We study event rates over time (event dynamics) in patients undergoing surgery for early-stage non–small-cell lung cancer (NSCLC).
Using a database of patients undergoing initial surgery for NSCLC, ...the event dynamics, based on the hazard rate, were evaluated. Events evaluated included time to any treatment failure, local recurrence, distant metastasis (DM), and development of a second primary lung cancer.
Among 1506 patients, time to any treatment failure dynamics demonstrated an initial surge in the hazard rate 9 months after surgery, followed by two smaller peaks at the end of the second and fourth years, respectively. This pattern was dominated by DM events. Two distinguishable peaks were noted for local recurrence in the first and second years. In contrast, the hazard rate for second primary lung cancer exhibited a more uniform pattern over time. The DM dynamics was analyzed by sex and three peaks emerged for both sexes. The timing of the first peak was similar for both sexes, at 7 to 9 months after surgery. The second peak occurred earlier in men (18–20 months) than women (24–26 months). For both sexes the third peak appeared during the fourth year.
Recurrence dynamics of resected early-stage NSCLC displays a multipeak pattern, which supports the hypothesis of a metastasis growth model previously described for early-stage breast cancer. The model assumes both cellular and micrometastatic tumor dormancy and a transient phase of acceleration of metastatic growth following surgical excision of the primary tumor.
Many algorithms have been proposed for the machine learning task of classification. One of the simplest methods, the naive Bayes classifier, has often been found to give good performance despite the ...fact that its underlying assumptions (of independence and a normal distribution of the variables) are perhaps violated. In previous work, we applied naive Bayes and other standard algorithms to a breast cancer database from Nottingham City Hospital in which the variables are highly non-normal and found that the algorithm performed well when predicting a class that had been derived from the same data. However, when we then applied naive Bayes to predict an alternative clinical variable, it performed much worse than other techniques. This motivated us to propose an alternative method, based on naive Bayes, which removes the requirement for the variables to be normally distributed, but retains the essential structure and other underlying assumptions of the method. We tested our novel algorithm on our breast cancer data and on three UCI datasets which also exhibited strong violations of normality. We found our algorithm outperformed naive Bayes in all four cases and outperformed multinomial logistic regression (MLR) in two cases. We conclude that our method offers a competitive alternative to MLR and naive Bayes when dealing with data sets in which non-normal distributions are observed.
An epidemic not attributable to plague caused thousands of deaths in Milan in the summer of 1629, a time of war and famine that immediately preceded the even more fatal Great Plague of 1630 that ...killed an estimated ten of thousands of people. The 5,993 deaths of 1629 recorded in the Liber Mortuorum of Milan (a city with an estimated population of 130,000 inhabitants at the time) were 45.7% more than the average number recorded between 1601 and 1628. Registered deaths peaked in July, and 3,363 of the deaths (56,1%) were attributed to a febrile illness which, in most cases (2,964, 88%), was not associated with a rash or organ involvement. These deaths involved 1,627 males and 1,334 females and occurred at a median age of 40 years (range 0-95). In this paper, we discuss the possible cause of the epidemic, which may have been an outbreak of typhoid fever.
Human epididymis protein 4 (HE4) measurements in serum have been proposed for improving the specificity of laboratory identification of ovarian cancer (OC).
To critically revise the available ...literature on the comparison between the diagnostic accuracy of HE4 and carbohydrate antigen 125 (CA-125) to confirm the additional clinical value of HE4.
A literature search was undertaken on electronic databases and references from retrieved articles; articles were analysed according to predefined criteria. Meta-analyses for HE4 and CA-125 biomarkers with OR, diagnostic sensitivity, specificity, positive (LR+) and negative (LR-) likelihood ratios as effect sizes were performed.
16 articles were originally included in meta-analyses, but two for HE4 and one for CA-125 were eliminated as outliers. Furthermore, for HE4 a publication bias was detected. ORs for both HE4 (37.2, 95% CI 19.0 to 72.7, adjusted for publication bias) and CA-125 (15.4, 95% CI 10.4 to 22.8) were significant, although in a heterogeneous set of studies (p<0.0001). By combining sensitivity and specificity, the overall LR+ and LR- were 13.0 (95% CI 8.2 to 20.7) and 0.23 (95% CI 0.19 to 0.28) for HE4 and 4.2 (95% CI 3.1 to 5.6) and 0.27 (95% CI 0.23 to 0.31) for CA-125, respectively.
HE4 measurement seems to be superior to CA-125 in terms of diagnostic performance for identification of OC in women with suspected gynaecological disease. Due to the high prevalence of OC in post-menopausal women and the need for data focused on early tumour stages, more studies tailored on these specific subsets are needed.
The purpose of this study was to characterize the recurrence dynamics in breast cancer patients after delayed reconstruction. We hypothesized that surgical reconstruction might stimulate dormant ...micrometastases and reduce time to recurrence. All mastectomy breast cancer patients with delayed surgical reconstruction at Haukeland University Hospital, between 1977 and 2007,
n
= 312, were studied. Our control group consisted of 1341 breast cancer patients without reconstruction. For each case, all patients in the control group with identical T and N stages and age ±2 years were considered. A paired control was randomly selected from this group. 10 years after primary surgery, 39 of the cases had relapsed, compared to 52 of the matched controls. The reconstructed group was analyzed for relapse dynamics after mastectomy; the first peak in relapses was similarly timed, but smaller than for the controls, while the second peak was similar in time and size. Second, the relapse pattern was analyzed with reconstruction as the starting point. A peak in recurrences was found after 18 months, and a lower peak at the 5th–6th year. The height of the peak correlated with the extent of surgery and initial T and N stages. Timing of the peak was not affected, neither was the cumulative effect. The relapse pattern, when time origin is placed both at mastectomy and at reconstruction, is bimodal with a peak position at the same time points, at 2 years and at 5–6 years. The timing of the transition from dormant micrometastases into clinically detectable macrometastases might be explained by an enhancing effect of surgery.
Background:
The best surgical choice for patients with familial adenomatous polyposis (FAP) is still debated. No prospective trials have been carried out to evaluate the pros and cons of the ...recommended procedures: total colectomy (ileorectal anastomosis IRA) vs restorative proctocolectomy (ileal pouch–anal anastomosis IPAA). The aim of this study was to provide a basis for tailored precision surgery in patients with FAP.
Methods:
We conducted a retrospective review of patients with FAP who underwent surgery and were registered in a dedicated database in Milan, Italy. Twenty-year survival related to surgical approach and prognostic factors were investigated using a Cox regression model.
Results:
A total of 925 patients underwent surgery between 1947 and 2015: 340 (36.8%) IPAA and 585 (63.2%) IRA. Colorectal cancer (CRC) at surgery was diagnosed in 28.6% of patients and a pathogenic APC variant was identified in 88%. During a median follow-up of 129 months, 150 patients died. The survival probability was significantly higher in the IRA than the IPAA group: 0.82 vs 0.75 (hazard ratio HR 0.6, 95% confidence interval CI 0.42–0.84). Multivariable regression modeling adjusted for propensity scores showed a similar difference, although no longer significant. Multivariable analysis indicated as independent risk factors CRC (HR 4.68, 95% CI 3.04–7.20) and age at surgery (HR 1.03, 95% CI 1.02–1.06). Among patients without cancer, the main risk factor for shorter survival was older age (HR 1.06, 95% CI 1.04–1.09).
Conclusion:
The study confirms excellent long-term results of surgical approaches with IRA and IPAA, suggesting that the best surgical choice may be an individually and clinically tailored approach, preferably at a young age.
The first case of Coronavirus Disease 2019 in Italy was detected on February the 20th in Lombardy region. Since that date, Lombardy has been the most affected Italian region by the epidemic, and its ...healthcare system underwent a severe overload during the outbreak. From a public health point of view, therefore, it is fundamental to provide healthcare services with tools that can reveal possible new health system stress periods with a certain time anticipation, which is the main aim of the present study. Moreover, the sequence of law decrees to face the epidemic and the large amount of news generated in the population feelings of anxiety and suspicion. Considering this whole complex context, it is easily understandable how people "overcrowded" social media with messages dealing with the pandemic, and emergency numbers were overwhelmed by the calls. Thus, in order to find potential predictors of possible new health system overloads, we analysed data both from Twitter and emergency services comparing them to the daily infected time series at a regional level. Particularly, we performed a wavelet analysis in the time-frequency plane, to finely discriminate over time the anticipation capability of the considered potential predictors. In addition, a cross-correlation analysis has been performed to find a synthetic indicator of the time delay between the predictor and the infected time series. Our results show that Twitter data are more related to social and political dynamics, while the emergency calls trends can be further evaluated as a powerful tool to potentially forecast new stress periods. Since we analysed aggregated regional data, and taking into account also the huge geographical heterogeneity of the epidemic spread, a future perspective would be to conduct the same analysis on a more local basis.
The report addresses the role of the hazard function in the analysis of disease-free survival data in breast cancer. An investigation on local recurrences after mastectomy provided evidence that ...uninterrupted growth is inconsistent with clinical findings and that tumor dormancy could be assumed as working hypothesis to understand the clinical course of the disease. Additionally, it was deemed that the lag-time between primary tumor removal and tumor recurrence is dynamically dependent on the subclinical metastasis development within the host-tumor system and, therefore, may be informative about the biology of the disease. Accordingly, the hazard function, which estimates the event risk pattern through the time, was adopted to analyze survival data. The multipeak pattern of the hazard function suggested that the process metastasis development has discontinuous features. A new paradigm of breast cancer metastatic development was proposed, involving the notions of tumor homeostasis, tumor quiescence in specific metastatic microscopic phases and surgery-related acceleration of the metastatic process. All analyses by prognostic factors (e.g., by menopausal status) or treatment modalities (e.g., by adjuvant chemotherapy) or other parameters (e.g., site of metastasis), provided coherent data in agreement with the model. The hazard rate function allowed addressing several clinical questions including meaning of ipsilateral breast tumor recurrence (IBTR), oncologic effect of delayed breast reconstruction, surgery related metastasis acceleration, possible role of anti-inflammatory drugs and body mass index (BMI) to modulate the recurrence risk. We conclude that the hazard function is a powerful tool to investigate the post-surgical course of early breast cancer and other operable tumors and to make inferences on their biology.
Dormant avascular micrometastases and single, or small groups of, non-proliferating cells are currently assumed to explain the multipeak dynamics of distant metastases (DM) following primary breast ...cancer surgical removal.
The hazard rate pattern for DM was analysed in 1518 premenopausal node-positive patients, enrolled in a series of randomized clinical trials on early breast cancer, which were carried out in Italy and Belgium. Patients underwent surgery alone (n = 397) or surgery plus adjuvant chemotherapy (n = 1121) and the minimal follow up was 15 years.
The DM hazard rate for patients undergoing surgery alone displayed two early sharp peaks at 9 and 33 months, a wide intermediate one spanning from about 50 to 90 months and a late peak at 115–120 months. Adjuvant chemotherapy was associated with a prominent reduction of the two early peaks leaving a residual one at about 18 months and a reduction of the intermediate peak leaving two small peaks at about 50 and 80 months. The late peak remained unchanged.
Present results reveal the ability of adjuvant chemotherapy to reduce not only the rate of early relapses, but also the rate of intermediate relapses at about the sixth year of follow up. Adjuvant chemotherapy is not impacting on the development of metastases underlying the late peak detected at the tenth year. These findings suggest the existence of a previously unknown dormancy state that, at the primary tumour surgical removal, results in evolving chemo-sensitive metastatic processes, and, moreover, of a later chemo-refractory dormancy state.
•Breast cancer removal wakes dormant micro foci causing peaks in recurrence dynamics.•Recurrence dynamics in premenopausal patients displays four peaks during 10 years.•Adjuvant chemo cuts peaks at years 1, 3, 6 while the peak at year 10 is unchanged.•Data support a multiplicity of chemo sensitive and chemo refractory dormant states.
PDF
