Anticancer chemotherapy in teenagers and young adults: managing long term side effects.

SSA is supported by the Cambridge Cancer Centre.This is the final version of the article. It first appeared from BMJ Group at http://dx.doi.org/10.1136/bmj.i4567

Teenage and Young Adult Cancer-Related Fatigue Is Prevalent, Distressing, and Neglected: It Is Time to Intervene. A Systematic Literature Review and Narrative Synthesis.

PURPOSE: Cancer-related fatigue in adults has been the subject of considerable recent research, confirming its importance as a common and debilitating symptom, and establishing a number of evidence-based interventions. There has, however, been limited focus on the fatigue suffered by teenagers and young adults with cancer, a group recognized as having unique experiences and developmental needs. We have undertaken a systematic review of the literature to provide a comprehensive overview of studies evaluating fatigue in this younger patient group in order to guide clinical practice and future research. METHOD: We searched MEDLINE, EMBASE, PsycINFO, and CINAHL databases for literature containing data relating to any aspect of fatigue in patients aged 13-24 at cancer diagnosis or treatment. RESULTS: Sixty articles were identified, of which five described interventional clinical trials. Cancer-related fatigue was consistently one of the most prevalent, severe, and distressing symptoms, and it persisted long-term in survivors. It was associated with a number of factors, including poor sleep, depression, and chemotherapy. There was little evidence for the effectiveness of any intervention, although exercise appears to be the most promising. Importantly, fatigue was itself a significant barrier to physical and social activities. CONCLUSION: Cancer-related fatigue is a major and disabling problem in young cancer patients. Effective management strategies are needed to avoid compounding the dependence and social isolation of this vulnerable patient group. Future research should focus on providing evidence for the effectiveness of interventions, of which activity promotion and management of concurrent symptoms are the most promising.SB and AS were funded by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care East of England at Cambridgeshire and Peterborough NHS Foundation Trust.This is the author accepted manuscript. The final version is available via Mary Ann Liebert at http://online.liebertpub.com/doi/abs/10.1089/jayao.2014.0023#/doi/abs/10.1089/jayao.2014.0023

Quantifying patient- and hospital-level antimicrobial resistance dynamics in Staphylococcus aureus from routinely collected data

Introduction. Antimicrobial resistance (AMR) to all antibiotic classes has been found in the pathogen Staphylococcus aureus . The reported prevalence of these resistances varies, driven by within-host AMR evolution at the patient level, and between-host transmission at the hospital level. Without dense longitudinal sampling, pragmatic analysis of AMR dynamics at multiple levels using routine surveillance data is essential to inform control measures. Gap Statement. The value and limitations of routinely collected hospital data to gain insight into AMR dynamics at the hospital and individual levels simultaneously are unclear. Methodology. We explored S. aureus AMR diversity in 70 000 isolates from a UK paediatric hospital between 2000–2021, using electronic datasets containing multiple routinely collected isolates per patient with phenotypic antibiograms and information on hospitalization and antibiotic consumption. Results. At the hospital level, the proportion of isolates that were meticillin-resistant (MRSA) increased between 2014–2020 from 25–50 %, before sharply decreasing to 30%, likely due to a change in inpatient demographics. Temporal trends in the proportion of isolates resistant to different antibiotics were often correlated in MRSA, but independent in meticillin-susceptible S. aureus . Ciprofloxacin resistance in MRSA decreased from 70–40 % of tested isolates between 2007–2020, likely linked to a national policy to reduce fluoroquinolone usage in 2007. At the patient level, we identified frequent AMR diversity, with 4 % of patients ever positive for S. aureus simultaneously carrying, at some point, multiple isolates with different resistances. We detected changes over time in AMR diversity in 3 % of patients ever positive for S. aureus . These changes equally represented gain and loss of resistance. Conclusion. Within this routinely collected dataset, we found that 65 % of changes in resistance within a patient’s S. aureus population could not be explained by antibiotic exposure or between-patient transmission of bacteria, suggesting that within-host evolution via frequent gain and loss of AMR genes may be responsible for these changing AMR profiles. Our study highlights the value of exploring existing routine surveillance data to determine underlying mechanisms of AMR. These insights may substantially improve our understanding of the importance of antibiotic exposure variation, and the success of single S. aureus clones

A Comprehensive Single Institutional Review of 2 Years in a Designated Fast-Track Sarcoma Diagnostic Clinic Linked with a Sarcoma Specialist Advisory Group: Meeting the Target but Failing the Task?

Background. National guidelines prompted the implementation of a designated two-week wait referral pathway to facilitate the early diagnosis of sarcomas, to improve treatment outcomes. Methods. Patients referred to the Cambridge Sarcoma Diagnostic Clinic between January 2013 and December 2014 were identified through the electronic appointments system. Information was retrospectively retrieved about patient characteristics and details of the diagnostic pathway. Results. 17.3% of patients referred (69/397) were diagnosed with a malignancy. Of these, 59.3% (41/69) had primary sarcomas, 17.4% (12/69) had metastatic cancer, and 23.2% (16/69) had a different primary malignancy. 15% of the 41 sarcomas were 10 cm. Sarcomas diagnosed through this clinic represented 13% (41/315) of sarcomas managed at the centre during the same 2 years. Conclusion. While we achieved the target of 10% (41/397) sarcoma diagnosis rate in the rapid access clinic, only 15% of these were <5 cm better prognosis lesions. This calls into question the "real world" impact of such diagnostic clinics on early diagnosis of sarcomas. In order to enhance generic cancer diagnostic skills, training in these diagnostic clinics could be usefully integrated into national training curricula for both surgical and nonsurgical oncologists.This is the final version of the article. It first appeared from the Hindawi Publishing Corporation via http://dx.doi.org/10.1155/2016/603260

Epirubicin, Cisplatin, and Capecitabine for Primary Platinum-Resistant or Platinum-Refractory Epithelial Ovarian Cancer: Results of a Retrospective, Single-Institution Study.

OBJECTIVE: Primary platinum-resistant epithelial ovarian cancer (EOC) is an area of unmet medical need. There is limited evidence from small studies that platinum-based combinations can overcome "resistance" in a proportion of patients. We investigated the efficacy and toxicity of platinum-based combination chemotherapy in the platinum-resistant and platinum-refractory setting. METHODS: Epirubicin, cisplatin, and capecitabine (ECX) combination chemotherapy was used at our institution for the treatment of relapsed EOC. From the institutional database, we identified all patients with primary platinum-refractory or platinum-resistant relapse treated with ECX as second-line therapy between 2001 and 2012. We extracted demographic, clinical, treatment, and toxicity data and outcomes. We used logistic and Cox regression models to identify predictors of response and survival respectively. RESULTS: Thirty-four 34 patients (8 refractory, 26 resistant) were treated with ECX. Response Evaluation Criteria In Solid Tumors (RECIST) response rate was 45%, median progression-free survival (PFS) was 6.4 months, and overall survival (OS) was 10.6 months. Platinum-resistant patients had better outcomes than did platinum-refractory patients (response rate, 54% vs 0%, P = 0.047; PFS 7.2 vs 1.8 months, P < 0.0001; OS 14.4 vs 3 months, P < 0.001). In regression models, time to progression after first-line treatment and platinum-refractory status were the strongest predictors of response and PFS or OS, respectively. Patients with time to progression after first-line treatment longer than 3 months showed PFS and OS of 7.9 and 14.7 months, respectively. Toxicity was manageable, with only 13% of cycles administered at reduced doses. CONCLUSIONS: Epirubicin, cisplatin, and capecitabine seems to be active in platinum-resistant relapsed EOC with manageable toxicity. Further prospective investigation of platinum-anthracycline combinations is warranted in patients who relapse 3 to 6 months after first-line platinum-taxane treatment

The Socio-Economic and Demographic Risk Factors for SARS-CoV-2 Seropositivity Among Healthcare Workers in a UK Hospital: A Prospective Cohort Study

BACKGROUND: In order to protect healthcare workers from the consequences of disease due to SARS-CoV-2 it is necessary to understand the risk factors that drive exposure and infection within hospitals. Insufficient consideration of key socio-economic variables is a limitation of existing studies that can lead to bias and residual confounding of proposed risk factors for infection. METHODS: The Co-STARS study prospectively enrolled 3679 HCWs between April 2020 and September 2020. We used multivariate logistic regression to comprehensively characterise the demographic, occupational, socio-economic and environmental risk factors for SARS-CoV-2 seropositivity. RESULTS: After adjusting for key confounders relative household overcrowding (OR 1.4 [CI 1.1-1.9] p = 0.006), Black, Black British, Caribbean or African ethnicity (OR 1.7 [CI 1.2-2.3] p = 0.003), increasing age (50-60 age group OR 1.8 [CI 1.3-2.4] p=<0.001), lack of access to sick pay (OR 1.8 [CI 1.3-2.4] p=<0.001) and out of hospital contact with COVID-19; staff contact (OR 1.8 [CI 1.4-2.4] p=<0.001), travel contact (OR 1.9 [CI 1.2-3.0] p = 0.008), household contact (OR 1.6 [CI 1.2-2.2] p = 0.002), other contact (OR 1.9 [CI 1.3-3.3] p = 0.029) were significantly associated with SARS-CoV-2 seropositivity. In this paediatric tertiary hospital setting, contact with known infected patients was not significantly associated with seropositivity (OR 1.2 [CI 0.6-2.1] p = 0.651). CONCLUSIONS: Socio-economic and demographic factors outside the hospital were the main drivers of infection and exposure to SARS-CoV-2 during the first wave of the pandemic in an urban paediatric referral hospital. Overcrowding and out of hospital SARS-CoV-2 contact are less amenable to intervention. However, lack of access to sick pay among externally contracted staff is more easily rectifiable. Our findings suggest that, if addressed, providing easier access to sick pay would lead to a decrease in SARS-CoV-2 transmission and potentially that of other infectious diseases in hospital settings

A randomized double-blind phase II study evaluating the role of maintenance therapy with cabozantinib in high-grade uterine sarcoma after stabilization or response to doxorubicin ± ifosfamide following surgery or in metastatic first line treatment (EORTC62113).

Funder: European Organisation for Research and Treatment of Cancer; FundRef: http://dx.doi.org/10.13039/501100004897Funder: Ligue Nationale de Lutte contre le Cancer (France)BACKGROUND: Uterine sarcomas are a group of rare tumors that include different subtypes. Patients with histopathological high-grade diseases are at high-risk of recurrence or progression, and have a poor prognosis. We aim to explore the most appropriate management in patients with uterine high-grade sarcomas. PRIMARY OBJECTIVE: To assess the efficacy of maintenance treatment with cabozantinib in patients with high-grade uterine sarcomas who achieved clinical benefit after standard chemotherapy. STUDY HYPOTHESIS: Maintenance treatment with cabozantinib after standard chemotherapy given as an adjuvant treatment after curative surgery, or in locally advanced or metastatic disease, increases progression-free survival compared with placebo TRIAL DESIGN: This is a randomized double blinded phase II trial. MAJOR INCLUSION/EXCLUSION CRITERIA: The study is enrolling adult patients with high-grade undifferentiated uterine sarcomas, high-grade endometrial stromal sarcomas, high-grade leiomyosarcoma, and high-grade adenosarcoma, FIGO (Federation International gynecologue Obstétricien) stage II/III to IV in stable disease or who achieved complete or partial response with doxorubicin ± ifosfamide, who are assigned 1:1 to 60 mg daily cabozantinib (experimental arm) or placebo (control arm), as maintenance therapy. Exclusion criteria include low-grade sarcoma. PRIMARY ENDPOINT: Progression-free survival at 4 months. SAMPLE SIZE: The study plans to enroll 90 patients to allow the randomization of 54 patients to detect an improvement in 4-month progression-free survival from 50% to 80% with 15% significance level and 85% power. Estimated dates for accrual completion: recruitment for the trial started in February 2015, and has currently enrolled 83 patients, of whom 35 patients have been randomized. The end of recruitment is anticipated for December 2020. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, number NCT01979393