Imaging Modality and Frequency in Surveillance of Stage I Seminoma Testicular Cancer: Results From a Randomized, Phase III, Noninferiority Trial (TRISST).

PURPOSE: Survival in stage I seminoma is almost 100%. Computed tomography (CT) surveillance is an international standard of care, avoiding adjuvant therapy. In this young population, minimizing irradiation is vital. The Trial of Imaging and Surveillance in Seminoma Testis (TRISST) assessed whether magnetic resonance images (MRIs) or a reduced scan schedule could be used without an unacceptable increase in advanced relapses. METHODS: A phase III, noninferiority, factorial trial. Eligible participants had undergone orchiectomy for stage I seminoma with no adjuvant therapy planned. Random assignment was to seven CTs (6, 12, 18, 24, 36, 48, and 60 months); seven MRIs (same schedule); three CTs (6, 18, and 36 months); or three MRIs. The primary outcome was 6-year incidence of Royal Marsden Hospital stage ≥ IIC relapse (> 5 cm), aiming to exclude increases ≥ 5.7% (from 5.7% to 11.4%) with MRI (v CT) or three scans (v 7); target N = 660, all contributing to both comparisons. Secondary outcomes include relapse ≥ 3 cm, disease-free survival, and overall survival. Intention-to-treat and per-protocol analyses were performed. RESULTS: Six hundred sixty-nine patients enrolled (35 UK centers, 2008-2014); mean tumor size was 2.9 cm, and 358 (54%) were low risk (< 4 cm, no rete testis invasion). With a median follow-up of 72 months, 82 (12%) relapsed. Stage ≥ IIC relapse was rare (10 events). Although statistically noninferior, more events occurred with three scans (nine, 2.8%) versus seven scans (one, 0.3%): 2.5% absolute increase, 90% CI (1.0 to 4.1). Only 4/9 could have potentially been detected earlier with seven scans. Noninferiority of MRI versus CT was also shown; fewer events occurred with MRI (two [0.6%] v eight [2.6%]), 1.9% decrease (-3.5 to -0.3). Per-protocol analyses confirmed noninferiority. Five-year survival was 99%, with no tumor-related deaths. CONCLUSION: Surveillance is a safe management approach-advanced relapse is rare, salvage treatment successful, and outcomes excellent, regardless of imaging frequency or modality. MRI can be recommended to reduce irradiation; and no adverse impact on long-term outcomes was seen with a reduced schedule.

Characterisation of the onset and severity of adrenal and thyroid dysfunction associated with CTLA4-related hypophysitis.

CONTEXT: The use of the CTLA4 inhibitor, ipilimumab, has proven efficacious in the treatment of melanoma, renal carcinoma and non-small cell lung cancer; however, it is associated with frequent immune-related adverse events (irAE). Ipilimumab-induced hypophysitis (IIH) is a well-recognised and not infrequent endocrine irAE. OBJECTIVE: To investigate the timing of onset and severity of adrenal and thyroid hormone dysfunction around the development of IIH in patients treated for melanoma. DESIGN: Aretrospective review of hormone levels in consecutive adult patients treated with ipilimumab (3 mg/kg) for advanced melanoma as monotherapy or in combination with a PD-1 inhibitor. RESULTS: Of 189 patients, 24 (13%; 13 males; 60.5 ± 12.2 years) presented with IIH at a median of 16.1 (range: 6.7-160) weeks after commencing treatment, occurring in 14 (58%) after the fourth infusion. At the presentation of IIH, corticotroph deficiency was characterised by an acute and severe decrease in cortisol levels to ≤83 nmol/L (≤3 µg/dL) in all patients, often only days after a previously recorded normal cortisol level. Free thyroxine (fT4) levels were observed to decline from 12 weeks prior to the onset of cortisol insufficiency, with the recovery of thyroid hormone levels by 12 weeks after the presentation of IIH. A median fall in fT4 level of 20% was observed at a median of 3 weeks (IQR: 1.5-6 weeks) prior to the diagnosis of IIH. CONCLUSION: IIH is characterised by an acute severe decline in cortisol levels to ≤83 nmol/L at presentation. A fall in fT4 can herald the development of ACTH deficiency and can be a valuable early indicator of IIH.

Comparative Diagnostic Performance of the Granulocyte and Neutrophil Counts.

OBJECTIVES: Use of point-of-care testing is increasing, however many haematology analysers can only determine granulocyte count without further differentiation into neutrophils, eosinophils and basophils. Since the diagnosis of life-threatening neutropenia in cancer patients requires a distinct neutrophil count, this study aimed to determine the comparative performance between the neutrophil and granulocyte count. DESIGN AND METHODS: A database of 508 646 venous full blood count results measured on a laboratory reference analyser was mined from a large oncology unit. The relationship between granulocyte and neutrophil counts was assessed. Multinomial logistic regression was used to classify results into neutropenia grades using an equivalent granulocyte count. RESULTS: Granulocyte to neutrophil count correlation was 0.997. The accuracy for classification into neutropenia grades using the derived equivalent granulocyte count ranges was 96.4%. Identification of results with a neutrophil count <1.5×109 cells/L using an equivalent granulocyte count of <1.69×109 cells/L resulted in sensitivity, specificity, positive and negative predictive values of 98.0%, 99.5%, 97.8% and 99.5%, respectively. CONCLUSIONS: These results describe the relationship between granulocyte and neutrophil counts, measured on a laboratory analyser, in a large population of patients with malignancies and receiving anti-cancer therapies. However, this relationship must be established using a point of care testing system with a three-part differential count before considering the possibility that a granulocyte count can guide clinical decisions in the absence of a definitive neutrophil count, to reduce the frequency and severity of neutropenic complications in patients receiving cancer treatments.

Process mining routinely collected electronic health records to define real-life clinical pathways during chemotherapy.

BACKGROUND: There is growing interest in the use of routinely collected electronic health records to enhance service delivery and facilitate clinical research. It should be possible to detect and measure patterns of care and use the data to monitor improvements but there are methodological and data quality challenges. Driven by the desire to model the impact of a patient self-test blood count monitoring service in patients on chemotherapy, we aimed to (i) establish reproducible methods of process-mining electronic health records, (ii) use the outputs derived to define and quantify patient pathways during chemotherapy, and (iii) to gather robust data which is structured to be able to inform a cost-effectiveness decision model of home monitoring of neutropenic status during chemotherapy. METHODS: Electronic Health Records at a UK oncology centre were included if they had (i) a diagnosis of metastatic breast cancer and received adjuvant epirubicin and cyclosphosphamide chemotherapy or (ii) colorectal cancer and received palliative oxaliplatin and infusional 5-fluorouracil chemotherapy, and (iii) were first diagnosed with cancer between January 2004 and February 2013. Software and a Markov model were developed, producing a schematic of patient pathways during chemotherapy. RESULTS: Significant variance from the assumed care pathway was evident from the data. Of the 535 patients with breast cancer and 420 with colorectal cancer there were 474 and 329 pathway variants respectively. Only 27 (5%) and 26 (6%) completed the planned six cycles of chemotherapy without having unplanned hospital contact. Over the six cycles, 169 (31.6%) patients with breast cancer and 190 (45.2%) patients with colorectal cancer were admitted to hospital. CONCLUSION: The pathways of patients on chemotherapy are complex. An iterative approach to addressing semantic and data quality issues enabled the effective use of routinely collected patient records to produce accurate models of the real-life experiences of chemotherapy patients and generate clinically useful information. Very few patients experience the idealised patient pathway that is used to plan their care. A better understanding of real-life clinical pathways through process mining can contribute to care and data quality assurance, identifying unmet needs, facilitating quantification of innovation impact, communicating with stakeholders, and ultimately improving patient care and outcomes.

Survival patterns in teenagers and young adults with cancer in the United Kingdom: Comparisons with younger and older age groups.

AIMS: We aimed to describe and compare survival in teenagers and young adults (TYAs) with cancer to that of younger children and older adults, to identify sub-populations at greater or lesser risk of death. METHODS: We compared survival in cancer patients diagnosed in the United Kingdom aged 13-24 years (TYAs) to those aged 0-12 (children) and 25-49 years (adults) using the National Cancer Data Repository. All cases had a first cancer diagnosis between 1st January 2001 and 31st December 2005 with censor date 31st December 2010 or death if earlier. RESULTS: We found six distinct statistically significant survival patterns. In pattern 1, the younger the age-group the better the 1- and 5-year survival (acute lymphoid leukaemia, carcinoma of ovary and melanoma). In pattern 2, TYAs had a worse 5-year survival than both children and young adults (bone and soft tissues sarcomas). In pattern 3, TYAs had a worse 1-year survival but no difference at 5-years (carcinoma of cervix and female breast). In pattern 4, TYAs had better 1-year survival than adults, but no difference at 5 years (carcinoma of liver and intrahepatic bile ducts, germ cell tumours of extra-gonadal sites). In pattern 5, the younger the age-group the better the 5-year survival, but the difference developed after 1-year (acute myeloid leukaemia, carcinoma of colon and rectum). In pattern 6, there was no difference in 1- and 5-year survival between TYAs and adults (testicular germ cell tumours, ovarian germ cell tumours and carcinoma of thyroid). CONCLUSION: TYAs with specific cancer diagnoses can be grouped according to 1- and 5-year survival patterns compared to children and young adults. To further improve survival for TYAs, age-specific biology, pharmacology, proteomics, genomics, clinician and patient behaviour studies embedded within clinical trials are required.