Correlates of fertility issues in an Internet survey of cancer survivors

Purpose. The objectives of this study were (1) to determine what young cancer survivors know about the effect of their cancer on fertility, how fertility difficulties affected their lives and whether they would opt for fertility preservation (FP) and (2) to assess the sources of information and the helpfulness of them. Methods. Women of at least 18 years with cancer affecting reproductive function were recruited from eight cancer websites for this online survey. The Cancer and Fertility Survey (CFS) contained items from validated inventories and items to assess fertility issues in cancer patients. Quantitative analyses (t-tests, χ2, analysis of variance) and thematic analysis of free text data were performed. Results. Of the 80 participating women, 68.1% rated the risk of infertility as high. The mean number of professionals consulted was 3.56 (SD = 2.7), but 20% of women had not discussed fertility with any professional. The weighted mean helpfulness index was the highest for spouses and oncologists. Strength of positive attitudes towards FP was significantly greater than that of negative attitudes. Conclusion. The need to discuss fertility is high among women searching for information on cancer websites. Options to preserve fertility were positively viewed but the actual use may be limited by concerns about safety

Guidelines for the diagnosis and management of primary central nervous system diffuse large B-cell lymphoma

Scope: This guideline is aimed at providing healthcare professionals with clear guidance on the diagnosis and management of primary central nervous system lymphoma (PCNSL), defined as diffuse large B‐cell lymphoma (DLBCL) solely confined to the central nervous system (CNS): brain, spinal cord, cranial nerves, eyes and meninges. Secondary CNS lymphoma, immunodeficiency‐associated lymphoma and rare forms of non‐DLBCL CNS lymphoma are outside the scope of this guideline. It is not the intention of this guideline to provide treatment recommendations for all situations and clinicians are advised to take individual patient circumstances into account when making management decisions

4 Gy versus 24 Gy radiotherapy for follicular and marginal zone lymphoma (FoRT):long-term follow-up of a multicentre, randomised, phase 3, non-inferiority trial

BACKGROUND: The optimal radiotherapy dose for indolent non-Hodgkin lymphoma is uncertain. We aimed to compare 24 Gy in 12 fractions (representing the standard of care) with 4 Gy in two fractions (low-dose radiation). METHODS: FoRT (Follicular Radiotherapy Trial) is a randomised, multicentre, phase 3, non-inferiority trial at 43 study centres in the UK. We enrolled patients (aged >18 years) with indolent non-Hodgkin lymphoma who had histological confirmation of follicular lymphoma or marginal zone lymphoma requiring radical or palliative radiotherapy. No limit on performance status was stipulated, and previous chemotherapy or radiotherapy to another site was permitted. Radiotherapy target sites were randomly allocated (1:1) either 24 Gy in 12 fractions or 4 Gy in two fractions using minimisation and stratified by histology, treatment intent, and study centre. Randomisation was centralised through the Cancer Research UK and University College London Cancer Trials Centre. Patients, treating clinicians, and investigators were not masked to random assignments. The primary endpoint was time to local progression in the irradiated volume based on clinical and radiological evaluation and analysed on an intention-to-treat basis. The non-inferiority threshold aimed to exclude the chance that 4 Gy was more than 10% inferior to 24 Gy in terms of local control at 2 years (HR 1·37). Safety (in terms of adverse events) was analysed in patients who received any radiotherapy and who returned an adverse event form. FoRT is registered with ClinicalTrials.gov, NCT00310167, and the ISRCTN Registry, ISRCTN65687530, and this report represents the long-term follow-up. FINDINGS: Between April 7, 2006, and June 8, 2011, 614 target sites in 548 patients were randomly assigned either 24 Gy in 12 fractions (n=299) or 4 Gy in two fractions (n=315). At a median follow-up of 73·8 months (IQR 61·9-88·0), 117 local progression events were recorded, 27 in the 24 Gy group and 90 in the 4 Gy group. The 2-year local progression-free rate was 94·1% (95% CI 90·6-96·4) after 24 Gy and 79·8% (74·8-83·9) after 4 Gy; corresponding rates at 5 years were 89·9% (85·5-93·1) after 24 Gy and 70·4% (64·7-75·4) after 4 Gy (hazard ratio 3·46, 95% CI 2·25-5·33; p<0·0001). The difference at 2 years remains outside the non-inferiority margin of 10% at -13·0% (95% CI -21·7 to -6·9). The most common events at week 12 were alopecia (19 [7%] of 287 sites with 24 Gy vs six [2%] of 301 sites with 4 Gy), dry mouth (11 [4%] vs five [2%]), fatigue (seven [2%] vs five [2%]), mucositis (seven [2%] vs three [1%]), and pain (seven [2%] vs two [1%]). No treatment-related deaths were reported. INTERPRETATION: Our findings at 5 years show that the optimal radiotherapy dose for indolent lymphoma is 24 Gy in 12 fractions when durable local control is the aim of treatment. FUNDING: Cancer Research UK

Association of early disease progression and very poor survival in the GALLIUM study in follicular lymphoma: benefit of obinutuzumab in reducing the rate of early progression

We evaluated early disease progression and its impact on overall survival in previously untreated follicular lymphoma patients in GALLIUM (NCT01332968), and investigated the effect on early disease progression of the 2 randomization arms: obinutuzumab- versus rituximab-based immunochemotherapy. Cause-specific Cox regression was used to estimate the effect of treatment on the risk of disease progression or death due to disease progression within 24 months of randomization and to analyze overall survival in patients with or without disease progression after 24 months. Mortality in both groups was analyzed 6, 12, and 18 months post-randomization (median follow-up, 41 months). Fewer early disease progression events occurred in obinutuzumab (57/601) versus rituximab (98/601) immunochemotherapy patients, with an average risk reduction of 46.0% (95% CI: 25.0-61.1%; cumulative incidence rate 10.1% versus 17.4%). At a median post-progression follow-up of 22.6 months, risk of mortality increased markedly following a progression event (HR of time-varying progression status, 25.5 [95% CI: 16.2-40.3]). Mortality risk was higher the earlier patients progressed within the first 24 months. Age-adjusted HR for overall survival after 24 months in surviving patients with disease progression versus those without was 12.2 (95% CI: 5.6-26.5). Post-progression survival was similar by treatment arm. In conclusion, obinutuzumab plus chemotherapy was associated with a marked reduction in the rate of early disease progression events relative to rituximab plus chemotherapy. Early disease progression in patients with follicular lymphoma was associated with poor prognosis, with mortality risk higher after earlier progression. Survival post-progression did not seem to be influenced by treatment arm. .</p