External Beam Radiotherapy Dose Research Articles

Abstract IA08: Theragnostics & external beam radiation dose absorbed - Similarities, differences and thoughts for the future

Abstract External Beam Radiotherapy (EBRT) and theragnostics share a key core characteristic – the use of radiation to exert its therapeutic benefit. However, the role radiation dose absorbed plays is significantly different between these two modalities in clinical practice. On the one hand it is a critical element of EBRT prescriptions (e.g. cGy), while on the other it is not even a requirement to document in theragnostic practices, where prescriptions are expressed as administered activities (e.g. GBq). Radiation dose absorbed by tumor and normal tissues is recognized to be variable across patients. It is acknowledged to be a critical metric in the safe use of radiopharmaceuticals and is required for all first in human studies and a priority for the development of any novel radiopharmaceutical. The process of individualized dosimetry is well described, enabling radiation dose absorbed estimates to regions of interest. There is an active debate currently as to when, in whom and how individualized dosimetry should be incorporated into clinical practice. The lack of high quality evidence to support radiation dose absorbed to patient outcomes, the lack of standardized methodologies to enable comparability of dose absorbed data across institutions, the burden on patients to return for dosimetry scans post treatment, the burden on the health care system to incorporate individualized dosimetry into treatment workflows and the lack of reimbursement codes for these activities are the main barriers cited against routine clinical use. In this session, we will review some of the theoretical and logistic considerations as well as evidence behind this debate. We will also take a broader view, of theragnostics as a rapidly growing modality, that patients and their oncology teams would need radiation absorbed dose information when considering “re-irradiation”, be it re-challenge with theragnostics, or to provide safety estimates when using different forms of radiation along patients’ cancer journey in the real world. Through a recently completed multi-center trial as a case study, we will review the processes involved in setting up individualized dosimetry across four academic institutions and our subsequent transition into standard of care. We will discuss the value of radiation dose information for our patients, at the systems and academic levels. Finally, we will consider radiation dose absorbed in the future of theragnostics - as a prognostic factor for response and toxicity, as a factor in understanding the mechanism of treatment resistance, as a strategy to create novel dosing approaches and as part of combined modality to strive for superior patient outcomes. We propose that we are at a critical time, where a collaborative strategy across theragnostic practices is critical. The adoption of the reporting of radiation dose absorbed as a quality metric, blending lessons learned across theragnostics and EBRT will set the stage for the future with excellent quality of care and accelerated discoveries for our patients. (458 words). Citation Format: Rebecca K.S. Theragnostics & external beam radiation dose absorbed - Similarities, differences and thoughts for the future. [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Targeted Therapies in Combination with Radiotherapy; 2025 Jan 26-29; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(2_Suppl):Abstract nr IA08

Interstitial High-Dose-Rate Brachytherapy Combined with External Beam Radiation Therapy for Dose Escalation in the Primary Treatment of Locally Advanced, Non-Resectable Superior Sulcus (Pancoast) Tumors: Results of a Monocentric Retrospective Study.

Objectives: To analyze the results of interstitial (IRT) high-dose-rate (HDR) brachytherapy (BT) in the primary treatment of patients with unresectable superior sulcus tumors (SST) combined with external beam radiotherapy (EBRT). Methods: Between 2013 and 2023, seven patients with unresectable SST were treated with combined BT and EBRT with or without concomitant chemotherapy. The patients' median age was 64 years (range, 49-79 years) and median tumor volume was 146.8 cm3 (range, 29.3-242.3 cm3). A median BT dose of 8 Gray (Gy) (range, 5-10 Gy) was prescribed and delivered in a single fraction. A median EBRT dose of 54 Gy (range, 30-59 Gy) was prescribed and administered normofractionated (single dose: 1.8 Gy). Results: We report the results of seven patients with SST treated with combined BT and EBRT and followed for a median of 38 months. The overall clinical response rate was 83.33% with five out of six patients achieving local control, while one out of six (16.66%) showed local and general progression. No deaths were attributed to the treatment itself; rather, one patient died during the course of therapy as a result of systemic progression. The most common radiation-related adverse events were grade I-II fatigue and mild paresthesia. No severe toxicity (CTCAE ≥ III°) was observed with interstitial high-dose-rate (HDR) BT combined with EBRT. Conclusions: For patients with unresectable superior sulcus tumors, interstitial HDR BT in combination with EBRT is a feasible treatment option that offers the potential for local control and long-term survival. The findings of this study should be validated in a larger patient cohort.

Optimizing the planning process in computed tomography-based image-guided adaptive brachytherapy for cervical cancer using a spreadsheet-based daily dose management system.

This study developed a system to reduce the treatment planning time for cervical cancer brachytherapy. An in-house Excel spreadsheet was developed to streamline dosimetric evaluation by combining external beam radiotherapy and brachytherapy doses, while also displaying daily dose constraints, a novel feature of the system. This system was validated in 46 consecutive patients who underwent intracavitary and interstitial brachytherapy using several applicators and required more complex dose calculation procedures than intracavitary brachytherapy alone. The proposed system included contouring and catheter reconstruction using multiple treatment planning systems simultaneously and was integrated with Excel spreadsheets for rapid dosimetric evaluation. The median time required for treatment planning was 36min (range: 12-72min), which was a much shorter time than those reported previously. This optimized system demonstrated the potential to increase the efficiency of brachytherapy planning to meet prescribed dose constraints without compromising treatment quality.

Comparison between The Efficacy of Concurrent Chemo-Radiation with Gemcitabine Followed by Intracavitary Radiotherapy in Patients with Locally Advanced Cervical Carcinoma

Introduction: Commonest threatening cancer in our Asian round is Cervical cancer. Currently, platinum-based concurrent chemo-radiation therapy is the standard of care for locally advanced cervical cancer but treatment results are disappointing, particularly for women with bulky tumors. To improve this result, several non-platinum-based agents with concurrent chemo-radiation have been evolved. Material and Methods: This was a quasi-experimental study, where 33 patients with untreated invasive squamous cell carcinoma of the cervix of stage IIB to stage IVA were enrolled in the study from the Radiation Oncology Department of Rajshahi Medical College Hospital from April 2019 to March 2020. Duration of the study was 2 years. All patients received 150 mg/m² of Gemcitabine weekly along with external beam radiation therapy (EBRT). EBRT dose was 50 Gy in 25 daily fractions followed by intracavitary radiotherapy (ICRT) of 21 Gy in 3 fractions. Results: The mean patient age was 45.4 years. Most patients were in stage IIB (59.1%) with moderately differentiated tumors (62.1%). After three months of treatment, 81.8% showed complete response, 12.1% partial response, and 6.1% disease progression. Grade 2 and 3 hematological toxicities were common, including anemia (60.6% grade 2; 24.2% grade 3) and neutropenia (24.2% grade 2; 6.1% grade 3). Other side effects included diarrhea (42.4%), proctitis (36.4%), skin toxicity (45.5%), mild renal toxicity (3%), and grade 2 cystitis (9.1%). Conclusion: Gemcitabine-based concurrent chemo-radiation is a potential alternative for patients contraindicated for Cisplatin. However, larger randomized studies are needed to confirm its safety and efficacy.

PSOR06 Presentation Time: 11:55 AM: Focal Intraprostatic Boost in Patients with Localized Prostate Cancer: High Dose Rate Brachytherapy versus External Beam Radiation Therapy

PSOR06 Presentation Time: 11:55 AM: Focal Intraprostatic Boost in Patients with Localized Prostate Cancer: High Dose Rate Brachytherapy versus External Beam Radiation Therapy

Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 trial

At the first interim analysis of the phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study, the addition of pembrolizumab to chemoradiotherapy provided a statistically significant and clinically meaningful improvement in progression-free survival in patients with locally advanced cervical cancer. We report the overall survival results from the second interim analysis of this study. Eligible patients with newly diagnosed, high-risk (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA regardless of nodal status), locally advanced, histologically confirmed, squamous cell carcinoma, adenocarcinoma, or adenosquamous cervical cancer were randomly assigned 1:1 to receive five cycles of pembrolizumab (200 mg) or placebo every 3 weeks with concurrent chemoradiotherapy, followed by 15 cycles of pembrolizumab (400 mg) or placebo every 6 weeks. Pembrolizumab or placebo and cisplatin were administered intravenously. Patients were stratified at randomisation by planned external beam radiotherapy type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), cervical cancer stage at screening (FIGO 2014 stage IB2-IIB node positive vs III-IVA), and planned total radiotherapy (external beam radiotherapy plus brachytherapy) dose (<70 Gy vs ≥70 Gy [equivalent dose of 2 Gy]). Primary endpoints were progression-free survival per RECIST 1.1 by investigator or by histopathological confirmation of suspected disease progression and overall survival defined as the time from randomisation to death due to any cause. Safety was a secondary endpoint. Between June 9, 2020, and Dec 15, 2022, 1060 patients at 176 sites in 30 countries across Asia, Australia, Europe, North America, and South America were randomly assigned to treatment, with 529 patients in the pembrolizumab-chemoradiotherapy group and 531 patients in the placebo-chemoradiotherapy group. At the protocol-specified second interim analysis (data cutoff Jan 8, 2024), median follow-up was 29·9 months (IQR 23·3-34·3). Median overall survival was not reached in either group; 36-month overall survival was 82·6% (95% CI 78·4-86·1) in the pembrolizumab-chemoradiotherapy group and 74·8% (70·1-78·8) in the placebo-chemoradiotherapy group. The hazard ratio for death was 0·67 (95% CI 0·50-0·90; p=0·0040), meeting the protocol-specified primary objective. 413 (78%) of 528 patients in the pembrolizumab-chemoradiotherapy group and 371 (70%) of 530 in the placebo-chemoradiotherapy group had a grade 3 or higher adverse event, with anaemia, white blood cell count decreased, and neutrophil count decreased being the most common adverse events. Potentially immune-mediated adverse events occurred in 206 (39%) of 528 patients in the pembrolizumab-chemoradiotherapy group and 90 (17%) of 530 patients in the placebo-chemoradiotherapy group. This study is registered with ClinicalTrials.gov, NCT04221945. Pembrolizumab plus chemoradiotherapy significantly improved overall survival in patients with locally advanced cervical cancer These data, together with results from the first interim analysis, support this immuno-chemoradiotherapy strategy as a new standard of care for this population. Merck Sharp & Dohme, a subsidiary of Merck & Co.

Advancing Cancer Care Infrastructure in Cambodia: Summary of the First 100 Patients with Cervical Cancer Treated at the National Cancer Centre

Background: Cervical cancer is Cambodia’s leading cause of female malignancy in both incidence and mortality. Cambodia’s first dedicated multidisciplinary cancer center, the National Cancer Centre (NCC), opened in January 2018 in Phnom Penh, and serves as the main public referral center for the region. Methods: This cross-sectional study retrospectively reviewed the care experience of the first 100 patients with cervical cancer treated at the NCC to collect demographic, diagnostic, and treatment characteristics. Results: The most common FIGO Stage was IIB (T2bN0M0) (n = 17). Squamous cell carcinoma represented 85% of cases. Definitive-intent therapy was recommended for 65 patients; neoadjuvant chemotherapy followed by external beam radiotherapy (EBRT) &amp; tandem and ovoid (T&amp;O) brachytherapy +/- concurrent cisplatin was the most common treatment regimen (n=23). Thirty-five patients presented with recurrent (n=22) or metastatic (n=13) disease and were treated with salvage/palliative intent; neoadjuvant chemotherapy followed by EBRT +/- concurrent cisplatin was the most common treatment regimen (n=10). Of the patients treated with definitive-intent treatment, 92% were prescribed an EBRT dose of 45 Gy in 25 fractions, and the median prescribed T&amp;O brachytherapy dose was 28 Gy in 4 fractions. Mean cumulative EQD2 HR-CTV D90 dose was 91.8 Gy, or ~69-70 Gy to Point A, depending on planning technique. Follow-up data was limited to 27 patients; of the 14 patients whose follow-up period exceeded 1 year, 13 (93%) were alive and disease-free at their last assessment. Conclusion: With multidisciplinary partnership, the NCC has demonstrated that high quality complex cancer care can be delivered in a resource-constrained setting. This early sample of patients treated for cervical cancer is an initial step towards a better understanding of Cambodia’s patient population and an early snapshot of their cancer care delivery capacity.

Pattern of care and clinical outcome of patients with carcinoma endometrium and the impact of central histopathological review on management: A tertiary cancer centre experience.

Endometrial carcinoma (EC) is the third most common gynecological malignancy in India. Recent PORTEC-3 analysis emphasized the role of central histopathological review. We aimed to retrospectively analyze the demographic and histopathological characteristics of EC patients treated at our institute and assess the impact of the central histopathological review on management and also analyze clinical outcomes in this cohort of patients. Data of 75 EC patients treated at our center between 2013 and 2022 were retrieved from our departmental archives. Patients were analyzed for demographic details, histopathological findings, details of surgery and histopathology (HPE), results of a review of HPE, adjuvant treatment details, and clinical outcomes. All patients with HPE outside of our institute were reviewed at our center prior to initiation of treatment. In cases of discordance, patients were discussed in the multidisciplinary tumor board for the final treatment decisions. Patients were staged as per International Federation of Gynaecology and Obstetrics 2018. The median age was 57 years (range: 37-74 years). Twenty-seven patients with HPE reported from the outside center were reviewed at our institute and changes were observed in 26 patients (96.3%). HPE review changes were observed in terms of histological grade, histological type, myometrial invasion, and lymph node involvement in five (18.5%), three (11.1%), seven (25.9%), and three (42.8%), respectively. HPE review leads to changes in the management of 19/26 patients. Stage distribution was I: II: III in 48 (64%): 9 (13.3%): 18 (24%) patients, respectively. The median external beam radiotherapy dose was 50 Gray (range: 45-50.4 Gray at 1.8-2 Gray per fraction). The median brachytherapy dose for patients treated with brachytherapy alone was 7 Gray each for three sessions and in combination with EBRT was 6 Gray each in two sessions. At a median follow-up of 51 months (range: 6-116 months), seven (9.3%) patients developed distant metastasis, two (2.7%) patients had local plus distant metastasis, and two (2.7%) patients had local recurrence. The overall survival and disease-free survival rates at 3 years were 93.5% and 86.7%, respectively. EC patients treated at our center have excellent local control rates with a combination of external beam radiotherapy and brachytherapy. The central histopathological review may result in changes impacting patient management and should be routinely done prior to initiation of treatment in EC.

Long-term outcomes of high-dose-rate brachytherapy and external beam radiotherapy without hormone therapy for high-risk localized prostate cancer

PurposeUntil March 2018, patients with high-risk localized prostate cancer had been administered high-dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy (EBRT) without additional hormone therapy (HT) at our institution. In this study, we aimed to evaluate long-term outcomes of this treatment.Materials and methodsPatients with prostate cancer who received HDR-BT and EBRT between April 1997 and March 2021 and who were followed up for at least 6 months were included in the study. High-risk groups were classified into five levels according to the National Comprehensive Cancer Network guidelines. The EBRT and HDR-BT doses were 39–45 Gy/13–25 fractions. and 16.5–22 Gy/2–4 fractions, respectively. None of the patients received HT during initial treatment. The Kaplan–Meier method was used to estimate biochemical freedom from failure (bFFF), cause-specific survival (CSS), and overall survival (OS) rates. Biochemical failure was also determined.ResultsSeventy-two patients were enrolled in the study, with a median follow-up of 91.9 months. The median age and initial prostate-specific antigen (iPSA) level were 71 years and 10.95 ng/mL, respectively. The median biologically effective dose for HDR-BT plus EBRT was 270.3 Gy. The 5- and 7-year bFFF, CSS, and OS rates were 85.2 and 74.2%, 100 and 100%, and 95.7 and 91.9%, respectively. Only the iPSA ≤ 20 group was associated with the higher bFFF rate. The 7-year bFFF rates in the groups with iPSA ≤ 20 and iPSA > 20 were 86.6 and 48.6%, respectively.ConclusionHDR-BT plus EBRT without HT might be an alternative treatment option for patients with high-risk localized prostate cancer and iPSA levels ≤ 20. Further studies are required to validate the efficacy of this treatment strategy.

Role of the gel spacer in safely delivering whole pelvic radiation therapy without central shielding in computed tomography-based image-guided adaptive brachytherapy for uterine cervical cancer patients

BackgroundTo protect the rectum and bladder from high dose exposure, the Japanese guidelines for managing uterine cervical carcinoma recommend pelvic irradiation with central shielding (CS). Conversely, the European Society for Radiotherapy and Oncology (ESTRO) and the American Brachytherapy Society (ABS) guidelines recommend delivering ≥ 85 Gy to high-risk clinical target volume D90 (CTVHR D90%). In this study, we investigated whether a gel spacer can enable the safe delivery of the ESTRO/ABS-recommended doses to the target while observing dose constraints for the OARs without using CS in external beam radiation therapy (EBRT). Materials and MethodsTwenty patients who received definitive radiation therapy without CS and were treated by brachytherapy with a gel spacer between April 2017 and May 2022 were retrospectively reviewed. The cumulative doses of EBRT and brachytherapy expressed in the form of the equivalent dose in 2 Gy fractions (EQD2) were calculated. Treatment outcomes and incidence of adverse events were also examined. ResultsThe median cumulative CTVHR D90%, rectum D2cm3, and bladder D2cm3 were 86.6 Gy (range, 69.8–103.7), 62.9 Gy (range, 55.3–72.5), and 72.0 Gy (range, 62.9–84.1), respectively. The median follow-up was 35.9 months (range, 10.9–70.3). The 2-year local control rate was 95% (95% CI: [69–99%]). There were no CTCAE ≥Grade 3 late gastrointestinal or genitourinary adverse events. ConclusionsThe use of gel spacer can enable ESTRO/ABS-recommended dose constraints even without using CS in EBRT, with favorable outcomes and low adverse event rates.

Success of Ultra-low Dose Radiation Therapy for Primary Cutaneous B-cell Lymphoma.

Primary cutaneous B-cell lymphoma (PCBCL) is a relatively rare disease, associated with 5-year overall survival of nearly 95% when treated with external beam radiation therapy (EBRT) alone. However, standard EBRT doses yield acute skin toxicity in more than 70% of patients and grade 3 to 4 acute skin toxicity in nearly 10% of patients. Consequently, the PCBCL treatment paradigm is shifting towards lower EBRT doses. This study evaluates our early experience with ultra-low dose EBRT (total dose of 4 Gy in 2 fractions) for PCBCL. Four biopsy-confirmed PCBCL lesions (1 anterior thigh and 3 chest) in 2 male patients were treated with 2 Gy×2 fraction EBRT using electrons through a clinical setup. The anterior thigh lesion was treated using a clamshell to protect the scrotum from scatter dose. Treatment was achieved using 9 MeV electrons to the 85% isodose line using no bolus, with follow-up every 4 months and potential retreatment if no visible response at 8 to 9 months. All lesions demonstrated a response to EBRT by 4 months, visibly manifesting as flattening with changes in pigmentation. At the last follow-up (20, 20, 16.5, and 4 mo, respectively), all lesions had flattened with no evidence of local recurrence and no skin toxicity. Treatment of PCBCL with ultra-low dose EBRT to 4 Gy total dose in 2 fractions provides durable local control with zero skin toxicity. These results are encouraging for both the success of treatment and the potential to use similarly low doses for retreatment should patients exhibit local recurrence.

The prognostic effect of tumor volume, reduction ratio, and cumulative doses on external beam radiotherapy with central-shielding method and image-guided adaptive brachytherapy for cervical cancer.

To evaluate the prognostic effect of tumor volume at diagnosis, tumor reduction ratio during external beam radiotherapy (EBRT) with central-shielding method, and cumulative minimal dose to 90% of the high-risk clinical target volume (CTVHR D90) on combined EBRT and image-guided adaptive brachytherapy (IGABT) for cervical cancer. Consecutive patients who underwent definitive radiotherapy or concurrent chemoradiotherapy for cervical cancer at Gunma University Hospital between January 2010 and December 2019 were retrospectively reviewed. Tumor volume at diagnosis and reduction ratio were calculated using magnetic resonance imaging at diagnosis and before the first IGABT session. The cumulative dose of EBRT and IGABT was calculated as an equivalent dose in 2 Gy fractions (EQD2). Optimal cutoff values were determined according to a receiver operating characteristic curve. Treatment outcomes were evaluated using the Kaplan-Meier method and compared using the log-rank test and Cox proportional hazards regression. A total of 254 patients were included in the analysis. The median follow-up for all patients was 57 (2-134) months. The 5-year overall survival (OS) was 81.9%, progression-free survival (PFS) was 71.3%, and local control (LC) was 94.5%. The patients were divided into four groups according to tumor volume at diagnosis and reduction ratio. The group with tumor volume at diagnosis ≥ 34.1 cm3 and reduction ratio < 68.8% showed significantly worse OS, PFS, and LC than the other three groups (All p < 0.05). In this group, the patients with a cumulative CTVHR D90 < 69.6 GyEQD2 showed significantly worse PFS and LC (p = 0.042 and p = 0.027, respectively). In the multivariate analysis of OS, adenocarcinoma/adenosquamous carcinoma, International Federation of Gynecology and Obstetrics 2009 stage III/IV, and a reduction ratio of < 68.8% were independent significant poor prognostic factors (p = 0.045, p = 0.009 and p = 0.001, respectively). In the univariate analysis of LC, a reduction ratio of < 68.8% was the only poor prognostic factor (p = 0.041). The patients with large and poorly responding tumors had significantly worse prognoses in terms of OS, PFS, and LC, suggesting that dose escalation should be considered for such tumors.

A Comparative Study of Clinical Outcomes in Locally Advanced Cervical Cancer: External Beam Radiotherapy (EBRT) and Sequential High Dose Rate Intracavitary Brachytherapy (HDRICBT) with or without Concurrent Cisplatin on the Day of ICBT Insertion - A Tertiary Care Center Randomized Controlled Trial in India.

The current study aimed to delve into the comparative clinical outcomes between external beam radiation therapy (EBRT) and sequential High Dose Rate Intracavitary Brachytherapy (HDRICBT) with or without concurrent cisplatin administration on the day of intracavitary brachytherapy (ICBT) insertion in women with locally advanced cervical cancer. In this study, conducted between January 2017 and July 2018 at a leading institute in India, diagnosed and untreated patients of locally advanced carcinoma cervix were randomized into two groups. Arm 1 received concurrent cisplatin before each course of brachytherapy, while Arm 2 underwent brachytherapy alone. The outcomes were compared in terms of acute and late toxicities, treatment response, and follow-up. Data analysis was performed using SPSS 16, with statistical significance set at p < 0.05. Both study arms showed similar complete response (CR) rates of 73.3%, with no significant advantage of concurrent cisplatin before brachytherapy. However, a noteworthy trend emerged during follow-up. In the concurrent cisplatin group, the CR rate increased from 73.3% post 1 month of brachytherapy to 86.7% at 3 months and 83.3% at 6 months. Contrastingly, the control group showed CR rates of 73.3% post 1 month, 80% at 3 months, and 76.6% at 6 months. While not statistically significant, this observation suggests a possible enhancement in response rates with concurrent cisplatin and ICBT. Future studies focusing on the optimal drug, dosage, scheduling, and combining cisplatin with other agents are recommended to further explore the potential benefits observed in this study.

Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): a randomised, double-blind, phase 3 clinical trial

Pembrolizumab has shown efficacy in persistent, recurrent, or metastatic cervical cancer. The effect of chemoradiotherapy might be enhanced by immunotherapy. In this phase 3 trial, we assessed the efficacy and safety of adding pembrolizumab to chemoradiotherapy in locally advanced cervical cancer. In this randomised, double-blind, placebo-controlled, phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 clinical trial, adults (age ≥18 years) at 176 medical centres in 30 countries with newly diagnosed, high-risk, locally advanced cervical cancer were randomly assigned (1:1) using an interactive voice-response system with integrated web response to receive 5 cycles of pembrolizumab (200 mg) or placebo every 3 weeks plus chemoradiotherapy, followed by 15 cycles of pembrolizumab (400 mg) or placebo every 6 weeks. Randomisation was stratified by planned external beam radiotherapy type (intensity-modulated radiotherapy or volumetric-modulated arc therapy vs non-intensity-modulated radiotherapy or non-volumetric-modulated arc therapy), cervical cancer stage at screening (International Federation of Gynecology and Obstetrics 2014 stage IB2-IIB node positive vs stage III-IVA), and planned total radiotherapy (external beam radiotherapy plus brachytherapy) dose (<70 Gy vs ≥70 Gy equivalent dose in 2 Gy fractions). Primary endpoints were progression-free survival per Response Evaluation Criteria in Solid Tumours version 1.1-by investigator or by histopathologic confirmation of suspected disease progression-and overall survival. Primary analysis was conducted in the intention-to-treat population, which included all randomly allocated participants. Safety was assessed in the as-treated population, which included all randomly allocated patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04221945, and is closed to new participants. Between June 9, 2020, and Dec 15, 2022, 1060 participants were randomly assigned to treatment, with 529 assigned to the pembrolizumab-chemoradiotherapy group and 531 to the placebo-chemoradiotherapy group. At data cutoff (Jan 9, 2023), median follow-up was 17·9 months (IQR 11·3-22·3) in both treatment groups. Median progression-free survival was not reached in either group; rates at 24 months were 68% in the pembrolizumab-chemoradiotherapy group versus 57% in the placebo-chemoradiotherapy group. The hazard ratio (HR) for disease progression or death was 0·70 (95% CI 0·55-0·89, p=0·0020), meeting the protocol-specified primary objective. Overall survival at 24 months was 87% in the pembrolizumab-chemoradiotherapy group and 81% in the placebo-chemoradiotherapy group (information fraction 42·9%). The HR for death was 0·73 (0·49-1·07); these data have not crossed the boundary of statistical significance. Grade 3 or higher adverse event rates were 75% in the pembrolizumab-chemoradiotherapy group and 69% in the placebo-chemoradiotherapy group. Pembrolizumab plus chemoradiotherapy significantly improved progression-free survival in patients with newly diagnosed, high-risk, locally advanced cervical cancer. Merck Sharp & Dohme, a subsidiary of Merck & Co (MSD).

Interstitial needles versus intracavitary applicators only for locally advanced cervical cancer: results from real-life dosimetric comparisons.

Image-guided adapted brachytherapy (IGABT) is superior to other radiotherapy techniques in the treatment of locally advanced cervical cancer (LACC). We aimed to investigate the benefit of interstitial needles (IN) for a combined intracavitary/interstitial (IC/IS) approach using IGABT over the intracavitary approach (IC) alone in patients with LACC after concomitant external beam radiotherapy (EBRT) and chemotherapy. We included consecutive patients with LACC who were treated with IC/IS IGABT after radiochemotherapy (RCT) in our retrospective, observational study. Dosimetric gain and sparing of organs at risk (OAR) were investigated by comparing the IC/IS IGABT plan with a simulated plan without needle use (IC IGABT plan) and the impact of other clinical factors on the benefit of IC/IS IGABT. Ninety-nine patients were analyzed, with a mean EBRT dose of 45.5 ± 1.7 Gy; 97 patients received concurrent chemotherapy. A significant increase in median D90% High Risk Clinical target volume (HR-CTV) was found for IC/IS (82.8 Gy) vs IC (76.2 Gy) (p < 10-4). A significant decrease of the delivered dose for all OAR was found for IC/IS vs IC for median D2cc to the bladder (77.2 Gy), rectum (68 Gy), sigmoid (53.2 Gy), and small bowel (47 Gy) (all p < 10-4). HR-CTV coverage was higher with IC/IS IGABT than with IC IGABT, with lower doses to the OAR in patients managed for LACC after RCT. Interstitial brachytherapy in the management of LACC after radiotherapy provides better coverage of the target volumes, this could contribute to better local control and improved survival of patients.

A Randomized Trial Comparing Quality of Life After Low-Dose Rate or High-Dose Rate Prostate Brachytherapy Boost With Pelvic External Beam Radiation Therapy

Purpose/ObjectivesTo compare health-related Quality of Life (QoL) in urinary, bowel and sexual domains after combined external beam radiotherapy (EBRT) and either low dose rate (LDR) or high dose rate (HDR) prostate brachytherapy (BT). Materials/MethodsEligible men with intermediate or high-risk prostate cancer, treated with combined pelvic EBRT and BT were randomly assigned to either HDR (15 Gy) or LDR (110 Gy) boost. International Prostate Symptom Score (IPSS), Index of Erectile Function (IIEF), Expanded Prostate Cancer Composite (EPIC-26) were collected at baseline, 1,3,6 and 12 months, q6 months to 3 years and then annually along with PSA/testosterone. Fisher's exact test compared categorical variables and the Mann Whitney U test EPIC domain scores. ResultsFrom 01/2014 to 12/2019, a random number generator assigned 195 men: 108 to HDR and 87 to LDR. Median age was 71 years. Risk group was high in 57% and unfavorable intermediate in 43%. Androgen deprivation (used in 74%) began with 3 months neoadjuvant and continued for median 12 months. Baseline EPIC scores were similar for the LDR/HDR cohorts: 89/88 for GU and 92/93 for GI. EPIC urinary scores decreased at one month for HDR but recovered promptly to a steady state by 6 months. LDR scores reached a nadir at 3 months with slow recovery to 18 months, after which urinary QoL was similar for HDR and LDR. Bowel QOL scores fell in both cohorts reaching respective nadirs at 12 months. HDR patients recovered close to baseline and maintained higher scores than LDR patients to 5 years. The decline for LDR patients remained > the MCID out to 5 years. ConclusionsPatient experience for combined EBRT and prostate BT is improved with HDR BT. Urinary QoL improves over time to be equivalent between the 2 modalities after 18 months, but LDR patients report lasting bowel symptoms.

TRImodal DEfinitive invasive vagiNal carcinoma Treatment (TRIDENT protocol): how a standardized approach may change prognostic outcomes

ObjectiveVaginal carcinoma is a rare malignancy accounting for 1–2% of all gynecological cancers. Surgery has a limited role, while definitive radiotherapy–chemotherapy followed by interventional radiotherapy is considered a valid alternative....

Practice and principles of stereotactic body radiation therapy for spine and non-spine bone metastases

Radiotherapy is the dominant treatment modality for painful spine and non-spine bone metastases (NSBM). Historically, this was achieved with conventional low dose external beam radiotherapy, however, stereotactic body radiotherapy (SBRT) is increasingly applied for these indications. Meta-analyses and randomized clinical trials have demonstrated improved pain response and more durable tumor control with SBRT for spine metastases. However, in the setting of NSBM, there is limited evidence supporting global adoption and large scale randomized clinical trials are in need. SBRT is technically demanding requiring careful consideration of organ at risk tolerance, and strict adherence to technical requirements including immobilization, simulation, contouring and image-guidance procedures. Additional considerations include follow up practices after SBRT, with appropriate imaging playing a critical role in response assessment. Finally, there is renewed research into promising new technologies that may further refine the use of SBRT in both spinal and NSBM in the years to come.

Online Adaptive Magnetic Resonance-guided Radiation Therapy for Gynaecological Cancers: Preliminary Results of Feasibility and Outcome

AimsTo present the preliminary results on the clinical utilisation of an online daily adaptive magnetic resonance-guided radiation therapy (MRgRT) for various gynaecological cancers. Materials and methodsTwelve patients treated between September 2018 and June 2022 were included. Six patients (50%) were treated with pelvic radiation therapy followed by MRgRT boost as brachytherapy boost was ineligible or unavailable, three patients (25%) were treated with pelvic MRgRT followed by high dose rate brachytherapy, two patients (16.7%) were treated with only MRgRT, one patient (8.3%) was treated with linear accelerator-based radiation therapy followed by MRgRT boost for bulky iliac lymph nodes. ResultsThe median age was 56.5 years (range 31–86 years). Eight patients (66.7%) had a complete response, three patients (25%) had a partial response and one patient (8.3%) died due to acute renal failure. The mean follow-up time was 11.2 months (range 3.1–42.6 months). The estimated 1-year overall survival was 88.9%. The median treatment time was 47 days (range 10–87 days). During external beam radiation therapy, 10 (83.3%) patients had concomitant chemoradiotherapy. Pelvic external beam radiation therapy doses for all cohorts were 45–50.4 Gy with a fraction dose of 1.8 Gy. The median magnetic resonance-guided boost dose was 32 Gy (range 20–50 Gy) and fraction doses ranged between 4 and 10 Gy. Three patients were treated with intracavitary high dose rate brachytherapy (26–28 Gy in four to five fractions). None of the patients had grade >3 late genitourinary toxicities. ConclusionMRgRT is reliable and clinically feasible for treating patients with gynaecological cancers alone or in combination with brachytherapy with an acceptable toxicity and outcome. MRgRT boost could be an option when brachytherapy is not available or ineligible.

Spatially Fractionated Radiation Therapy in Sarcomas: A Large Single-Institution Experience

ObjectiveSpatially fractionated radiation therapy (SFRT) is a recognized technique for enhancing tumor response in radioresistant and bulky tumors. We analyzed clinical and treatment outcomes in patients with bone and soft tissue sarcomas treated with modern SFRT techniques. MethodsPatients with metastatic and/or unresectable sarcoma treated with brass collimator, volumetric modulated arc therapy (VMAT) lattice, or proton SFRT from December 2019-June 2022 were retrospectively reviewed. Consolidative external beam radiation therapy (EBRT) was delivered at the physician's discretion. Patient and treatment characteristics, treatment response (symptom improvement, local control, and imaging response), and toxicity data were collected. ResultsThe cohort consisted of 53 patients treated with 61 SFRT treatments. Median age at treatment was 60.0 years. The primary location was soft tissue in 46 courses (75%) and bone in 15 (25%). Fifty-three courses (87%) were treated for symptom relief. The most utilized SFRT technique was VMAT lattice (n=52, 85%) to a dose of 20 Gy (n=48, 79%, range: 16-20 Gy). EBRT was delivered post-SFRT in 55 (90%) treatment courses with a median time interval from SFRT to EBRT of 5 days (range: 0-14 days). Median physical EBRT dose and fractionation was 40 Gy (range: 9-73.5 Gy) and 10 fractions (range: 3-33 fractions). Median follow up was 7.4 months (range: 0.2-30 months). One-year overall survival and local control rates were 53% and 82%. Symptom relief was documented with 32 treatment courses (60%). Stable or partial response was observed with 47 treatment courses (90%). Four grade 3-4 acute and subacute toxicities were attributable to SFRT (8%). ConclusionsThe current series is the largest to date documenting outcomes for SFRT in sarcomas. Our results suggest combined SFRT with EBRT is associated with a favorable toxicity profile and high rates of symptomatic and radiographic responses for metastatic and/or unresectable sarcomas.