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.

Neoadjuvant volumetric modulated arc radiochemotherapy with a simultaneous integrated boost technique compared to standard chemoradiation for locally advanced rectal cancer

Background/aim: The present study aimed to examine whether the combination of neoadjuvant volumetric modulated arc radiotherapy (VMAT) using simultaneous integrated boost (SIB-VMAT) techniques and chemotherapy with capecitabine is associated with better clinical and dosimetric outcomes compared to the standard treatment. Materials and methods: The study included 59 patients with cT2­T4 rectal cancer. In the standard arm, patients (n = 37) were treated preoperatively with image-guided VMAT plus capecitabine. In the SIB arm, patients (n = 22) were treated with the SIB-VMAT technique plus capecitabine. All patients underwent radical surgical resection after neoadjuvant radiochemotherapy. Results: In the standard arm, cT0N0 was reached in 12 patients (32.4%), primary tumor clinical downstaging was observed in 22 patients (59.5%), and disease stability was achieved in 3 patients (8.1%). In the SIB arm, cT0N0 was reached in 15 patients (68.2%), primary tumor clinical downstaging was observed in 6 patients (27.3%), and disease stability was achieved in 1 patient (4.5%) (P = 0.028). Complete pathological response was observed in 11 patients (29.7%) in the standard arm and in 13 patients (59.1%) in the SIB arm (P = 0.026). In the SIB arm mild diarrhea appeared in 59.1%, moderate in 40.9%, and severe in 0% of the cases. In the standard arm mild, moderate, and severe diarrhea rates were in 54.1%, 43.2%, and 2.7%, respectively. In the SIB arm mild, moderate, and severe cystitis appeared in 63.6%, 22.7%, and 13.6%, while in the standard group mild cystitis developed in 67.6%, moderate in 24.3%, and severe in 8.1%. Mild, moderate, and severe radiation dermatitis rates were 45.5%, 45.5%, and 9.1% in the SIB group and 40.5%, 48.6%, and 10.8% in the standard group, respectively. Conclusion: The SIB-VMAT technique is effective and safe for irradiating locally advanced rectal cancer. Its effectiveness is expressed in higher clinical and pathological complete response rates and safety with the same rates of acute toxicity.

Effect of Age at Diagnosis on the Prognosis of Gastric Cancer Patients: A Population-Based Study in Georgia.

INTRODUCTION: The national burden of gastric cancer (GC) is high in Georgia, which is determined by its high mortality and low survival. The study aimed to estimate the effect of age at diagnosis on the prognosis of GC patients diagnosed between 2015 and 2020 in Georgia. MATERIALS AND METHODS: We obtained data for the study from the national population-based cancer registry. All patients 15 years of age or older, diagnosed during 2015-2020 with invasive GC (site codes C16.0 to C16.9, International Classification of Diseases for Oncology), were eligible for inclusion in the analysis. We produced survival curves using the Kaplan-Meier method, and the log-rank test was used to compare survival between groups. Hazard ratios (HR) were estimated using univariate Cox proportional models and multivariate Cox proportional hazard models. The endpoint of the study was overall survival (OS). The level of statistical significance of the study findings was estimated using p-values and 95% confidence intervals (CI). A p-value<0.05 was considered statistically significant.  Results: A total of 1,828 gastric cancer cases were included in the statistical analysis. The average age of patients was 65 years. The bivariate Cox's regression analysis demonstrated that the risk of gastric cancer mortality increased gradually with the age of cancer patients. The HR and 95% CI were as follows: 1.5 (1.1-1.8) and 2.1 (1.5-2.5) in the 46-65 years and >65 years groups, respectively, with the <46 years group as a reference. Moreover, multivariable Cox's regression analysis proved that age is an independent risk factor for GC mortality (HR = 1.4; 95% CI = 1.2-1.8; p<.001).  Conclusion: We found that age at diagnosis was a significant predictor of the worse survival of GC patients diagnosed between 2015 and 2020 in Georgia.

Descriptive Epidemiology of Gastric Cancer: A Population-Based Study From Georgia.

Background Gastric cancer (GC) remains a significant public health issue in many countries globally due to its high morbidity and mortality rates. In Georgia, the incidence of GC reflects the prevalence patterns of established risk factors. To develop appropriate prevention and treatment strategies, GC requires a comprehensive approach and research. This study aims to review and describe GC epidemiologic characteristics in the country. Methodology We conducted a descriptive analysis utilizing data from the national population-based cancer registry. All patients diagnosed with invasive GC between 2015 and 2022 were eligible for inclusion in the analysis. To calculate age-standardized incidence (ASIR) and mortality (ASMR) rates we used a direct method, standardized to the World (WHO 2000-2025) standard population. Trends in Incidence and mortality were assessed using standardized rate ratios (SRRs). The mortality-to-incidence ratio (MIR) was defined as the ratio of the ASMR to the ASIR for the corresponding year. The Kaplan-Meier method was utilized to construct survival curves with survival comparisons performed using the log-rank test. Results A total of 2,707 GC cases with 62% (n = 1,668) of patients being male were enrolled in this descriptive study. The median age at diagnosis was 65 years, and about 70% (n = 1,893) of cases were detected at advanced (III and IV) stages. Over the study period, the ASIR per 100,000 population for both sexes decreased from 8.4 to 7.3. The SRR and 95% confidence interval indicated no significant change in ASIR for males but it decreased for females in 2022 compared to 2015. In 2022, the ASMR decreased compared to 2015 for males (from 10.5 to 7.3/100,00) and for females (from 5.8 to 3.0/100,000) as well. However, the MIR ​​indicated an unstable reduction in mortality, fluctuating over the observation period. The five-year survival rate was around 22.0%. Conclusions This study provides a comprehensive overview of GC epidemiology in Georgia between 2015 and 2022. GC remains a significant public health challenge, characterized by the high proportion of late-stage diagnoses and high mortality rates. The implementation of prevention and early diagnosis strategies is crucial to reduce the burden of GC in the country.

Radiotherapy with 15 × 2.633 Gy vs. 20 × 2.0 Gy in Patients with Malignant Spinal Cord Compression and Favorable Survival Prognoses: A Secondary Analysis of the RAMSES-01 Trial.

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.

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 and Easy-to-Use Survival Score for Patients Irradiated for Metastatic Epidural Spinal Cord Compression.

PURPOSE: A survival score was created in 2008 to improve treatment personalization of patients irradiated for metastatic epidural spinal cord compression (MESCC). Since then, targeted therapies improved survival of patients with cancer, which may decrease this score's predictive value. A new score appears necessary. METHODS AND MATERIALS: Two hundred sixty-four patients receiving radiation therapy without surgery in prospective trials (2010-2021) were included. A dose-fractionation regimen plus 15 factors were analyzed: age, sex, tumor type, interval tumor diagnosis to MESCC, MESCC sites, affected vertebrae, additional bone lesions, other distant lesions (yes or no), number of organs involved by metastases, time developing motor deficits, ambulatory status, sensory function, sphincter dysfunction, pain, and distress. Six-month survival rates (%) of independent prognostic factors were divided by 10 and summed for each patient. The score was compared with the previous tool for predicting death ≤6 months and survival ≥6 months. RESULTS: In a multivariate analysis, tumor type (P = .001), other distant lesions (P < .001), and ambulatory status (P < .001) were significant. Based on 6-month survival rates, 4 groups (8-9, 10-13, 14-17, and 18 points) were created with 6-month survival rates of 12.8%, 34.7%, 62.8%, and 90.0%, respectively (version A). For version B, "other distant lesions" was replaced by "number of organs involved by metastases." Version B included 4 groups (8-10, 11-14, 15-16, and 17 points) with 6-month survival rates of 11.1%, 42.0%, 68.6%, and 91.7%, respectively. Positive predictive values to predict death ≤6 months were 87.2% (version A) and 88.9% (version B) versus 76.6% (3 groups) and 84.6% (5 groups) for the previous score. Positive predictive values to predict survival ≥6 months were 90.0% and 91.7% versus 59.0% and 64.3%. CONCLUSIONS: Both versions of the new score were more precise than the previous tool. Version B appears slightly superior to version A but requires more extensive diagnostic staging that may not be readily available when emergently treating.

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.

Advanced Esophageal Squamous Cell Carcinoma in Young Female Patient With Durable Complete Response on Treatment.

Esophageal carcinoma is the seventh most common cancer and the sixth most lethal cancer worldwide. There are two main histological types of esophageal carcinoma: adenocarcinoma (AC) and squamous cell carcinoma (SCC). Both histological types are more common in males than females. Menopause is an independent risk factor for esophageal cancer while usage of hormonal therapy (estrogen plus progesterone) is associated with a lower risk of esophageal SCC in postmenopausal women. Gender differences have an impact on SCC incidence, however, it is unclear if gender has a prognostic value for survival. The present case report describes a young woman who developed SCC of the esophagus. The disease was diagnosed in the locally advanced stage. Definitive chemo-radiotherapy induced complete response. These findings might suggest that in young women esophageal SCC may have a better prognosis.