Caregiver condition management and family functioning after pediatric cancer treatment: Moderation by race and ethnicity.

OBJECTIVE: End of pediatric cancer treatment requires family adjustment. Caregivers who struggle to incorporate the child's condition into family life have poorer family outcomes. To better understand factors that contribute to successful transition off active childhood cancer treatment, we sought to examine caregiver perceived management ability of the youth's condition and family functioning as predictors of caregiver distress, evaluate family functioning as a mediator between perceived ability and distress, and explore race and ethnicity as a moderator between perceived ability and family functioning. METHODS: Caregivers (N = 141) completed measures assessing family management (condition management ability; CMA), family functioning, and distress as part of a clinical education and screening program within 1 year of the end of treatment. Bias-corrected bootstrap regression analyses examined mediation and moderated mediation models with patient race and ethnicity as the moderator. RESULTS: The overall mediation model was statistically significant for CMA→family functioning→distress. Race and ethnicity moderated the relationship between CMA and family functioning, but the full model was not significant. CMA was related to family functioning for caregivers of non-Hispanic white youth, but not caregivers of Hispanic youth. Family functioning was related to distress for all caregivers. CONCLUSIONS: Family functioning serves as an initial intervention target to reduce caregiver distress. Caregiver perceived management ability of their child's condition is a meaningful predictor of family functioning and distress for caregivers of non-Hispanic white youth, yet CMA may be limited as a screener of family management patterns for diverse populations, and other family management dimension may be more applicable.

Predictive value on advance hodgkin lymphoma treatment outcome of end-of treatment FDG PET/CT in the HD0607 clinical trial.

The Lugano classification for response assessment in lymphoma recommends the use of the 5-point-scale Deauville Score (DS) to assess response evaluation of end-of-treatment FDG-PET/CT (eotPET) in Hodgkin Lymphoma (HL); nevertheless, there is a paucity of data on its accuracy and reproducibility. We focus here on the cohort of advanced stage IIb-IV HL patients enrolled in the HD0607 clinical trial (NCT identifier 00795613) that having had a negative interim PET performed 6 cycles of ABVD (Doxorubicin, Vinblastine, Vincristine and Dacarbazine) and then performed an eotPET. Negative patients were randomized to radiotherapy and no further treatment while positive patients were treated based on local policies. eotPET was re-evaluated independently by two readers evaluated and progression free survival was analysed (PFS). eotPET of 254 patients were analysed. The median follow-up was 43 months. The best receiver operator characteristics cut-off values to distinguish positive and negative patients was 4. The area-under-the-curve was 0.81 (95%CI, 0.70-0.91). Three-years PFS was 0.95 (95% CI 0.90-0.97) in eotPET negative and 0.22 (95% CI 0.11-0.43) in eotPET positive. DS demonstrated a good reproducibility of positivity/negativity between the readers consensus and local site evaluation where the agreement occurred on 95.0% of patients. The present study demonstrates that eotPET is an accurate tool to predict treatment outcome in HL and confirms the appropriateness of the Lugano classification for eotPET evaluation.

Psychosocial needs of pediatric cancer patients and their caregivers at end of treatment: Why psychosocial screening remains important.

OBJECTIVE: The pediatric cancer Psychosocial Standards of Care calls for psychosocial screening across the cancer trajectory. The current study aims to describe pediatric cancer family needs at the end of treatment (EOT) and summarize feedback on a clinical EOT screening and education program. METHODS: During a clinic visit, families attended an education session regarding general EOT considerations and caregivers and youth aged 11+ years completed questionnaires. Scores were coded for clinical significance based on cutoff scores per questionnaire, and clinical significance frequencies were calculated. Caregivers provided qualitative feedback on the EOT program via an open-ended prompt. RESULTS: Screening was completed by 151 families. Ninety-four patients (67.1%) endorsed risk by self- or proxy-report in at least one domain. Across all patient age groups, a symptom of neurocognitive functioning was the most frequently endorsed risk, including executive functioning, sustained focused, and thinking slower than others. For caregivers, 106 (74.1%) endorsed risk in at least one domain, with concerns for ability to manage their child's medical condition as the most frequent endorsement. Families were agreeable to an EOT program with many caregivers advocating for receiving this program earlier. CONCLUSIONS: Both patients and caregivers experienced clinically significant needs that require intervention at EOT. While patients are experiencing neurocognitive effects and distress, their caregivers are balancing management of their own distress with management of their child's needs during a transition to decreased support from the medical team. The findings affirm the need for systematic screening at EOT and anticipatory guidance for off treatment expectations.

Personalising care for patients: implementing a treatment summary folder following cytoreductive surgery.

BACKGROUND: A patient survey highlighted that patients treated with cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) at one NHS trust lacked confidence with the transition of care between teams. A personalised folder of treatment information was designed and given to patients prior to discharge. AIMS: To obtain patient feedback on the implementation and content of the folder. METHODS: 30 consecutive patients were given the folder at discharge. Participants completed an online questionnaire to determine whether the information in the folder was appropriate, given at the right time in the pathway and enhanced confidence on discharge. FINDINGS: 90% response rate was achieved. Of the respondents, 96% strongly agreed/agreed that the folder was helpful, 4% disagreed; 92% strongly agreed/agreed that the amount of information was right, 8% preferred more information, none less; 74% agreed/strongly agreed that the folder was provided at the right time; 96% said that the content met their expectations. CONCLUSION: Patients treated with CRS and HIPEC have specific needs related to their treatment. Implementation of the patient information folder at discharge increases patient confidence.

The prognostic value of end-of-treatment FDG-PET/CT in diffuse large B cell lymphoma: comparison of visual Deauville criteria and a lesion-to-liver SUVmax ratio-based evaluation system.

PURPOSE: The aim of this study was to determine a better criterion for end-of-treatment PET (EoT-PET) assessment and prognostic evaluation of patients with diffuse large B cell lymphoma (DLBCL). METHOD: EoT-PET scans were assessed using the visual Deauville 5-point scale (5PS) and LLR, the maximum standard uptake value ratio between the lesion and the liver. The cutoff value of LLR was obtained by receiver operator characteristic curve analysis. Patient outcomes were compared using Kaplan-Meier survival analysis. Prognostic indexes of different criteria were compared. Multivariate Cox regression analysis was performed to evaluate the prognostic factors. RESULTS: Four hundred forty-nine newly diagnosed DLBCL patients who received rituximab-based immunochemotherapy were included, and the median follow-up duration was 41.4 months. Patients with Deauville score (DS) 4 displayed significantly longer PFS and OS compared with patients with DS 5 (both p < 0.001), and they had significantly shorter PFS (p < 0.01) but similar OS (p = 0.057) compared with patients with DS 1-3. The differences in PFS and OS between groups were all significant whether positive EoT-PET was defined as DS 4-5 or DS 5 (all p < 0.001). The optimal cutoff of LLR was 1.83, and both PFS and OS were significantly different between EoT-PET-positive and EoT-PET-negative patients as defined by the cutoff (both p < 0.001). LLR-based criterion displayed higher specificity, positive predictive value, and accuracy than 5PS-based criterion in the prediction of disease progression and death events. In the multivariate analysis, positive EoT-PET (as defined by LLR) was related to unfavorable PFS and OS (both p < 0.001). Additional treatment was not correlated with outcomes of EoT-PET-negative patients either defined by LLR or 5PS or EoT-PET-positive patients classified by 5PS, but it was the only beneficial factor for OS (p < 0.05) in EoT-PET-positive patients with LLR ≥ 1.83. CONCLUSION: The optimal cutoff of LLR may be superior to Deauville criteria in identifying low-risk DLBCL patients with negative EoT-PET after the first-line immunochemotherapy and sparing them the cost and toxicity of additional treatment.

The Continuity of Cancer: Children and Adolescent's Experiences of Ending Cancer Treatment - A Systematic Review.

As the research and treatment of childhood cancer steadily progresses, so has the interest in children's needs, not only throughout such treatment but also following completion. Whilst there is increased literature focussing on the long-term psychosocial impact of treatment completion, little is currently known about how children and young people (CYP) experience the more immediate end of their cancer treatment. The current review seeks to examine CYP's experiences of the end of their cancer treatment. Sixteen studies were retrieved using a systematic search strategy across five databases, all of which used qualitative methodology. Thematic synthesis was chosen to analyse the data. Four overarching themes were generated, which encompassed 'the continuity of cancer', 'ambivalence of needs', 'making sense of the cancer experience' and 'sense of self following the ending'. The end of treatment is a time of complexity for CYP, yet it is currently largely overlooked. In order to scaffold these endings for CYP, increased emphasis and thought needs to be placed on the end of treatment and the support that is provided within it.

Positron emission tomography/computed tomography in the management of Hodgkin and B-cell non-Hodgkin lymphoma: An update.

18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is now an integral part of lymphoma staging and management. Because of its greater accuracy compared with CT alone, PET/CT is currently routinely performed for staging and for response assessment at the end of treatment in the vast majority of FDG-avid lymphomas and is the cornerstone of response classification for these lymphomas according to the Lugano classification. Interim PET/CT, typically performed after 2 to 4 of 6 to 8 chemotherapy/chemoimmunotherapy cycles with or without radiation, is commonly performed for prognostication and potential treatment escalation or de-escalation early in the course of therapy, a concept known as response-adapted or risk-adapted treatment. Quantitative PET is an area of growing interest. Metrics, such as the standardized uptake value, changes (Δ) in the standardized uptake value, metabolic tumor volume, and total lesion glycolysis, are being investigated as more reproducible and potentially more accurate predictors of response and prognosis. Despite the progress made in standardizing the use of PET/CT in lymphoma, challenges remain, particularly with respect to its limited positive predictive value, emphasizing the need for more specific molecular probes. This review highlights the most relevant applications of PET/CT in Hodgkin and B-cell non-Hodgkin lymphoma, its strengths and limitations, as well as recent efforts at implementing PET/CT-based metrics as promising tools for precision medicine.

The support and information needs of adolescents and young adults with cancer when active treatment ends.

BACKGROUND: The end of active treatment is a period of high stress for young people with cancer, but limited literature exists about their information and support needs during this phase. This study aimed to understand the needs of young people with cancer, how these needs are currently being met, and how best to provide information and support at the end of active treatment. METHODS: This was a multi-stage, mixed methods study exploring the end of treatment experience from the perspectives of young people, and the healthcare professionals caring for them. Semi-structured interviews were undertaken with healthcare professionals, which informed a survey administered nationally. Subsequently, semi-structured interviews were conducted with young people. These combined results informed a co-design workshop to develop recommendations. RESULTS: Telephone interviews were conducted with 12 healthcare professionals and 49 completed the online survey. A total of 11 young people aged 19-26 years (female = 8; 73%) were interviewed. The stakeholder workshop was attended by both healthcare professionals (n = 8) and young people (n = 3). At the end of treatment young people experience numerous ongoing physical issues including pain, fatigue and insomnia; in addition to a range of psychosocial and emotional issues including anxiety, fear of recurrence and isolation. The top three priorities for end of treatment care were: earlier provision and preparation around on-going impact of cancer and cancer treatment; standardised and continued follow-up of young people's emotional well-being; and development of more information and resources specific to young people. CONCLUSION: The access and availability of appropriate information and sources of support at the end of treatment is variable and inequitable. Young people's needs would be more effectively met by timely, structured and accessible information, and support provision at the end of treatment to both prepare and enable adaptation across their transition to living with and beyond cancer. This will require both organisational and practical adjustments in care delivery, in addition to a renewed and updated understanding of what the 'end of treatment' transition process means.

Systematic review on the value of end-of-treatment FDG-PET in improving overall survival of lymphoma patients.

This study aimed to systematically review the value of end-of-treatment 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) in improving overall survival (OS) of lymphoma patients. Medline was systematically searched for (1) randomized trials comparing the OS of patients who underwent end-of-treatment FDG-PET to those without and FDG-PET-based end-of-treatment evaluation and for (2) non-randomized studies comparing the OS of patients who underwent end-of-treatment FDG-PET to a (historical) cohort of patients without an FDG-PET-based end-of-treatment evaluation. The Medline search revealed 6284 articles. However, none of these reported data on the value of end-of-treatment FDG-PET in improving OS of lymphoma patients. In conclusion, the present systematic review reveals that there is currently no study at all that evaluates the value of end-of-treatment FDG-PET in improving OS of lymphoma patients. As a result, it remains unknown whether end-of-treatment FDG-PET increases OS and in which lymphoma subtype these examinations are of particular value. Future studies are required to demonstrate its value in this setting before it can be recommended as an evidence-based diagnostic tool by guidelines on the use of imaging in lymphoma.

HBsAg quantification predicts off-treatment response to interferon in chronic hepatitis B patients: a retrospective study of 250 cases.

BACKGROUND: For chronic hepatitis B (CHB) patients without willingness to extend the routine duration of interferon (IFN) therapy, it is important to identify patients who will benefit from treatment cessation. Hepatitis B surface antigen (HBsAg) quantification is recommended for management of IFN therapy. At present, the understanding on end-of-treatment (EOT) HBsAg level predicting post-treatment response to IFN is still finite. METHODS: A total of 2451 non-cirrhosis, HBsAg-postive patients treated with IFN-based therapy during the period from December 2010 to December 2017 at Nanfang Hospital were enrolled in this study. Serum HBsAg levels at EOT were measured to evaluate the associations between EOT HBsAg levels (Group 1, HBsAg > 0.05 and ≤ 10 IU/mL; Group 2, HBsAg > 10 and ≤ 200 IU/mL; Group 3, HBsAg > 200 IU/mL) with post-treatment HBsAg loss. Chi-squared, t-test,,Kaplan-Meier analysis, Cox regression analysis, and Multivariate Logistic regression analysis were used to analyse and evaluate differences between the there groups. RESULTS: The cumulative HBsAg loss rates 5 years after treatment in Group 1-3 were 30.4% (17/56), 9.8%(4/41) and 0%(0/153) (p < 0.001). An EOT HBsAg level of > 10 IU/mL showed relatively high negative predictive value (NPV) of up to 97.9% for HBsAg loss. Low baseline HBsAg level < 25,000 IU/mL, on-treatment HBsAg decline > 1 log10IU/mL at week 24 and EOT HBsAg level ≤ 10 IU/mL were found significantly associated with HBsAg loss. A total of 6 patients have achieved HBsAg loss at EOT and 17 patients with EOT HBsAg level ≤ 10 IU/mL have achieved post-treatment HBsAg loss. Baseline characteristics, dynamic changes of on-treatment HBsAg and duration of IFN therapy were balanced across patients with EOT or post-treatment HBsAg loss. CONCLUSION: EOT HBsAg level can serve as a monitoring indicator for IFN therapy. EOT HBsAg level ≤ 10 IU/mL was found to lead to high rate of post-treatment HBsAg loss. For patients without willingness to extend IFN treatment, off-treatment follow-up could be considered when HBsAg level decreased to ≤10 IU/mL.

The end of cancer treatment experience for children, adolescents, and their parents: A systematic review of the literature.

PROBLEM IDENTIFICATION: To date, there is limited study of the end of treatment (EOT) transition experiences and needs of children/adolescents with cancer and their parents. LITERATURE SEARCH: A systematic search identified primary research focusing on EOT, describing child, adolescent, and parental perceptions, experiences, and needs during this transition period. Of 170 articles identified, 22 met inclusion criteria. DATA EVALUATION/SYNTHESIS: Studies were appraised for level and quality of evidence. Narrative synthesis was performed to extract themes and integrate the literature. Family members' perceived needs, factors influencing the EOT experience, and consequences of this transition emerged as themes. CONCLUSIONS: Uncertainty and heightened anxiety at EOT highlight the need for increased education and support for family members. Family functioning and distress influence the EOT experience, with variable effects on each family member. There is a call for individualized interventions to promote coping and positive outcomes.

Significance of detectable HCV RNA below the limit of quantification in patients treated with DAAs using standard and ultrasensitive protocols.

Predictive factors of HCV relapse after treatment with DAAs are poorly understood. In this study, we aimed to assess whether the residual viral load positivity observed during or at the end of treatment (EOT) has an impact on viral outcome. Blood samples were collected from 337 patients with genotypes (GT) 1a, 1b, 2, 3, and 4 HCV chronic infection, treated with DAAs to determine HCV RNA load by the Abbott RealTime HCV (ART) assay at treatment week (W) 4, at EOT, and 4, 12, 24 weeks after discontinuation. EOT and other samples with "detected <12/mL" (DNQ) were retested by an ultrasensitive protocol (USP) to confirm the result. Frequency of DNQ was analyzed in subgroups of patients and clinical conditions to assess potential correlations. At W4, 22% and 30.9% of the samples were undetectable and DNQ by ART assay, respectively, but no correlation for achieving SVR was found. In contrast, an HCV RNA cut-off of ≥50/mL at W4 was a significant predictor of therapy failure (P = 0.036, univariate analysis). At EOT, DNQ was associated to 12W treatment duration (P < 0.001) and GT1a infection (P = 0.036). Overall, 20/41 (48.8%) of DNQ samples at EOT or post-treatment W4, were confirmed by USP but only in a single case the patient experienced viral relapse. HCV RNA at W4 can predict SVR, irrespective to genotype or DAA regimen. HCV RNA DNQ at EOT is associated to shorter treatment duration and to GT1a, but is not a predictor of therapy failure.

Clinical significance of detectable and quantifiable HCV RNA at the end of treatment with ledipasvir/sofosbuvir in GT1 patients.

BACKGROUND & AIMS: AASLD/IDSA treatment guidelines for hepatitis C virus (HCV) infection state that testing for quantitative HCV RNA can be considered at the end of antiviral treatment (EOT) with interferon-free regimens. However, it remains unclear how to respond to a detectable or even quantifiable HCV RNA result. The aim of this study was to analyse the frequency and predictive value of detectable and quantifiable HCV RNA results at the EOT in patients with HCV genotype 1 infection treated with ledipasvir (LDV) and sofosbuvir (SOF) ± ribavirin (RBV) in a large real-world cohort. METHODS: A retrospective analysis of the DHC-R (Deutsches Hepatitis C-Register, German Hepatitis C-Registry) cohort was performed including all patients who were treated with LDV/SOF ± RBV and in whom HCV RNA testing was done with either the Roche COBAS AmpliPrep/COBAS TaqMan (CAP/CTM) or the Abbott RealTime HCV assay (ART). RESULTS: The frequency of detectable HCV RNA at the EOT was 7% in this real-world study involving 471 patients. Furthermore, 3% of the patients (n = 14/471) even had quantifiable viral load at the EOT. Detectable and quantifiable results were more frequent if the ART was used for testing. However, SVR was achieved by 32/33 patients (97%) with detectable and even by all 14 patients (100%) with quantifiable HCV RNA results at the EOT. CONCLUSION: Detectable and even quantifiable HCV RNA results are quite frequent if highly sensitive HCV RNA assays are used. However, treatment prolongation is not indicated, as SVR rates remain high in these patients.

Issues experienced and support provided to adolescents and young adults at the end of active treatment for cancer: A rapid review of the literature.

INTRODUCTION: The end of active treatment is a stressful period for adolescents and young adults (AYA), but little is known about AYA experiences at this time point. The aim was to describe the issues young people experienced and identify interventions to support AYA at the end of treatment. METHODS: We conducted a rapid review of published primary research to identify what is currently known about AYA experiences of the end of treatment, the issues which arise and existing interventions to support AYA at this time. RESULTS: Searches identified 540 papers of which 16 met the inclusion criteria. Five main themes were identified: physical/medical issues; psychological, social and emotional issues; information and support needs; sources of information and support; and difficulties accessing information and support. Within these broader themes, several subthemes were identified and explored further. CONCLUSION: Adolescents and young adults are under prepared for the unpredictable and ongoing nature of the physical, psychological and social issues they face at the end of cancer treatment. Enabling young people's inclusion within their relevant social and educational peer networks should be a priority. Timely, structured and equitable information/support is needed to prepare AYA for treatment ending and subsequent reintegration to "everyday" life.

Hodgkin lymphoma: a negative interim-PET cannot circumvent the need for end-of-treatment-PET evaluation.

We examined the outcome of a cohort of patients with Hodgkin lymphoma (HL) in order to assess if fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) at the end of treatment (end-PET) can be omitted when the interim PET (int-PET) is negative. Seventy-six ABVD(adriamycin, bleomycin, vinblastine, dacarbazine)-treated patients were retrospectively included. No change in treatment was made on the basis of int-PET results. Suspicious foci on end-PET received biopsy confirmation whenever possible. Median follow-up was 58·9 months. Uptake on int-PET higher than liver (scores 4-5) was rated positive according to the Lugano classification, while a positive end-PET corresponded to scores 3, 4 and 5. Fifteen patients had treatment failure. Sensitivity, specificity, positive predictive value (PPV), negative predictive value and accuracy of int-PET were 46·7%, 85·2%, 43·8%, 86·7% and 77·6%, respectively. For end-PET the figures were: 80%, 93·4%, 75%, 95% and 90·8%. Eight patients with negative int-PET had treatment failure; six of them were identified as non-responders with end-PET. The 5-year progression-free survival (PFS) was 87% for patients with negative int-PET versus 56% with positive int-PET. The 5-year PFS was 96% with negative end-PET versus 23% with positive end-PET. The prognostic information from int-PET as regards PFS (log-rank test P = 0·0048) was lower than that provided by end-PET (P < 0·0001). Int-PET predicted only half of the failures. When used in clinical routine, a negative int-PET study cannot obviate the need for end-PET examination.

Prognostic value of interim and end-of-treatment FDG-PET in follicular lymphoma: a systematic review.

This study aimed to systematically review the prognostic value of interim and end-of-treatment (18)F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in follicular lymphoma during and after first-line therapy. The PubMed/MEDLINE database was searched for relevant original studies. Included studies were methodologically assessed, and their results were extracted and descriptively analyzed. Three studies on the prognostic value of interim FDG-PET and eight studies on the prognostic value of end-of-treatment FDG-PET were included. Overall, studies were of poor methodological quality. In addition, there was incomplete reporting of progression-free survival (PFS) and overall survival (OS) data by several studies, and none of the studies incorporated the Follicular Lymphoma International Prognostic Index (FLIPI) in the OS analyses. Two studies reported no significant difference in PFS between interim FDG-PET positive and negative patients, whereas one study reported a significant difference in PFS between the two groups. Two studies reported no significant difference in OS between interim FDG-PET positive and negative patients. Five studies reported end-of-treatment FDG-PET positive patients to have a significantly worse PFS than end-of-treatment FDG-PET negative patients, and one study reported a non-significant trend towards a worse PFS for end-of-treatment FDG-PET positive patients. Three studies reported end-of-treatment FDG-PET positive patients to have a significantly worse OS than end-of-treatment FDG-PET negative patients. In conclusion, the available evidence does not support the use of interim FDG-PET in follicular lymphoma. Although published studies suggest end-of-treatment FDG-PET to be predictive of PFS and OS, they suffer from numerous biases and failure to correct OS prediction for the FLIPI.

Simeprevir increases rate of sustained virologic response among treatment-experienced patients with HCV genotype-1 infection: a phase IIb trial.

BACKGROUND & AIMS: Simeprevir (TMC435) is an oral NS3/4 protease inhibitor in phase III trials for chronic hepatitis C virus (HCV) infection. We performed a phase IIb, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of the combination of simeprevir, peginterferon-α2a (PegIFN), and ribavirin (RBV) in patients with HCV genotype-1 infection previously treated with PegIFN and RBV. METHODS: We analyzed data from patients who did not respond (null response), had a partial response, or relapsed after treatment with PegIFN and RBV, randomly assigned to receive simeprevir (100 or 150 mg, once daily) for 12, 24, or 48 weeks plus PegIFN and RBV for 48 weeks (n = 396), or placebo plus PegIFN and RBV for 48 weeks (n = 66). All patients were followed for 24 weeks after planned end of treatment; the primary end point was the proportion of patients with sustained virologic response (SVR; undetectable HCV RNA) at that time point. RESULTS: Overall, rates of SVR at 24 weeks were significantly higher in the groups given simeprevir than those given placebo (61%-80% vs 23%; P < .001), regardless of prior response to PegIFN and RBV (simeprevir vs placebo: prior null response, 38%-59% vs 19%; prior partial response, 48%-86% vs 9%; prior relapse, 77%-89% vs 37%). All groups had comparable numbers of adverse events; these led to discontinuation of simeprevir or placebo and/or PegIFN and RBV in 8.8% of patients given simeprevir and 4.5% of those given placebo. CONCLUSIONS: In treatment-experienced patients, 12, 24, or 48 weeks simeprevir (100 mg or 150 mg once daily) in combination with 48 weeks PegIFN and RBV significantly increased rates of SVR at 24 weeks compared with patients given placebo, PegIFN, and RBV and was generally well tolerated. ClinicalTrials.gov number: NCT00980330.

Eltrombopag increases platelet numbers in thrombocytopenic patients with HCV infection and cirrhosis, allowing for effective antiviral therapy.

BACKGROUND & AIMS: Thrombocytopenia is common among patients with hepatitis C virus (HCV) infection and advanced fibrosis or cirrhosis, limiting initiation and dose of peginterferon-alfa (PEG) and ribavirin (RBV) therapy. The phase 3 randomized, controlled studies, Eltrombopag to Initiate and Maintain Interferon Antiviral Treatment to Benefit Subjects with Hepatitis C-Related Liver Disease (ENABLE)-1 and ENABLE-2, investigated the ability of eltrombopag to increase the number of platelets in patients, thereby allowing them to receive initiation or maintenance therapy with PEG and RBV. METHODS: Patients with HCV infection and thrombocytopenia (platelet count <75,000/µL) who participated in ENABLE-1 (n = 715) or ENABLE-2 (n = 805), from approximately 150 centers in 23 countries, received open-label eltrombopag (25-100 mg/day) for 9 weeks or fewer. Patients whose platelet counts reached the predefined minimal threshold for the initiation of PEG and RBV therapy (95% from ENABLE-1 and 94% from ENABLE-2) entered the antiviral treatment phase, and were assigned randomly (2:1) to groups that received eltrombopag or placebo along with antiviral therapy (24 or 48 weeks, depending on HCV genotype). The primary end point was sustained virologic response (SVR) 24 weeks after completion of antiviral therapy. RESULTS: More patients who received eltrombopag than placebo achieved SVRs (ENABLE-1: eltrombopag, 23%; placebo, 14%; P = .0064; ENABLE-2: eltrombopag, 19%; placebo, 13%; P = .0202). PEG was administered at higher doses, with fewer dose reductions, in the eltrombopag groups of each study compared with the placebo groups. More patients who received eltrombopag than placebo maintained platelet counts of 50,000/µL or higher throughout antiviral treatment (ENABLE-1, 69% vs 15%; ENABLE-2, 81% vs 23%). Adverse events were similar between groups, with the exception of hepatic decompensation (both studies: eltrombopag, 10%; placebo, 5%) and thromboembolic events, which were more common in the eltrombopag group of ENABLE-2. CONCLUSIONS: Eltrombopag increases platelet numbers in thrombocytopenic patients with HCV and advanced fibrosis and cirrhosis, allowing otherwise ineligible or marginal patients to begin and maintain antiviral therapy, leading to significantly increased rates of SVR. Clinical trial no: NCT00516321, NCT00529568.

Safety and efficacy of protease inhibitors to treat hepatitis C after liver transplantation: a multicenter experience.

BACKGROUND & AIMS: Protease inhibitors (PI) with peginterferon/ribavirin have significantly improved SVR rates in HCV G1 patients. Their use to treat HCV recurrence after liver transplantation (LT) is a challenge. METHODS: This cohort study included 37 liver transplant recipients (male, 92%, age 57 ± 11 years), treated with boceprevir (n=18) or telaprevir (n=19). The indication for therapy was HCV recurrence (fibrosis stage ≥F2 (n=31, 83%) or fibrosing cholestatic hepatitis (n=6, 16%). RESULTS: Eighteen patients were treatment-naive, five were relapsers and fourteen were non-responders to dual therapy after LT. Twenty-two patients received cyclosporine and fifteen tacrolimus. After 12 weeks of PI therapy, a complete virological response was obtained in 89% of patients treated with boceprevir, and 58% with telaprevir (p=0.06). The end of treatment virological response rate was 72% (13/18) in the boceprevir group and 40% (4/10) in the telaprevir group (p=0.125). A sustained virological response 12 weeks after treatment discontinuation was observed in 20% (1/5) and 71% (5/7) of patients in the telaprevir and boceprevir groups, respectively (p=0.24). Treatment was discontinued in sixteen patients (treatment failures (n=11), adverse events (n=5)). Infections occurred in ten patients (27%), with three fatal outcomes (8%). The most common adverse effect was anemia (n=34, 92%), treated with erythropoietin and/or a ribavirin dose reduction; thirteen patients (35%) received red blood cell transfusions. The cyclosporine dose was reduced by 1.8 ± 1.1-fold and 3.4 ± 1.0-fold with boceprevir and telaprevir, respectively. The tacrolimus dose was reduced by 5.2 ± 1.5-fold with boceprevir and 23.8±18.2-fold with telaprevir. CONCLUSIONS: Our results suggest that triple therapy is effective in LT recipients, particularly those experiencing a severe recurrence. The occurrence of anemia and drug-drug interactions, and the risk of infections require close monitoring.

Evaluating end of treatment care of young people with cancer.

BACKGROUND: Existing literature implies there may be gaps in post-treatment support for young people with cancer. This service evaluation explored the needs and experiences of young people when ending cancer treatment in a UK children's hospital to inform service provisions. METHODS: Semi-structured interviews were conducted with nine young people, aged 13-18 years, who had finished active cancer treatment and were receiving follow-up care. The data was analysed using thematic analysis. RESULTS: Four main themes were developed: being in the dark (i.e. limited awareness of what happens when treatment ends); separation from the hospital (i.e. the loss of valued support from staff); consequences of cancer (i.e. managing ongoing psychological and physical effects); and getting back to normal life (i.e. shifting from hospital to everyday life). CONCLUSIONS: Recommendations for improving clinical practice were made. Greater preparedness for ending treatment could be achieved by clearly setting out ongoing care arrangements, providing resource packs, having opportunities to mark the end of treatment, and offering peer support. To identify specific post-treatment needs, there should be an end of treatment multidisciplinary review and space for young people to share how they are feeling in follow-up medical appointments.