Intermediate-risk endometrial cancer treated with adjuvant brachytherapy using single dosimetric planning: long-term outcome and toxicity assessment.

OBJECTIVE: Brachytherapy of the vaginal dome is the recommended adjuvant treatment for intermediate-risk endometrial cancer. This study assessed the results of dosimetric planning of high-dose-rate brachytherapy exclusively in the first treatment session. STUDY DESIGN: This retrospective study included all patients who underwent hysterectomy for endometrial cancer followed by adjuvant brachytherapy of the vaginal dome between 2012 and 2015. Local recurrence rates, overall survival (OS) rates, recurrence-free survival (RFS) rates, and related acute and late toxicity rates were evaluated. RESULTS: This analysis included 250 patients, of whom 208 were considered to be at high-intermediate risk of disease recurrence. After a median follow-up of 56 months, the cumulative incidence of local recurrence was 4.8% at 3 years [95% confidence interval (CI) 2.8-8.3] and 7.8% at 5 years (95% CI 4.8-12.6). The 5-year OS rate was 86.2% (95% CI 80.6-90.3), and the 5-year RFS rate was 77.5% (95% CI 71.1-82.7). Acute toxicity occurred in 20 (8%) patients, of which two patients had grade ≥3 toxicity. Only one patient (0.4%) presented with late grade ≥3 toxicity. CONCLUSION: These findings confirm the tolerability of this brachytherapy approach, indicating minimal cases of late grade ≥3 toxicity, associated with a good 5-year OS rate. With the advent of molecular prognostic factors, the current focus revolves around discerning those individuals who gain the greatest benefit from adjuvant therapy, and tailoring treatment more effectively.

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

Background and purpose: 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. Materials and methods: 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. Results: 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). Conclusion: 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.

The Safety and Efficacy of Salvage Stereotactic Radiation Therapy in Patients with Intraprostatic Tumor Recurrence After Previous External Radiation Therapy: Phase 1 Results from the GETUG-AFU 31 Study.

BACKGROUND: There is no consensus on the best local salvage treatment for prostate cancer recurrence after primary external beam radiotherapy. Prospective data on stereotactic body radiation therapy (SBRT) are very scarce. OBJECTIVE: To determine the optimal dose regimen for salvage SBRT. DESIGN, SETTING, AND PARTICIPANTS: The present report concerns the phase 1 part of the GETUG-AFU 31 multicenter open-label study. The main inclusion criteria were histologically proven biochemical recurrence, clinical stage T1-T2 upon relapse, multiparametric magnetic resonance imaging data, prostate-specific antigen (PSA) level ≤10 ng/ml prior to salvage SBRT, PSA doubling time >10 mo, and an International Prostate Symptom Score of ≤12. INTERVENTION: Five or six fractions of 6 Gy were delivered using focal SBRT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Dose-limiting toxicity (DLT) was defined as grade ≥3 gastrointestinal or genitourinary tract toxicity, or any grade 4 toxicity (according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03) occurring in the first 18 wk following treatment initiation. A time-to-event continual reassessment method was used to select the dose regimen. RESULTS AND LIMITATIONS: Twenty-one patients were treated (median [interquartile range] age: 76.8 yr [72.2-80.8]), including 12 at 6 × 6 dose level. No DLT was observed. The acute grade 2 genitourinary tract toxicity rate was 19%. With a median follow-up of 12.3 mo, the estimated cumulative incidence of late grade 2 genitourinary toxicity was 41.2% (95% confidence interval: 18.1-63.1%). No grade >2 genitourinary toxicity and no grade ≥2 gastrointestinal toxicity were reported. All treated patients were alive and relapse free at the last follow-up. CONCLUSIONS: A 6 × 6 Gy dose regimen was selected for our phase 2 study of salvage SBRT. With a short follow-up period, the level of toxicity appears to be acceptable. PATIENT SUMMARY: There is no consensus on the best local treatment for patients with local relapse after radiotherapy for prostate cancer. Prospective data are very scarce. Our early phase trial allowed us to recommend six fractions of 6 Gy using high-precision radiotherapy for further studies.

Stereotactic Body Radiation Therapy for the Management of Hepatocellular Carcinoma: Efficacy and Safety.

This study aimed to describe patient characteristics, treatment efficacy, and safety in patients with hepatocellular carcinoma (HCC) undergoing stereotactic body radiation therapy (SBRT). We retrospectively analyzed data of 318 patients with 375 HCC treated between June 2007 and December 2018. Efficacy (overall survival [OS], relapse-free survival, and local control) and acute and late toxicities were described. The median follow-up period was 70.2 months. Most patients were treated with 45 Gy in three fractions. The median (range) PTV volume was 90.7 (2.6-1067.6) cc. The local control rate at 24 and 60 months was 94% (91-97%) and 94% (91-97%), respectively. Relapse-free survival at 12, 24, and 60 months was 62% (55-67%), 29% (23-36%), and 13% (8-19%), respectively. OS at 12, 24, and 60 months was 72% (95%CI 67-77%), 44% (38-50%), and 11% (7-15%), respectively. Approximately 51% and 38% experienced acute and late toxicity, respectively. Child-Pugh score B-C, high BCLC score, portal thrombosis, high GTV volume, and higher PTV volume reported on total hepatic volume ratio were significantly associated with OS. SBRT is efficient for the management of HCC with a favorable toxicity profile. The outcome is highly related to the natural evolution of the underlying cirrhosis.

Studies of Intra-Fraction Prostate Motion During Stereotactic Irradiation in First Irradiation and Re-Irradiation.

BACKGROUND: Understanding intra-fractional prostate motions is crucial for stereotactic body radiation therapy (SBRT). No studies have focused on the intra-fractional prostate motions during re-irradiation with SBRT. The objective was to evaluate these translational and rotational motions in primary treated patients and in the context of re-irradiation. METHODS: From January 2011 to March 2020, 162 patients with histologically proven prostate cancer underwent prostate SBRT, including 58 as part of a re-irradiation treatment. We used the continuous coordinates of the fiducial markers collected by an orthogonal X-ray dual-image monitoring system. The translations and rotations of the prostate were calculated. Prostate deviations representing overall movement was defined as the length of the 3D-vectors. RESULTS: A total of 858 data files were analyzed. The deviations over time in the group of primary treated patients were significantly larger than that of the group of re-irradiation, leading to a mean deviation of 2.73 mm (SD =1.00) versus 1.90 mm (SD =0.79), P<0.001. In the re-irradiation group, we identified displacements of -0.05 mm (SD =1.53), 0.20 mm (SD =1.46); and 0.42 mm (SD =1.24) in the left-right, superior-inferior and anterior-posterior planes. Overall, we observed increasing deviations over the first 30 min followed by a stabilization related to movements in the three translational axes. CONCLUSION: This is the first study to focus on intrafraction prostate motions in the context of re-irradiation. We observed that intra-fraction prostate motions persisted in the setting of re-irradiation, although they showed a significant reduction when compared with the first irradiation. These results will help to better estimate random errors during SBRT treatment of intra-prostatic recurrence after irradiation.

Real-time mechanical characterization of DNA degradation under therapeutic X-rays and its theoretical modeling.

The killing of tumor cells by ionizing radiation beams in cancer radiotherapy is currently based on a rather empirical understanding of the basic mechanisms and effectiveness of DNA damage by radiation. By contrast, the mechanical behaviour of DNA encompassing sequence sensitivity and elastic transitions to plastic responses is much better understood. A novel approach is proposed here based on a micromechanical Silicon Nanotweezers device. This instrument allows the detailed biomechanical characterization of a DNA bundle exposed to an ionizing radiation beam delivered here by a therapeutic linear particle accelerator (LINAC). The micromechanical device endures the harsh environment of radiation beams and still retains molecular-level detection accuracy. In this study, the first real-time observation of DNA damage by ionizing radiation is demonstrated. The DNA bundle degradation is detected by the micromechanical device as a reduction of the bundle stiffness, and a theoretical model provides an interpretation of the results. These first real-time observations pave the way for both fundamental and clinical studies of DNA degradation mechanisms under ionizing radiation for improved tumor treatment.

Multi institutional phase II study of concomitant stereotactic reirradiation and cetuximab for recurrent head and neck cancer.

PURPOSE: Recurrent head and neck cancer is associated to a poor survival prognosis. A high toxicity rate is demonstrated when surgery and/or radiotherapy and/or chemotherapy are combined. Furthermore, the duration of treatment is often not ethically compatible with the expected survival (median survival<1year). Normal tissues tolerance limits the use of reirradiation and stereotactic body radiotherapy (SBRT) could offer precise irradiation while sparing healthy tissues. After completion of a feasibility study, results of a multicentric study (Lille, Nancy & Nice) using SBRT with cetuximab are reported. The aim of the study was to deliver non toxic short course SBRT (2weeks) in order to get the same local control as the one demonstrated with longer protocols. METHODS AND MATERIALS: Patients with inoperable recurrent, or new primary tumor in a previously irradiated area, were included (WHO<3). Reirradiation (RT) dose was 36Gy in six fractions of 6Gy to the 85% isodose line covering 95% of the PTV with 5 injections of concomitant cetuximab (CT). All patients had previous radiotherapy, 85% had previous surgery and 48% previous chemotherapy. RESULTS: Between 11/2007 and 08/2010, 60 were included (46 men and 14 women), 56 received CT+RT, 3 were not treated and 1 received only CT. Median age was 60 (42-87)) and all 56 patients had squamous carcinoma and received concomitant cetuximab. Mean time between previous radiotherapy and the start of SBRT was 38months. Cutaneous toxicity was observed for 41 patients. There was one toxic death from hemorrhage and denutrition. Median follow-up was 11.4months. At 3months, response rate was 58.4% (95% CI: 43.2-72.4%) and disease control rate was 91.7% (95% CI: 80.0-97.7%). The one-year OS rate was 47.5% (95% CI: 30.8-62.4). CONCLUSION: These results suggest that short SBRT with cetuximab is an effective salvage treatment with good response rate in this poor prognosis population with previously irradiated HNC. Treatment is feasible and, with appropriate care to limiting critical structure, acute toxicities are acceptable. This combination may be the reference treatment is this population.

Salvage stereotactic reirradiation with or without cetuximab for locally recurrent head-and-neck cancer: a feasibility study.

PURPOSE: Normal tissues tolerance limits the use of reirradiation for recurrent head-and-neck cancers (HNC). Stereotactic body radiotherapy (SBRT) could offer precise irradiation while sparing healthy tissues. Results of a feasibility study using SBRT with or without cetuximab are reported for reirradiation of recurrent primary HNC. METHODS AND MATERIALS: Patients with inoperable recurrent, or new primary tumor, in a previously irradiated area were included. Reirradiation dose was 36 Gy in six fractions of 6 Gy to the 85% isodose line covering 95% of the planning target volume. Patients with squamous cell carcinoma received concomitant cetuximab. RESULTS: Between June 2007 and January 2010, 40 patients were prospectively treated for 43 lesions. Median age was 60 and median tumor size was 29 mm. Fifteen patients received concomitant cetuximab and 1 received concomitant cisplatin. Median follow-up was 25.6 months with 34 patients evaluable for tumor response. Median overall survival was 13.6 months and response rate was 79.4% (15 complete and 12 partial responses). Grade 3 toxicity occurred in 4 patients. CONCLUSION: These results suggest that short SBRT with or without cetuximab is an effective salvage treatment with good response rate in this poor prognosis population with previously irradiated HNC. Treatment is feasible and, with appropriate care to limiting critical structure, acute toxicities are acceptable. A prospective multicenter Phase II trial of SRT and concomitant cetuximab in recurrent HNC squamous cell carcinoma is ongoing.