Rades, Dirk

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.

Many patients with malignant spinal cord compression (MSCC) who are not candidates for neurosurgery receive radiotherapy alone. This study compared 15 × 2.633 Gy over three weeks to 20 × 2.0 Gy over four weeks in patients with favorable survival prognoses. The outcomes of 34 patients treated with 15 × 2.633 Gy (equivalent dose 41.6 Gy10) in the RAMSES-01 trial were compared to 239 patients from an existing database receiving 20 × 2.0 Gy using propensity-score-adjusted Cox and logistic regression models. All patients had favorable survival prognoses. Endpoints included local progression-free survival (LPFS), improvement of motor function, post-treatment ambulatory status, and overall survival (OS). After propensity score adjustment, the 12-month rates of LPFS and OS were 98.1% (RAMSES-01 cohort) vs. 91.6% (p = 0.265) and 79.1% vs. 82.2% (p = 0.704), respectively. Regarding improvement of motor function, 15 × 2.633 Gy appeared superior (p = 0.073). No significant difference was observed regarding ambulatory status (p = 0.822). The three-week regimen for MSCC has similar outcomes and reduces treatment time when compared to a four-week regimen.

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.

Patients with metastatic epidural spinal cord compression (MESCC) and favorable survival prognoses may benefit from radiation doses exceeding 10 × 3.0 Gy. In a multi-center phase 2 trial, patients receiving 15 × 2.633 Gy (41.6 Gy10) or 18 × 2.333 Gy (43.2 Gy10) were evaluated for local progression-free survival (LPFS), motor/sensory functions, ambulatory status, pain, distress, toxicity, and overall survival (OS). They were compared (propensity score-adjusted Cox regression) to a historical control group (n = 266) receiving 10 × 3.0 Gy (32.5 Gy10). In the phase 2 cohort, 50 (of 62 planned) patients were evaluated for LPFS. Twelve-month rates of LPFS and OS were 96.8% and 69.9%, respectively. Motor and sensory functions improved in 56% and 57.1% of patients, and 94.0% were ambulatory following radiotherapy. Pain and distress decreased in 84.4% and 78.0% of patients. Ten and two patients experienced grade 2 and 3 toxicities, respectively. Phase 2 patients showed significantly better LPFS than the control group (p = 0.039) and a trend for improved motor function (p = 0.057). Ambulatory and OS rates were not significantly different. Radiotherapy with 15 × 2.633 Gy or 18 × 2.333 Gy was well tolerated and appeared superior to 10 × 3.0 Gy.

Many head and neck cancer patients assigned to definitive or adjuvant chemoradiation treatment do not complete the concurrent cisplatin dose. We determined corresponding risk factors and developed a prognostic instrument to help identify these patients. Ten pre-treatment characteristics were retrospectively analyzed in 154 patients with head and neck cancer who were treated via chemoradiation with cisplatin. These pre-treatment characteristics included age, sex, Karnofsky performance score, tumor site, primary tumor stage, nodal stage, histologic grade, upfront surgery, human papilloma virus status, and history of smoking. The characteristics significantly associated with the completion of cisplatin-based treatment, the receipt of ≥80% cisplatin, or showing a strong trend of association after multivariate analyses were used for the prognostic instrument. For each characteristic, 0 points were assigned for worse outcomes, and 1 point was assigned for better outcomes. Patients’ scores were calculated by adding these points. Age ≤ 60 years and a Karnofsky performance score of 90–100 were significantly associated with both endpoints after multivariate analysis, and male gender showed a trend for association with the receipt of ≥80% cisplatin. Patient scores were 0, 1, 2, and 3 points. The corresponding rates of completion of cisplatin-based treatment were 14%, 41%, 62%, and 72%, respectively (p = 0.004). The rates of receipt of ≥80% cisplatin were 29%, 54%, 72%, and 94%, respectively (p < 0.001). This new prognostic instrument helps to predict whether head and neck cancer patients scheduled for chemoradiation will receive cisplatin as planned.

Cisplatin is the standard for the chemoradiation of squamous cell carcinoma of the head and neck (HNSCC). Many patients cannot receive cisplatin due to impaired renal function. This study investigated carboplatin as an alternative option. In total, 131 patients assigned to two courses of cisplatin (20 mg/m2/d1-–5 or 25 mg/m2/d1–4) were matched to 45 patients not suitable for cisplatin and receiving carboplatin (AUC 1.0/d1–5 or AUC 1.5/d1–4). The endpoints included loco-regional control (LRC), metastases-free survival (MFS), overall survival (OS), toxicities, and the completion of chemotherapy. The patients in the carboplatin group were significantly older and had more G3 tumors. Otherwise, the baseline characteristics were balanced. The LRC rates at 2 and 3 years were 77% and 76% in the cisplatin group vs. 69% and 65% in the carboplatin group (p = 0.21). The MFS rates were 83% and 78% vs. 78% and 74% (p = 0.34) and the OS rates 83% and 79% vs. 83% and 75% (p = 0.64), respectively. The outcomes were not significantly different in the subgroups receiving definitive or adjuvant chemoradiation. No significant differences were found regarding toxicities. Non-significantly more patients in the carboplatin group completed their chemotherapy (78% vs. 66%, p = 0.15). Carboplatin was associated with similar outcomes and toxicities as cisplatin, although these patients had worse renal function, more aggressive tumors, and were older. Given the limitations of this study, carboplatin appears an option for patients not suitable for cisplatin.

Many patients with squamous cell carcinoma of the head and neck (SCCHN) receive cisplatin-based chemoradiation. Cisplatin 100 mg/m2 every three weeks is toxic and alternative cisplatin regimens are desired. Two courses of 20 mg/m2/day 1–5 (cumulative 200 mg/m2) were shown to be similarly effective and better tolerated than 100 mg/m2 every three weeks. Previous studies suggested that cumulative doses >200 mg/m2 may further improve outcomes. In this study, 10 patients (group A) receiving two courses of 25 mg/m2/day 1–5 (cumulative 250 mg/m2) in 2022 were retrospectively matched and compared to 98 patients (group B) receiving two courses of 20 mg/m2/day 1–5 or 25 mg/m2/day 1–4 (cumulative 200 mg/m2). Follow-up was limited to 12 months to avoid bias. Group A achieved non-significantly better 12-month loco-regional control (100% vs. 83%, p = 0.27) and metastases-free survival (100% vs. 88%, p = 0.38), and similar overall survival (89% vs. 88%, p = 0.90). No significant differences were found regarding toxicities, completion of chemotherapy, and interruption of radiotherapy. Given the limitations of this study, chemoradiation with two courses of 25 mg/m2/day 1–5 appears an option for carefully selected patients as a personalized treatment approach. Longer follow-up and a larger sample size are needed to properly define its role.

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.

A modern approach for brain metastases includes whole-brain radiotherapy plus simultaneous boost (WBRT+SIB). We developed a survival score in 128 patients treated with WBRT+SIB. Three models, each including three prognostic groups, were created. Positive predictive values (PPVs) for death ≤6 and survival ≥6 months were calculated. On multivariate analyses, performance score (KPS) and the number of brain metastases were significantly associated with survival. On univariate analyses, age showed a strong trend, and extra-cerebral cranial metastases a trend. In Model 1 (KPS, number of lesions), compared groups had 6-month survival rates of 15%, 38% and 57%. In Model 2 (KPS, lesions, age), rates were 17%, 33% and 75%, and in Model 3 (KPS, lesions, age, extra-cerebral metastases), 14%, 34% and 78%. PPVs for death ≤6 and survival ≥6 months were 85% and 57% (Model 1), 83% and 75% (Model 2), and 86% and 78% (Model 3). Thus, all models were accurate in predicting death ≤ 6 months; poor-prognosis patients may not benefit from SIB. Models 2 and 3 were superior in predicting survival ≥ 6 months. Given that Model 3 requires more data (including extensive staging), Model 2 is considered favorable for many patients. If extra-cerebral metastases are already known or extensive staging has been performed, Model 3 can also be used.