Neoadjuvant hypofractionated radiotherapy and chemotherapy for extremity soft tissue sarcomas: Safety, feasibility, and early oncologic outcomes of a phase 2 trial.

BACKGROUND AND PURPOSE: Optimal treatment of extremity soft tissue sarcomas (ESTS) is controversial. The aim of this study was to evaluate neoadjuvant chemotherapy (ChT) plus concomitant hypofractionated RT (hypo-RT) in local and distant disease relapse. Here we report safety, feasibility and early outcomes. MATERIALS AND METHODS: This was a prospective, single arm study with a goal accrual of 70 patients. Between 2015 and 2018, 18 patients with histologically confirmed nonmetastatic ESTS were assigned to receive doxorubicin and ifosfamide for three neoadjuvant cycles, concomitant with hypo-RT (25 Gy in 5 fractions) followed by surgery. The primary endpoint was disease-free survival (DFS). Secondary outcomes were pathologic response, wound complications (WC), and morbidity rates. RESULTS: Median follow-up was 29 months. At last follow-up, 13/18 patients were alive without evidence of local or systemic disease (DFS 72%), 1 had died due to metastatic disease, and 3 were alive with distant metastasis. One patient presented with local relapse within the irradiated field. Mean DFS time was 48.6 months (95% CI: 37.3-59.9). Six patients (33%) had no residual viable tumor detected in pathologic specimens (3 of these myxoid liposarcomas). There was a significant difference in WC among patients with acute RT skin toxicity. Six patients (33%) developed major WC. No grade 3 or 4 ChT adverse events were reported. CONCLUSION: Despite the limited sample size, these early outcomes demonstrate that this treatment regimen is feasible and well tolerated with high rates of limb preservation, local control, and pathologic complete response, supporting further investigation in a multi-institutional setting. TRIAL REGISTRATION: ClinicalTrials.gov NCT02812654; https://clinicaltrials.gov/ct2/show/NCT02812654.

Prospective Assessment of the Association Between Circulating Tumor Cells and Control of Brain Disease After Focal Radiation Therapy of Breast Cancer Brain Metastases.

PURPOSE: Predicting the risk of early distant brain failure (DBF) is in demand for management decisions in patients who are candidates for local treatment of brain metastases. This study aimed to analyze the association between circulating tumor cells (CTCs) and brain disease control after stereotactic radiation therapy/radiosurgery (SRT) for breast cancer brain metastasis (BCBM). METHODS AND MATERIALS: We prospectively assessed CTCs before (CTC1) and 4 to 5 weeks after (CTC2) SRT and their relationship with the number of new lesions (NL) suggestive of BCBM before SRT. CTC were quantified and analyzed by immunocytochemistry to evaluate the expression of the proteins COX2, EGFR, ST6GALNAC5, NOTCH1, and HER2. Distant brain failure-free survival (DBFFS), the primary endpoint, diffuse DBFFS (D-DBFFS), and overall survival were estimated. Analysis for DBF within 6 months, with death as competing risk, was performed. RESULTS: Patients were included between 2016 and 2018. CTCs were detected in all 39 patients before and in 34 of 35 patients after SRT. After median follow-up of 16.6 months, median DBFFS, D-DBFFS, and overall survival were 15.3, 14.1, and 19.5 months, respectively. DBF at 6 months was 40% with CTC1 ≤0.5 and 8.82% with CTC1 >0.5 CTC/mL (P = .007), and D-DBF at 6 months was 40% with CTC1 ≤0.5 and 0 with CTC1 >0.5 CTC/mL (P = .005) and 25% with NL/CTC1 >6.8 and 2.65% with NL/CTC1 ≤6.8 (P = .063). On multivariate analysis, DBFFS was inferior with CTC1 ≤0.5 (hazard ratio, 8.27; 95% confidence interval, 2.12-32.3; P = .002), and D-DBFFS was inferior with CTC1 ≤0.5 (hazard ratio, 10.22; 95% confidence interval, 1.99-52.41; P = .005). Protein expression was not associated with outcomes. CONCLUSIONS: These data suggest that CTC1 and NL/CTC1 may have a role as a biomarker of early diffuse DBF and as a subsequent guide between focal or whole-brain radiation therapy in patients with BCBM.

HDR brachytherapy as monotherapy for prostate cancer: A systematic review with meta-analysis.

PURPOSE: The effectiveness and safety of high dose brachytherapy as monotherapy (HDR-BRT-M) in prostate cancer is limited to retrospective studies. We performed a meta-analysis to summarize existing data and identify trends in biochemical recurrence-free survival (bRFS) and toxicity after HDR-BRT-M in patients with prostate cancer. METHODS AND MATERIALS: Retrospective, prospective, or randomized clinical trials were identified on electronical databases through June 2020. We followed the PRISMA and MOOSE guidelines. A meta-regression analysis was performed to assess if there is a relationship between moderator variables and bRFS. A p-value < 0.05 was considered significant. RESULTS: Fourteen studies with a total of 3534 patients treated were included. The cumulative size of the bRFS at 5 years was 0.92 (95% confidence interval (CI) 0.48-0.61). The five-year bRFS for low, intermediate, and high risk was 97.5% (95% CI 96-98%), 93.5% (95% CI 91-96%), and 91% (95% CI 88-93%), respectively. The total biological effective dose (BED) (p = 0.02), the BED per fraction (p = 0.001), androgen deprivation therapy usage (p = 0.04), and the number of fractions of HDR-BRT-M (p = 0.024) were significantly associated with bRFS rate. The rate of late Grade 2/3 or > genitourinary and gastrointestinal toxicity was 22.4% (95% CI 9-35,2%)/1.4% (95% CI 0.8-2.1%) and 2.7% (95% CI 0-6.8%) and 0.2% (95% CI 0.1%-0.4%), respectively. CONCLUSIONS: HDR-BRT-M is safe with excellent rates of bRFS for all risk groups. The total BED, the BED per fraction, and number of fractions were the key factors associated with the biochemical control. These data can be useful to choose the size and number of BRT fractionation.

Three photobiomodulation protocols in the prevention/treatment of radiotherapy-induced oral mucositis.

PURPOSE: To compare three Photobiomodulation protocols to prevent/treat oral mucositis associated to radiotherapy. METHODS: Seventy-three patients with cancer in oral cavity, oropharynx, and nasopharynx, who underwent RT with dose in facial fields equal or higher than 6000 cGy were randomized into three groups (mean RT dose = 66 cGy ±4.9). Protocols of Group 1 was 660 nm, 15 mW, 3.8 J/cm2, Group 2 660 nm, 25 mW, 6.3 J/cm2 both starting on the first day of radiotherapy, and group 3 660 nm, 15 mW, 3.8 J/cm2 for therapeutic purpose. The patients of group 1 and 2 were irradiated at 40 points daily covering non-keratinizing oral mucosa. The spot size (probe's tip surface size) was 0.040 cm2 for all groups. Oral mucositis was evaluated according to both WHO and NCI scales, and pain related to oral mucositis was scored using the VAS. RESULTS: Patients from group 1 presented with grade II oral mucositis later than groups 2 and 3 (p < 0.001). Moreover, groups 2 and 3 also presented with a mean higher of oral mucositis grade than group 1, p < 0.001. Pain scores were lower in group 1 (p = 0.002). CONCLUSIONS: The Photobiomodulation used in Group 1 was more effective than the protocols used in groups 2 and 3 in controlling the grade II oral mucositis intensity, and mean pain scores.

Volumetric (3D) bladder dose parameters are more reproducible than point (2D) dose parameters in vaginal vault high-dose-rate brachytherapy.

There is no consensus on the use of computed tomography in vaginal cuff brachytherapy (VCB) planning. The purpose of this study was to prospectively determine the reproducibility of point bladder dose parameters (DICRU and maximum dose), compared with volumetric-based parameters. Twenty-two patients who were treated with high-dose-rate (HDR) VCB underwent simulation by computed tomography (CT-scan) with a Foley catheter at standard tension (position A) and extra tension (position B). CT-scan determined the bladder ICRU dose point in both positions and compared the displacement and recorded dose. Volumetric parameters (D0.1cc, D1.0cc, D2.0cc, D4.0cc and D50%) and point dose parameters were compared. The average spatial shift in ICRU dose point in the vertical, longitudinal and lateral directions was 2.91 mm (range: 0.10-9.00), 12.04 mm (range: 4.50-24.50) and 2.65 mm (range: 0.60-8.80), respectively. The DICRU ratio for positions A and B was 1.64 (p < 0.001). Moreover, a decrease in Dmax was observed (p = 0.016). Tension level of the urinary catheter did not affect the volumetric parameters. Our data suggest that point parameters (DICRU and Dmax) are not reproducible and are not the ideal choice for dose reporting.

Benefits of an intraoral stent in decreasing the irradiation dose to oral healthy tissue: dosimetric and clinical features.

OBJECTIVE: To determine whether an intraoral stent may decrease radiation dose to health tissues during intensity-modulated radiotherapy (IMRT) and to evaluate the effect on mucositis. STUDY DESIGN: A total of 33 patients with tongue or floor of the mouth cancer were retrospectively evaluated and divided into 2 groups: group 1 (with stent, n = 19) and group 2 (without stent, n = 14). Data were collected on dosimetric and mucositis outcomes. RESULTS: The mean dose to the maxilla was significantly lower in group 1 (20.9 Gy) than in group 2 (35.8 Gy) (P = .05). The mean dose to the ipsilateral parotid was 35.0 Gy in group 1 vs 41.8 Gy in group 2 (P = .05). No difference was seen in the severity of mucositis between groups (P = .82). However, grade III mucositis was present in group 1 at 4 weeks after IMRT, 1 week after its occurrence in group 2. CONCLUSIONS: A stent was effective in decreasing doses to healthy structures and delaying the emergence of mucositis.

Reirradiation of the eye with plaque brachytherapy: a single institution experience report of eight consecutive patients submitted to retreatment after local relapse of malignant disease of the eye.

PURPOSE: To evaluate the feasibility of reirradiation of the eye with plaque brachytherapy (REPBT) for local recurrence (LR) of malignant disease of the eye as an alternative to enucleation or other local salvage treatments. METHODS AND MATERIALS: It was performed a retrospective analysis of all patients who underwent REPBT for LR. The main parameters evaluated were local control and progression-free survival, besides the toxicity profile. RESULTS: There were eight patients who underwent REPBT, seven due to uveal melanoma and one due to retinoblastoma. The median time between the first plaque brachytherapy and the salvage plaque brachytherapy was 24 months (8-49 months). After a median followup of 30 months (8-70 months), the actuarial 2-year local control and progression-free survival was 87.5% and 60%, respectively. All patients evolved with worsening of the visual acuity and cataract. Other complications observed were maculopathy (two patients) and glaucoma (one patient). CONCLUSIONS: REPBT should be considered as an option for salvage therapy of LR of malignant disease of the eyes as it provides a high probability of tumor control and eye preservation without compromising disease-free survival.

Tumor control, eye preservation, and visual outcomes of ruthenium plaque brachytherapy for choroidal melanoma.

PURPOSE: To evaluate outcomes in patients with posterior choroidal melanoma treated with ruthenium ((106)Ru) brachytherapy. METHODS AND MATERIALS: A retrospective single institutional analysis of 83 of 94 consecutive patients who underwent (106)Ru brachytherapy was performed. Disease was mainly staged as small- and medium-sized nonmetastatic melanoma. The main parameters evaluated were tumor control (local control [LC] and progression-free survival [PFS]) and ocular preservation (enucleation-free survival [EFS]). Besides, functional evaluation was performed and complications were described. RESULTS: The median follow-up was 39 (6-83) months. The median values of height and maximal basal diameter were 4.3 and 9.3mm, respectively. Median apical and basal doses were 100 and 307Gy, respectively. The actuarial 2-year LC, PFS, and EFS were 96.2%, 96.2%, and 95.5%, respectively. Actuarial 5-year LC, PFS, and EFS were 93.6%, 93.6%, and 84.1%, respectively. Preinsertion visual acuity (VA) maintenance was 34% (equal or better than before treatment). Approximately 56% of patients stayed with a minimum functional VA of 0.1 or more, from whom more than half stayed with 0.5 or more. Cataract was seen in 16% of treated eyes, and glaucoma was the rarest complication, with an incidence of 3%. CONCLUSIONS: Small- and medium-sized choroidal melanomas can be adequately treated with (106)Ru brachytherapy, with high rates of tumor control and ocular preservation. Moreover, acceptable incidence of complications such as glaucoma and cataract are seen, and a reasonable part of patients stay with a minimum functional VA.