Long-Term Results of Intraoperative Radiation Therapy for Early Breast Cancer Using a Nondedicated Linear Accelerator.

Purpose: To present the long-term results of intraoperative radiation therapy (IORT) for early breast cancer using a nondedicated linear accelerator. Methods and Materials: The eligibility criteria were biopsy-proven invasive carcinoma, age ≥40 years, tumor size ≤3 cm, and N0M0. We excluded multifocal lesions and sentinel lymph node involvement. All patients had previously undergone breast magnetic resonance imaging. Breast-conserving surgery with margins and sentinel lymph node evaluation using frozen sections were performed in all cases. If there were no margins or involved sentinel lymph nodes, the patient was transferred from the operative suite to the linear accelerator room, where IORT was delivered (21 Gy). Results: A total of 209 patients who were followed up for ≥1.5 years from 2004 to 2019 were included. The median age was 60.3 years (range, 40-88.6), and the mean pT was 1.3 cm (range, 0.2-4). There were 90.5% pN0 cases (7.2% of micrometastases and 1.9% of macrometastases). Ninety-seven percent of the cases were margin free. The rate of lymphovascular invasion was 10.6%. Twelve patients were negative for hormonal receptors, and 28 patients were HER2 positive. The median Ki-67 index was 29% (range, 0.1-85). Intrinsic subtype stratification was as follows: luminal A, 62.7% (n = 131); luminal B, 19.1% (n = 40); HER2 enriched 13.4% (n = 28); and triple negative, 4.8% (n = 10). Within the median follow-up of 145 months (range, 12.8-187.1), the 5-year, 10-year, and 15-year overall survival rates were 98%, 94.7%, and 88%, respectively. The 5-year, 10-year, and 15-year disease-free rates were 96.3%, 90%, and 75.6%, respectively. The 15-year local recurrence-free rate was 76%. Fifteen local recurrences (7.2%) occurred throughout the follow-up period. The mean time to local recurrence was 145 months (range, 12.8-187.1). As a first event, 3 cases of lymph node recurrence, 3 cases of distant metastasis, and 2 cancer-related deaths were recorded. Tumor size >1 cm, grade III, and lymphovascular invasion were identified as risk factors. Conclusions: Despite approximately 7% of recurrences, we may infer that IORT may still be a reasonable option for selected cases. However, these patients require a longer follow-up as recurrences may occur after 10 years.

Radiosurgery for multiple brain metastases using volumetric modulated arc therapy: a single institutional series.

Background: Patients with brain metastases (BM) live longer due to improved diagnosis and oncologic treatments. The association of volumetric modulated arc therapy (VMAT) and image-guided radiation therapy (IGRT) with brain radiosurgery (SRS) allows complex dose distributions and faster treatment delivery to multiple lesions. Materials and methods: This study is a retrospective analysis of SRS for brain metastasis using VMAT. The primary endpoints were local disease-free survival (LDFS) and overall survival (OS). The secondary outcomes were intracranial disease-free survival (IDFS) and meningeal disease-free survival (MDFS). Results: The average number of treated lesions was 5.79 (range: 2-20) per treatment in a total of 113 patients. The mean prescribed dose was 18 Gy (range: 12-24 Gy). The median LDFS was 46 months. The LDFS in 6, 12, and 24 months was for 86%, 79%, and 63%, respectively. Moreover, brain progression occurred in 50 patients. The median overall survival was 47 months. The OS in 75%, 69%, and 61% patients was 6, 12, and 24 months, respectively. IDFS was 6 and 24 months in 35% and 14% patients, respectively. The mean MDFS was 62 months; it was 6 and 24 months for 87% and 83% of patients. Acute severe toxicity was relatively rare. During follow-up, the rates of radionecrosis and neurocognitive impairment were low (10%). Conclusion: The use of VMAT-SRS for multiple BM was feasible, effective, and associated with low treatment-related toxicity rates. Thus, treatment with VMAT is a safe technique to plan to achieve local control without toxicity.

Prostate brachytherapy with iodine-125 seeds: analysis of a single institutional cohort.

OBJECTIVES: Brachytherapy (BT) with iodine-125 seeds placement is a consolidated treatment for prostate cancer. The objective of this study was to assess the clinical outcomes in patients with prostate cancer who underwent low-dose-rate (LDR) -BT alone in a single Brazilian institution. MATERIALS AND METHODS: Patients treated with iodine-125 BT were retrospectively assessed after at least 5 years of follow-up. Patients who received combination therapy (External beam radiation therapy-EBRT and BT) and salvage BT were not included. RESULTS: 406 men were included in the study (65.5% low-risk, 30% intermediate-risk, and 4.5% high-risk patients). After a median follow-up of 87.5 months, 61 (15.0%) patients developed biochemical recurrence. The actuarial biochemical failure-free survival (BFFS) at 5 and 10 years were 90.6% and 82.2%, respectively. A PSA nadir ≥ 1 ng / mL was associated with a higher risk of biochemical failure (HR = 5.81; 95% CI: 3.39 to 9.94; p ≤ 0.001). The actuarial metastasis-free survival (MFS) at 5 and 10 years were 98.3% and 94%, respectively. The actuarial overall survival (OS) at 5 and 10 years were 96.2% and 85.1%, respectively. Acute and late grade 2 and 3 gastrointestinal toxicities were observed in 5.6%, 0.5%, 4.6% and 0.5% of cases, respectively. For genitourinary the observed acute and late grade 2 and 3 toxicities rates were 57.3%, 3.6%, 28% and 3.1%, respectively. No grade 4 and 5 were observed. CONCLUSIONS: BT was effective as a definitive treatment modality for prostate cancer, and its endpoints and toxicities were comparable to those of the main series in the literature.

Incidental irradiation of internal mammary lymph nodes in breast cancer: conventional two-dimensional radiotherapy versus conformal three-dimensional radiotherapy.

OBJECTIVE: To evaluate incidental irradiation of the internal mammary lymph nodes (IMLNs) through opposed tangential fields with conventional two-dimensional (2D) or three-dimensional (3D) radiotherapy techniques and to compare the results between the two techniques. MATERIALS AND METHODS: This was a retrospective study of 80 breast cancer patients in whom radiotherapy of the IMLNs was not indicated: 40 underwent 2D radiotherapy with computed tomography for dosimetric control, and 40 underwent 3D radiotherapy. The total prescribed dose was 50.0 Gy or 50.4 Gy (2.0 or 1.8 Gy/day, respectively). We reviewed all plans and defined the IMLNs following the Radiation Therapy Oncology Group recommendations. For the IMLNs, we analyzed the proportion of the volume that received 45 Gy, the proportion of the volume that received 25 Gy, the dose to 95% of the volume, the dose to 50% of the volume, the mean dose, the minimum dose (Dmin), and the maximum dose (Dmax). RESULTS: Left-sided treatments predominated in the 3D cohort. There were no differences between the 2D and 3D cohorts regarding tumor stage, type of surgery (mastectomy, breast-conserving surgery, or mastectomy with immediate reconstruction), or mean delineated IMLN volume (6.8 vs. 5.9 mL; p = 0.411). Except for the Dmin, all dosimetric parameters presented higher mean values in the 3D cohort (p < 0.05). The median Dmax in the 3D cohort was 50.34 Gy. However, the mean dose to the IMLNs was 7.93 Gy in the 2D cohort, compared with 20.64 Gy in the 3D cohort. CONCLUSION: Neither technique delivered enough doses to the IMLNs to achieve subclinical disease control. However, all of the dosimetric parameters were significantly higher for the 3D technique.

OBJETIVO: Avaliar a irradiação incidental dos linfonodos da cadeia mamária interna (LCMIs) com campos tangenciais opostos por meio de radioterapia bidimensional (2D) convencional ou tridimensional (3D) e comparar as duas técnicas quanto aos resultados obtidos. MATERIAIS E MÉTODOS: Trata-se de um estudo retrospectivo com 80 pacientes com câncer de mama sem indicação de radioterapia dos LCMIs: 40 foram submetidos a radioterapia 2D com tomografia computadorizada para controle dosimétrico e 40 foram submetidos a radioterapia 3D. A dose total prescrita foi 50,0 Gy ou 50,4 Gy (2,0 ou 1,8 Gy/dia, respectivamente). Os planos de tratamento foram analisados e os LCMIs foram definidos conforme as recomendações do Radiation Therapy Oncology Group. No tocante aos LCMIs, foram analisadas a proporção do volume que recebeu 45 Gy, a proporção do volume que recebeu 25 Gy, a dose para 95% do volume, a dose para 50% do volume, a dose média, a dose mínima (Dmín) e a dose máxima (Dmáx). RESULTADOS: Tratamentos do lado esquerdo predominaram na coorte 3D. Não houve diferenças entre as coortes 2D e 3D quanto ao estágio do tumor, ao tipo de cirurgia (mastectomia, cirurgia conservadora ou mastectomia com reconstrução imediata) ou à média do volume delineado dos LCMIs (6,8 vs. 5,9 mL; p = 0,411). À exceção da Dmín, todos os parâmetros dosimétricos apresentaram médias maiores na coorte 3D (p < 0,05). A mediana da Dmáx na coorte 3D foi 50,34 Gy. No entanto, a dose média nos LCMIs foi 7,93 Gy na coorte 2D e 20,64 Gy na coorte 3D. CONCLUSÃO: Nenhuma das duas técnicas emitiu doses suficientes aos LCMIs para que se alcançasse o controle subclínico da doença. No entanto, todos os parâmetros dosimétricos foram significativamente maiores com a técnica 3D.

Radiation dose distribution in the teeth, maxilla, and mandible of patients with oropharyngeal and nasopharyngeal tumors who were treated with intensity-modulated radiotherapy.

BACKGROUND: The purpose of this study was to evaluate the distribution of the intensity-modulated radiotherapy (IMRT) dose delivered to the teeth, maxilla, and mandible. METHODS: The mean dose (Dmean) and maximum dose (Dmax) of radiation for the maxilla, mandible, and teeth of 63 patients with oropharyngeal (n = 44) or nasopharyngeal (n = 19) tumors were retrospectively evaluated. RESULTS: The posterior regions of the mandible received the highest doses, and the teeth received lower doses than the bones (maximum dose, p < .001; average dose, p < .001). The Dmax (p < .001) and Dmean (p < .001) depended on primary tumor location. The superior bones and teeth of patients with nasopharyngeal tumors received more radiation than those of patients with oropharyngeal tumors. CONCLUSION: A dose distribution map was generated based on the estimated doses received, which could allow prediction of the areas most affected by radiation and facilitate further correlations with dental complications after radiotherapy. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1708-1716, 2016.

Effects of Different Radiation Doses on the Bond Strengths of Two Different Adhesive Systems to Enamel and Dentin.

PURPOSE: To evaluate the effects of three different radiation doses on the bond strengths of two different adhesive systems to enamel and dentin. MATERIALS AND METHODS: Eighty human third molars were randomly divided into four groups (n = 20) according to the radiation dose (control/no radiation, 20 Gy, 40 Gy, and 70 Gy). The teeth were sagittally sectioned into three slices: one mesial and one distal section containing enamel and one middle section containing dentin. The sections were then placed in the enamel and dentin groups, which were further divided into two subgroups (n = 10) according to the adhesive used. Three restorations were performed in each tooth (one per section) using Adper Single Bond 2 (3M ESPE) or Universal Single Bond (3M ESPE) adhesive system and Filtek Z350 XT (3M ESPE) resin composite and subjected to the microshear bond test. Data were analyzed using a two-way ANOVA followed by Tukey's test. Failure modes were examined under a stereoscopic loupe. RESULTS: Radiotherapy did not affect the bond strengths of the adhesives to either enamel or dentin. In dentin, the Universal Single Bond adhesive system showed higher bond strength values when compared with the Adper Single Bond adhesive system. More adhesive failures were observed in the enamel for all radiation doses and adhesives. CONCLUSION: Radiotherapy did not influence the bond strength to enamel or dentin, irrespective of the adhesive or radiation dose used.

Accelerated partial irradiation for breast cancer: systematic review and meta-analysis of 8653 women in eight randomized trials.

BACKGROUND AND PURPOSE: Accelerated partial breast irradiation (APBI) is the strategy that allows adjuvant treatment delivery in a shorter period of time in smaller volumes. This study was undertaken to assess the effectiveness and outcomes of APBI in breast cancer compared with whole-breast irradiation (WBI). MATERIAL AND METHODS: Systematic review and meta-analysis of randomized controlled trials of WBI versus APBI. Two authors independently selected and assessed the studies regarding eligibility criteria. RESULTS: Eight studies were selected. A total of 8653 patients were randomly assigned for WBI versus APBI. Six studies reported local recurrence outcomes. Two studies were matched in 5 years and only one study for different time of follow-up. Meta-analysis of two trials assessing 1407 participants showed significant difference in the WBI versus APBI group regarding the 5-year local recurrence rate (HR=4.54, 95% CI: 1.78-11.61, p=0.002). Significant difference in favor of WBI for different follow-up times was also found. No differences in nodal recurrence, systemic recurrence, overall survival and mortality rates were observed. CONCLUSIONS: APBI is associated with higher local recurrence compared to WBI without compromising other clinical outcomes.

Hypofractioned radiotherapy in prostate cancer: is it the next step?

There are many available options for prostate cancer treatment, including active surveillance, surgery, brachytherapy and external beam radiotherapy. Based on a radiobiological rationale, which considers the prostate tumor as a low α/ß tumor, the use of higher and fewer fractions to prostate cancer external beam radiotherapy treatment has been proposed. Instead of the traditional fractions of 1.8-2.0 Gy per day, fractions higher than 2 Gy per day were the subject of a number of studies. In addition, new technologies such as intensity-modulated radiation therapy, image-guided radiation therapy, volumetric-modulated arch therapy and others have emerged as background for changing paradigms. Meanwhile, moderate and ultra-hypofractionation have been the subject of studies in recent years. Some moderate hypofractionation data from randomized controlled trials are ready to use, though other non-inferiority data are still lacking. The data on ultra-hypofractionation are still very new and require further evaluation to determine its long-term safety and efficacy.

Intraoperative radiation therapy in early breast cancer using a linear accelerator outside of the operative suite: an "image-guided" approach.

PURPOSE: To present local control, complications, and cosmetic outcomes of intraoperative radiation therapy (IORT) for early breast cancer, as well as technical aspects related to the use of a nondedicated linear accelerator. METHODS AND MATERIALS: This prospective trial began in May of 2004. Eligibility criteria were biopsy-proven breast-infiltrating ductal carcinoma, age >40 years, tumor <3 cm, and cN0. Exclusion criteria were in situ or lobular types, multicentricity, skin invasion, any contraindication for surgery and/or radiation therapy, sentinel lymph node involvement, metastasis, or another malignancy. Patients underwent classic quadrantectomy with intraoperative sentinel lymph node and margins evaluation. If both free, the patient was transferred from operative suite to linear accelerator room, and IORT was delivered (21 Gy). Primary endpoint: local recurrence (LR); secondary endpoints: toxicities and aesthetics. Quality assurance involved using a customized shield for chest wall protection, applying procedures to minimize infection caused by patient transportation, and using portal films to check collimator-shield alignment. RESULTS: A total of 152 patients were included, with at least 1 year follow-up. Median age (range) was 58.3 (40-85.4) years, and median follow-up time was 50.7 (12-110.5) months. The likelihood of 5-year local recurrence was 3.7%. There were 3 deaths, 2 of which were cancer related. The Kaplan-Meier 5-year actuarial estimates of overall, disease-free, and local recurrence-free survivals were 97.8%, 92.5%, and 96.3%, respectively. The overall incidences of acute and late toxicities were 12.5% and 29.6%, respectively. Excellent, good, fair, and bad cosmetic results were observed in 76.9%, 15.8%, 4.3%, and 2.8% of patients, respectively. Most treatments were performed with a 5-cm collimator, and in 39.8% of the patients the electron-beam energy used was ≥12 MeV. All patients underwent portal film evaluation, and the shielding was repositioned in 39.9% of cases. No infection or anesthesia complications were observed. CONCLUSIONS: Local control with IORT was adequate, with low complication rates and good cosmetic outcomes. More than one-third of patients benefited from the "image-guidance" approach, and almost 40% benefited from the option of higher electron beam energies.

Intensity-modulated radiation therapy for head and neck cancer: systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Intensity-modulated radiation therapy (IMRT) provides the possibility of dose-escalation with better normal tissue sparing. This study was performed to assess whether IMRT can improve clinical outcomes when compared with two-dimensional (2D-RT) or three-dimensional conformal radiation therapy (3D-CRT) in patients with head and neck cancer. METHODS AND MATERIALS: Only prospective phase III randomized trials comparing IMRT with 2D-RT or 3D-CRT were eligible. Combined surgery and/or chemotherapy were allowed. Two authors independently selected and assessed the studies regarding eligibility criteria and risk of bias. RESULTS: Five studies were selected. A total of 871 patients were randomly assigned for 2D-RT or 3D-CRT (437), versus IMRT (434). Most patients presented with nasopharyngeal cancers (82%), and stages III/IV (62.1%). Three studies were classified as having unclear risk and two as high risk of bias. A significant overall benefit in favor of IMRT was found (hazard ratio - HR=0.76; 95% CI: 0.66, 0.87; p<0.0001) regarding xerostomia scores grade 2-4, with similar loco-regional control and overall survival. CONCLUSIONS: IMRT reduces the incidence of grade 2-4 xerostomia in patients with head and neck cancers without compromising loco-regional control and overall survival.

Role of intra- or periprostatic calcifications in image-guided radiotherapy for prostate cancer.

PURPOSE: Image-guided radiotherapy (IGRT) allows more precise localization of the prostate, thus minimizing errors resulting from organ motion and set-up during treatment of prostate cancer. Using megavoltage cone-beam computed tomography (MVCBCT), references such as bones, the prostate itself or implanted fiducial markers can be used as surrogates to correct patient positioning immediately before each treatment fraction. However, the use of fiducials requires an invasive procedure and may increase costs. We aimed to assess whether intra- or periprostatic calcifications (IPC) could be used as natural fiducials. METHODS AND MATERIALS: Data on patients treated with IGRT for prostate cancer with clearly visible IPC and implanted fiducials in both planning CT and MVCBCT images were reviewed. IPC were classified as central when inside the prostate and peripheral when within the planning target volume. Daily deviations in lateral, longitudinal, and vertical directions from baseline positioning using fiducials and using IPC were compared. RESULTS: A total of 287 MVCBCT images were obtained and analyzed from 10 patients. The mean ± standard deviation daily deviation (mm) in the lateral, longitudinal, and vertical coordinates were 0.55 ± 3.11, 0.58 ± 3.45, and -0.54 ± 4.03, respectively, for fiducials, and 0.72 ± 3.22, 0.63 ± 3.58, and -0.69 ± 4.26, for IPC. The p values for comparisons (fiducials vs. IPC) were 0.003, 0.653, and 0.078 for lateral, longitudinal, and vertical coordinates, respectively. When cases with central IPC were analyzed (n = 7), no significant difference was found in such comparisons. Central IPC and fiducials exhibited a similar pattern of displacement during treatment, with equal values for daily displacements in the three directions for more than 90% of measurements. CONCLUSIONS: Our data suggest that centrally located IPC may be used as natural fiducials for treatment positioning during IGRT for prostate cancer, with potential reductions in the risks and costs associated with fiducial implantation.