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Background Calreticulin (CALR) mutations are commonly identified in patients with essential thrombocythaemia or myelofibrosis. CALR type 1 mutations are known to have a higher overall incidence in males but little is known about the risks of mutation subtypes on myelofibrotic change across patient age and sex. Aims To identify differences in the incidence of myelofibrotic change within subgroups of patients with CALR type 1 mutations. Methods All patients with a positive CALR exon 9 mutation identified within our unit between February 2016 and September 2020 were reviewed with note taken of patient sex, age at diagnosis, initial MPN diagnosis, and subsequent disease transformation. Results In our cohort, young male patients with CALR type 1 mutations were shown to be at significantly increased risk of myelofibrosis compared to age matched female patients. Conclusions Male patients have a worse myeloproliferative neoplasm phenotype than female patients with it occurring at a younger age and being more myelofibrotic in nature. Further investigation is needed into the reasons for this variability.

Essential thrombocythaemia (ET) is driven by somatic mutations involving the JAK2, CALR and MPL genes. Approximately 10% of patients lack driver mutations and are referred as ‘triple-negative’ ET (TN-ET). The diagnosis of TN-ET, however, relies on bone marrow examination that is not always performed in routine practice, and thus in the real-world setting, there are a group of cases with suspected TN-myeloproliferativeneoplasm.In this real-world cohort, patients with suspected TN-ET were initially rescreened for JAK2, CALR and MPL and then targeted next-generation sequencing (NGS) was applied.The 35 patients with suspected TN-ET had a median age at diagnosis of 43 years (range 16–79) and a follow-up of 10 years (range 2–28). The median platelet count was 758×109/L (range 479–2903). Thrombosis prior to and following diagnosis was noted in 20% and 17% of patients. Six patients were JAK2V617F and two patients were CALR positive on repeat screening. NGS results showed that 24 of 27 patients harboured no mutations. Four mutations were noted in three patients.There was no evidence of clonality for the majority of patients with suspected TN-ET with targeted NGS analysis. Detection of driver mutations in those who were previously screened suggests that regular rescreening is required. This study also questions the diagnosis of TN-ET without the existence of a clonal marker.

Summary Background Individual patient data from two randomised trials comparing neoadjuvant chemotherapy with upfront debulking surgery in advanced tubo-ovarian cancer were analysed to examine long-term outcomes for patients and to identify any preferable therapeutic approaches for subgroup populations. Methods We did a per-protocol pooled analysis of individual patient data from the European Organisation for Research and Treatment of Cancer (EORTC) 55971 trial ( NCT00003636 ) and the Medical Research Council Chemotherapy Or Upfront Surgery (CHORUS) trial (ISRCTN74802813). In the EORTC trial, eligible women had biopsy-proven International Federation of Gynecology and Obstetrics (FIGO) stage IIIC or IV invasive epithelial tubo-ovarian carcinoma. In the CHORUS trial, inclusion criteria were similar to those of the EORTC trial, and women with apparent FIGO stage IIIA and IIIB disease were also eligible. The main aim of the pooled analysis was to show non-inferiority in overall survival with neoadjuvant chemotherapy compared with upfront debulking surgery, using the reverse Kaplan-Meier method. Tests for heterogeneity were based on Cochran's Q heterogeneity statistic. Findings Data for 1220 women were included in the pooled analysis, 670 from the EORTC trial and 550 from the CHORUS trial. 612 women were randomly allocated to receive upfront debulking surgery and 608 to receive neoadjuvant chemotherapy. Median follow-up was 7·6 years (IQR 6·0–9·6; EORTC, 9·2 years [IQR 7·3–10·4]; CHORUS, 5·9 years [IQR 4·3–7·4]). Median age was 63 years (IQR 56–71) and median size of the largest metastatic tumour at diagnosis was 8 cm (IQR 4·8–13·0). 55 (5%) women had FIGO stage II–IIIB disease, 831 (68%) had stage IIIC disease, and 230 (19%) had stage IV disease, with staging data missing for 104 (9%) women. In the entire population, no difference in median overall survival was noted between patients who underwent neoadjuvant chemotherapy and upfront debulking surgery (27·6 months [IQR 14·1–51·3] and 26·9 months [12·7–50·1], respectively; hazard ratio [HR] 0·97, 95% CI 0·86–1·09; p=0·586). Median overall survival for EORTC and CHORUS patients was significantly different at 30·2 months (IQR 15·7–53·7) and 23·6 months (10·5–46·9), respectively (HR 1·20, 95% CI 1·06–1·36; p=0·004), but was not heterogeneous (Cochran's Q, p=0·17). Women with stage IV disease had significantly better outcomes with neoadjuvant chemotherapy compared with upfront debulking surgery (median overall survival 24·3 months [IQR 14·1–47·6] and 21·2 months [10·0–36·4], respectively; HR 0·76, 95% CI 0·58–1·00; p=0·048; median progression-free survival 10·6 months [7·9–15·0] and 9·7 months [5·2–13·2], respectively; HR 0·77, 95% CI 0·59–1·00; p=0·049). Interpretation Long-term follow-up data substantiate previous results showing that neoadjuvant chemotherapy and upfront debulking surgery result in similar overall survival in advanced tubo-ovarian cancer, with better survival in women with stage IV disease with neoadjuvant chemotherapy. This pooled analysis, with long-term follow-up, shows that neoadjuvant chemotherapy is a valuable treatment option for patients with stage IIIC–IV tubo-ovarian cancer, particularly in patients with a high tumour burden at presentation or poor performance status. Funding National Cancer Institute and Vlaamse Liga tegen kanker (Flemish League against Cancer).

INTRODUCTION: Brain lymphoma is known to be more common in immuno-compromised patients. There have been no phase III trials comparing treatment. The literature implies that chemotherapy is the treatment of choice, but in practice many patients do not receive this, or any treatment. We aimed to determine the outlook for such patients treated at Royal Preston Hospital. METHOD: A retrospective review of casenotes of patients treated by one clinician (AH) over a 13 year period obtained from neuropathology and radiotherapy databases. Kaplan-Myer survival curves were generated using SPSS software. RESULTS: 40 Patients were studied. The following symptoms were recorded at presentation;- confusion in 40%, headache in 28%, falls in 22%, weakness in 18%, visual problems in 12%, memory loss in 10%, incontinence in 10%, dysphasia in 8%, impotence in 2%. 35% had multifocal disease, 5% had vitreous involvement and 7% did not undergo biopsy. 38% of patients received radiotherapy alone. 32% received primary chemotherapy, median survivals were 11.5 and 18 months respectively. Untreated patients (30%) had a median survival of 1.5 months. Patients who received radiotherapy alone had a mean age of 69 and a mean WHO score of 1.9;- those who received chemotherapy had a mean age of 53 years and a mean WHO score of 0.9. 31% of patients died during chemotherapy. 54% of patients who had radiotherapy exhibited symptoms of neurotoxicity. 61% of these patients were over 60 years old. CONCLUSION: Primary brain lymphoma is rapidly fatal if untreated. Chemotherapy +/- radiotherapy produces the best survival, but often leads to toxicity which may be fatal. Radiotherapy alone produces long survival but at the cost of neurotoxicity.

Purpose: The aims of this randomized controlled trial were to determine whether there were differences in the disease-free survival (DFS) and toxicity between conventional radiotherapy (CRT) and a continuous 3 week accelerated radiotherapy regimen (ART) in stage III and IV squamous cell carcinoma of the oral cavity, oropharynx, larynx and hypopharynx. Patients and methods: Patients from 14 centres throughout Australia and New Zealand were randomly assigned to either CRT, using a single 2 Gy/day to a dose of 70 Gy in 35 fractions in 49 days or to ART, using 1.8 Gy twice a day to a dose of 59.4 Gy in 33 fractions in 24 days. Treatment allocation was stratified for site and stage. The accrual began in 1991 and the trial was closed in 1998 when the target of 350 patients was reached. Results: The median potential follow-up time was 53 months (range, 14‐101). The DFS at 5 years was 41% (95% CI, 33‐50%) for ART and 35% (95% CI, 27‐43%) for CRT (Pa 0:323) and the hazard ratio was 0.87 in favour of ART (95% CI, 0.66‐1.15). The 5-year diseasespecific survival rates were 40% for CRT and 46% for ART (Pa 0:398) and the loco-regional control was 47% for CRT vs. 52% for ART (Pa 0:300). The respective hazard ratios were 0.88 (95% CI, 0.65‐1.2) and 0.85 (0.62‐1.16), favouring the accelerated arm. In the ART arm, confluent mucositis was more severe (94 vs. 71%; P , 0:001) and peaked about 3 weeks earlier than in the CRT arm, but healing appeared complete in all cases. There were statistically significant reductions in the probability of grade 2 or greater late soft tissue effects over time in the ART arm (P , 0:05), except for the mucous membrane where late effects were similar in both arms. Conclusions: Differences in DFS, disease-specific survival and loco-regional control have not been demonstrated. ART resulted in more acute mucosal toxicity, but this did not result in greater prolongation of the treatment time compared with the CRT arm. There were less late effects in the ART arm, with the exception of late mucosal effects. This trial has confirmed that tumour cell repopulation occurs during conventionally fractionated radiotherapy for head and neck cancer. However, it has also provided additional evidence that overall improvements in the therapeutic ratio using accelerated fractionation strategies are seriously constrained by the need to limit total doses to levels that do not exceed acute mucosal tolerance. The accelerated schedule tested has been shown in this trial to be an acceptable alternative to conventionally fractionated irradiation to 70 Gy. q 2001 Elsevier Science Ireland Ltd. All rights reserved.

The Trans-Tasman Radiation Oncology Group (TROG) initiated a randomized trial, testing accelerated (twice daily) radiotherapy against conventional radiotherapy for stage III and stage IV squamous cell carcinoma of the head and neck in 1991. In 1996, the Trial Management Committee arranged for a technical audit of 76 cases from 11 institutions, conducted by investigators from interstate institutions. A 10% unacceptable protocol violation rate was detected, which compares favourably with initial Radiation Therapy Oncology Group (RTOG) experience in the late 1970s. Infrastructural deficits with poor quality of documentation, incomplete retrieval of films and document return have been demonstrated in some cases. The Trans-Tasman Radiation Oncology Group is actively pursuing procedural and resourcing issues in order to redress this and is actively expanding its Quality Assurance (QA) Programme with an intercentre dosimetry study. Ultimately, comprehensive clinical and technical QA site visits are planned.

Purpose We wanted to confirm the benefit of mometasone furoate (MF) in preventing acute radiation reactions, as shown in a previous study (Bostrom et al, Radiother Oncol 2001;59:257-265). Methods and Materials The study was a double-blind comparison of MF with D (Diprobase), administered daily from the start of radiation therapy for 5 weeks in patients receiving breast radiation therapy, 40 Gy in 2.67-Gy fractions daily over 3 weeks. The primary endpoint was mean modified Radiation Therapy Oncology Group (RTOG) score. Results Mean RTOG scores were significantly less for MF than for D ( P =.046). Maximum RTOG and mean erythema scores were significantly less for MF than for D ( P =.018 and P =.012, respectively). The Dermatology Life Quality Index (DLQI) score was significantly less for MF than for D at weeks 4 and 5 when corrected for Hospital Anxiety and Depression (HAD) questionnaire scores. Conclusions MF cream significantly reduces radiation dermatitis when applied to the breast during and after radiation therapy. For the first time, we have shown a significantly beneficial effect on quality of life using a validated instrument (DLQI), for a topical steroid cream. We believe that application of this cream should be the standard of care where radiation dermatitis is expected.

Background and purpose : Regeneration of the aerodigestive mucosa is known to occur during conventionally fractionated radiotherapy. The circumstances surrounding its time of onset and magnitude are not well understood, however. Material and methods : Mucosal reactions were observed in 100 patients undergoing conventionally fractionated treatment at 2 Gy/day over 7 weeks and 88 receiving accelerated treatment at 1.8 Gy twice daily over 312 weeks on the Trans Tasman Radiation Oncology Group head and neck cancer trials. Similar observations in 61 patients treated palliatively at dose rates between 0.8 and 240 Gy/h using ten 3.0–4.2 Gy fractions over 2 weeks are compared. Results : Several findings emerged from these studies: 1. Reactions evolved more quickly at oropharyngeal sites than in the hypopharynx. 2. Reactions at both sites evolved more rapidly at greater rates of dose accumulation. 3. The timing of reactions suggested the presence of a strong regenerative mucosal response that started before the manifestation of ‘patchy' (grade II) mucosal reactions. 4. The regenerative response was strong enough to ‘make good' damage accumulated at a rate of 2 Gy/day in over a third of cases. 5. The linear quadratic model without time correction failed to provide an adequate prediction of the frequency or intensity of mucosal reactions produced by any of the regimes. A simple model of the regenerative response is presented. Conclusions : This study suggests that the timing and magnitude of the regenerative response vary between sites and individuals but are linked to the amount of epithelial cellular depletion occurring during treatment.

BackgroundThis was an economic evaluation of hospital versus telephone follow-up by specialist nurses after treatment for breast cancer.MethodsA cost minimization analysis was carried out from a National Health Service (NHS) perspective using data from a trial in which 374 women were randomized to telephone or hospital follow-up. Primary analysis compared NHS resource use for routine follow-up over a mean of 24 months. Secondary analyses included patient and carer travel and productivity costs, and NHS and personal social services costs of care in patients with recurrent breast cancer.ResultsPatients who had telephone follow-up had approximately 20 per cent more consultations (634 versus 524). The longer duration of telephone consultations and the frequent use of junior medical staff in hospital clinics resulted in higher routine costs for telephone follow-up (mean difference £55 (bias-corrected 95 per cent confidence interval (b.c.i.) £29 to £77)). There were no significant differences in the costs of treating recurrence, but patients who had hospital-based follow-up had significantly higher travel and productivity costs (mean difference £47 (95 per cent b.c.i. £40 to £55)).ConclusionTelephone follow-up for breast cancer may reduce the burden on busy hospital clinics but will not necessarily lead to cost or salary savings.

Objective To compare traditional hospital follow-up with telephone follow-up by specialist nurses after treatment for breast cancer.\ud \ud \ud Design A two centre randomised equivalence trial in which women remained in the study for a mean of 24 months.\ud \ud \ud Setting Outpatient clinics in two NHS hospital trusts in the north west of England\ud \ud \ud Participants 374 women treated for breast cancer who were at low to moderate risk of recurrence.\ud \ud Interventions Participants were randomised to traditional hospital follow-up (consultation, clinical examination, and mammography as per hospital policy) or telephone follow-up by specialist nurses (consultation with structured intervention and mammography according to hospital policy).\ud \ud Main outcome measures Psychological morbidity (state-trait anxiety inventory, general health questionnaire (GHQ-12)), participants’ needs for information, participants’ satisfaction, clinical investigations ordered, and time to detection of recurrent disease.\ud \ud Results The 95% confidence interval for difference in mean state-trait scores adjusted for treatment received (−3.33 to 2.07) was within the predefined equivalence region (−3.5 to 3.5). The women in the telephone group were no more anxious as a result of foregoing clinic examinations and face-to-face consultations and reported higher levels of satisfaction than those attending hospital clinics (intention to treat P\ud Conclusions Telephone follow-up was well received by participants, with no physical or psychological disadvantage. It is suitable for women at low to moderate risk of recurrence and those with long travelling distances or mobility problems and decreases the burden on busy hospital clinics.\ud \ud Trial registration National Cancer Research Institute 1477.

Background: This paper will report on the findings from an economic evaluation of traditional hospital follow-up versus telephone follow-up by specialist breast care nurses for patients treated for breast cancer in the United Kingdom (UK). Materials and Methods: We conducted a cost minimisation analysis from a National Health Service (NHS) perspective using data from a randomised controlled trial that demonstrated equivalence between hospital and telephone follow-up in terms of psychological morbidity; 374 participants at low-moderate risk of recurrence were recruited to the study. The study was carried out at two hospitals in the North West of Engalnd. In a primary analysis we compared NHS resource use for routine follow-up (i.e. consultations, investigations and referrals) during a mean follow-up period of 24 months. Secondary analyses included patient and carer travel and productivity costs incurred and the NHS and personal social services costs of care in the minority of patients who developed a recurrence of their breast cancer. Results: Participants in the telephone follow-up group had approximately 20% extra consultations (634 versus 524). Telephone consultations were of longer duration and conducted by senior nurses whereas hospital clinic appointments were of shorter duration and often conducted by junior medical staff; this resulted in higher routine follow-up costs in the telephone follow-up group (mean difference £55, 95% bCI £29-£77). There were no significant differences in the costs of treating recurrence between groups. Participants receiving hospital follow-up had significantly higher travel and productivity costs (mean difference £47; 95% bCI £40-£55). Conclusions: Telephone follow-up by specialist nurses may be a useful strategy for reducing the burden on busy hospital clinics and providing a quality service. Although patients and carers will have fewer costs with telephone follow-up, this approach will not necessarily lead to cost or salary savings for the health service.

Background and purpose : The relationship between acute and late mucosal reactions remains ill defined but is of considerable relevance to efforts to produce therapeutic gains through the use of altered fractionation schemes and concurrent chemotherapy. We therefore investigated whether acute mucosal reactions in patients treated with an accelerated and a conventionally fractionated radiotherapy regime predicted the severity of late mucosal reactions. Patients and methods : The study population consisted of 191 patients randomised on a prospective trial comparing conventional fractionation at 2 Gy/fraction per day, 70 Gy over 47 days with an accelerated regimen of 59.4 Gy, 1.8 Gy BID over 24 days for Stage III–IV carcinoma of the head and neck. Acute and late mucosal reactions were scored according to RTOG/EORTC criteria and analyzed using multiple regression techniques. Results : The duration of time spent by patients at the acute confluent mucositis grade 3 level was inversely related to the time to onset of the reaction for both fractionation schedules. Time to onset was more rapid for patients treated on the accelerated schedule but time spent at the reaction grade did not differ significantly between the schedules. After correction for treatment and patient related factors, anatomical site (oral cavity/oropharynx versus hypopharynx/larynx) and increasing duration of confluent mucositis emerged as independent predictors of the hazard of late mucosal reactions with the latter effect being more pronounced in the accelerated treatment arm. The expected reduction in late mucosal effects in the accelerated fractionation arm, predicted by the LQ model for late effects was identified only in patients whose acute confluent mucosal reactions lasted less than 20 days. Conclusions : The presence of individual patient susceptibility factors that determine the severity of acute mucosal reactions is suggested. A link between severe and prolonged acute reactions and the risk of developing late mucosal reactions that is independent of biological dose, has also been found. Purpose designed prospective studies of these issues are necessary.