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Simple Summary: This multicenter study (n = 1133, inclusion criteria: 3.5 cm maximum tumor size and preoperative indication for a boost) provides detailed data on acute and long-term toxicities in breast cancer patients undergoing breast-conserving surgery combined with an anticipated intraoperative boost with low-energy X-rays followed by whole breast irradiation. Toxicity assessments, based on LENT SOMA criteria, were performed annually up to 10 years of follow-up. IORT boost was completed in 90% and EBRT in 97% of cases. No grade 3 or 4 acute toxicities were observed, with mild acute side effects reported in a small proportion of patients. Chronic toxicities were seen in 16.2% of patients with teleangiectasia, 14.3% with grade ≥ 2 fibrosis, 3.4% with grade ≥ 2 pain, and 1.1% with hyperpigmentation. The results show that the therapy is safe and feasible in terms of toxicity and confirms intraoperative boost as a standard method of boost application in a large prospective cohort. In the context of breast cancer treatment optimization, this study prospectively examines the feasibility and outcomes of utilizing intraoperative radiotherapy (IORT) as a boost in combination with standard external beam radiotherapy (EBRT) for high-risk patients. Different guidelines recommend such a tumor bed boost in addition to whole breast irradiation with EBRT for patients with risk factors for local breast cancer recurrence. The TARGIT BQR (NCT01440010) is a prospective, multicenter registry study aimed at ensuring the quality of clinical outcomes. It provides, for the first time, data from a large cohort with a detailed assessment of acute and long-term toxicity following an IORT boost using low-energy X-rays. Inclusion criteria encompassed tumors up to 3.5 cm in size and preoperative indications for a boost. The IORT boost, administered immediately after tumor resection, delivered a single dose of 20 Gy. EBRT and systemic therapy adhered to local tumor board recommendations. Follow-up for toxicity assessment (LENT SOMA criteria: fibrosis, teleangiectasia, retraction, pain, breast edema, lymphedema, hyperpigmentation, ulceration) took place before surgery, 6 weeks to 90 days after EBRT, 6 months after IORT, and then annually using standardized case report forms (CRFs). Between 2011 and 2020, 1133 patients from 10 centers were preoperatively enrolled. The planned IORT boost was conducted in 90%, and EBRT in 97% of cases. Median follow-up was 32 months (range 1–120, 20.4% dropped out), with a median age of 61 years (range 30–90). No acute grade 3 or 4 toxicities were observed. Acute side effects included erythema grade 1 or 2 in 4.4%, palpable seroma in 9.1%, punctured seroma in 0.3%, and wound healing disorders in 2.1%. Overall, chronic teleangiectasia of any grade occurred in 16.2%, fibrosis grade ≥ 2 in 14.3%, pain grade ≥ 2 in 3.4%, and hyperpigmentation in 1.1%. In conclusion, a tumor bed boost through IORT using low-energy X-rays is a swift and feasible method that demonstrates low rates in terms of acute or long-term toxicity profiles in combination with whole breast irradiation. [ABSTRACT FROM AUTHOR]

Simple Summary: The aim of the present study is to assess, for the first time, the feasibility and safety of combining photon IORT with ultrahypofractionated WBI after breast-conserving surgery (BCS). From July 2020 to December 2022, seventy-two patients diagnosed with low-risk early BC were included in this prospective study. IORT was administered at a dose of 20 Gy to the surface's applicator, and WBI was to be administered 3–5 weeks after surgery at a total dose of 26 Gy in five consecutive days. All patients completed the proposed treatment schedule, and no severe acute or late grade 3 toxicity was observed at 3 and 12 months after WBI, respectively. Our results confirm, for the first time, that the combination of ultrafractionation WBI after BCS and photon-IORT is a feasible and safe option in patients with early BC. Background: The current standard of local treatment for patients with localized breast cancer (BC) includes whole breast irradiation (WBI) after breast-conserving surgery (BCS). Ultrahypofractionated WBI schemes (1-week treatment) were shown not to be inferior to the standard WBI. Tumor bed boost using photon intraoperative radiotherapy (IORT) is safe and feasible in combination with standard WBI. The aim of the present study is to assess, for the first time, the feasibility and safety of combining photon IORT with ultrahypofractionated WBI. Methods: Patients diagnosed with low-risk early BC candidates for BCS were included in this prospective study. IORT was administered at a dose of 20 Gy to the surface's applicator, and WBI was administered 3–5 weeks after surgery at a total dose of 26 Gy in five consecutive days. Results: From July 2020 to December 2022, seventy-two patients diagnosed with low-risk early BC and treated in our institution were included in this prospective study. All patients completed the proposed treatment, and no severe acute or late grade 3 toxicity was observed 3 and 12 months after WBI, respectively. Conclusions: Our results confirm for the first time that the combination of ultrafractionation WBI and photon-IORT after BCS is a feasible and safe option in patients with early BC. [ABSTRACT FROM AUTHOR]

Simple Summary: Current guidelines recommend treatment planning using [18F]FDG-PET/CT for the management of advanced cervical cancer, where suspicious lymph nodes may be treated with nodal boosting, extended-field radiotherapy, and/or debulking in addition to standard chemoradiotherapy to improve survival. However, caution must be exercised because of the risk of unnecessary therapy-related toxicity due to the overtreatment of false-positive nodes. Despite this daily dilemma in clinical practice, only a few studies have evaluated the management of [18F]FDG-positive nodes. Therefore, this study aimed to assess how often [18F]FDG-PET/CT lymph node information is used in the management of advanced-stage cervical cancer. We found that a total of 380/434 patients (88%) received interventions targeting [18F]FDG-positive nodes, with the following distribution: nodal boosting (84%), extended-field radiotherapy (78%), and debulking (12%). Despite existing guidelines advocating [18F]FDG-PET/CT-guided treatment planning for the management of advanced cervical cancer, this study highlights that not all cases of [18F]FDG-positive nodes received an intervention. Background: Modern treatment guidelines for women with advanced cervical cancer recommend staging using 2-deoxy-2-[18F]fluoro-D-glucose positron emission computed tomography ([18F]FDG-PET/CT). However, the risk of false-positive nodes and therapy-related adverse events requires caution in treatment planning. Using data from the Netherlands Cancer Registry (NCR), we estimated the impact of [18F]FDG-PET/CT on treatment management in women with locally advanced cervical cancer, i.e., on nodal boosting, field extension, and/or debulking in cases of suspected lymph nodes. Methods: Women diagnosed between 2009 and 2017, who received chemoradiotherapy for International Federation of Gynaecology and Obstetrics (2009) stage IB2, IIA2-IVB cervical cancer with an [18F]FDG-positive node, were retrospectively selected from the NCR database. Patients with pathological nodal examination before treatment were excluded. The frequency of nodal boosting, extended-field radiotherapy, and debulking procedures applied to patients with [18F]FDG-positive lymph nodes was evaluated. Results: Among the 434 eligible patients with [18F]FDG-positive nodes, 380 (88%) received interventions targeting these lymph nodes: 84% of these 380 patients received nodal boosting, 78% extended-field radiotherapy, and 12% debulking surgery. [18F]FDG-positive nodes in patients receiving these treatments were more likely to be classified as suspicious than inconclusive (p = 0.009), located in the para-aortic region (p < 0.001), and larger (p < 0.001) than in patients who did not receive these treatments. Conclusion: While existing guidelines advocate [18F]FDG-PET/CT-guided treatment planning for the management of advanced cervical cancer, this study highlights that not all cases of [18F]FDG-positive nodes received an intervention, possibly due to the risk of false-positive results. Improvement of nodal staging may reduce suboptimal treatment planning. [ABSTRACT FROM AUTHOR]

Simple Summary: Brachytherapy for prostate cancer is a method where radiotherapy is directly delivered to the prostate via surgical insertion of the radioactive source. Brachytherapy can increase the amount of radiation delivered to the prostate cancer but sometimes at the cost of increased side effects. Here, we review promising early results from alternative non-invasive techniques that now exist and can deliver similar radiotherapy doses without the need for the surgical procedure required for brachytherapy. Prostate cancer (PC) is the most common malignancy in men. Internal radiotherapy (brachytherapy) has been used to treat PC successfully for over a century. In particular, there is level-one evidence of the benefits of using brachytherapy to escalate the dose of radiotherapy compared with standard external beam radiotherapy approaches. However, the use of PC brachytherapy is declining, despite strong evidence for its improved cancer outcomes. A method using external beam radiotherapy known as virtual high-dose-rate brachytherapy boost (vHDRB) aims to noninvasively mimic a brachytherapy boost radiation dose plan. In this review, we consider the evidence supporting brachytherapy boosts for PC and the continuing evolution of vHDRB approaches, culminating in the current generation of clinical trials, which will help define the role of this emerging modality. [ABSTRACT FROM AUTHOR]

Simple Summary: Radiotherapy plays an important role in the multidisciplinary management of breast cancer. Historically, techniques for radiation treatment of breast carcinomas have been based upon two-dimensional planning and dose application. This treatment has been associated with a relatively high risk of chronic toxicity. Modern radiotherapy techniques have made it possible to achieve a better target volume coverage with a lower critical organ radiation burden. New fractionation methods have led to shorter treatment times while improving the therapeutic ratio. All of this has permitted a reduction in both acute and chronic toxicity, and led to improvements in treatment effectiveness. Currently, partial breast irradiation is used effectively in indicated cases. This can be achieved through utilizing various irradiation techniques and a number of fractionation schemes (e.g., partial breast irradiation and accelerated partial breast irradiation). Problematic issues are related to the application of adjuvant radiotherapy in patients immediately after breast replacement surgery. Modern radiotherapy techniques are designed to permit reduced irradiation of healthy tissue, resulting in a diminished risk of adverse effects and shortened recovery times. Several randomized studies have demonstrated the benefits of increased dosage to the tumor bed area in combination with whole breast irradiation (WBI). Conventional WBI treatment following breast-conserving procedures, which required 5–7 weeks of daily treatments, has been reduced to 3–4 weeks when using hyperfractionated regimens. The dosage administration improves local control, albeit with poorer cosmesis. The method of accelerated partial breast irradiation (APBI) shortens the treatment period whilst reducing the irradiated volume. APBI can be delivered using intraoperative radiation, brachytherapy, or external beam radiotherapy. Currently available data support the use of external beam partial breast irradiation in selected patients. Modern radiotherapy techniques make it possible to achieve favorable cosmesis in most patients undergoing immediate breast reconstruction surgery, and studies confirm that current methods of external beam radiation allow an acceptable coverage of target volumes both in the reconstructed breast and in the regional lymphatic nodes. [ABSTRACT FROM AUTHOR]

Simple Summary: The benefit of administering an extra dose to the tumor bed (boost) prior or simultaneously to adjuvant breast radiotherapy in terms of local recurrence rate has already been the subject of several studies and, thus, has already found justification in appropriate patient cases. In this study, we compared two boost techniques, an intraoperative radiotherapy (IORT) boost and an intensity-modulated radiotherapy boost (IMRT), analyzing two patient collectives to determine the equivalence of the two techniques or which of the two proves superior. According to our monocenter data on tumor control, survival rates, toxicities, and cosmetic results, no significant differences were revealed between the two boost techniques, and it cannot be generalized that one technique is more advantageous than the other. The aim of this retrospective study is to compare the two boost subgroups, IORT or IMRT, in terms of overall survival (OS), progression-free survival (PFS), cosmesis, and acute and late toxicity. It shall be shown whether and which of the boost techniques offers better results with respect to the facial points, since there are already many studies on applying boost to the tumor bed after/during breast conserving surgery, and there are few which compare the different techniques. For this comparison, two subgroups of 76 patients each (n = 152), treated between 2002 and 2015, were enrolled in the study. In one subgroup, the 9 Gy boost was intraoperatively administered after complete removal of the primary tumor, while the other subgroup received the boost of 8.4 Gy percutaneously and simultaneously integrated into the tumor bed after breast conserving surgery. Both subgroups have subsequently undergone whole breast irradiation (WBI) of 50.4/50 Gy in 1.8–2 Gy per fraction. OS and the incidence of late toxicity did not differ between the two subgroups and no risk factor was found regarding PFS. Acute toxicities initially occurred significantly less (p < 0.001) in the IORT subgroup; however, after WBI took place, this difference vanished. Therefore, boost application by means of IORT or IMRT can be considered equivalent. [ABSTRACT FROM AUTHOR]

Simple Summary: Intraoperative electron radiation therapy (IOERT) has repeatedly demonstrated its power to yield high local control rates in all risk constellation of patients with invasive breast cancer when given as tumor bed boost prior to conventional whole breast irradiation (WBI) after breast conserving surgery (BCS). Since the standard for WBI continuously moved towards hypofractionation, we initiated a prospective trial in 2011 where we combined a high precision IOERT boost with a "moderate" hypofractionation schedule (15 × 2.7 Gy), the HIOB-trial [NCT01343459], as clinical evidence for this combination was scarce. Our results demonstrated a low five-year local recurrence rate (overall two events in a population of 1119 patients), which undershot such best evidences in two age groups (41–50 y and >50 y). As acute and late toxicity were mild with no impaired cosmetic outcome, the HIOB-concept seems to be a viable treatment option for patients who underwent BCS and intended WBI. Background and purpose: To investigate intraoperative electron radiation therapy (IOERT) as a tumor bed boost during breast conserving surgery (BCS) followed by hypofractionated whole breast irradiation (HWBI) on age-correlated in-breast recurrence (IBR) rates in patients with low- to high-risk invasive breast cancer. Material and methods: BCS and IOERT (11.1 Gy) preceded a HWBI (40.5 Gy) in 15 fractions. Five-year IBR-rates were compared by a sequential ratio test (SQRT) with best evidences in three age groups (35–40 y and 41–50 y: 3.6%, >50 y: 2%) in a prospective single arm design. Null hypothesis (H0) was defined to undershoot these benchmarks for proof of superiority. Results: Of 1445 enrolled patients, 326 met exclusion criteria, leaving 1119 as eligible for analysis. After a median follow-up of 50 months (range 0.7–104), we detected two local recurrences, both in the age group >50 y. With no observed IBR, superiority was demonstrated for the patient groups 41–50 and >50 y, respectively. For the youngest group (35–40 y), no appropriate statistical evaluation was yet possible due to insufficient recruitment. Conclusions: In terms of five-year IBR-rates, Boost-IOERT followed by HWBI has been demonstrated to be superior in patients older than 50 and in the age group 41–50 when compared to best published evidence until 2010. [ABSTRACT FROM AUTHOR]

Modern radiotherapy techniques are designed to permit reduced irradiation of healthy tissue, resulting in a diminished risk of adverse effects and shortened recovery times. Several randomized studies have demonstrated the benefits of increased dosage to the tumor bed area in combination with whole breast irradiation (WBI). Conventional WBI treatment following breast-conserving procedures, which required 5-7 weeks of daily treatments, has been reduced to 3-4 weeks when using hyperfractionated regimens. The dosage administration improves local control, albeit with poorer cosmesis. The method of accelerated partial breast irradiation (APBI) shortens the treatment period whilst reducing the irradiated volume. APBI can be delivered using intraoperative radiation, brachytherapy, or external beam radiotherapy. Currently available data support the use of external beam partial breast irradiation in selected patients. Modern radiotherapy techniques make it possible to achieve favorable cosmesis in most patients undergoing immediate breast reconstruction surgery, and studies confirm that current methods of external beam radiation allow an acceptable coverage of target volumes both in the reconstructed breast and in the regional lymphatic nodes.