Janssen, Stefan

Background/Objectives: Pneumonitis caused by radiotherapy for lung cancer may be missed since it often occurs only several months later. In a previous trial including patients of any age, a scoring system was tested to facilitate the correct diagnosis of radiation pneumonitis. Since elderly lung cancer patients have a greater risk of developing this complication, a separate scoring system for this group appears useful. Our prospective multi-center trial (NCT06480734) investigates a specific tool for elderly patients irradiated for lung cancer. Methods: Patients aged ≥65 years with lung cancer will complete paper-based questionnaires and rate symptoms potentially caused by pneumonitis weekly during and up to 24 weeks following radiotherapy. The total score of this symptom-based scoring system ranging from 0 to 9 points is correlated to pneumonitis. The discriminative power of the scoring system is evaluated by calculating the area under the receiver operating characteristic curve. Optimality is defined as a cut-off score with sensitivity ≥90% and specificity ≥80%. Moreover, the Youden index will be applied. Fifty-nine patients are required for the full analysis set. Assuming 5% will not qualify for this set, 65 patients should be enrolled. Moreover, patient satisfaction with the scoring system is evaluated. If the dissatisfaction rate is >20%, the system needs modifications; if the dissatisfaction rate is >40%, it is considered not useful. An optimal cut-off score facilitating the diagnosis of pneumonitis and its discrimination from other lung diseases will contribute to a corresponding mobile application to be used by elderly lung cancer patients at home.

Abstract Background Radiotherapy of breast cancer can be associated with dermatitis. Grade ≥ 2 radiation dermatitis can be painful and impair the patients’ quality of life. To reduce the risk of this complication, patients have to perform skin care several times each day. This may require a considerable level of compliance. This randomized DAI-BREAC trial investigates whether a mobile application reminding the patients four times per day to perform skin care (reminder app) will contribute to reduction of grade ≥ 2 radiation dermatitis. Methods This multinational, randomized, active-controlled, parallel-group, multicenter trial compares standard skin care supported by a reminder app (Arm A) versus standard skin care alone (Arm B) regarding grade ≥ 2 radiation dermatitis in patients receiving adjuvant radiotherapy for breast cancer. The effect of the app will be considered clinically relevant, if the rate of grade ≥ 2 radiation dermatitis is reduced from 25.4% (rate identified in a preceding study) to 15%. A total of 134 patients per arm including drop-outs are required. Secondary aims include pain (visual analogue scale), patient satisfaction with the app (questionnaire), impact of the app on the use of health technology (questionnaire), and benefit from support (coaching) by staff members regarding the use of the app (questionnaire). Discussion If reminder app contributes to a decrease of grade ≥ 2 radiation dermatitis in patients irradiated for breast cancer, it will likely become a useful instrument for these patients. Trial registration: clinicaltrials.gov (NCT06483477; URL: https://clinicaltrials.gov/show/NCT06483477). Registered on 1st of July, 2024. First patient is planned to be included in September 2024.

Abstract Background: Pneumonitis caused by radiotherapy for lung cancer may be missed, since it often occurs only several months later. In a previous trial including patients of any age, a symptom-based scoring system was tested to facilitate the correct diagnosis of radiation pneumonitis. Since elderly lung cancer patients have a greater risk of developing this complication, a separate scoring system particularly for this age group appears reasonable. This trial investigates such a specific tool for elderly patients irradiated for lung cancer. Methods: Patients with lung cancer patients aged ≥65 years will be included in this prospective multi-center trial and complete paper-based questionnaires (symptom-based scoring system). Patients indicate and rate symptoms potentially caused by pneumonitis, namely cough, dyspnea, and fever, once a week during and up to 24 weeks following their radiotherapy course. If symptomatic (grade ≥2) pneumonitis is confirmed by corresponding diagnostic procedures, patients receive prednisolone whenever possible. The total score of the symptom-based scoring system, which ranges between 0 and 9 points, is correlated to pneumonitis (yes or no). The discriminative power of the scoring system is evaluated by calculating the area under the receiver operating characteristic curve (AUC). Optimality is defined as a cut-off score with sensitivity ≥90% and specificity ≥80%. In addition, the Youden index (sensitivity + specificity – 1) will be applied. Fifty-nine patients (18 with and 41 without pneumonitis) are required in the full analysis set. Assuming that 5% of the patients will not qualify for this set, 62 patients should be enrolled. In addition, patient satisfaction with the scoring system is evaluated. If the dissatisfaction rate is >20%, the score needs modifications; if the dissatisfaction rate is >40%, the scoring system is considered not useful. Discussion: If the optimal cut-off score facilitates the diagnosis of radiation pneumonitis and its discrimination from other lung diseases in elderly patients with lung cancer, it will contribute to the development of a mobile application for identification of radiation pneumonitis, which can be used by the patients at home. Trial registration: clinicaltrials.gov (NCT06480734; URL: https://clinicaltrials.gov/show/NCT06480734); protocol version 1.2, registered on 27th of June, 2024.

In Radiation Therapy Oncology Group 90-05, the maximum tolerated dose of single-fraction radiosurgery (SRS) for brain metastases of 21–30 mm was 18 Gy (biologically effective dose (BED) 45 Gy12). Since the patients in this study received prior brain irradiation, tolerable BED may be >45 Gy12 for de novo lesions. We investigated SRS and fractionated stereotactic radiotherapy (FSRT) with a higher BED for radiotherapy-naive lesions. Patients receiving SRS (19–20 Gy) and patients treated with FSRT (30–48 Gy in 3–12 fractions) with BED > 49 Gy12 for up to 4 brain metastases were compared for grade ≥ 2 radiation necrosis (RN). In the entire cohort (169 patients with 218 lesions), 1-year and 2-year RN rates were 8% after SRS vs. 2% and 13% after FSRT (p = 0.73) in per-patient analyses, and 7% after SRS vs. 7% and 10% after FSRT (p = 0.59) in per-lesion analyses. For lesions ≤ 20 mm (137 patients with 185 lesions), the RN rates were 4% (SRS) vs. 0% and 15%, respectively, (FSRT) (p = 0.60) in per-patient analyses, and 3% (SRS) vs. 0% and 11%, respectively, (FSRT) (p = 0.80) in per-lesion analyses. For lesions > 20 mm (32 patients with 33 lesions), the RN rates were 50% (SRS) vs. 9% (FSRT) (p = 0.012) in both per-patient and per-lesion analyses. In the SRS group, a lesion size > 20 mm was significantly associated with RN; in the FSRT group, lesion size had no impact on RN. Given the limitations of this study, FSRT with BED > 49 Gy12 was associated with low RN risk and may be safer than SRS for brain metastases > 20 mm.

Radiotherapy of lung cancer may cause pneumonitis that generally occurs weeks or months following therapy and can be missed. This prospective trial aimed to pave the way for a mobile application (app) allowing early diagnosis of pneumonitis. The primary goal was the identification of the optimal cut-off of a score to detect pneumonitis of grade ≥2 after radiotherapy for lung cancer. Based on the severity of symptoms (cough, dyspnea, fever), scoring points were 0–9. Receiver operating characteristic (ROC)-curves were used to describe the sensitivity and specificity. The area under the ROC-curve (AUC) was calculated to judge the accuracy of the score, Youden-index was employed to define the optimal cut-off. Until trial termination, 57 of 98 patients were included. Eight of 42 patients evaluable for the primary endpoint (presence or absence of radiation pneumonitis) experienced pneumonitis. AUC was 0.987 (0.961–1.000). The highest sensitivity was achieved with 0–4 points (100%), followed by 5 points (87.5%), highest specificity with 5–6 points (100%). The highest Youden-index was found for 5 points (87.5%). The rate of patient satisfaction with the symptom-based scoring system was 93.5%. A cut-off of 5 points was identified as optimal to differentiate between pneumonitis and no pneumonitis. Moreover, pneumonitis was significantly associated with an increase of ≥3 points from baseline (p < 0.0001). The scoring system provided excellent accuracy and high patient satisfaction. Important foundations for the development of a mobile application were laid.

Survival scores facilitate personalized cancer treatment. Due to demographic changes, very elderly patients are more prevalent than in the past. A score was developed in 94 patients aged ≥ 80 years undergoing whole-brain radiotherapy for brain metastases. Dose fractionation, treatment period, age, sex, performance score (ECOG-PS), tumor type, count of lesions, metastases outside the brain, and interval tumor diagnosis to radiotherapy were retrospectively evaluated. Independent predictors of survival were used for the score. Based on individual scoring points obtained from 3-month survival rates, prognostic groups were designed. Additionally, the score was compared to an existing tool developed in patients ≥ 65 years. ECOG-PS, count of lesions, and extra-cranial metastases were independent prognostic factors. Three groups were created (7, 10, and 13–16 points) with 3-month survival of 6%, 25%, and 67% (p < 0.001), respectively. Positive predictive values (PPVs) regarding death ≤ 3 and survival ≥ 3 months were 94% and 67% (new score) vs. 96% and 48% (existing tool), respectively. PPVs for survival ≥1 and ≥2 months were 88% and 79% vs. 63% and 58%, respectively. Both tools were accurate in predicting death ≤2, ≤3, and ≤6 months. The new score was more precise regarding death ≤1 month and survival (all time periods) and appeared preferable. However, it still needs to be validated.

Survival scores are important for personalized treatment of bone metastases. Elderly patients are considered a separate group. Therefore, a specific score was developed for these patients. Elderly patients (≥65 years) irradiated for bone metastases were randomly assigned to the test (n = 174) or validation (n = 174) cohorts. Thirteen factors were retrospectively analyzed for survival. Factors showing significance (p < 0.05) or a trend (p < 0.06) in the multivariate analysis were used for the score. Based on 6-month survival rates, prognostic groups were formed. The score was compared to an existing tool developed in patients of any age. In the multivariate analysis, performance score, tumor type, and visceral metastases showed significance and gender was a trend. Three groups were designed (17, 18–25 and 27–28 points) with 6-month survival rates of 0%, 51%, and 100%. In the validation cohort, these rates were 9%, 55%, and 86%. Comparisons of prognostic groups between both cohorts did not reveal significant differences. In the test cohort, positive predictive values regarding death ≤6 and survival ≥6 months were 100% with the new score vs. 80% and 88% with the existing tool. The new score was more accurate demonstrating the importance of specific scores for elderly patients.

An easy-to-use survival score was developed specifically for older patients with cerebral metastases from colorectal cancer, and was compared to existing tools regarding the accuracy of identifying patients who die in ≤6 months and those who survive for ≥6 months. The new score was built from 57 patients receiving whole-brain irradiation. It included three groups identified from 6-month survival rates based on two independent predictors (performance status and absence/presence of non-cerebral metastases), with 6-month survival rates of 0% (0 points), 26% (1 point), and 75% (2 points), respectively. This score was compared to diagnosis-specific scores, namely the diagnosis-specific graded prognostic assessment (DS-GPA), the Dziggel-Score and the WBRT-30-CRC (whole-brain radiotherapy with 30 Gy in 10 fractions for cerebral metastases from colorectal cancer) score and to a non-diagnosis-specific score for older persons (Evers-Score). Positive predictive values were 100% (new score), 87% (DS-GPA), 86% (Dziggel-Score), 91% (WBRT-30-CRC), and 100% (Evers-Score), respectively, for patients dying ≤6 months, and 75%, 33%, 75%, 60%, and 45%, respectively, for survivors ≥6 months. Of the five tools, the new score and the Evers-Score were most precise in identifying patients dying ≤6 months. The new score and the Dziggel-Scores were best at identifying patients surviving ≥6 months. When combining the results, the new score appeared preferable to the existing tools. The score appears not necessary for patients with additional liver metastases, since their 6-month survival rate was 0%.

Abstract Background Previous survival scores for breast cancer patients with cerebral metastases were developed in cohorts receiving heterogeneous treatments, which could have introduced selection biases. A new instrument (WBRT-30-BC) was created from 170 patients receiving whole-brain radiotherapy (WBRT) alone with 30 Gy in 10 fractions. Methods Characteristics showing significant associations (p < 0.05) with overall survival (OS) or a trend (p < 0.08) on multivariate analysis were used for the WBRT-30-BC. For each characteristic, 6-month OS rates were divided by 10. These scoring points were added for each patient (patient scores). The WBRT-30-BC was compared to the diagnosis- specific graded prognostic assessment (DS-GPA) classification and Rades-Score for breast cancer regarding positive predictive values (PPVs) to identify patients dying within 6 months and patients surviving at least 6 months following WBRT. Results On multivariate analysis, Karnofsky performance score (KPS) was significant (risk ratio [RR]: 2.45, p < 0.001). In addition, extra-cerebral metastatic disease (RR: 1.52, p = 0.071) and time between breast cancer diagnosis and WBRT (RR: 1.37, p = 0.070) showed a trend. Based on these three characteristics, four predictive groups were designed: 7–9, 10–12, 13–15 and 16 points. Six-month OS rates were 8%, 41%, 68% and 100% (p < 0.001). PPVs to identify patients dying within 6 months were 92% (WBRT-30-BC), 84% (DS-GPA) and 92% (Rades-Score). PPVs to identify patients surviving for at least 6 months were 100% (WBRT-30-BC), 74% (DS-GPA) and 68% (Rades-Score). Conclusions The WBRT-30-BC appeared very accurate in predicting death ≤ 6 months and survival ≥ 6 months of breast cancer patients receiving WBRT. It was superior to previous instruments in predicting survival ≥ 6 months.

Diagnosis-specific survival scores including a new score developed in 157 patients with brain metastases from small-cell lung cancer (SCLC) receiving whole-brain radiotherapy (WBRT) with 30 Gy in 10 fractions (WBRT-30-SCLC) were compared. Three prognostic groups were designed based on the 6-month survival probabilities of significant or almost significant factors, (age, performance score, number of brain metastases, extra-cerebral metastasis). Six-month survival rates were 6% (6–11 points), 44% (12–14 points) and 86% (16–19 points). The WBRT-30-SCLC was compared to three disease-specific scores for brain metastasis from SCLC, the original and updated diagnosis-specific graded prognostic assessment DS-GPA classifications and the Rades-SCLC. Positive predictive values (PPVs) used to correctly predict death ≤6 months were 94% (WBRT-30-SCLC), 88% (original DS-GPA), 88% (updated DS-GPA) and 100% (Rades-SCLC). PPVs to predict survival ≥6 months were 86%, 75%, 76% and 100%. For WBRT-30-SCLC and Rades-SCLC, differences between poor and intermediate prognoses groups and between intermediate and favorable prognoses groups were significant. For both DS-GPA classifications, only the difference between poor and intermediate prognoses groups was significant. Of these disease-specific tools, Rades-SCLC appeared to be the most accurate in identifying patients dying ≤6 months and patients surviving ≥6 months after irradiation, followed by the new WBRT-30-SCLC and the DS-GPA classifications.