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

Simple Summary Patients with MESCC and favorable survival prognoses assigned to radiotherapy alone may benefit from increased doses. In a multi-center phase 2 trial, patients receiving 15 x 2.633 Gy or 18 x 2.333 Gy were evaluated and subsequently compared to a historical control group receiving 10 x 3.0 Gy. The phase 2 cohort, including 50 (of 62 planned) evaluable patients, showed promising results regarding 12-month local progression-free survival (LPFS), 12-month overall survival (OS), improvement of motor and sensory functions, post-radiotherapy ambulatory status, and relief of pain and distress. Radiotherapy with 15 x 2.633 Gy or 18 x 2.333 Gy was well tolerated and appeared more effective than 10 x 3.0 Gy with respect to LPFS and improvement of motor function.Abstract Patients with metastatic epidural spinal cord compression (MESCC) and favorable survival prognoses may benefit from radiation doses exceeding 10 x 3.0 Gy. In a multi-center phase 2 trial, patients receiving 15 x 2.633 Gy (41.6 Gy10) or 18 x 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 x 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 x 2.633 Gy or 18 x 2.333 Gy was well tolerated and appeared superior to 10 x 3.0 Gy

Biomarker Expression and Clinical Outcomes in International Study of Chemoradiation and Magnetic Resonance Imaging-Based Image-Guided Brachytherapy for Locally Advanced Cervical Cancer:BIOEMBRACE

Purpose: BIOEMBRACE was designed to study the impact of biomarkers in addition to clinicopathological factors on disease outcomes in patients treated with chemoradiation and magnetic resonance imaging (MRI)-guided brachytherapy (BT) for locally advanced cervical cancer in the EMBRACE study. Methods and Materials: Between 2018 and 2021, 8 EMBRACE-I sites contributed tumor tissue for the immunohistochemistry of p16, PD-L1, and L1CAM. These biomarkers and clinicopathological factors (International Federation of Gynecology and Obstetrics 2009 stage, nodal status, histology, and necrosis on MRI) were analyzed to predict poor response at BT (high-risk clinical target volume [HR-CTV] ≥ 40 cc) at BT) and 5-year local control, pelvic control, and disease-free survival. Interaction between p16, PD-L1, radiation therapy dose (HR-CTV D90), and disease outcomes was investigated. Univariable and multivariable analyses were performed. Results: Two hundred sixty-four patients were included. The median HR-CTV D90 was 89 Gy (86-95). P-16 positive status, PD-L1 &gt; 1%, and L1CAM ≥ 10% was noted in 86.6%, 20.1%, and 17.8% of patients, respectively. P16 negative status (odds ratio, 2.0; 95% CI, 1.0-5.7; P = .04) and necrosis on MRI (odds ratio, 2.1; 95% CI, 1.1-4.3; P &lt; .02) independently predicted for HR-CTV ≥ 40 cc, as did the International Federation of Gynecology and Obstetrics stage and tumor width &gt;5 cm. PD-L1 &gt; 1% was associated with reduced local (82% vs 94%; P = .02) and pelvic control (79% vs 89%; P = .02). HR-CTV D90 &lt; 85 Gy was associated with inferior 5-year local control in p16-positive patients, especially if PD-L1 was coexpressed. On multivariable analysis, PD-L1 &gt; 1% was the only independent factor for 5-year local control (hazard ratio, 3.3; P = .04) and L1CAM ≥ 50% for pelvic control (hazard ratio, 5.5; 95% CI, 1.3-23.3; P = .02). Conclusions: P16 negative status and tumor necrosis on MRI are independently associated with poor response to chemoradiation, whereas PD-L1 &gt; 1% and L1CAM ≥ 50% have an independent impact on local and pelvic control, suggesting an impact of biomarker expression on outcomes. Further validation is needed.</p

Distant Metastasis After Chemoradiation and Image Guided Adaptive Brachytherapy in Locally Advanced Cervical Cancer

Purpose: This study aimed to assess patterns and risks of distant metastasis (DM) in patients with cervical cancer treated with chemoradiation therapy and MR-image guided adaptive brachytherapy (IGABT) and to explore a potential dose-effect relationship of concomitant cisplatin. Methods and Materials: Data were derived from EMBRACE I, an international, prospective, and multicenter cohort study conducted at 24 centers across Europe, Asia, and North America from July 30, 2008, to December 29, 2015. The study included 1416 patients with biopsy-confirmed cervical cancer (International Federation of Gynecology and Obstetrics [FIGO2009] stage IB-IVA or stage IVB limited to paraaortic lymph nodes below the L1/L2 interspace). Treatment involved external beam radiation therapy (45-50.4 Gy), weekly cisplatin (40 mg/m², 30 mg/m², or paused), and IGABT. DM was defined as extra-pelvic recurrence excluding paraaortic nodes. Results: The analysis included 1318 patients with a median age of 49 years and a median follow-up of 52 months. The 5-year cumulative incidence of DM was 14%, with the lungs (26%), mediastinal lymph nodes (15%), and bones (10%) identified as the most common metastatic sites. Key risk factors for DM included nonsquamous histology (HR, 1.89; 95% CI, 1.30-2.75), nodal involvement at diagnosis (pelvic-only nodes: HR, 1.56; 95% CI, 1.07-2.26; paraaortic nodes: HR, 3.15; 95% CI, 1.93-5.16), and large target volume at brachytherapy (HR, 1.93; 95% CI, 1.21-3.08). Patients receiving fewer than 4 cycles of chemotherapy demonstrated a significantly higher risk of DM (HR, 1.52; 95% CI, 1.08-2.13). Conclusion: DM is a substantial burden in patients with locally advanced cervical cancer, with the lungs, distant lymph nodes, and bones being the most frequent sites. Risk factors such as nonsquamous histology, nodal involvement, and large target volumes at brachytherapy are critical considerations for identifying high-risk patients in future studies. These findings highlight the need for tailored strategies to mitigate DM in this patient population.</p

Natural history specimens collected and/or identified and deposited.

Natural history specimen data collected and/or identified by Barbara P. Segedin, &lt;a href="http://www.wikidata.org/entity/Q21608609"&gt;http://www.wikidata.org/entity/Q21608609&lt;/a&gt;. Claims or attributions were made on Bionomia, &lt;a href="http://bionomia.net"&gt;https://bionomia.net&lt;/a&gt; using specimen data from the Global Biodiversity Information Facility, &lt;a href="https://gbif.org"&gt;https://gbif.org&lt;/a&gt;.http://www.wikidata.org/entity/Q2160860

Uncertainties in target volume delineation in radiotherapy – are they relevant and what can we do about them?

Modern radiotherapy techniques enable delivery of high doses to the target volume without escalating dose to organs at risk, offering the possibility of better local control while preserving good quality of life. Uncertainties in target volume delineation have been demonstrated for most tumour sites, and various studies indicate that inconsistencies in target volume delineation may be larger than errors in all other steps of the treatment planning and delivery process. The aim of this paper is to summarize the degree of delineation uncertainties for different tumour sites reported in the literature and review the effect of strategies to minimize them

The Role of MRI and PET/CT in Radiotherapy Target Volume Determination in Gastrointestinal Cancers&mdash;Review of the Literature

Positron emission tomography with computed tomography (PET/CT) and magnetic resonance imaging (MRI) could improve accuracy in target volume determination for gastrointestinal cancers. A systematic search of the PubMed database was performed, focusing on studies published within the last 20 years. Articles were considered eligible for the review if they included patients with anal canal, esophageal, rectal or pancreatic cancer, as well as PET/CT or MRI for radiotherapy treatment planning, and if they reported interobserver variability or changes in treatment planning volume due to different imaging modalities or correlation between the imaging modality and histopathologic specimen. The search of the literature retrieved 1396 articles. We retrieved six articles from an additional search of the reference lists of related articles. Forty-one studies were included in the final review. PET/CT seems indispensable for target volume determination of pathological lymph nodes in esophageal and anal canal cancer. MRI seems appropriate for the delineation of primary tumors in the pelvis as rectal and anal canal cancer. Delineation of the target volumes for radiotherapy of pancreatic cancer remains challenging, and additional studies are needed