients with and without diabetes, diabetes alone should not be a reason for withholding adjuvant chemotherapy

High ctDNA molecule numbers relate with poor outcome in advanced ER+, HER2- postmenopausal breast cancer patients treated with everolimus and exemestane

We determined whether progression-free survival (PFS) in metastatic breast cancer (MBC) patients receiving everolimus plus exemestane (EVE/EXE) varies depending on circulating tumour DNA (ctDNA) characteristics. Baseline plasma cell-free DNA (cfDNA) from 164 postmenopausal women with ER-positive, HER2-negative MBC refractory to a non-steroidal aromatase inhibitor and treated with standard EVE/EXE (Everolimus Biomarker Study, Eudract 2013-004120-11) was characterised for 10 relevant breast cancer genes by next generation sequencing with molecular barcoding. ctDNA molecule numbers, number of mutations and specific variants were related with PFS and overall survival (OS). Missense hotspot mutations in cfDNA were detected in 125 patients. The median of 54 ctDNA molecules per mL plasma distinguished patients with high and low/no ctDNA load. Patients with low/no ctDNA load (N=102) showed longer median PFS of 5.7 months (P=0.006) and OS of 124.8 months (P=0.008) than patients with high ctDNA load (N=62) (4.4 months and 107.7 months, respectively) in multivariate analyses. Patients with <3 specific mutations (N=135) had longer median PFS of 5.4 months compared to those with ≥3 mutations (3.4 months) (p<0.001). In conclusion, MBC patients with low/no ctDNA load or <3 hotspot mutations experience longer PFS while treated with EVE/EXE

High ctDNA molecule numbers relate with poor outcome in advanced ER+, HER2− postmenopausal breast cancer patients treated with everolimus and exemestane

We determined whether progression-free survival (PFS) in metastatic breast cancer (MBC) patients receiving everolimus plus exemestane (EVE/EXE) varies depending on circulating tumour DNA (ctDNA) characteristics. Baseline plasma cell-free DNA (cfDNA) from 164 postmenopausal women with ER-positive, HER2-negative MBC refractory to a non-steroidal aromatase inhibitor and treated with standard EVE/EXE (Everolimus Biomarker Study, Eudract 2013-004120-11) was characterised for 10 relevant breast cancer genes by next generation sequencing with molecular barcoding. ctDNA molecule numbers, number of mutations and specific variants were related with PFS and overall survival (OS). Missense hotspot mutations in cfDNA were detected in 125 patients. The median of 54 ctDNA molecules per mL plasma distinguished patients with high and low/no ctDNA load. Patients with low/no ctDNA load (N=102) showed longer median PFS of 5.7 months (P=0.006) and OS of 124.8 months (P=0.008) than patients with high ctDNA load (N=62) (4.4 months and 107.7 months, respectively) in multivariate analyses. Patients with <3 specific mutations (N=135) had longer median PFS of 5.4 months compared to those with ≥3 mutations (3.4 months) (p<0.001). In conclusion, MBC patients with low/no ctDNA load or <3 hotspot mutations experience longer PFS while treated with EVE/EXE

Unique Metastatic Patterns in Neuroendocrine Neoplasms of Different Primary Origin

Introduction: Neuroendocrine neoplasms (NEN) can originate in different organs, for example, the gastroenteral tract (GE), pancreas (Pan), or lungs (L). Our aim was to examine metastatic patterns for patients with NEN of various primary origins with a special focus on brain metastases to indicate utility for screening.   Methods: All NEN patients except for small cell lung cancer registered in the Netherlands Cancer Registry from 2008 to 2018 were selected. Metastatic patterns at initial diagnosis for NEN with different primary origins were compared. In a subcohort of patients from 2 referral hospitals (2014-2019), additional information on, for example, development of metastases after initial presentation was available.   Results: In the nationwide cohort, 4,768/11,120 (43%) patients had metastatic disease at diagnosis (GE: 1,504/4,710 [32%]; Pan: 489/1,150 [43%]; and L: 1,230/2,978 [41%]). For GE- and Pan-NEN, the most prevalent metastatic site was the liver (25 and 39%), followed by distant lymph nodes (8 and 8%), whereas only few patients with brain metastases were identified (0% in both). In contrast, for L-NEN, prevalence of metastases in the liver (19%), brain (9%), lung (7%), and bone (14%) was more equal. In the reference network cohort, slightly more NEN patients had metastatic disease (260/539, 48%) and similar metastatic patterns were observed.   Conclusion: Almost half of NEN patients were diagnosed with synchronous metastatic disease. L-NEN have a unique metastatic pattern compared to GE- and Pan-NEN. Remarkably, an important part of L-NEN metastases was in the brain, whereas brain metastases were almost absent in GE- and Pan-NEN, indicating utility of screening in L-NEN

Quality of life in a real-world cohort of advanced breast cancer patients:a study of the SONABRE Registry

Purpose We aimed to evaluate quality of life (QoL) using the European Quality of Life Five-Dimensions questionnaire (EQ-5D-3L) in a real-world cohort of Dutch advanced breast cancer (ABC) patients. Secondary, we reported differences in QoL between subgroups of patients based on age, comorbidity, tumor-, and treatment characteristics, and assessed the association of duration of metastatic disease and time to death with QoL. Methods ABC patients who attended the outpatient clinic between October 2010 and May 2011 were asked to fill out the EQ-5D-3L questionnaire. Patient-, disease-, and treatment characteristics were obtained from the medical files. Health-utility scores were calculated. Subgroups were described and compared for utility scores by parametric and non-parametric methods. Results A total of 92 patients were included with a median utility score of 0.691 (Interquartile range [IQR] 0.244). Patients &gt;= 65 years had significantly worse median utility scores than younger patients; 0.638 versus 0.743, respectively (p = 0.017). Moreover, scores were significantly worse for patients with versus those without comorbidity (medians 0.620 versus 0.725,p = 0.005). Utility scores did not significantly differ between subgroups of tumor type, type of systemic treatment, number of previous palliative treatment(s), or number or location of metastatic site(s). The remaining survival was correlated with utility scores (correlation coefficient (r) = 0.260,p = 0.0252), especially in the subgroup &lt;65 years (r = 0.340,p = 0.0169), whereas there was no significant correlation with time since metastatic diagnosis (r = - 0.106,p = 0.3136). Conclusion Within this real-world cross-sectional study, QoL was significantly associated with age, comorbidity, and remaining survival duration. The observation of a lower QoL in ABC patients, possibly indicating the last period of life, may assist clinical decision-making on timing of cessation of systemic antitumor therapy.</p

The role of histological subtype in hormone receptor positive metastatic breast cancer: similar survival but different therapeutic approaches

INTRODUCTION: This study describes the differences between the two largest histological breast cancer subtypes (invasive ductal carcinoma (IDC) and invasive (mixed) lobular carcinoma (ILC) with respect to patient and tumor characteristics, treatment-choices and outcome in metastatic breast cancer. RESULTS: Patients with ILC were older at diagnosis of primary breast cancer and had more often initial bone metastasis (46.5% versus 34.8%, P = 0.01) and less often multiple metastatic sites compared to IDC (23.7% versus 30.9%, P = 0.11). Six months after diagnosis of metastatic breast cancer, 28.1% of patients with ILC and 39.8% of patients with IDC had received chemotherapy with a longer median time to first chemotherapy for those with ILC (P = 0.001). After six months 84.8% of patients with ILC had received endocrine therapy versus 72.5% of patients with IDC (P = 0.0001). Median overall survival was 29 months for ILC and 25 months for IDC (P = 0.53). MATERIALS AND METHODS: We included 437 patients with hormone receptor-positive IDC and 131 patients with hormone receptor-positive ILC, all diagnosed with metastatic breast cancer between 2007–2009, irrespective of date of the primary diagnosis. Patient and tumor characteristics and data on treatment and outcome were collected. Survival curves were obtained using the Kaplan-Meier method. CONCLUSIONS: Treatment strategies of hormone receptor-positive metastatic breast cancer were remarkably different for patients with ILC and IDC. Further research is required to understand tumor behavior and treatment-choices in real-life

Primary granulocyte colony-stimulating factor prophylaxis during the first two cycles only or throughout all chemotherapy cycles in patients with breast cancer at risk for febrile neutropenia

Item does not contain fulltextPURPOSE: Early breast cancer is commonly treated with anthracyclines and taxanes. However, combining these drugs increases the risk of myelotoxicity and may require granulocyte colony-stimulating factor (G-CSF) support. The highest incidence of febrile neutropenia (FN) and largest benefit of G-CSF during the first cycles of chemotherapy lead to questions about the effectiveness of continued use of G-CSF throughout later cycles of chemotherapy. PATIENTS AND METHODS: In a multicenter study, patients with breast cancer who were considered fit enough to receive 3-weekly polychemotherapy, but also had > 20% risk for FN, were randomly assigned to primary G-CSF prophylaxis during the first two chemotherapy cycles only (experimental arm) or to primary G-CSF prophylaxis throughout all chemotherapy cycles (standard arm). The noninferiority hypothesis was that the incidence of FN would be maximally 7.5% higher in the experimental compared with the standard arm. RESULTS: After inclusion of 167 eligible patients, the independent data monitoring committee advised premature study closure. Of 84 patients randomly assigned to G-CSF throughout all chemotherapy cycles, eight (10%) experienced an episode of FN. In contrast, of 83 patients randomly assigned to G-CSF during the first two cycles only, 30 (36%) had an FN episode (95% CI, 0.13 to 0.54), with a peak incidence of 24% in the third cycle (ie, first cycle without G-CSF prophylaxis). CONCLUSION: In patients with early breast cancer at high risk for FN, continued use of primary G-CSF prophylaxis during all chemotherapy cycles is of clinical relevance and thus cannot be abandoned