Combined intra-cavitary and interstitial image-guided adaptative brachytherapy for cervical stump carcinomas: technical and clinical results of six patients.

Purpose: According to European guidelines for cervix cancers, the management of cervical stump cancers should follow recommendations for patients without previous sub-total hysterectomy, but may require adaptation of radiotherapy modalities, especially brachytherapy (BT). However, data with modern BT technics are very scarce. Material and methods: From May 2013 to March 2020, 6 patients (age range, 71-88 years) with cervical stump squamous cell carcinoma (previously treated by sub-total hysterectomy) have been treated with external beam radiotherapy (intensity-modulated radiation therapy - IMRT, 45 Gy in 25 fractions, 5 patients, or 50.4 Gy in 28 fractions, 1 patient), with concomitant chemotherapy in 2 patients, followed by image-guided adaptive brachytherapy with pulsed-dose-rate in 5 patients or high-dose-rate in 1 patient. We used Utrecht BT applicator (Elekta®), with the implant of interstitial needles within the parametrium (unilaterally in 3 and bilaterally in 3 patients), and/or within the residual cervix (3 patients). Dosimetry was based on GEC-ESTRO recommendations. Results: The median high-risk (HR) and intermediate-risk (IR) clinical target volumes (CTV) were 14.5 cc (range, 12-35 cc) and 40 cc (range, 31-62 cc), respectively. The median dose (D90) delivered to HR and IR CTVs were 81.2 (range, 78.2-89.8) and 68.95 (range, 64.3-72.3) Gy EQD2, respectively. With a 26.5 months median follow-up (range, 10-92 months), we did not observe any local or distant recurrence. No grade 2 or more acute or late toxicities were reported. Conclusions: Cervix brachytherapy with Utrecht applicator using interstitial needle is safe and effective in cervical stump cancer patients.

Minimum non-isotropic and asymmetric margins for taking into account intrafraction prostate motion during moderately hypofractionated radiotherapy.

PURPOSE: To investigate the impact on dose distribution of intrafraction motion during moderate hypofractionated prostate cancer treatments and to estimate minimum non-isotropic and asymmetric (NI-AS) treatment margins taking motion into account. METHODS: Prostate intrafraction 3D displacements were recorded with a transperineal ultrasound probe and were evaluated in 46 prostate cancer patients (876 fractions) treated by moderate hypofractionated radiation therapy (60 Gy in 20 fractions). For 18 patients (346 fractions), treatment plans were recomputed increasing CTV-to-PTV margins from 0 to 6 mm with an auto-planning optimization algorithm. Dose distribution was estimated using the voxel shifting method by displacing CTV structure according to the retrieved movements. Time-dependent margins were finally calculated using both van Herk's formula and the voxel shifting method. RESULTS: Mean intrafraction prostate displacements observed were -0.02 ± 0.52 mm, 0.27 ± 0.78 mm and -0.43 ± 1.06 mm in left-right, supero-inferior and antero-posterior directions, respectively. The CTV dosimetric coverage increased with increased CTV-to-PTV margins but it decreased with time. Hence using van Herk's formula, after 7 min of treatment, a margin of 0.4 and 0.5 mm was needed in left and right, 1.5 and 0.7 mm in inferior and superior and 1.1 and 3.2 mm in anterior and posterior directions, respectively. Conversely, using the voxel shifting method, a margin of 0 mm was needed in left-right, 2 mm in superior, 3 mm in inferior and anterior and 5 mm in posterior directions, respectively. With this latter NI-AS margin strategy, the dosimetric target coverage was equivalent to the one obtained with a 5 mm homogeneous margin. CONCLUSIONS: NI-AS margins would be required to optimally take into account intrafraction motion.

Eligibility criteria according to EAU/ESTRO/SIOG guidelines for exclusive iodine-125 brachytherapy for intermediate-risk prostate adenocarcinoma patients: impact on relapse-free survival.

PURPOSE: Iodine-125 (125I) brachytherapy (BT) alone for intermediate-risk (IR) prostate adenocarcinoma (PCA) is controversial. The purpose of the study was to investigate potential predictive factors in selected IR-PCA patients treated with BT. MATERIAL AND METHODS: Among 547 patients treated with 125I BT between 2003 and 2013, 149 IR-PCA cases were selected according to NCCN classification after an additional exclusion of patients with prostate specific antigen (PSA) > 15 ng/ml and ISUP group 3. A relapse was defined as a biochemical failure, using ASTRO Phoenix definition, or a relapse identified on imaging. Survival curves were estimated with Kaplan-Meier method. Potential prognostic variables including EAU/ESTRO/SIOG guidelines eligibility criteria were analyzed using univariate and Cox's proportional hazards regression analysis. RESULTS: Of the 149 IR patients, 112 were classified as favorable, with 69 cases eligible to BT according to EAU/ESTRO/SIOG guidelines, and 37 patients were identified as unfavorable as per NCCN. Androgen deprivation therapy (ADT) was applied in 6 patients only. Percentage of positive biopsy cores were ≤ 33% and ≥ 50% for 119 and 11 patients, respectively. With a median follow-up of 8.5 years, 30 patients experienced a relapse. 10-year overall survival, progression-free survival (PFS), and relapse-free survival (RFS) were 84% (95% CI: 75-90%), 66% (95% CI: 56-75%), and 77% (95% CI: 67-84%), respectively. Failure to meet EAU/ESTRO/SIOG criteria was significantly associated with a lower RFS (p = 0.0267, HR = 2.37 [95% CI: 1.10-5.08%]). CONCLUSIONS: Brachytherapy is an effective treatment for selected IR-PCA cases. Patients who were not eligible according to EAU/ESTRO/SIOG guidelines demonstrated a lower RFS.

Salvage brachytherapy with or without external beam radiotherapy for oral or oropharyngeal squamous cell carcinomas in previously irradiated areas: carcinologic and toxicity outcomes of 25 patients.

PURPOSE: The aim of this study was to assess outcomes of salvage brachytherapy for oral and oropharyngeal squamous cell carcinoma in previously irradiated areas. MATERIAL AND METHODS: This was a retrospective study with 25 patients, treated between 1997 and 2016 for primary (21 cases) or recurrent (4 cases) oral or oropharyngeal squamous cell carcinomas in previously irradiated areas. Fifteen patients were treated with salvage brachytherapy (BT) alone, while 10 patients additionally received external beam radiotherapy (EBRT). Median BT dose was 45 Gy (range, 15-64 Gy), and a median total cumulative dose was 57 Gy (range, 40-70 Gy). Patient age, tumor stage, radiotherapy dose, and time between first treatment and recurrence were analyzed as prognostic factors. RESULTS: Median overall survival (OS) was 16 months. Patients with less advanced (T1) tumors survived significantly longer (27 vs. 14.5 months, p = 0.046). Five patients experienced a local recurrence, and only one of them was treated with a total dose greater than 60 Gy. In multivariate analysis, patients with T1 lesions had a significant higher OS rate compared to patients with larger lesions (HR = 6.25, 95% CI: 1.18-33.1%, p = 0.031). Patients who received more than 60 Gy had a non-significant, 80% increased OS than those treated with a lower dose (p = 0.072). There was four grade 3 acute toxicities, and no grade 3 or more late toxicities. CONCLUSIONS: Multimodal treatment, including salvage BT, may offer a curative option for selected patients with an acceptable risk of severe toxicity for the treatment of primary or recurrent tumors in previously irradiated areas.

Evaluation of fully automated a priori MCO treatment planning in VMAT for head-and-neck cancer.

PURPOSE: Automated planning techniques aim to reduce manual planning time and inter-operator variability without compromising the plan quality which is particularly challenging for head-and-neck (HN) cancer radiotherapy. The objective of this study was to evaluate the performance of an a priori-multicriteria plan optimization algorithm on a cohort of HN patients. METHODS: A total of 14 nasopharyngeal carcinoma (upper-HN) and 14 "middle-lower indications" (lower-HN) previously treated in our institution were enrolled in this study. Automatically generated plans (autoVMAT) were compared to manual VMAT or Helical Tomotherapy planning (manVMAT-HT) by assessing differences in dose delivered to targets and organs at risk (OARs), calculating plan quality indexes (PQIs) and performing blinded comparisons by clinicians. Quality control of the plans and measurements of the delivery times were also performed. RESULTS: For the 14 lower-HN patients, with equivalent planning target volume (PTV) dosimetric criteria and dose homogeneity, significant decrease in the mean doses to the oral cavity, esophagus, trachea and larynx were observed for autoVMAT compared to manVMAT-HT. Regarding the 14 upper-HN cases, the PTV coverage was generally significantly superior for autoVMAT which was also confirmed with higher calculated PQIs on PTVs for 13 out of 14 patients, whereas PQIs calculated on OARs were generally equivalent. Number of MUs and total delivery time were significantly higher for autoVMAT compared to manVMAT. All plans were considered clinically acceptable by clinicians. CONCLUSIONS: Overall superiority of autoVMAT compared to manVMAT-HT plans was demonstrated for HN cancer. The obtained plans were operator-independent and required no post-optimization or manual intervention.

Salvage low-dose-rate brachytherapy for local recurrences after prostatectomy and adjuvant or salvage external beam irradiation: Feasibility study on five patients and literature review.

PURPOSE: To assess the feasibility and tumor outcome of re-irradiation with low-dose-rate brachytherapy for macroscopic local recurrences after radical prostatectomy (RP) followed by adjuvant or salvage external beam radiation therapy (EBRT). METHODS AND MATERIALS: Between 2011 and 2018, five men with histologically proven local failure within the prostate (4) or seminal vesicle bed (1) after RP and adjuvant or salvage EBRT (median dose: 67.5 Gy) underwent a salvage brachytherapy (S-BT). The median delay after EBRT was 86 months (range 75-234). Two patients were castration-resistant at the time of S-BT. The gross tumor volume was defined on a multiparametric MRI and transrectal US imaging. Echo-guided transperineal implants of Iodine-125 seeds were optimized with a per-operative dosimetry and delivered with the seed-selectron. RESULTS: A high conformity was achieved with a high dose to the CTV (D95% > 145 Gy in all but one) and very low dose to the rectum, urethra, and bladder. With a median followup of 21 months, all but one patient experienced nodes and/or bone metastases. Local control was achieved in 3/4 of evaluable patients (local failure distant to the treated volume in one). To date, no Grade 2 or more late toxicities were observed. CONCLUSION: For selected patients, focal local recurrence brachytherapy after PR and EBRT appears technically feasible and safe, but the efficacy remains uncertain as the majority of patients quickly relapsed at other sites. Large prospective studies are still required to better select patients who will benefit from this strategy.

A comparison of two modalities of stereotactic body radiation therapy for peripheral early-stage non-small cell lung cancer: results of a prospective French study.

OBJECTIVES: This prospective, observational, non-randomized multicentric study was conducted to compare efficiency and toxicity using different modalities of stereotactic body radiation therapy (SBRT) in early-stage peripheral non-small cell lung cancer (NSCLC). METHODS: From 9 April to 11 December, 106 patients were treated according to the local equipment availability for peripheral NSCLC with SBRT: 68 by linear accelerator equipped for SBRT and 38 by Cyberknife®. Multivariate analysis and propensity score analysis using Inverse Probability Treatment Weighting (IPTW) were undertaken in an effort to adjust for potential bias due to non-randomization. RESULTS: 2-year local control rates were 97.0% (95% CI: [90.6%; 99.4%]) with SBRT by Linac vs 100% (95% CI: ([100%; 100%]) with Cyberknife® (p = 0.2839). 2-year PFS and 2-year OS rates were 52.7% (95% CI [39.9%;64.0%]) versus 54.1% (95% CI [36.8; 68.6%]) (p = 0.8582) and 65.1% (95% CI: [51.9%; 75.5%] versus 83.9% (95% CI: [67.5%; 92.4%] (p = 0.0831) using Linac and Cyberknife® respectively. Multivariate regression analysis indicates no significant effect of SBRT treatment type on PFS or OS. Local relapse could not be modeled due to the small number of events (n = 2). Acute and late toxicity rates were not significantly different. After IPTW adjustment, results were unchanged. CONCLUSIONS: No difference in efficiency or toxicity was shown after SBRT of peripheral NSCLC treatment using Linac or Cyberknife®. ADVANCES IN KNOWLEDGE: This is the first large prospective non-randomized study focusing on peripheral localized NSCLC comparing SBRT using an appropriately equipped linac with Cyberknife®. No significant difference in efficiency or toxicity was shown in this situation.

Comparison among four immobilization devices for whole breast irradiation with Helical Tomotherapy.

PURPOSE: To evaluate the repositioning accuracy of 4 immobilization devices (ID) used for whole breast Helical Tomotherapy treatments: arm float with VacFix® (Par Scientific, Denmark), all-in-one® (AIO®) system (Orfit, Belgium), MacroCast thermoplastic mask (Macromedics, The Netherlands) and BlueBag® system with Arm-Shuttle (Elekta, Sweden). MATERIALS AND METHODS: Twenty four women with breast cancer with PTV including the breast/chest wall and lymph nodes were involved in this study (6 women per group). Pretreatment registration results were first collected using automatic bone registration + manual adjustment on the vertebra followed by independent registrations on different ROIs representing each treated area (axillary, mammary chain, clavicular, breast/chest wall). The differences in translations and rotations between reference registration and the above mentionned ROIs were calculated. A total of 120 MVCT images were analyzed. RESULTS: Significant differences were found between IDs (p < 0.0001), ROIs (p = 0.0002) and the session number (p < 0.0001) on the observed shifts, when examining 3D translation vectors. 3D-vectors were significantly lower for the BlueBag® than for the VacFix® or for the AIO® (p < 0.0001), but differences were not significant compared to the mask (p = 0.674). Finally, setup margins were overall smaller for the BlueBag® than for other IDs, with values ranging from 1.53 to 1.91 mm on the mammary chain area, 4.52-6.07 mm on the clavicular area, 2.71-4.62 mm on the axillary area, and 3.39-5.10 mm on the breast. CONCLUSION: We demonstrated in this study that the BlueBag® combined with arm shuttle is a robust solution for breast and nodes immobilization during HT treatments.

Comparison between two treatment planning systems for volumetric modulated arc therapy optimization for prostate cancer.

PURPOSE: To investigate the performances of two commercial treatment planning systems (TPS) for Volumetric Modulated Arc Therapy (VMAT) optimization regarding prostate cancer. The TPS were compared in terms of dose distributions, treatment delivery parameters and quality control results. MATERIALS AND METHODS: For ten patients, two VMAT plans were generated: one with Monaco TPS (Elekta) and one with Pinnacle TPS (Philips Medical Systems). The total prescribed dose was 78 Gy delivered in one 360° arc with a Synergy(®) linear accelerator equipped with a MLCi2(®). RESULTS: VMAT with Monaco provided better homogeneity and conformity indexes but lower mean dose to PTVs than Pinnacle. For the bladder wall (p = 0.019), the femoral heads (p = 0.017), and healthy tissues (p = 0.005), significantly lower mean doses were found using Monaco. For the rectal wall, VMAT with Pinnacle provided a significantly (p = 0.047) lower mean dose, and lower dose into 50% of the volume (p = 0.047) compared to Monaco. Despite a greater number of monitor units (factor 1.5) for Monaco TPS, the total treatment time was equivalent to that of Pinnacle. The treatment delivery parameter analysis showed larger mean MLC area for Pinnacle and lower mean dose rate compared to Monaco. The quality control results gave a high passing rate (>97.4%) for the gamma index for both TPS but Monaco provided slightly better results. CONCLUSION: For prostate cancer patients, VMAT treatment plans obtained with Monaco and Pinnacle offered clinically acceptable dose distributions. Further investigations are in progress to confirm the performances of the two TPS for irradiating more complex volumes.

Permanent 125I-seed prostate brachytherapy: early prostate specific antigen value as a predictor of PSA bounce occurrence.

PURPOSE: To evaluate predictive factors for PSA bounce after 125I permanent seed prostate brachytherapy and identify criteria that distinguish between benign bounces and biochemical relapses. MATERIALS AND METHODS: Men treated with exclusive permanent 125I seed brachytherapy from November 1999, with at least a 36 months follow-up were included. Bounce was defined as an increase ≥ 0.2 ng/ml above the nadir, followed by a spontaneous return to the nadir. Biochemical failure (BF) was defined using the criteria of the Phoenix conference: nadir +2 ng/ml. RESULTS: 198 men were included. After a median follow-up of 63.9 months, 21 patients experienced a BF, and 35.9% had at least one bounce which occurred after a median period of 17 months after implantation (4-50). Bounce amplitude was 0.6 ng/ml (0.2-5.1), and duration was 13.6 months (4.0-44.9). In 12.5%, bounce magnitude exceeded the threshold defining BF. Age at the time of treatment and high PSA level assessed at 6 weeks were significantly correlated with bounce but not with BF. Bounce patients had a higher BF free survival than the others (100% versus 92%, p = 0,007). In case of PSA increase, PSA doubling time and velocity were not significantly different between bounce and BF patients. Bounces occurred significantly earlier than relapses and than nadir + 0.2 ng/ml in BF patients (17 vs 27.8 months, p < 0.0001). CONCLUSION: High PSA value assessed 6 weeks after brachytherapy and young age were significantly associated to a higher risk of bounces but not to BF. Long delays between brachytherapy and PSA increase are more indicative of BF.

Head and neck sarcoma: report of a case treated by intensity-modulated radiation therapy.

We report on a 71-year-old woman with parapharyngeal sarcoma. Surgery could not be performed because of the size and location of the tumor. After failure of four cycles of chemotherapy, intensity-modulated radiation therapy (IMRT) achieved complete clinical response and partial magnetic resonance imaging response (80%) at 24 months of follow-up. The results of radiotherapy, especially IMRT, for nonresectable head and neck soft tissue sarcoma are discussed.