Efficacy of Anastrozole after Tamoxifen in Early Breast Cancer Patients with Chemotherapy‐Induced Ovarian Function Failure

The DATA study (NCT00301457) compared 6 and 3 years of anastrozole in postmenopausal women with hormone receptor‐positive early breast cancer after 2‐3 years tamoxifen. Patients with chemotherapy‐induced ovarian function failure (CIOFF) were also eligible, but could be at risk of ovarian function recovery (OFR). The current analysis compared the survival of women with CIOFF with definitely postmenopausal women and examined the influence of OFR on survival. Therefore, we selected patients from the DATA study aged 45‐57 years at randomization who had received (neo)‐adjuvant chemotherapy. They were classified by reversibility of postmenopausal status: possibly reversible in case of CIOFF (n=395) versus definitely postmenopausal (n=261). The former were monitored by E2 measurements for OFR. The occurrence of OFR was incorporated as a time‐dependent covariate in a Cox‐regression model for calculating the hazard ratio (HR). We used the landmark method to calculate residual 5‐year survival rates.

When comparing CIOFF women with definitely postmenopausal women, the survival was not different. Amongst CIOFF women with available E2 follow‐up values (n= 329), experiencing OFR (n=39) had an unfavourable impact on distant recurrence‐free survival (HR 2.27 (95% CI 0.98‐5.25;P=0.05) and overall survival (HR 2.61 (95% CI 1.11‐6.13;P=0.03)). After adjusting for tumor features, the HRs became 2.11 (95% CI 0.89‐5.02;P=0.09) and 2.24 (95% CI 0.92‐5.45;P=0.07) respectively.

The residual 5‐year rate for distant recurrence‐free survival was 76.9% for women with OFR and 92.1% for women without OFR, and for 5‐year overall survival 80.8% and 94.4%, respectively.

Women with CIOFF receiving anastrozole may be at increased risk of disease recurrence if experiencing OFR.

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Adherence to the Mediterranean diet and lymphoma risk in the European Prospective Investigation into Cancer and Nutrition

There is growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, no prospective study has yet investigated its influence on lymphoma. We evaluated the association between adherence to the MD and risk of lymphoma and its subtypes in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The analysis included 476,160 participants, recruited from ten European countries between 1991 and 2001. Adherence to the MD was estimated through an adapted relative Mediterranean diet (arMED) score excluding alcohol. Cox proportional hazards regression models were used while adjusting for potential confounders. During an average follow‐up of 13.9 years, 3,136 lymphomas (135 Hodgkin lymphoma (HL), 2,606 non‐Hodgkin lymphoma and 395 lymphoma NOS) were identified. Overall, a 1‐unit increase in the arMED score was associated with a 2% lower risk of lymphoma (95% CI: 0.97; 1.00, p‐trend=0.03) while a statistically non‐significant inverse association between a high versus low arMED score and risk of lymphoma was observed (HR: 0.91 (95% CI 0.80; 1.03), p‐trend=0.12). Analyses by lymphoma subtype did not reveal any statistically significant associations. Albeit with small numbers of cases (N= 135), a suggestive inverse association was found for HL (HR 1‐unit increase= 0.93 (95% CI: 0.86; 1.01), p‐trend=0.07). However, the study may have lacked statistical power to detect small effect sizes for lymphoma subtype. Our findings suggest that an increasing arMED score was inversely related to the risk of overall lymphoma in EPIC, but not by subtypes. Further large prospective studies are warranted to confirm these findings.

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Microfluidic enrichment, isolation and characterization of disseminated melanoma cells from lymph node samples

For the first time in melanoma, novel therapies have recently shown efficacy in the adjuvant therapy setting, which makes companion diagnostics to guide treatment decisions a desideratum. Early spread of disseminated cancer cells (DCC) to sentinel lymph nodes (SLN) is indicative of poor prognosis in melanoma and early DCCs could therefore provide important information about the malignant seed. Here, we present a strategy for enrichment of DCCs from SLN suspensions using a microfluidic device (Parsortix^TM, Angle plc). This approach enables the detection and isolation of viable DCCs, followed by molecular analysis and identification of genetic changes. By optimizing the workflow, the established protocol allows a high recovery of DCC from melanoma patient‐derived LN suspensions with harvest rates above 60%. We then assessed the integrity of the transcriptome and genome of individual, isolated DCCs. In LNs of melanoma patients, we detected the expression of melanoma‐associated transcripts including MLANA (encoding for MelanA protein), analysed the BRAF and NRAS mutational status and confirmed the malignant origin of isolated melanoma DCCs by comparative genomic hybridization. We demonstrate the feasibility of epitope‐independent isolation of LN DCCs using Parsortix^TM for subsequent molecular characterization of isolated single DCCs with ample application fields including the use for companion diagnostics or subsequent cellular studies in personalized medicine.

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Impact of screening programme using the faecal immunochemical test on stage of colorectal cancer. Results from the IMPATTO study

To evaluate the impact of faecal immunochemical test (FIT) screening on stage distribution at diagnosis, and to estimate relative incidence rates by stage in screened at first and subsequent rounds vs. unscreened. We included all incident cases occurring in 2000‐2008 in 50‐71‐year‐olds residing in areas with an FIT‐screening programme. Multinomial logistic models were computed to estimate the relative risk ratio (RRR) of stages I and IV, compared to stage II+III, adjusting for age, sex, geographical area, and incidence year. Proportions were then used to estimate incidence rate ratios (IRR) by stage for screened subjects at the first and at subsequent rounds vs. unscreened subjects, applying the expected changes in overall incidence during screening phases. 11663 cancers were included: 5965 in not‐invited and 5698 in invited subjects, 3425 of whom attendees. Compared to not‐invited, invited subjects had RRR 2.04 (95%CI:1.84;2.46) of stage I and RRR 0.77 (95%CI:0.69; 0.87) of stage IV. Differences were stronger comparing attendees vs. non‐attendees. Interval cancers were more frequently stage I compared to non‐invited (RRR 1.54; 95%CI:1.15;2.04), but there was no difference for stage IV. IRRs in screened at first round vs. unscreened were 4.6 (95%CI:4.2;5.1), 1.4 (95%CI:1.3;1.5) and 0.7 (95%CI:0.6;0.9) for stages I, II+III and IV, respectively; in the following rounds the IRRs of screened vs. unscreened. were 1.4 (95%CI:1.2;1.6), 0.8 (95%CI:0.7;0.9) and 0.3 (95%CI:0.1;0.4) for stages I, II+III and IV, respectively. FIT screening reduces the incidence of metastatic cancers by about 70% after the first round.

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Gallstones and incident colorectal cancer in a large pan‐European cohort study

Gallstones, a common gastrointestinal condition, can lead to several digestive complications and can result in inflammation. Risk factors for gallstones include obesity, diabetes, smoking and physical inactivity, all of which are known risk factors for colorectal cancer (CRC), as is inflammation. However, it is unclear whether gallstones are a risk factor for CRC. We examined the association between history of gallstones and CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a prospective cohort of over half a million participants from ten European countries. History of gallstones was assessed at baseline using a self‐reported questionnaire. The analytic cohort included 334,986 participants; a history of gallstones was reported by 3,917 men and 19,836 women, and incident CRC was diagnosed among 1,832 men and 2,178 women (mean follow‐up: 13.6 years). Hazard ratios (HR) and 95% confidence intervals (CI) for the association between gallstones and CRC were estimated using Cox proportional hazards regression models, stratified by sex, study centre, and age at recruitment. The models were adjusted for body mass index, diabetes, alcohol intake, and physical activity. A positive, marginally significant association was detected between gallstones and CRC among women in multivariable analyses (HR=1.14, 95%CI 0.99–1.31, p=0.077). The relationship between gallstones and CRC among men was inverse but not significant (HR=0.81, 95%CI 0.63–1.04, p=0.10). Additional adjustment for details of reproductive history or waist circumference yielded minimal changes to the observed associations. Further research is required to confirm the nature of the association between gallstones and CRC by sex.

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Erratum

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Adult convulsive status epilepticus(CSE)

Determinants of outcome in convulsive status epilepticus in adults: An ambispective study from central India

p. 84

Raunak Dani, Ajoy Sodani, Kapil Telang, Richa Nigam DOI:10.4103/aian.AIAN_466_17   Background: The determinants of the outcome in adult convulsive status epilepticus(CSE), also the implication of the value of mean arterial blood pressure (MAP), and random blood sugar at admission on the outcome are not clear. Objectives: The objective of this study is to look for the determinants of unfavorable outcome in CSE. Materials and Methods: Ambispectively gathered data from 55 patients, treated consecutively with identical protocol during January 2010–December 2016, were analyzed. The demographic and clinical variables were identified and correlated with outcome in each individual. Results: There were 65.45% males and 34.55% females. Favorable outcome (conscious and discharged) was seen in 63.6%, unfavorable (death 14.5%, absent cortical functions 10.9%, and inability to wean-off anesthetic agents 10.9%). The parameters associated with unfavorable outcome were female gender (odds ratio [OR]: 1.45), MAP ≤80 mmHg (OR: 2.57), time to first medical attention >5 h (OR: 127.8), and time to control clinical seizures >3.5 h (OR: 7.87). Almost 44.2% of patients with SE severity score >2 had unfavorable outcome (sensitivity 75% and specificity 45.7%). New scoring system, the CSE outcome score (CSEOS, developed by combining the predictors associated with higher odds of poor outcome), predicted the poor outcome with the sensitivity and specificity of 90% and 54.29%, respectively. Discussion and Conclusion: Low MAP and delay of >3.5 h in treatment initiation or seizure control are the key determinants of poor outcome in CSE. With the incorporation of CSEOS, we believe that our findings can be helpful in the process of clinical decision-making and prognostication of patients with CSE.