Kristiansen, Charlotte

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.

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.

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.

Estimating post-treatment ambulatory status can improve treatment personalization of patients irradiated for malignant spinal cord compression (MSCC). A new clinical score was developed from data of 283 patients treated with radiotherapy alone in prospective trials. Radiotherapy regimen, age, gender, tumor type, interval from tumor diagnosis to MSCC, number of affected vertebrae, other bone metastases, visceral metastases, time developing motor deficits, ambulatory status, performance score, sensory deficits, and sphincter dysfunction were evaluated. For factors with prognostic relevance in the multivariable logistic regression model after backward stepwise variable selection, scoring points were calculated (post-radiotherapy ambulatory rate in % divided by 10) and added for each patient. Four factors (primary tumor type, sensory deficits, sphincter dysfunction, ambulatory status) were used for the instrument that includes three prognostic groups (17–21, 22–31, and 32–37 points). Post-radiotherapy ambulatory rates were 10%, 65%, and 97%, respectively, and 2-year local control rates were 100%, 75%, and 88%, respectively. Positive predictive values to predict ambulatory and non-ambulatory status were 97% and 90% using the new score, and 98% and 79% using the previous instrument. The new score appeared more precise in predicting non-ambulatory status. Since patients with 32–37 points had high post-radiotherapy ambulatory and local control rates, they may not require surgery.