6096 Background: Treatment intensification with antiPD-(L)1 agents given concurrently to definitive CRT in LA-HNSCC have failed to improve survival. Beyond radiation sensitization, PARP inhibition is predicted to trigger immune responses via STING pathway activation and synergize with anti-PD-(L)1 agents. TTCC-2022-01 RADIAN Trial evaluates niraparib and dostarlimab in LA-HNSCC patients (pts) treated with CRT (cohort A) or RT alone (Cohort B-cisplatin ineligible) (Oliva M et al ASCO 2024). Results of cohort A are presented. Methods: Investigator-initiated, non-randomized phase 1b/II study of niraparib and dostarlimab in LA-HNSCC pts candidates for definitive CRT or RT alone conducted in 7 Spanish sites. In cohort A, pts received 500 mg dostarlimab intravenously on week (w)-3 prior to RT and 200-300 mg/day niraparib from w-2 until 48h before start of CRT (70Gy/35 fractions plus cisplatin 100mg/m 2 w1,4 and 7). Maintenance dostarlimab (500 mg/3w) plus daily niraparib started 4w post-CRT for up to 14 cycles. Eligibility criteria: newly-diagnosed stage III-IVA-IVB HPV-negative oro-hipopharyngeal or laryngeal SCC and stage III HPV-related oropharyngeal, ECOG 0-1, centrally-confirmed PD-L1 CPS≥1, and with no cisplatin/dostarlimab/niraparib contraindications. Primary endpoint was 1-year disease-free survival (1y-DFS). Secondary objectives include safety; overall response rate (ORR) and ctDNA dynamics. 17 pts per cohort were planned. Experimental treatment was expected to increase 1y-DFS up to 75.9 % vs 65% historical control. Results: From Dec 23 to Jun 25, 17 pts were enrolled: median age 65 y (41-68); 71% male; 88% smokers; larynx/hypopharynx/oropharynx (HPV-related)= 53/6/41% (43%); stage III/IVA/IVB=29/53/18%. All pts completed dostarlimab and niraparib pre-CRT with no serious or Grade(G) 3-4 treatment-related adverse events (TRAEs); 15/17 completed CRT: 2 pts died during this phase (1 G5 febrile neutropenia cisplatin-niraparib-related; 1 unknown cause); 14/17 pts started maintenance: 2 completed, 7 ongoing and 5 (36%) discontinued due to TRAEs. The most common grade ≥3 TRAEs were neutropenia (71%), lymphopenia and dysphagia (29% each). Niraparib dose reductions/interruptions occurred in 12 (71%) pts. Most common TRAEs leading to dostarlimab+niraparib maintenance discontinuation were immune-mediated pneumonitis (18%) and respiratory tract edema (12%). ORR was 100% (14 complete+1 partial response) in 15 evaluable pts. With a median follow-up of 8.5 months (95% CI: 8.3-11.1), 15/17 were alive with no disease recurrence or progression. Intention-to-treat 1y-DFS was 88% (95% CI:74.1-100). Conclusions: Dostarlimab and niraparib with CRT showed promising efficacy results in this preliminary analysis. Maintenance post-CRT was poorly tolerated leading to high rate of discontinuation. Clinical trial information: NCT05784012 .

Metastatic spinal cord compression (MSCC) is a severe oncological emergency that may cause irreversible neurological damage if not recognized and treated promptly. In patients with known or suspected malignancy, spinal pain, particularly if progressive, or new motor, sensory, or sphincter symptoms should raise immediate suspicion of MSCC. MRI should be performed within 24 h of clinical suspicion. In patients with neurological signs or symptoms, initial emergency management should include immediate corticosteroid administration, urgent multidisciplinary assessment, and rapid initiation of definitive treatment. Surgery, when indicated, should be performed as early as feasible (ideally within 8-24 h when indicated); when surgery is not planned or not indicated, radiotherapy should be started promptly. This multidisciplinary expert opinion document provides practical recommendations to support standardized urgent pathways and coordinated multidisciplinary management of MSCC.

BACKGROUND/AIM:Many patients with prostate cancer receive moderately hypo-fractionated radiotherapy (mHF-RT). Inappropriate bladder filling during the mHF-RT course increases urinary toxicity. This study investigated the impact of pre-RT bladder volumes on the subsequent filling status. PATIENTS AND METHODS:One-hundred-and-nineteen prostate cancer patients irradiated with mHF-RT (60 Gy in 20 fractions) were included in this retrospective study from three European countries. The impact of pre-RT bladder volumes on the number of fractions with a volume <200 ml was examined. RESULTS:In case of a pre-RT bladder volume <200, <250, and <300 ml, the corresponding mean number of fractions with a bladder volume <200 ml during mHF-RT was 16.6 (±5.0), 15.9 (±5.6), and 15.1 (±5.9), respectively. The impact of the pre-RT volume (<200 vs. ≥200 ml, <250 vs. ≥250, <300 vs. ≥300 ml) on the number of fractions with a volume <200 ml was always highly significant (p<0.0001). CONCLUSION:Pre-RT bladder volumes <200 ml, <250 ml, and <300 ml were significantly associated with higher numbers of bladder volumes <200 ml during mHF-RT. These findings will lead to an amendment to a prospective trial.

BACKGROUND/AIM:Patients receiving radiotherapy for lung cancer may experience treatment-related adverse effects that reduce physical activity. Smartphone-based reminder applications may help patients maintain daily activity; however, information on changes in step counts during radiotherapy is limited. The APART-LUNG study investigated changes in physical activity between the first and fifth weeks of radiotherapy and explored potential factors associated with decreased activity. PATIENTS AND METHODS:Twenty patients were enrolled, of whom 19 were eligible for analysis. Physical activity was assessed as the weekly mean number of steps per smartphone wear-hour during weeks 1 and 5 of radiotherapy. The primary endpoint was the within-patient difference between week 5 and week 1. Associations between changes in step counts and age, sex, performance status, comorbidity, body-mass index, histology, and concurrent systemic treatment were explored. RESULTS:The mean numbers of steps per wear-hour were 344.3±171.6 in week 1 and 363.5±189.9 in week 5. Median values were 318.4 (range=123.3-762.9) and 300.3 (range=108.3-704.7) steps, respectively (p=0.465). The weekly average number of steps per wear-hour decreased in nine patients, increased in nine patients, and remained almost constant (plus three steps) in one patient. No characteristic was significantly associated with a decrease in steps. The greatest difference regarding the proportion of patients with a decrease in steps was observed for concurrent systemic treatment (no vs. yes, difference=37%). CONCLUSION:In this pilot study, step counts did not significantly decrease during radiotherapy for lung cancer. No investigated characteristic was significantly associated with decreased physical activity, although concurrent systemic treatment showed the strongest signal and should be considered in the design of future prospective trials.

Background/Objectives: A considerable number of patients with malignant spinal cord compression (MSCC) and a longer expected lifespan do not receive upfront surgery but radiation therapy alone. These patients were suggested to benefit from radiation programs with total doses > 30 Gy in terms of better local progression-free survival (LPFS). A previous study compared such regimens, namely 15 × 2.633 Gy over three weeks (34 patients, prospective cohort) and 20 × 2.0 Gy over four weeks (239 patients, control), using a propensity score-adjusted approach. Both regimens were associated with similar rates of overall survival (OS) and LPFS. However, follow-up was limited to 12 months. For long-term survivors, a longer period of follow-up would be desirable. Therefore, the present study was initiated. Methods: Retrospective collection of additional data enabled us to provide OS- and LPFS-rates at 36 months following radiation therapy. Results: In the prospective cohort, 36-month rates of OS and LPFS were 27.0% and 89.7%, respectively. After application of the propensity score-adjusted Cox regression model, 36-month OS-rates (HR 1.454; 95% CI 0.748-2.828; p = 0.270) and LPFS-rates (HR 0.311; 95% CI 0.041-2.352; p = 0.258) appeared not considerably different. Late radiation myelopathy and pathologic vertebral fractures were not identified. Conclusions: The results of the current study suggest that the role of 15 × 2.633 Gy should be further investigated in selected patients with MSCC, particularly when considering its shorter overall treatment time in comparison to 20 × 2.0 Gy. Overall, our findings are hypothesis-generating rather than confirmatory.

Reirradiation can be considered for some patients with recurrent or second primary head and neck squamous cell carcinoma arising within previously irradiated regions, a clinical scenario associated with few therapeutic options. The increasing use of modern conformal radiotherapy techniques, including intensity-modulated radiotherapy, proton therapy, and stereotactic body radiotherapy, has expanded the feasibility of reirradiation in clinical practice. However, evidence remains heterogeneous, and clinical choices are challenged by substantial variability in patient presentation, previous treatments, and toxicity risk. This international expert consensus statement aims to provide pragmatic guidance across key domains, including patient selection, imaging, target delineation, treatment planning, dose accumulation, and toxicity management. Developed through a structured expert consensus process with formal agreement assessment, this document reflects current expert practice. By offering a shared clinical framework, this consensus seeks to promote more consistent practice, facilitate communication across centres, and support future research efforts in this complex and evolving field.

Despite the increasing popularity of upfront decompressive surgery, there are still patients with malignant spinal cord compression (MSCC) and expected longer-term survival receiving irradiation alone. In these patients, local progression-free survival (LPFS) may be improved with doses beyond the commonly applied regimen of 10 × 3.0 Gy. A prospective phase 2 trial (RAMSES-01) investigated the benefit of two regimens, 15 × 2.633 and 18 × 2.333 Gy, compared with a 10 × 3.0 Gy (historical control). Patients in the phase 2 cohort had significantly better local progression-free survival (LPFS) after 1 year. Since recurrent MSCC-related motor weakness is a serious situation, it must be avoided as long as possible. In this respect, it is important to know whether the superiority of 15 × 2.633 and 18 × 2.333 Gy found in the RAMSES-01 trial still exists after 2 or 3 years. This led to the current study. In the phase 2 group, 2- and 3-year LPFS rates were 93.1% and 93.1%, respectively, and survival rates were 54.2% and 36.1%, respectively. According to propensity-adjusted Cox regression analyses, radiotherapy regimens in the phase 2 cohort resulted in significantly better LPFS at 2 (p = 0.017) and 3 (p = 0.013) years. In contrast, survival was not significantly different (p = 0.251 and p = 0.288, respectively). Radiation myelopathy and pathologic vertebral fractures were not observed in any group. Given the limitations of this study, irradiation 15 × 2.633 or 18 × 2.333 Gy may be an alternative option for patients with MSCC and longer expected survival treated with irradiation alone.

BACKGROUND:Oropharyngeal cancer (OPC) exhibits distinct clinical behaviors according to HPV/p16 status and smoking exposure. While HPV-positive OPC generally shows superior survival, differences in recurrence patterns remain unclear. METHODS:A retrospective multicenter analysis of 674 AJCC VII edition Stage III-IVa/b OPC patients treated with definitive IMRT ± systemic therapy was conducted across 14 Southern European centers. Recurrence patterns, disease-free survival (DFS), overall survival (OS), and survival after recurrence (rOS) were compared between p16 groups and across smoking categories. RESULTS:HPV-positive tumors showed a higher incidence of distant recurrence, particularly among heavy smokers, while p16-negative OPC displayed predominantly locoregional failure. p16-positive patients had significantly better DFS, OS, and rOS. CONCLUSION:Recurrence patterns in OPC differ by HPV status and smoking history. HPV-positive heavy smokers represent a distinct high-risk subgroup characterized by increased distant metastasis and inferior survival, warranting refined stratification beyond p16 status alone.

Background: Radiation therapy with or without systemic treatment for lung cancer can cause adverse reactions, e.g., fatigue. Affected patients may experience a decrease in physical activity and, as a consequence, be unable to receive the complete assigned treatment. Physical exercise may be helpful. A benefit of exercise regarding completion of systemic treatment and quality of life was previously suggested. Irradiated patients may benefit as well. A smartphone-based app reminding patients to make a minimum number of steps might positively influence physical activity. The prototype of an app called "Step Reminder" was recently finalized. The randomized APPAREL trial (NCT07627022) evaluates whether this app can improve physical activity during irradiation for lung cancer. Methods: The primary endpoint of this phase 2 trial focuses on the within-patient change regarding the mean number of daily steps (week 5 minus week 1). Secondary objectives include satisfaction with the application and its impact on the perception of digital health technology. Patients are randomized 1:1 to be treated with a standard approach (conventionally fractionated irradiation with or without systemic treatment) supported by the "Step Reminder" app (Arm A) or standard treatment without the app (Arm B). The app provides reminders several times per day to walk a pre-defined number of steps. To make sure that the required 28 patients are included in the primary analysis population (full analysis set), 32 patients have to be randomized. Results: At this stage, results are not available. Conclusions: It is expected that the app will have a positive effect on the patients' physical activity (number of steps).

In this report, we discuss this clinical case, when the laryngeal remnant, or “neo-larynx”, is not part of the clinical target volume, it should be delineated as a bona-fide organ at risk or avoidance structure: recognizing the post-surgical anatomy could help maximize the preservation of the functional outcome. In addition, raising awareness on this rare yet very challenging disease presentation could foster a more homogeneous practice among radiation oncologists treating laryngeal cancer analogue to thoracic cancer.

PURPOSE:Brachytherapy boost is an established dose-escalation strategy in intermediate- and high-risk prostate cancer, while stereotactic body radiotherapy (SBRT) offers treatment efficiency with favourable radiobiology. We report mature results of a prospective phase II trial combining single-fraction high-dose-rate (HDR) brachytherapy with prostate-only SBRT. MATERIALS AND METHODS:Seventy-six patients with intermediate- or high-risk prostate cancer were enrolled between 2019 and 2021. Treatment consisted of MRI-TRUS fusion HDR brachytherapy (15 Gy, single fraction) followed by SBRT (25 Gy in 5 fractions). Androgen deprivation therapy was prescribed according to risk group. The primary endpoint was patient-reported quality of life (EPIC-26, EORTC QLQ-PR25). Secondary endpoints included acute and late genitourinary (GU) and gastrointestinal (GI) toxicity (CTCAE v5), PSA response, biochemical relapse-free survival (bRFS), metastasis-free survival (MFS), and overall survival (OS). RESULTS:With a median follow-up of 48 months, no acute or late grade 3 GI toxicity was observed. Two patients (2.6 %) developed late grade 3 GU toxicity. Acute and late grade 2 GU toxicity occurred in 11.8 % and 28.9 % of patients, respectively. Urinary and bowel quality of life showed a transient and non-significant decline at one month, returning to baseline by six months. The median PSA nadir was 0.04 ng/mL. The 4-year bRFS and MFS were both 91 % (95 % CI 84-98 %). The median PSA at 4 years was 0.06 ng/mL. CONCLUSIONS:Single-fraction HDR brachytherapy combined with SBRT achieved high biochemical control with limited toxicity and preserved quality of life, representing an efficient dose-escalation strategy for intermediate- and high-risk prostate cancer.

Background/Objectives: During radiotherapy for prostate cancer, the risk of radiation cystitis is increased if the volume of the bladder is small. According to previous studies, it is important that bladder volumes are ≥200 mL. Drinking protocols may be helpful in this context. Adherence to such protocols can be challenging, and may be improved by an app reminding patients before each session of radiotherapy to drink a certain amount of water. Our prospective phase 2 trial (REFILL-PAC-HYPO, NCT06784115) evaluates the impact of a reminder app on bladder filling in prostate cancer patients treated with hypo-fractionated radiotherapy. Methods: Twenty-seven patients need to be recruited for the REFILL-PAC-HYPO trial. Radiotherapy, preferably with volumetric-modulated arc therapy, uses hypo-fractionation with 20 × 3.0 Gy over four weeks. An app reminds patients to drink water (300 mL) 45 min before each session of hypo-fractionated irradiation. On the last day of their treatment, patients are asked about their satisfaction with the app. In the case of a dissatisfaction rate of >20%, the app requires modifications. If this rate is >40%, the app is considered not useful. Additionally, patients are asked about the impact of their participation in the trial and using the app on their general attitude towards health technology. Furthermore, the phase 2 cohort is compared to a historical control group treated with hypo-fractionated radiotherapy during recent years but not supported by an app. The REFILL-PAC-HYPO trial will contribute to identifying the potential value of a reminder app for bladder filling during hypo-fractionated radiotherapy for prostate cancer.

Background/Objectives: For many patients with malignant spinal cord compression (MSCC) not suitable for surgery, irradiation alone is the preferred treatment. A dose-fractionation regimen of 10 × 3 Gy is common for this situation. Since most patients suffer from motor deficits and pain, the number of radiotherapy sessions should be as low as possible. A secondary analysis of a phase 2 trial compared 5 × 5 Gy to a historical control group treated with 10 × 3 Gy. After 1:2 matching, 5 × 5 Gy appeared similarly effective regarding local progression-free survival (LPFS) at 6 months, motor function, walking ability, and overall survival. Methods: This retrospective study investigated whether these findings are consistent in a larger cohort and after longer follow-up. Additional data were gathered for the phase 2 cohort, follow-up in the control group was not limited to 6 months, and the number of patients in the control group increased from 213 to 728. Results: After propensity-score matching, no significant differences were found regarding LPFS after 12 (p = 0.198), 18 (p = 0.139), and 24 (p = 0.117) months, effect on motor function (p = 0.393), walking ability (p = 0.079), 24-month local control (p = 0.655), and 24-month OS (p = 0.403). Conclusions: Given the limitations of this study, 5 × 5 Gy appears preferable to 10 × 3 Gy in selected patients receiving irradiation without upfront surgery. Clinicians should balance initial convenience for the patients and future limitations when re-irradiation in the same part of the spine is required.

Aim: To estimate the cost–effectiveness of cetuximab in combination with radiotherapy compared with radiotherapy alone, for the treatment of locally advanced head and neck cancer patients in Spain. Methods: A probabilistic Markov model (second-order Monte Carlo simulation) with a five-year time horizon and quarterly Markov cycles was performed from the perspective of the Spanish National Health System (NHS). Results: The additional cost and quality-adjusted life-year (QALY) gain per patient receiving radiotherapy in combination with cetuximab compared with radiotherapy alone was €4356 (95% CI: €4350–4362) and 0.2380 (95% CI: 0.2370–0.2391) QALY, respectively. The incremental cost per QALY gain was €18,303 (95% CI: €18,243–18,354) with a probability of cost–effectiveness of 65.4% for a willingness to pay of €30,000 per QALY gained. Conclusion: According to the results of this analysis, the addition of cetuximab to radiotherapy would be a cost-effective alternative to radiotherapy alone in the treatment of locally advanced head and neck cancer in Spain.

BACKGROUND/AIM:Many patients with high-risk prostate cancer receive normo-fractionated irradiation. Previously, high-risk cancer and pre-treatment bladder volumes <200 ml were associated with inappropriate bladder filling during the radiotherapy course. A prospective trial will investigate the value of an app reminding patients to drink water before each radiotherapy session. This study provides information regarding magnitude of inappropriate bladder filling and risk factors required for the prospective trial. PATIENTS AND METHODS:In 23 patients with high-risk prostate cancer and inappropriate pre-treatment bladder filling, mean and median numbers of radiation fractions with bladder volumes less than 200 ml and potential risk factors were retrospectively investigated. RESULTS:Mean and median numbers of fractions with volumes less than 200 ml were 29.2±6.6 and 32.0 (interquartile range=24.0-35.0) of 35 fractions. Higher numbers were significantly associated with a lower performance score (p <0.029). CONCLUSION:Bladder filling was inappropriate during most radiotherapy fractions and, therefore, must be considered a significant problem. Our results are relevant for a subsequent prospective trial.

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.

BACKGROUND/OBJECTIVES:Despite increasing use of upfront decompressive surgery for malignant epidural compression of the myelon (MESCC), a substantial number of affected patients still receive radiotherapy (RT) alone. Many of these patients would benefit from a personalized treatment approach including the most appropriate dose-fractionation regimen. The PRE-MODE trial (NCT03070431) compared precision RT with 5 × 5 Gy (prospective cohort, n = 40) to conventional RT with 5 × 4 Gy (historical control, n = 676)). After propensity-score matching, 5 × 5 Gy resulted in significantly increased local progression-free survival (LPFS) at 6 months than 5 × 4 Gy. The question arose whether this benefit is still present after a longer period of follow-up. METHODS:For this additional study, supplementary data were retrospectively captured, resulting in prolongation of follow-up until 24 months. RESULTS:5 × 5 Gy resulted in LPFS of 80.9% at each investigated time point (12, 18, and 24 months) without reported radiation myelopathy. Moreover, 5 × 5 Gy showed a trend towards improved LPFS after 12 (p = 0.070), 18 (p = 0.060), and 24 (p = 0.054) months. Similarly to the original PRE-MODE trial, OS-rates were not significantly different in the dose groups of this supplementary study. CONCLUSION:Since 5 × 5 Gy resulted in excellent long-term LPFS and showed a trend towards better outcomes up to 24 months following RT, it appears preferable to 5 × 4 Gy and will contribute to the personalized treatment of patients with MESCC who are assigned to RT alone without upfront neurosurgical intervention.