Radiotherapy for metastatic spinal cord compression with increased radiation doses (RAMSES-01): a prospective multicenter study.

BACKGROUND: Patients with metastatic spinal cord compression (MSCC) and favorable survival prognoses can benefit from radiation doses greater than 30Gy in 10 fractions in terms of improved local progression-free survival (LPFS) and overall survival (OS). METHODS/DESIGN: This prospective study mainly investigates LPFS after precision radiotherapy (volumetric modulated arc therapy or stereotactic body radiotherapy) with 18 × 2.33Gy in 3.5 weeks. LPFS is defined as freedom from progression of motor deficits during radiotherapy and an in-field recurrence of MSCC following radiotherapy. The maximum relative dose allowed to the spinal cord is 101.5% of the prescribed dose, resulting in an equivalent dose in 2Gy-fractions (EQD2) for radiation myelopathy is 45.5Gy, which is below the tolerance dose of 50Gy according to the Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC). The EQD2 of this regimen for tumor cell kill is 43.1Gy, which is 33% higher than for 30Gy in 10 fractions (EQD2 = 32.5Gy). Primary endpoint is LPFS at 12 months after radiotherapy. Secondary endpoints include the effect of 18 × 2.33Gy on motor function, ambulatory status, sensory function, sphincter dysfunction, LPFS at other follow-up times, overall survival, pain relief, relief of distress and toxicity. Follow-up visits for all endpoints will be performed directly and at 1, 3, 6, 9 and 12 months after radiotherapy. A total of 65 patients are required for the prospective part of the study. These patients will be compared to a historical control group of at least 235 patients receiving conventional radiotherapy with 10x3Gy in 2 weeks. DISCUSSION: If precision radiotherapy with 18 × 2.33Gy results in significantly better LPFS than 10x3Gy of conventional radiotherapy, this regimen should be strongly considered for patients with MSCC and favorable survival prognoses. TRIAL REGISTRATION: Clinicaltrials.gov NCT04043156. Registered 30-07-2019.

Radiotherapy for Metastatic Epidural Spinal Cord Compression with Increased Doses: Final Results of the RAMSES-01 Trial.

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.

A New Clinical Instrument for Estimating the Ambulatory Status after Irradiation for Malignant Spinal Cord Compression.

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.

Palliative Radiotherapy for Cutaneous Squamous Cell Carcinoma of the Head-and-Neck Region.

BACKGROUND/AIM: Cutaneous squamous cell carcinoma (cSCC) is a common type of skin cancer. Options for palliative treatment include systemic agents and radiotherapy. Selection of a radiation regimen should consider the patient's survival prognosis. This study aimed to identify prognostic factors of survival after palliative radiotherapy for cSCC of the head-and-neck. PATIENTS AND METHODS: Ten factors were analyzed for survival in 12 patients including age, gender, tumor site, histological grade, primary tumor stage, lymph node involvement, distant metastases, upfront surgery, radiation dose and completion of radiotherapy. RESULTS: On univariate analysis, improved survival was significantly associated with lower histological grade (better differentiation) (p=0.022), no distant metastases (p=0.040) and completion of radiotherapy (p=0.014). In the multivariate analysis, lower histological grade (risk ratio=6.05, p=0.100) and completion of radiotherapy (risk ratio=4.87, p=0.115) showed trends. CONCLUSION: Predictors of survival were identified that can help design individual treatments. Patients require optimal supportive care as completion of radiotherapy was associated with better survival.

Karnofsky Performance Score - An Independent Prognostic Factor of Survival After Palliative Irradiation for Sino-nasal Cancer.

BACKGROUND/AIM: Sino-nasal cancer is rare and often diagnosed at advanced stages. Some patients cannot receive curative treatment and are treated with palliative irradiation. We aimed to identify prognostic factors for survival to facilitate treatment personalization for this group. PATIENTS AND METHODS: Twelve patients treated with palliative radiotherapy for locally advanced sino-nasal cancer were retrospectively analyzed for survival. Ten characteristics were evaluated including age, gender, Karnofsky performance score (KPS), pre-radiotherapy hemoglobin, tumor site, lymph node involvement, histology, equivalent dose in 2 Gy-fractions, completion of radiotherapy and concurrent chemotherapy. RESULTS: On univariate analysis, KPS ≥70 (p<0.001) and completion of radiotherapy (p<0.001) were significantly associated with better survival. Chemotherapy showed a trend (p=0.097). In the multivariate analysis, KPS ≥70 was significant (p=0.025), and completion of radiotherapy showed a trend (p=0.080). CONCLUSION: KPS is an independent predictor of survival for palliative irradiation of sino-nasal cancer. Patients require close monitoring and care for side effects, since completion of radiotherapy is important for survival.

A New Survival Score for Patients Scheduled for Palliative Irradiation of Locally Advanced Carcinoma of the Head-and-Neck.

BACKGROUND/AIM: Patients with advanced squamous cell carcinoma of the head-and-neck (SCCHN) may be assigned to palliative irradiation. A survival score was developed for this group to support treatment personalization. PATIENTS AND METHODS: Seventy-eight patients who received palliative irradiation for SCCHN and had complete data regarding performance score, pre-radiotherapy hemoglobin levels, and main tumor site were included in this retrospective study. Six-month survival rates of these factors were divided by 10 (factor scores) and added for each patient (total patient scores). RESULTS: Total patient scores ranged between 8 and 15 points. Three groups were designed based on the 6-month survival rates, namely 8-9 (n=15), 11-13 (n=36), and 14-15 (n=27) points. Six-month survival rates were 13%, 28%, and 63%, and median survival times were 1, 2, and 11 months (p=0.001). CONCLUSION: A new survival score including three prognostic groups was developed. This new tool can help physicians when designing personalized treatments for patients with SCCHN scheduled for palliative irradiation.

Palliative Local Radiotherapy for Advanced Squamous Cell Carcinoma of the Head-and-Neck: Prognostic Factors of Survival.

BACKGROUND/AIM: A considerable number of patients with advanced head-and-neck cancer (SCCHN) receive palliative radiotherapy. This study aimed to identify prognostic factors for survival to facilitate personalized treatment for these patients. PATIENTS AND METHODS: Ninety-two patients receiving palliative radiotherapy for SCCHN were retrospectively analyzed. Fourteen characteristics were evaluated for survival including age, gender, performance score, pre-radiotherapy hemoglobin, tumor site and stage, histologic grade, p16-status, equivalent dose in 2 Gy-fractions (EQD2), completion of radiotherapy, upfront surgery and systemic therapy. RESULTS: On univariate analysis, improved survival was significantly associated with pre-radiotherapy hemoglobin ≥12 g/dl (p=0.003), EQD2 >42.3 Gy (p=0.003) and completion of radiotherapy (p<0.001). In the multivariate analysis, hemoglobin levels remained significant (p=0.024). Trends were found for EQD2 (p=0.057) and completion of radiotherapy (p=0.093). CONCLUSION: Prognostic factors for survival were identified that can facilitate treatment personalization. The fact that higher EQD2 and completion of radiotherapy were associated with improved survival demonstrates the importance of close monitoring and care of these patients during radiotherapy.

Are radiation-induced cavernomas clinically relevant findings? Results from long-term follow-up with brain magnetic resonance imaging of childhood cancer survivors.

INTRODUCTION: Radiation-induced cavernomas (RIC) after cranial radiotherapy have an unknown risk of hemorrhage. Zabramski magnetic resonance imaging (MRI) classification is touted as being able to indicate non-radiation-induced cavernomas hemorrhage risk. The aim of our study was to assess the hemorrhage risk of RIC during long-term follow-up of childhood cancer survivors based on brain MRI examinations. PATIENTS AND METHODS: We analyzed retrospectively long-term follow-up data of 36 childhood cancer survivors after initial diagnosis with acute leukemia (n = 18) or brain tumor (n = 18), all treated with cranial radiotherapy. Detected RIC in long-term follow-up brain MRI (1.5 or 3 Tesla) were classified following the Zabramski MRI classification and were categorized into "high" (Zabramski type I, II or V) or "low" (type III or IV) risk of hemorrhage. RESULTS: 18 patients (50%) showed RIC with a significant relation to the original tumor entity (p = 0.023) and the cumulative radiation dose to the brain (p = 0.016): all 9 childhood cancer survivors diagnosed with medulloblastoma developed RIC. We classified RIC in only 3/36 childhood cancer survivors (8%) (1 patient with acute lymphoblastic leukemia [Zabramski type II] and 2 patients with medulloblastoma [type I and type II]) as high risk for hemorrhage, the remaining RIC were classified as Zabramski type IV with low risk for hemorrhage. None of the childhood cancer survivors with RIC showed symptomatic hemorrhages. CONCLUSIONS: RIC are common late effects in childhood cancer survivors treated with cranial radiotherapy affecting half of these patients. However, only a few RIC (occurring in 8% of all reviewed childhood cancer survivors) were classified as high risk for hemorrhage and none of the childhood cancer survivors with RIC developed symptomatic hemorrhages. Thus, we conclude that RIC are low-risk findings in brain MRI and the course is mainly benign.

BIT-ART: Multicentric Comparison of HDR-brachytherapy, Intensity-modulated Radiotherapy and Tomotherapy for Advanced Radiotherapy in Prostate Cancer.

BACKGROUND/AIM: The aim of the study was to evaluate acute and late genitourinary (GU) and gastrointestinal (GI) toxicity in patients with high- or intermediate-risk prostate cancer. PATIENTS AND METHODS: We evaluated data of patients from three Radiation Oncology Departments (Rome, Lübeck and Perugia). Patients treated in Rome underwent exclusive intensity-modulated-radiotherapy (IMRT) or IMRT plus high-dose-rate interventional radiotherapy (HDR-IRT). IMRT plus two fractions HDR-IRT was performed in Lübeck, while in Perugia Helical Tomotherapy was performed. The Common Toxicity Criteria for Adverse Event (Version 4.03) scale was used to describe acute and late toxicity. RESULTS: At a median follow-up of 28 months, all 51 patients were alive and disease-free. Patients treated by HDR-IRT plus VMAT showed only G1-2 genitourinary- gastrointestinal (GU-GI) acute and late toxicity. Univariate analysis showed a lower risk of acute GU toxicity (p=0.048) in IMRT+HDR-IRT. CONCLUSION: Low grade and less acute GU toxicity was observed in patients undergoing HDR-IRT boost.

Predicting the Ambulatory Status of Patients Irradiated for Metastatic Spinal Cord Compression (MSCC) from Head-and-neck Cancer.

BACKGROUND/AIM: Personalized cancer care can improve patient outcomes and is facilitated by scoring systems. This study aimed to create an instrument to estimate ambulatory status after radiotherapy for metastatic spinal cord compression (MSCC) from head-and-neck cancer. PATIENTS AND METHODS: In 60 patients, fractionation regimen plus 10 pre-treatment factors were analyzed for post-treatment ambulatory status. Significant factors were used for the scoring system by dividing the ambulatory rate (in %) by 10. Patients' scores were received by adding the factor scores. RESULTS: Time developing motor deficits >7 days (p=0.011), being ambulatory prior to radiotherapy (p<0.001) and ECOG performance score 1-2 (p<0.001) showed significant associations with post-treatment ambulatory status. Patients' scores were 7, 12, 15, 20, 22 and 27 points. Three groups were designed (7-12, 15-20 and 22-27 points) with post-treatment ambulatory rates of 11%, 62% and 96% (p<0.001). CONCLUSION: This scoring system helps predict ambulatory status after radiotherapy for MSCC from head-and-neck cancer.

A Tool to Predict the Probability of Intracerebral Recurrence or New Cerebral Metastases After Whole-brain Irradiation in Patients with Head-and-Neck Cancer.

BACKGROUND/AIM: Patients with metastatic head-and-neck cancer require individual therapies facilitated by prognostic tools. A tool to estimate the risk of recurrent or new cerebral metastases following whole-brain irradiation (WBI) is presented. PATIENTS AND METHODS: Age, gender, performance status, cancer site, number of cerebral lesions, extracerebral metastases, and time between cancer diagnosis and treatment of cerebral metastases were evaluated for intracerebral control in 23 patients. For characteristics showing a trend (p<0.07), points for these characteristics were created by dividing 6-month intracerebral control rates by 10. Patient scores were obtained by adding these points. RESULTS: Better intracerebral control was significantly associated with oropharyngeal and laryngeal cancer (p=0.014). Absence of extra-cerebral metastases (p=0.069) and longer time between cancer diagnosis and treatment of cerebral metastases (p=0.053) showed trends. Three groups were identified, namely with 3-11, 13-18 and 20-24 points. Six-month intracerebral control rates were 0%, 50% and 100% (p=0.003), respectively, for these groups. CONCLUSION: A new tool was created to predict intracerebral control following WBI and should contribute to personalization of treatment for patients with cerebral metastases of head-and-neck cancer.