Growth exponents reflect evolutionary processes and treatment response in brain metastases.

Tumor growth is the result of the interplay of complex biological processes in huge numbers of individual cells living in changing environments. Effective simple mathematical laws have been shown to describe tumor growth in vitro, or simple animal models with bounded-growth dynamics accurately. However, results for the growth of human cancers in patients are scarce. Our study mined a large dataset of 1133 brain metastases (BMs) with longitudinal imaging follow-up to find growth laws for untreated BMs and recurrent treated BMs. Untreated BMs showed high growth exponents, most likely related to the underlying evolutionary dynamics, with experimental tumors in mice resembling accurately the disease. Recurrent BMs growth exponents were smaller, most probably due to a reduction in tumor heterogeneity after treatment, which may limit the tumor evolutionary capabilities. In silico simulations using a stochastic discrete mesoscopic model with basic evolutionary dynamics led to results in line with the observed data.

A comprehensive dataset of annotated brain metastasis MR images with clinical and radiomic data.

Brain metastasis (BM) is one of the main complications of many cancers, and the most frequent malignancy of the central nervous system. Imaging studies of BMs are routinely used for diagnosis of disease, treatment planning and follow-up. Artificial Intelligence (AI) has great potential to provide automated tools to assist in the management of disease. However, AI methods require large datasets for training and validation, and to date there have been just one publicly available imaging dataset of 156 BMs. This paper publishes 637 high-resolution imaging studies of 75 patients harboring 260 BM lesions, and their respective clinical data. It also includes semi-automatic segmentations of 593 BMs, including pre- and post-treatment T1-weighted cases, and a set of morphological and radiomic features for the cases segmented. This data-sharing initiative is expected to enable research into and performance evaluation of automatic BM detection, lesion segmentation, disease status evaluation and treatment planning methods for BMs, as well as the development and validation of predictive and prognostic tools with clinical applicability.

Growth dynamics of brain metastases differentiate radiation necrosis from recurrence.

Background: Radiation necrosis (RN) is a frequent adverse event after fractionated stereotactic radiotherapy (FSRT) or single-session stereotactic radiosurgery (SRS) treatment of brain metastases (BMs). It is difficult to distinguish RN from progressive disease (PD) due to their similarities in the magnetic resonance images. Previous theoretical studies have hypothesized that RN could have faster, although transient, growth dynamics after FSRT/SRS, but no study has proven that hypothesis using patient data. Thus, we hypothesized that lesion size time dynamics obtained from growth laws fitted with data from sequential volumetric measurements on magnetic resonance images may help in discriminating recurrent BMs from RN events. Methods: A total of 101 BMs from different institutions, growing after FSRT/SRS (60 PDs and 41 RNs) in 86 patients, displaying growth for at least 3 consecutive MRI follow-ups were selected for the study from a database of 1031 BMs. The 3 parameters of the Von Bertalanffy growth law were determined for each BM and used to discriminate statistically PDs from RNs. Results: Growth exponents in patients with RNs were found to be substantially larger than those of PD, due to the faster, although transient, dynamics of inflammatory processes. Statistically significant differences (P < .001) were found between both groups. The receiver operating characteristic curve (AUC = 0.76) supported the ability of the growth law exponent to classify the events. Conclusions: Growth law exponents obtained from sequential longitudinal magnetic resonance images after FSRT/SRS can be used as a complementary tool in the differential diagnosis between RN and PD.

Cost-effectiveness analysis of a lung cancer screening programme in Spain.

OBJECTIVE: To evaluate the cost-effectiveness of the implementation of national lung cancer (LC) screening programme (SP) in a high-risk population from the perspective of the Spanish National Health System (NHS). METHODS: A cost-effectiveness analysis for a LC SP was carried out on a lifetime horizon. A Markov model was designed that assumed two scenarios, one with the implementation of the SP and another one without it. Effectiveness and cost of LC management, diagnosis and screening were included in the different health states. Deterministic and probabilistic sensitivity analyses were conducted to evaluate its robustness. A discount rate was set at 3% both for effectiveness and cost. RESULTS: In the base-case, an increase of 4.80 quality-adjusted life years (QALY) per patient was obtained, resulting in an incremental cost-effectiveness ratio of €2345/QALY. Probabilistic sensitivity analysis showed the national LC SP to be cost-effective in 80% of cases (probability=0.8) for a willingness-to-pay threshold equivalent to the gross domestic product per capita in Spain, which was set at €25 854/QALY in 2018 based on the per capita income of Spain. The sensitivity analysis indicates that the obtained results are robust in terms of changes in the presentation rates and costs, and the cost-effectiveness thresholds. CONCLUSIONS: This analysis suggests that the implementation of a LC SP in the high-risk Spanish population would be a cost-effective strategy for the Spanish NHS.

Sparing fertility in young patients with endometrial cancer.

The objective of this review is to recognize the characteristics of endometrial adenocarcinoma in young patients and to evaluate the published experience with conservative approach in patients with endometrial adenocarcinoma. We searched MEDLINE articles describing patients with endometrial adenocarcinoma who were treated with hormonal therapy. The search included articles published between January 1966 and January 2007. Endometrial carcinoma in patients under 45 years of age is an unusual condition that shows a more favorable pattern than in older patients. One hundred thirty three patients were found in the search. The average duration of hormonal therapy was approximately 6 months. The average response time was 12 weeks. Seventy six percent of patients treated with hormonal therapy had a complete response and the other 24% never responded to treatment. Of those who initially responded, 66% didn't show recurrence of disease. The other 34% had a relapse. There have been published 4 deaths of patients conservatively managed. A conservative approach in these patients can offer reasonable oncological security and the opportunity of fulfilling their maternal desires in selected cases. However, consideration should be taken regarding the potential adverse outcomes that have been recently published in the literature.

Surgical treatment of recurrent cervical cancer: state of the art and new achievements.

This article review the current situation of the exenterative procedures as part of the treatment of recurrent cervical cancer after radiation. Pelvic exenteration has been proven the only curative choice of treatment in selected cases of this clinical situation. A review of historical and recent published series have shown an increase of 5-y survival from 30 to 42 %. Almost one out of two patients will suffer complications of some kind, and one out of three will have a severe complication with pelvic exenteration. During the past sixty years, a number of outstanding improvements have been achieved - not only in surgical outcomes, but also in quality of life - owing to new reconstructive approaches. Women facing an exenterative procedure must be counseled carefully about the risks and long-term concerns related to the procedure. Each should undergo a comprehensive evaluation to make sure there is no evidence of unresectable or metastatic disease that would make her an unsuitable candidate for exenteration.

The current role of neoadjuvant chemotherapy in the management of cervical carcinoma.

The role of neoadjuvant chemotherapy (NACT) in cervical cancer has been a matter of investigation over the last 20 years. A systematic review and meta-analysis of individual patient data (IPD) demonstrated that NACT followed by surgery is superior to radiotherapy alone in terms of overall survival. However, in spite of the results of the meta-analysis, NACT has not been adopted as the new standard of care. In the present paper, we review the reasons why NACT is still considered an investigational approach in cervical cancer.

Dosimetric implications of changes in patient repositioning and organ motion in conformal radiotherapy for prostate cancer.

PURPOSE: To assess the influence of patient repositioning and organ motion on dose distribution within the prostate and the seminal vesicles (clinical target volume, (CTV)). MATERIAL AND METHODS: Nine patients were simulated and treated in the supine position, with an empty bladder, and without immobilization devices. While on treatment, patients underwent weekly pelvic computed tomography (CT) scans under conditions identical to those at simulation. Patients were aligned using lasers on anterior and lateral skin tattoos, onto which lead markers were placed. After each CT scan (n=53) the CTV was redefined by contouring, and a new isocenter was obtained. A six-field technique was used. The field margins around the CTV were 20 mm in the cranio-caudal axis, and 13 mm in the other axes, except in the lateral fields where a 10 mm posterior margin was used. Dose-volume histograms (DVHs) for each organ were compared with those determined at simulation, using the notion of the proportional change in the area under the CTV-DVH curve resulting from a change in treatment plan (cDVH). RESULTS: The reproducibility of the dose distribution was good for the prostate (%cDVH, mean+/-SD: -0.97+/-2.11%) and less than optimal for the seminal vesicles (%cDVH, mean+/-SD: -4.66+/-10.45%). When correlating prostate %cDVH variations with displacements of the isocenter in the Y axis (antero-posterior) the %cDVH exceeded (-)5% in only two dosimetries, both with an isocenter shift of >10 mm. For the seminal vesicles, however, ten out of 53 dosimetries showed a %cDVH exceeding (-) 5%. In nine of these ten dose distribution studies the posterior shift of the isocenter exceeded 8 mm. CONCLUSIONS: Precise targeting of prostate radiotherapy is primarily dependent on careful daily set-up and on random changes in rectal geometry. Margins no less than 10 mm around the prostate and at least 15 mm around the seminal vesicles are probably necessary to insure adequate target coverage with a six-field technique.