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A positive association has been demonstrated between social supports, quality of life, and survival outcomes in cancer. This study assessed levels of social supports among patients with cancer in an Irish institution, with an age- and gender-specific stratification. The study highlights relatively low levels of perceived socio-emotional support and social connectedness, but good levels of tangible and informational support in our cohort of patients with cancer. Cancer clinicians should consider social supports as a factor when deciding upon cancer therapies and surveillance programs, and link in available support services for individuals with low levels of social supports where feasible. A positive association has been shown between social support, quality of life, and survival outcomes in cancer. This study assessed levels of social support among patients with cancer in an Irish institution, with an age- and gender-specific stratification.

•A niraparib population PK model was developed using pooled data from clinical trials.•PopPK/exposure-response analyses support niraparib individualized starting dose (ISD).•Use of a niraparib ISD improved the safety profile without compromising efficacy. Niraparib is a poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitor approved for the maintenance treatment of advanced ovarian cancer (OC). Niraparib was originally approved in recurrent OC at a fixed starting dose (FSD) of 300 mg once daily (QD). This analysis characterized the population pharmacokinetics (PK) of niraparib and evaluated the relationships between exposure, efficacy, and safety to support clinical use of an individualized dosing strategy, in which the starting dose of niraparib was adjusted based on patient characteristics to improve the benefit-risk profile. A population PK model was developed by pooling data from four niraparib clinical trials (PN001 [n = 104], QUADRA [n = 455], NOVA [n = 403], and PRIMA [n = 480]) in patients with solid tumors, including OC. Exposure-response analyses were conducted to explore the relationships of niraparib exposure with progression-free survival (PFS) and adverse events in the PRIMA study. A multivariate logistic regression model was also developed to estimate the probability of grade ≥3 thrombocytopenia, using data from patients enrolled in PRIMA and NOVA. The impact of an individualized starting dose (ISD) regimen (200 mg QD in patients with body weight [BW] <77 kg or platelet count [PLT] <150,000/µL, or 300 mg QD in patients with BW ≥77 kg and PLT ≥150,000/µL) on systemic exposure, efficacy, and safety was assessed. Niraparib disposition was best described by a 3-compartment model with linear elimination. Key covariates included baseline creatinine clearance, BW, albumin, and age, all of which had minor effects on niraparib exposure. Comparable model-predicted exposure up to the time of disease progression/death or censoring in the 300-mg FSD and 200-/300-mg ISD groups was consistent with the lower rate of dose reduction in the ISD groups. No consistent niraparib exposure-response relationship was observed for efficacy in all PRIMA patients (first-line OC), and no statistically significant difference was seen in PFS curves for patients receiving a niraparib dose of 200 mg versus 300 mg. In the multivariate regression model, performed using combined data from PRIMA and NOVA, higher niraparib exposure (area under the concentration-time curve at steady-state [AUCss]), lower BW, and lower PLT were associated with an increased risk of grade ≥3 thrombocytopenia. Population PK and exposure-response analyses support use of an ISD to improve the safety profile of niraparib, including reducing the rate of grade ≥3 thrombocytopenia, without compromising efficacy. ClinicalTrials.gov, NCT01847274 (NOVA), NCT00749502 (PN001), NCT02655016 (PRIMA), NCT02354586 (QUADRA), www.clinicaltrials.gov.

Colon cancer is a common disease that can be sporadic, familial, or inherited. Recent advances have contributed to the understanding of the molecular basis of these various patterns of colon cancer. Germline genetic mutations are the basis of inherited colon cancer syndromes; an accumulation of somatic mutations in a cell is the basis of sporadic colon cancer; and, in Ashkenazi Jewish persons, a mutation that was previously thought to be a polymorphism may cause familial colon cancer. Mutations of three different classes of genes have been described in colon cancer etiology: oncogenes, suppressor genes, and mismatch repair genes. Knowledge of many of the specific mutations responsible for colon carcinogenesis allows an understanding of the phenotypic manifestations observed and forms the basis of genetic testing for inherited disease. Although genetic testing is possible and available, it is only an adjunct to the clinical management of persons at risk for colon cancer and patients with colon cancer. As a result of advances in the understanding of the molecular causes of colon cancer and the availability of colon cancer screening methods such as colonoscopy, it should be possible to prevent the vast majority of colon cancer in our society. Practicing clinicians should recognize the patterns of clinical colon cancer, understand its causes, and be able to use genetic testing and endoscopic screening for prevention.

BackgroundImmune checkpoint inhibitors (ICI) have altered the therapeutic paradigm of advanced non-small cell lung cancer (NSCLC) and have become an attractive treatment strategy in several malignancies. The identification of reliable predictors associated with resistance is essential to dictate new approaches to broaden responder groups.Growing evidence has shown that the gut microbiome is an important regulator of the systemic immune system and is involved in the response to ICI. The aim of the study was to evaluate the association between antibiotics use & ICI efficacy in advanced NSCLCMethodsA retrospective, single-centre study of unselected patients with advanced NSCLC treated with ICI between June 2016 to May 2019. We included consecutive patients who received at least one dose of PD-1 inhibitors (Nivolumab or pembrolizumab) Clinicopathologic characteristics and the status of any oral or intravenous antibiotic use were evaluated. Antibiotic use was defined as antibiotic treatment at any time between 4-weeks pre- and 4-weeks post the start of ICI (table 1).Progression-Free Survival (PFS) & Overall Survival (OS) were estimated with Kaplan-Meier method & compared between Abx groups. Cox proportional model was used for multivariate analysesResultsAfter a median follow-up of 8.5 months [0.3–56.4], a significant improvement in PFS was observed in untreated group compared to Antibiotics treated group. 12.4 months (95%CI, 1.9–22.9) vs 4.1 months (95%CI, 2.6–5.6) (p < 0.001; figure 1). Similarly, OS among patients with no Antibiotics usage was significantly higher: 28.2 months (95%CI, not calculated) vs 12.5 months (95%CI, 10.8–14.2) (p < 0.001; figure 2).Abstract 728 Table 1Abstract 728 Figure 1Kaplan-Meier curves for PFS in patients with and without antibiotics useAbstract 728 Figure 2Kaplan-Meier curves for OS in patients with and without antibiotics useConclusionsOur results point to a detrimental effect of antibiotics on treatment outcome to ICI therapy.The antibiotics use was significantly associated with attenuated efficacy of anti-PD-1 therapies in patients with NSCLC Modulation of antibiotic-related changes of gut microbiota may be important to improve clinical outcomes in ICI for cancer treatmentIn patients needing antibiotics, careful selection to avoid antimicrobial agents that modulate immune responses should also be taken into considerationFurther studies are needed to determine the regimen, length of antibiotics treatment and its relation to survival benefitsReferencesWilson, Brooke E., et al. ‘The effect of antibiotics on clinical outcomes in immune-checkpoint blockade: a systematic review and meta-analysis of observational studies.’ Cancer Immunology, Immunotherapy 2019:1–12.Elkrief, A., et al. ‘The negative impact of antibiotics on outcomes in cancer patients treated with immunotherapy: a new independent prognostic factor?.’ Annals of Oncology 2019;30(10): 1572–1579.Villéger, Romain, et al. ‘Intestinal microbiota: a novel target to improve anti-tumor treatment?.’International Journal of Molecular Sciences 2019;20(18):4584

Background The (derived) neutrophil-to-lymphocyte ratio (dNLR) is a potential predictive biomarker in the era of checkpoint inhibitors (CPI). An elevated dNLR is associated with worse outcomes across several malignancies. However, there is no clearly defined cut-off in the clinical setting. Aim To compare outcomes in patients prescribed CPI with a baseline dNLR 0  > 3 and dNLR 0  ≤ 3. The dNLR 6 was measured 6 weeks later to determine its impact on patient overall survival (OS). Methods Prospectively maintained pharmacy databases in a regional cancer centre were interrogated for patients who were prescribed CPI in the advanced setting between January 2017 and May 2020. Results There were 121 patients with advanced cancer and a median age of 68 (range 30 to 88) years. Forty-four percent ( n  = 53) received prior systemic therapy. Patients with an initial dNLR 0  > 3 when compared with a dNLR 0  ≤ 3 had significantly shorter median progression-free survival (PFS), 3 vs. 14 months ( p  = 0.001) and median OS, 6.4 vs. 30.2 months ( p  = 0.001). Patients with an initial dNLR 0  > 3 and increased dNLR at 6 weeks (dNLR 6 ) had significantly reduced median PFS (3.5 vs. 14.7 months, p  = 0.03) and OS (5.7 vs. 16.3, p  = 0.03) when compared with those whose dNLR decreased. In the dNLR 0  ≤ 3 cohort, any increased dNLR when compared with decreased dNLR after 6 weeks of CPI had significantly reduced PFS (8.4 months vs. NR, p  = 0.01) and OS (24.2 months vs. NR, p  = 0.02). Conclusions Lower pre-CPI treatment dNLR is associated with improved OS. A decrease in dNLR during treatment confers improved OS.

Abstract Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer. Surgery is usually curative; however, some locally advanced or metastatic CSCC may be unresectable. Current novel therapeutic options with immune checkpoint inhibition (ICI) of programmed-death receptor 1 (PD-1) such as cemiplimab and nivolumab have demonstrated promising and sustained results with good tolerability in patients with CSCC. This study looks at 2 cases of CSCC treated with cemiplimab and nivolumab, respectively, demonstrating dramatic response within 2 cycles with significant reduction in tumour size and minimal toxicities or adverse outcomes reported. Immunotherapy has shown positive results as an effective treatment option for unresectable, recurrent, or metastatic CSCC. It is currently approved for use in the USA and Europe.

The colon is an uncommon secondary site for metastasis of lung adenocarcinoma. Distinguishing primary colonic carcinoma from metastatic spread of lung carcinoma can be difficult. We present a case of a patient with lung adenocarcinoma who, on abdominal computed tomography scan examination, was found to have a sigmoid tumor that was thought to represent a synchronous primary colorectal adenocarcinoma. Histological examination of endoscopic sigmoid tumor biopsies confirmed this to be metastasis from the lung adenocarcinoma. The patient subsequently developed major rectal bleeding and deteriorated significantly. This case also illustrates the poor prognosis association with colorectal metastasis of lung cancer.

Background: Combining bevacizumab and chemotherapy produced superior response rates compared with chemotherapy alone in metastatic breast cancer. As bevacizumab may cause hypertension (HTN) and increase the risk of cardiac failure, we performed a pilot study to evaluate the feasibility and toxicity of a non-anthracycline-containing combination of docetaxel with cyclophosphamide and bevacizumab in early stage breast cancer patients. Methods: Treatment consisted of four 3-weekly cycles of docetaxel and cyclophosphamide (75/600 mg/m2). Bevacizumab was administered 15 mg/kg intravenously on day 1, and then every 3 weeks to a total of 18 cycles of treatment. Serum biomarker concentrations of vascular endothelial growth factor (VEGF), cardiac troponin-I (cTnI), myeloperoxidase (MPO), and placental growth factor (PlGF) were quantified using enzyme-linked immunosorbent assay (ELISA) in 62 patients at baseline and whilst on treatment to determine their utility as biomarkers of cardiotoxicity, indicated by left ventricular ejection fraction (LVEF). Results: A total of 106 patients were accrued in nine sites. Median follow up was 65 months (1–72 months). Seventeen protocol-defined relapse events were observed, accounting for an overall disease-free survival (DFS) rate of 84%. The DFS rates for hormone receptor positive (HR+) and triple-negative (TN) patients were 95% versus 43%, respectively. The median time to relapse was 25 (12–54) months in TN patients versus 38 (22–71) months in HR+ patients. There have been 13 deaths related to breast cancer . The overall survival (OS) rate was 88%. The 5-year OS rate in HR+ versus TN was 95% versus 57%. None of the measured biomarkers predicted the development of cardiotoxicity. Conclusions: We observed a low relapse rate in node-positive, HR+ patients; however, results in TN breast cancer were less encouraging. Given the negative results of three large phase III trials, it is unlikely that this approach will be investigated further. Trial Registration ClinicalTrials.gov Identifier: NCT00911716.

Non-gestational choriocarcinoma is an extremely rare and highly aggressive malignant tumor that arises independent of gestational events, making less than 0.6% of all ovarian germ cell tumors. Unlike the more common gestational choriocarcinoma, which is associated with pregnancy, non-gestational choriocarcinoma originates from germ cells within the ovary. It accounts for a small fraction of ovarian malignancies and is often characterized by elevated levels of serum beta-human chorionic gonadotropin (β-HCG). The rarity and clinical overlap with other ovarian tumors pose significant diagnostic challenges, necessitating a thorough histopathological and immunohistochemical examination for accurate diagnosis. A 39-year-old female presented with a two-week history of right-sided migraine and general malaise, followed by a three-day onset of vision loss in the right eye. Initial evaluation in the emergency department included a chest X-ray, which revealed a 10 cm rounded opacity in the upper lobe of the left lung. A CT scan of the head showed a 4.5 cm rim-enhancing lesion in the left occipital lobe, along with a left middle cerebral artery (MCA) aneurysm. Notably, her serum β-HCG levels were significantly elevated at 5,642 mIU/mL despite the absence of intrauterine or extrauterine pregnancy on abdominal and pelvic ultrasound. Further workup included a CT thorax and MRI of the brain, which confirmed the isolated lung mass and left occipital lobe mass with no other sites of disease, leading to her transfer to the neurosurgery department. The patient underwent a left occipital craniotomy with tumor resection. Histopathological analysis confirmed the diagnosis of choriocarcinoma. Chromosomal analysis showed no evidence of the Y chromosome and confirmed the non-gestational origin of the choriocarcinoma. This case report discusses the non-specific presentation, radiological features, current treatment options, and potential safety strategies for managing this rare condition.

Introduction/BackgroundThe treatment of older women with ovarian cancer is challenging due to increased pre-existing co-morbidities and frailty, often leading to less radical treatment than the standard of care. Older women are frequently excluded from clinical trials. Recent studies such as the EWOC-1 study focused on elderly women with ovarian cancer suggest worse outcomes associated with less radical treatment approaches.MethodologyWomen diagnosed with ovarian cancer ≥65 years old referred to oncology services at three Irish University Hospitals between 2015 and 2021 were included. We evaluated patterns regarding surgery and chemotherapy sequencing, choice of agent and completion rates, according to age group. Survival outcomes were examined by Kaplan Meier analysis. The study received ethical approval.Results190 patients were included in this study. 65.26% (124) of these women had an ECOG performance status of 0–1 at diagnosis. 129 patients (67.89%) had (FIGO) stage III or stage IV disease at diagnosis. 55% of all stage III/IV patients had optimal debulking surgery. 37% of stage III/IV patients received neoadjuvant chemotherapy followed by surgery and 27% had surgery followed by chemotherapy. Women in the ≥75 group were more likely to receive single agent carboplatin (38%), compared to women aged 65–74 years (30%). Median overall survival for all stage III/IV patients who received SA Carboplatin was 15 months versus 22 months for Carboplatin and Paclitaxel groups. BRCA testing was sub-optimal in this age group at 28% of all patients although routine BRCA testing has only been available in Ireland since 2019.ConclusionElderly ovarian cancer patients, particularly those ≥75 years, may receive less radical treatment approaches than standard of care. Our cohort suggests improved survival with carboplatin/paclitaxel, although our cohort is too small to draw significant conclusions. Rates of BRCA testing were low. Geriatric oncology assessments should be incorporated into treatment decisions.