Electronic patient-reported outcomes and machine learning in predicting immune-related adverse events of immune checkpoint inhibitor therapies.

BACKGROUND: Immune-checkpoint inhibitors (ICIs) have introduced novel immune-related adverse events (irAEs), arising from various organ systems without strong timely dependency on therapy dosing. Early detection of irAEs could result in improved toxicity profile and quality of life. Symptom data collected by electronic (e) patient-reported outcomes (PRO) could be used as an input for machine learning (ML) based prediction models for the early detection of irAEs. METHODS: The utilized dataset consisted of two data sources. The first dataset consisted of 820 completed symptom questionnaires from 34 ICI treated advanced cancer patients, including 18 monitored symptoms collected using the Kaiku Health digital platform. The second dataset included prospectively collected irAE data, Common Terminology Criteria for Adverse Events (CTCAE) class, and the severity of 26 irAEs. The ML models were built using extreme gradient boosting algorithms. The first model was trained to detect the presence and the second the onset of irAEs. RESULTS: The model trained to predict the presence of irAEs had an excellent performance based on four metrics: accuracy score 0.97, Area Under the Curve (AUC) value 0.99, F1-score 0.94 and Matthew's correlation coefficient (MCC) 0.92. The prediction of the irAE onset was more difficult with accuracy score 0.96, AUC value 0.93, F1-score 0.66 and MCC 0.64 but the model performance was still at a good level. CONCLUSION: The current study suggests that ML based prediction models, using ePRO data as an input, can predict the presence and onset of irAEs with a high accuracy, indicating that ePRO follow-up with ML algorithms could facilitate the detection of irAEs in ICI-treated cancer patients. The results should be validated with a larger dataset. Trial registration Clinical Trials Register (NCT3928938), registration date the 26th of April, 2019.

Guideline of guidelines: primary monotherapies for localised or locally advanced prostate cancer.

Decisions regarding the primary treatment of prostate cancer depend on several patient- and disease-specific factors. Several international guidelines regarding the primary treatment of prostate cancer exist; however, they have not been formally compared. As guidelines often contradict each other, we aimed to systematically compare recommendations regarding the different primary treatment modalities of prostate cancer between guidelines. We searched Medline, the National Guidelines Clearinghouse, the library of the Guidelines International Network, and the websites of major urological associations for prostate cancer treatment guidelines. In total, 14 guidelines from 12 organisations were included in the present article. One of the main discrepancies concerned the definition of 'localised' prostate cancer. Localised prostate cancer was defined as cT1-cT3 in most guidelines; however, this disease stage was defined in other guidelines as cT1-cT2, or as any T-stage as long as there is no lymph node involvement (N0) or metastases (M0). In addition, the risk stratification of localised cancer differed considerably between guidelines. Recommendations regarding radical prostatectomy and hormonal therapy were largely consistent between the guidelines. However, recommendations regarding active surveillance, brachytherapy, and external beam radiotherapy varied, mainly as a result of the inconsistencies in the risk stratification. The differences in year of publication and the methodology (i.e. consensus-based or evidence-based) for developing the guidelines might partly explain the differences in recommendations. It can be assumed that the observed variation in international clinical practice regarding the primary treatment of prostate cancer might be partly due to the inconsistent recommendations in different guidelines.

Does the outcome of prostate cancer patients with large prostates differ from small prostate size in permanent seed, low dose-rate brachytherapy?

OBJECTIVE: Brachytherapy has good results in the treatment of early prostate cancer (PC). The procedure is challenging in large prostates, and the optimal prostate volume for brachytherapy was previously defined as ≤40 ml. This study analysed the outcome of PC patients with small (group A) and large (group B) prostate volume in prospective data. MATERIAL AND METHODS: The material consisted of 535 consecutive patients treated with brachytherapy in Kuopio University Hospital. The mean follow-up time was nearly 6 years. Prostate-specific antigen (PSA) failure was defined as PSA rising ≥2.0 µg/l above nadir. A PSA bounce was defined as a rise in PSA of ≥0.2 µg/l. The causes of death were recorded. RESULTS: A bounce was recorded more frequently in group A (30%) than in group B (18%) (p = 0.006). A bounce correlated with young age predicted a favourable outcome in both groups. PSA failure rate was similar in both groups: 13% and 12% in groups A and B, respectively. Post-treatment PSA ≤0.5 µg/l was the only independent prognostic factor associated with PSA failure in both groups (p < 0.0001, both groups). PC survival was 98.4% in both groups. Overall survival was 91% and 94% in groups A and B, respectively (p = not significant). CONCLUSIONS: There were no differences between the PC patients with small and large prostate volumes treated with brachytherapy with respect to PSA failure rate, PC survival or overall survival. All patients, independent of prostate size, are potential candidates for brachytherapy.

Eight years experience of local prostate cancer treatment with permanent I125 seed brachytherapy--morbidity and outcome results.

BACKGROUND AND PURPOSE: There are only a limited number of reports of treatment of prostate cancer with permanent prostate seed I(125) brachytherapy (PPB) in Europe. We describe results from one Finnish institution having treated 444 patients with a follow-up of eight years. MATERIAL AND METHODS: Morbidity was evaluated by International Prostate Symptom Score and International Index of Erectile Function questionnaires. Urine flow, residual urine volume and the PSA values were measured pre-treatment and during follow-up. Any additional treatments were recorded. RESULTS: PPB was well tolerated. Median IPSS increased from 8 at baseline to 18 at three months post-therapy and returned to baseline score within 12 months. Median urine flow decreased from 15.2 ml/s at baseline to 10.2 ml/s at three months and returned to baseline value within two years. Acute urinary retention, potency preservation and severe proctitis were observed in 11%, 86% and 2% of patients, respectively. The PSA bounce was observed in 13% and PSA nadir < or =0.5 microg/l was reached by 81% of patients. Disease-free survival (DFS) was 90.2%. In the Cox regression analysis, the independent predictors of DFS were risk group and PSA nadir < or =0.5 microg/l (p<0.0001 for both). PC-specific survival was 98.5% and overall survival was 94.6%. CONCLUSIONS: Our results are in concordance and comparable with other reports on PPB.

Expression of matrix metalloproteinase (MMP)-2 and MMP-9 in breast cancer with a special reference to activator protein-2, HER2, and prognosis.

PURPOSE: In the present study, we investigated the expression and prognostic value of matrix metalloproteinase (MMP)-2 and MMP-9 in breast cancer as well as their relation to transcription factor activator protein (AP)-2 and HER2 oncogene. The role of invasion and metastasis-promoting MMPs and their potential regulators, AP-2 and HER2, is currently still unclear in breast cancer. EXPERIMENTAL DESIGN: MMP-2 and MMP-9 expressions were analyzed immunohistochemically in a large prospective series of 421 breast cancer patients diagnosed and treated between 1990 and 1995 at Kuopio University Hospital (Kuopio, Finland). The relation of MMP-2 and MMP-9 expressions to AP-2, HER2, clinicopathological data, and survival was investigated. RESULTS: Both MMP-2 and MMP-9 were expressed in the cytoplasm of malignant and stromal cells. High expression of MMPs in carcinoma cells was related to small tumors (T1, stage I), whereas positive stromal expression of MMPs was associated with aggressive factors. High expression of MMP-2 and MMP-9 in carcinoma cells, but not in stromal cells, was related to high AP-2 expression. Positive stromal MMP-2 expression was associated with HER2 overexpression in the whole patient group and in the node-negative patient subgroup. Positive stromal MMP-9 expression was related to HER2 overexpression in estrogen receptor (ER)-positive disease. In the univariate survival analysis, positive stromal MMP-9 predicted shorter recurrence-free survival (RFS; P=0.0389) and breast cancer-related survival (BCRS; P=0.0081) in ER+ disease, especially in the subgroup of ER+ tumors of < or =2 cm in diameter (T1; P=0.0031 for RFS, and P=0.0089 for BCRS). High MMP-9 expression in cancer cells predicted longer RFS (P=0.0351) in the whole patient group. In the multivariate analysis of the whole patient group, the independent predictors of shorter RFS were reduced MMP-9 expression in carcinoma cells (P=0.0248), HER2 overexpression (P=0.0001), and advanced-stage disease (P=0.0002). Shorter BCRS was predicted by advanced-stage disease (P <0.0001). CONCLUSIONS: Expression of MMP-2 and MMP-9 in breast cancer seems to be partly related to expression of AP-2 and HER2. Positive stromal MMP-9 expression predicts poor survival in the hormone-responsive small tumors, whereas MMP-9 expression in carcinoma cells favors survival. Evaluation of MMP-9 expression seems to add valuable information on breast cancer prognosis.