Questionnaire-based detection of immune-related adverse events in cancer patients treated with PD-1/PD-L1 immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICI) have become standard treatment in different tumor entities. However, safe treatment with ICI targeting the PD-1/PD-L1 axis requires early detection of immune-related adverse events (irAE). There exist different questionnaires of drug manufacturers for the detection of irAE that have not been validated so far. METHODS: The prospective non-interventional ST-ICI trial studied treatment with PD-1/PD-L1 ICI alone or combined with radiotherapy. In the current analysis, the detection rate of self-reported irAE with a patient questionnaire containing 41 different questions was compared to clinician-reported irAE. RESULTS: Between April 2017 and August 2019, a total of 104 patients were prospectively enrolled. NSCLC (44%) and HNSCC (42%) were the most frequent tumor entities. A total of 784 questionnaires were collected. A total of 29 irAE were reported by clinicians. The most frequent irAE was hypothyroidism (9%), followed by skin reactions (5%), hepatitis (4%), diarrhea (3%), and pneumonitis (3%). Questions that became significantly more often positive at time points of clinician-reported irAE were "weight change", "difficulty to grip things", "bloody or mucous stool" and "insomnia". Self-reported organ-specific questions detected at least 50% of clinician-reported irAE of gastrointestinal, lung, endocrine, and skin irAE. It was not possible to detect hepatic irAE with the questionnaire. CONCLUSION: Questionnaires can help to detect gastrointestinal, lung, endocrine, or skin irAE, but not hepatic irAE. Questions on "weight change" and "insomnia" may help to increase the detection rate of irAE, besides organ-specific questions. These results are a valuable contribution to the future development of a specific and practicable questionnaire for early self-reported detection of irAE during ICI therapy in cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03453892 . Registered on 05 March 2018.

Stereotactic radiotherapy as primary definitive or postoperative treatment of intracranial meningioma of WHO grade II and III leads to better disease control than stereotactic radiotherapy of recurrent meningioma.

The aim of this study was to evaluate long-term clinical outcome, prognostic factors and quality of life after adjuvant or definitive fractionated stereotactic radiotherapy (SRT) of meningioma WHO grade II and III or at recurrence. 131 patients with 138 meningioma (64 WHO grade II, 16 WHO grade III, 58 without histology) of the skull base, falx and convexity were treated between 01/2002 and 01/2015 at the Erlangen University Hospital by fractionated stereotactic radiotherapy (SRT) as primary treatment (adjuvant or definitive) and at recurrence. 53% (n = 53) lesions of patients with primary tumour received postoperative SRT and 47% (n = 47) as definitive treatment (without surgery). All 38 lesions (100%) of recurrent meningioma underwent surgery followed by SRT. SRT was mostly given in 28, 30 or 25 fractions to a median dose of 54.0 Gy in the reference point. Progression-free-survival at 8 years for patients with meningioma at primary treatment were significantly better with 100% for patients with definitive SRT (p = 0.008) or 85% for patients with adjuvant SRT (p = 0.009) compared to 42% after treatment (surgery + SRT) of recurrence. Progression-free-survival at 8 years for patients with SRT as adjuvant treatment after gross total resection of WHO grade II meningioma were significantly better at 83% (p = 0.016) compared to 46% after adjuvant SRT of recurrence. In 31% of patients after primary treatment and in 38.5% after recurrence treatment an improvement of pain symptoms was achieved. The favourable prognostic factor for better PFS at recurrence treatment was tumor location (skull base or convexity better compared to the falx). Postoperative SRT of WHO grade II meningioma after gross total resection (GTR) can effectively reduce recurrence risk.

Baseline Quality of Life of Physical Function Is Highly Relevant for Overall Survival in Advanced Rectal Cancer.

In advanced rectal cancer, neoadjuvant radiochemotherapy and total mesorectal excision lead to long overall survival. The quality of life (QOL) of the patients is clearly related to the prognosis. Our question was whether the prognosis can be represented with only one question or one score from the QOL questionnaires. 360 consecutively recruited patients diagnosed with advanced rectal cancer were questioned during radiochemotherapy and a follow-up of 8 years. The questionnaires QLQ-C30 and QLQ-CR38 were used; 10 functional and 17 symptom scores were calculated. The functional score "physical function" and the symptom scores "fatigue", "nausea and vomiting", "pain" and "appetite loss" were highly prognostic (p < 0.001) for overall survival. "Physical function" was highly prognostic at all time points up to 1 year after starting therapy (p ≤ 0.001). The baseline "physical function" score divided the cohort into a favorable group with an 8-year overall survival rate of 70.4% versus an unfavorable group with 47.5%. In the multivariable analysis, baseline "physical function", age and distant metastases were independent predictors of overall survival. The score "physical function" is a powerful unrelated risk factor for overall survival in patients with rectal cancer. Future analyses should study whether increased "physical function" after diagnosis could improve survival.

Transient Enlargement in Meningiomas Treated with Stereotactic Radiotherapy.

To investigate the occurrence of pseudoprogression/transient enlargement in meningiomas after stereotactic radiotherapy (RT) and to evaluate recently proposed volumetric RANO meningioma criteria for response assessment in the context of RT. Sixty-nine meningiomas (benign: 90%, atypical: 10%) received stereotactic RT from January 2005-May 2018. A total of 468 MRI studies were segmented longitudinally during a median follow-up of 42.3 months. Best response and local control were evaluated according to recently proposed volumetric RANO criteria. Transient enlargement was defined as volumetric increase ≥20% followed by a subsequent regression ≥20%. The mean best volumetric response was -23% change from baseline (range, -86% to +19%). According to RANO, the best volumetric response was SD in 81% (56/69), MR in 13% (9/69) and PR in 6% (4/69). Transient enlargement occurred in only 6% (4/69) post RT but would have represented 60% (3/5) of cases with progressive disease if not accounted for. Transient enlargement was characterized by a mean maximum volumetric increase of +181% (range, +24% to +389 %) with all cases occurring in the first year post-RT (range, 4.1-10.3 months). Transient enlargement was significantly more frequent with SRS or hypofractionation than with conventional fractionation (25% vs. 2%, p = 0.015). Five-year volumetric control was 97.8% if transient enlargement was recognized but 92.9% if not accounted for. Transient enlargement/pseudoprogression in the first year following SRS and hypofractionated RT represents an important differential diagnosis, especially because of the high volumetric control achieved with stereotactic RT. Meningioma enlargement during subsequent post-RT follow-up and after conventional fractionation should raise suspicion for tumor progression.

Induction chemoimmunotherapy followed by CD8+ immune cell-based patient selection for chemotherapy-free radioimmunotherapy in locally advanced head and neck cancer.

PURPOSE: The first aim of the trial is to study feasibility of combined programmed death protein ligand 1/cytotoxic T-lymphocyte-associated protein 4 inhibition concomitant to radiotherapy. In addition, efficacy of the entire treatment scheme consisting of induction chemoimmunotherapy followed by chemotherapy-free radioimmunotherapy (RIT) after intratumoral CD8 +immune cell-based patient selection will be analyzed. METHODS: Patients with stage III-IVB head and neck squamous cell carcinoma were eligible for this multicenter phase II trial. Treatment consisted of a single cycle of cisplatin 30 mg/m² days 1-3, docetaxel 75 mg/m² day 1, durvalumab 1500 mg fix dose day 5 and tremelimumab 75 mg fix dose day 5. Patients with increased intratumoral CD8 +immune cell density or pathological complete response (pCR) in the rebiopsy entered RIT up to a total dose of 70 Gy. Patients received further three cycles of durvalumab/tremelimumab followed by eight cycles of durvalumab mono (every 4 weeks). The intended treatment for patients not meeting these criteria was standard radiochemotherapy outside the trial. Primary endpoint was a feasibility rate of patients entering RIT to receive treatment until at least cycle 6 of immunotherapy of ≥80%. RESULTS: Between September 2018 and May 2020, 80 patients were enrolled (one excluded). Out of these, 23 patients had human papilloma virus (HPV)-positive oropharyngeal cancer. Median follow-up was 17.2 months. After induction chemoimmunotherapy 41 patients had pCR and 31 had increased intratumoral CD8 +immune cells. Of 60 patients entering RIT (primary endpoint cohort), 10 experienced imiting toxic (mainly hepatitis) and four discontinued for other reasons, resulting in a feasibility rate of 82%. The RIT cohort (n=60) had a progression-free survival (PFS) rate at one and 2 years of 78% and 72%, respectively, and an overall survival rate at one and 2 years of 90% and 84%, respectively. Patients with HPV-positive oropharyngeal cancers had greater benefit from RIT with a 2-year PFS rate of 94% compared with 64% for HPV-negative oropharyngeal cancers and other locations. In the entire study cohort (n=79) the 2-year PFS rate was 68% (91% for HPV-positive oropharynx vs 59% for others). Toxicity grade 3-4 mainly consisted of dysphagia (53%), leukopenia (52%) and infections (32%). CONCLUSIONS: The trial met the primary endpoint feasibility of RIT. Induction chemo-immunotherapy followed by chemotherapy-free RIT after intratumoral CD8 +immune cell-based patient selection has promising PFS. TRIAL REGISTRATION NUMBER: The trial was registered with ClinicalTrials.gov (identifier: NCT03426657). The trial was conducted as investigator-sponsored trial (IST).

Predictive Value of Multiparametric MRI for Response to Single-Cycle Induction Chemo-Immunotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma.

OBJECTIVES: To assess the predictive value of multiparametric MRI for treatment response evaluation of induction chemo-immunotherapy in locally advanced head and neck squamous cell carcinoma. METHODS: Twenty-two patients with locally advanced, histologically confirmed head and neck squamous cell carcinoma who were enrolled in the prospective multicenter phase II CheckRad-CD8 trial were included in the current analysis. In this unplanned secondary single-center analysis, all patients who received contrast-enhanced MRI at baseline and in week 4 after single-cycle induction therapy with cisplatin/docetaxel combined with the immune checkpoint inhibitors tremelimumab and durvalumab were included. In week 4, endoscopy with representative re-biopsy was performed to assess tumor response. All lesions were segmented in the baseline and restaging multiparametric MRI, including the primary tumor and lymph node metastases. The volume of interest of the respective lesions was volumetrically measured, and time-resolved mean intensities of the golden-angle radial sparse parallel-volume-interpolated gradient-echo perfusion (GRASP-VIBE) sequence were extracted. Additional quantitative parameters including the T1 ratio, short-TI inversion recovery ratio, apparent diffusion coefficient, and dynamic contrast-enhanced (DCE) values were measured. A model based on parallel random forests incorporating the MRI parameters from the baseline MRI was used to predict tumor response to therapy. Receiver operating characteristic (ROC) curves were used to evaluate the prognostic performance. RESULTS: Fifteen patients (68.2%) showed pathologic complete response in the re-biopsy, while seven patients had a residual tumor (31.8%). In all patients, the MRI-based primary tumor volume was significantly lower after treatment. The baseline DCE parameters of time to peak and wash-out were significantly different between the pathologic complete response group and the residual tumor group (p < 0.05). The developed model, based on parallel random forests and DCE parameters, was able to predict therapy response with a sensitivity of 78.7% (95% CI 71.24-84.93) and a specificity of 78.6% (95% CI 67.13-87.48). The model had an area under the ROC curve of 0.866 (95% CI 0.819-0.914). CONCLUSIONS: DCE parameters indicated treatment response at follow-up, and a random forest machine learning algorithm based on DCE parameters was able to predict treatment response to induction chemo-immunotherapy.

Prospective development and validation of a liquid immune profile-based signature (LIPS) to predict response of patients with recurrent/metastatic cancer to immune checkpoint inhibitors.

BACKGROUND: The predictive power of novel biological markers for treatment response to immune checkpoint inhibitors (ICI) is still not satisfactory for the majority of patients with cancer. One should identify valid predictive markers in the peripheral blood, as this is easily available before and during treatment. The current interim analysis of patients of the ST-ICI cohort therefore focuses on the development and validation of a liquid immune profile-based signature (LIPS) to predict response of patients with metastatic cancer to ICI targeting the programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) axis. METHODS: A total of 104 patients were prospectively enrolled. 54 immune cell subsets were prospectively analyzed in patients' peripheral blood by multicolor flow cytometry before treatment with ICI (pre-ICI; n=89), and after the first application of ICI (n=65). Pre-ICI, patients were randomly allocated to a training (n=56) and a validation cohort (n=33). Univariate Cox proportional hazards regression analysis and least absolute shrinkage and selection operator Cox model were used to create a predictive immune signature, which was also checked after the first ICI, to consider the dynamics of changes in the immune status. RESULTS: Whole blood samples were provided by 89 patients pre-ICI and by 65 patients after the first ICI. We identified a LIPS which is based on five immune cell subtypes: CD14high monocytes, CD8+/PD-1+ T cells, plasmacytoid dendritic cells, neutrophils, and CD3+/CD56+/CD16+ natural killer (NK)T cells. The signature achieved a high accuracy (C-index 0.74 vs 0.71) for predicting overall survival (OS) benefit in both the training and the validation cohort. In both cohorts, the low-risk group had significantly longer OS than the high-risk group (HR 0.26, 95% CI 0.12 to 0.56, p=0.00025; HR 0.30, 95% CI 0.10 to 0.91, p=0.024, respectively). Regarding the whole cohort, LIPS also predicted progression-free survival (PFS). The identified LIPS was not affected by clinicopathological features with the exception of brain metastases. NKT cells and neutrophils of the LIPS can be used as dynamic predictive biomarkers for OS and PFS after first administration of the ICI. CONCLUSION: Our study identified a predictive LIPS for survival of patients with cancer treated with PD-1/PD-L1 ICI, which is based on immune cell subsets in the peripheral whole blood. TRIAL REGISTRATION NUMBER: NCT03453892.

Implementation of Double Immune Checkpoint Blockade Increases Response Rate to Induction Chemotherapy in Head and Neck Cancer.

To determine whether a single dose of double immune checkpoint blockade (induction chemoimmunotherapy (ICIT)) adds benefit to induction single-cycle platinum doublet (induction chemotherapy (IC)) in locally advanced head and neck squamous cell carcinoma (HNSCC), patients treated with cisplatin 30 mg/m2 d1-3 and docetaxel 75 mg/m2 d1 combined with durvalumab 1500 mg fixed dose d5 and tremelimumab 75 mg fixed dose d5 (ICIT) within the CheckRad-CD8 trial were compared with a retrospective cohort receiving the same chemotherapy (IC) without immunotherapy. The endpoint of this analysis was the complete response rate (CR). A total of 53 patients were treated with ICIT and 104 patients with IC only. CR rates were 60.3% for ICIT and 40.3% for IC (p = 0.018). In the total population (n = 157), the most important predictor to achieve a CR was treatment type (OR: 2.21 for ICIT vs. IC; p = 0.038, multivariate analysis). The most diverse effects in CR rates between ICIT and IC were observed in younger (age ≤ 60) patients with HPV-positive OPSCCs (82% vs. 33%, p = 0.176), while there was no difference in older patients without HPV-positive OPSCCs (53% vs. 48%). The analysis provides initial evidence that ICIT could result in higher CR rates than IC. Young patients with HPV-positive OPSCCs may have the greatest benefit from additional immune checkpoint inhibitors.

Differences in and Prognostic Value of Quality of Life Data in Rectal Cancer Patients with and without Distant Metastases.

(1) Background: Individualization of treatment is a major challenge in oncology and requires a variety of predictive and prognostic parameters. In addition to tumor biology analyses, baseline health-related quality of life might be a valid tool to predict overall survival. This study was conducted to evaluate the prognostic relevance of baseline quality of life data in patients with rectal cancer. In this context, differences between patients with and without distant metastases were of particular interest. (2) Methods: Our cohort included 258 patients with rectal cancer treated in the radiotherapy department of the University Hospital Erlangen. Patients completed the European Organisation for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ C30) and colorectal cancer questionnaire (CR38). Clinical and survival data were provided by the Gießener Tumor Documentation System (GTDS) of the Comprehensive Cancer Center Erlangen-EMN (CCC, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany). Statistical analyses were performed using Kaplan-Meier analyses and univariate and multivariate Cox regression. (3) Results: A cohort of 258 patients with rectal adenocarcinoma was analyzed including 50 patients (19.4%) with metastatic disease. No differences were observed between patients with and without distant metastases in most areas of quality of life studied, with the exception of physical function, loss of appetite, chemotherapy side effects and weight loss. Gender, baseline physical function, sexual function, diarrhea, and weight loss over time had a prognostic value in the entire cohort. Appetite loss was an additional prognostic parameter in patients with distant metastases. (4) Conclusions: The quality of life of patients with metastatic disease differed only slightly from non-metastatic patients. Health-related quality of life data provide prognostic information for patients with rectal cancer.

Deterioration of Health-Related Quality of Life Scores under Treatment Predicts Longer Survival.

OBJECTIVES: Baseline health-related quality of life (HRQoL) scores predict survival, which has already been demonstrated in various studies. However, we were interested in whether changes in baseline scores during treatment are also significant predictors of survival. METHODS AND MATERIALS: We analysed the data of 400 consecutive cancer patients receiving radiochemotherapy. Leading diagnoses were head and neck cancer (34.5%), rectal cancer (24.5%), and lung cancer (13%). HRQoL was studied at baseline, six weeks after therapy and after each completed year after the start of therapy until drop out of the study using the EORTC QLQ-C30 questionnaire. The change score was calculated as the baseline score subtracted from the score after therapy. Statistics included Kaplan-Meier estimates and Cox regression. RESULTS: High global health status (p = 0.005) and low pain scores (p = 0.040) at baseline were related to favourable overall survival. Change scores of role functioning (p = 0.027), global health status (p < 0.018), and pain (p < 0.001) were predictive of overall survival. Pain was the superior predictor of survival (p = 0.001) among all variables and QoL scores studied by multivariate analysis. A deterioration in pain was associated with a 2.8 times higher chance of survival (HR 0.36). CONCLUSIONS: Deterioration of HRQoL baseline pain score by cancer treatment is a favourable and superior prognostic factor for survival.

Prospective Evaluation of All-lesion Versus Single-lesion Radiotherapy in Combination With PD-1/PD-L1 Immune Checkpoint Inhibitors.

BACKGROUND: Local ablative treatments improve survival in patients with oligometastatic disease in addition to chemotherapy. The application of immune checkpoint inhibitors prolonged patients' survival in different tumor entities. This raises the question if patients still benefit from intensified local treatments in combination with a more efficient systemic treatment with immune checkpoint inhibitors. METHODS: The prospective non-interventional ST-ICI trial investigates treatment with PD-1/PD-L1 (Programmed cell death protein 1/Programmed cell death 1 ligand 1) immune checkpoint inhibitors and radiotherapy in different tumor entities. Patients who started radiotherapy and immunotherapy concomitantly were included in this interim analysis. In this cohort patients with all-lesion radiotherapy (all tumor lesions irradiated, al-RT) were compared to patients with radiotherapy to only a single of their tumor lesions (single-lesion radiotherapy, sl-RT). Endpoints of the interim analysis were progression-free survival (PFS), overall survival (OS) and time to progression (TTP). RESULTS: A total of 104 patients were registered between April 2017 and August 2019. Fifty patients started immune checkpoint inhibitor treatment and radiotherapy concomitantly and were included. Most frequent tumor entities were non-small cell lung cancer (62%) followed by head and neck squamous cell cancer (26%). Most frequent location of radiotherapy was lung (34%) and central nervous system (20%). Median duration of follow-up was 8.6 months beginning with first administration of the immune-checkpoint-inhibitor. Median PFS was 9.2 months (95% CI, 5.8 - 12.6) in the al-RT group and 3.0 months (95% CI, 2.5 - 3.5) in the sl-RT group (p<0.001). Median OS was 11.6 months (95% CI, 8.1 - 15.1) in the al-RT group and 4.2 months (95% CI, 3.0 - 5.4) in the sl-RT group (p=0.007). Median TTP was not reached in the al-RT group compared to 4.6 months (95% CI, 1.1-8.0) in the sl-RT group (p=0.028). Univariate Cox regression analyses computed tumor entity, histology, central nervous system metastases, immunotherapy drug and al-RT as predictors of OS (with an effect p-value of ≤ 0.1). In the multivariable analysis only tumor entity and al-RT remained prognostic factors for OS. CONCLUSION: Patients with PD-1/PD-L1 immune checkpoint inhibitor therapy benefit from local radiotherapy to all known lesions compared to single-lesion radiotherapy regarding PFS and OS.

Prospective evaluation of the prognostic value of immune-related adverse events in patients with non-melanoma solid tumour treated with PD-1/PD-L1 inhibitors alone and in combination with radiotherapy.

BACKGROUND: Prospective data about the prognostic value of immune-related adverse events (irAEs) in non-melanoma solid tumours are rare. The prognostic value of irAEs in patients treated with combined radiotherapy and immunotherapy is currently unknown. PATIENTS AND METHODS: The prospective non-interventional ST-ICI trial investigates treatment response of tumour patients to anti-programmed cell death-ligand 1 (PD-L1) immune checkpoint inhibitors alone and in combination with radiotherapy and possible predictive markers. Patients undergoing immunotherapy or immunoradiotherapy were surveyed for irAEs. RESULTS: A total of 104 patients were included of whom 29 patients (28%) developed irAEs. Additional radiotherapy was performed in 50 patients (48%). Main tumour entities within the entire cohort were non-small cell lung cancer (NSCLC) (44%) and head and neck squamous cell carcinoma (42%). The rate of irAEs did not differ in patients with and without radiotherapy (p = 0.668). Patients who developed irAEs had longer overall survival (OS) (median: 22.8 months versus 9.0 months without irAEs, p = 0.001) and progression-free survival (PFS) (median: 7.8 months versus 3.2 months without irAEs, p = 0.002). In the subgroup with combined radiotherapy, patients with irAEs also had longer OS (median: 22.8 months versus 7.1 months without irAEs, p = 0.005) and PFS (median: 8.8 months versus 3.0 months without irAEs, p = 0.005). On multivariate analysis only PD-L1 on tumour cells (p = 0.049) and irAEs (p = 0.001) remained independent predictors of OS. CONCLUSION: The development of irAEs represents a favourable prognostic parameter in patients undergoing immunotherapy and immunoradiotherapy for solid tumours.

Safety and efficacy of single cycle induction treatment with cisplatin/docetaxel/ durvalumab/tremelimumab in locally advanced HNSCC: first results of CheckRad-CD8.

BACKGROUND: To determine safety and efficacy of single cycle induction treatment with cisplatin/docetaxel and durvalumab/tremelimumab in stage III-IVB head and neck cancer. METHODS: Patients received a single cycle of cisplatin 30 mg/m² on days 1-3 and docetaxel 75 mg/m² on day 1 combined with durvalumab 1500 mg fix dose on day 5 and tremelimumab 75 mg fix dose on day 5. Patients with pathologic complete response (pCR) in the rebiopsy after induction treatment or at least 20% increase of intratumoral CD8+ cell density in the rebiopsy compared with baseline entered radioimmunotherapy with concomitant durvalumab/tremelimumab. The objective of this interim analysis was to analyze safety and efficacy of the chemoimmunotherapy-induction treatment before radioimmunotherapy. RESULTS: A total of 57 patients were enrolled, 56 were treated. Median pretreatment intratumoral CD8+ cell density was 342 cells/mm². After induction treatment, 27 patients (48%) had a pCR in the rebiopsy and further 25 patients (45%) had a relevant increase of intratumoral CD8+ cells (median increase by a factor of 3.0). Adverse event (AE) grade 3-4 appeared in 38 patients (68%) and mainly consisted of leukopenia (43%) and infections (29%). Six patients (11%) developed grade 3-4 immune-related AE. Univariate analysis computed p16 positivity, programmed death ligand 1 immune cell area and intratumoral CD8+ cell density as predictors of pCR. On multivariable analysis, intratumoral CD8+ cell density predicted pCR independently (OR 1.0012 per cell/mm², 95% CI 1.0001 to 1.0022, p=0.016). In peripheral blood CD8+ cells, the coexpression of programmed death protein 1 significantly increased especially in patients with pCR. CONCLUSIONS: Single cycle induction treatment with cisplatin/docetaxel and durvalumab/tremelimumab is feasible and achieves a high biopsy-proven pCR rate.

Noncurated Data Lead to Misinterpretation of Treatment Outcomes in Patients With Prostate Cancer After Salvage or Palliative Radiotherapy.

PURPOSE: Clinical data warehouses (cDWHs) and cancer registry databases have enabled researchers to conduct clinical analytics with structured electronic health record data. However, these secondary electronic health record sources are often limited in scope because they do not capture the clinical information needed to understand complex clinical questions. Thus, we evaluated the effect of additional curation of data. MATERIALS AND METHODS: Clinical data sets of 149 patients with prostate cancer with biochemical recurrence after radical prostatectomy treated with salvage or palliative radiotherapy between 2008 and 2017 from our institutional cDWH and Gießener Tumor Documentation System (GTDS) were linked (data warehouse [DWH] population) for analyzing treatment outcomes. The linked data sets were manually curated (manual postprocessing [MPP], eg, incorporate data from established urologists). The primary outcomes were the impact on data quality of treatment outcomes and the time spent on data curation. RESULTS: We obtained significantly more information on disease progression and patient survival (nonsignificant) when using curated data; the biochemical progression-free survival rate at 5 years for the DWH and DWH plus MPP populations was 63% v 30% (P ≤ .001) and the overall survival rate was 84% v 81% (P = .479), respectively. The median deviation of completeness and the median concordance of clinical data values were 21.47% (range, 55.38%-100%) and 95.00% (range, 63.40%-100%), respectively. We spent 121 hours, 42 minutes on data curation, with most time required for laboratory values, accounting, for a total of 45 hours, 20 minutes (37.26%). CONCLUSION: Our analysis indicates that time-to-event outcomes for patients with prostate cancer cannot be extracted using secondary data sources (cDWH plus GTDS) only. Outcomes data differed between the electronic data (DWH) and the second manual extraction (DWH plus MPP) because of a lack of follow-up data. When using such unique database resources, only baseline characteristics can reliably be extracted.

Electronic Support for Retrospective Analysis in the Field of Radiation Oncology: Proof of Principle Using an Example of Fractionated Stereotactic Radiotherapy of 251 Meningioma Patients.

INTRODUCTION: The purpose of this study is to verify the possible benefit of a clinical data warehouse (DWH) for retrospective analysis in the field of radiation oncology. MATERIAL AND METHODS: We manually and electronically (using DWH) evaluated demographic, radiotherapy, and outcome data from 251 meningioma patients, who were irradiated from January 2002 to January 2015 at the Department of Radiation Oncology of the Erlangen University Hospital. Furthermore, we linked the Oncology Information System (OIS) MOSAIQ® to the DWH in order to gain access to irradiation data. We compared the manual and electronic data retrieval method in terms of congruence of data, corresponding time, and personal requirements (physician, physicist, scientific associate). RESULTS: The electronically supported data retrieval (DWH) showed an average of 93.9% correct data and significantly (p = 0.009) better result compared to manual data retrieval (91.2%). Utilizing a DWH enables the user to replace large amounts of manual activities (668 h), offers the ability to significantly reduce data collection time and labor demand (35 h), while simultaneously improving data quality. In our case, work time for manually data retrieval was 637 h for the scientific assistant, 26 h for the medical physicist, and 5 h for the physician (total 668 h). CONCLUSION: Our study shows that a DWH is particularly useful for retrospective analysis in the radiation oncology field. Routine clinical data for a large patient group can be provided ready for analysis to the scientist and data collection time can be significantly reduced. Furthermore, linking multiple data sources in a DWH offers the ability to improve data quality for retrospective analysis, and future research can be simplified.