Total skin electron beam therapy (TSEBT) in female patients with large or pendulous breasts is usually associated with shaded inframammary folds. In this analysis, 18 patients with cutaneous malignancy and pendulous breasts were irradiated with a radiation bra and five patients received TSEBT without bra. All patients had moderate or severe sagging of the breasts. The median inframammary dose in the radiation bra group was 89% of the prescription dose versus 4% in the group without bra. The usage of the radiation bra enables an adequate radiation dose for the inframammary folds during TSEBT with no additional local irradiation.

BACKGROUND: A radiation (RT) boost to the tumor bed is an important component of breast-conserving therapy (BCT) in early breast cancer (BC). This prospective phase II study assessed the feasibility of delivering the RT boost pre-operatively. We hypothesize wound complication rates to be comparable to post-operative RT and the target boost volume to be smaller than standard post-operative RT.
METHODS: This prospective phase II trial accrued 55 patients with clinically node negative BC eligible for BCT. Patients were treated with pre-operative RT boost of 1332 cGy in 4 fractions, followed by lumpectomy and post-operative adjuvant whole breast RT to 3663 cGy in 11 fractions. The primary outcome was to demonstrate the incidence of grade 3 or more wound complications was not inferior to lumpectomy with standard postoperative whole breast RT and boost (6- 20%). We also compared the pre-op boost volume to a mock boost volume that would have been done post-operatively.
RESULTS: Fifty-five women were enrolled between June 2021 and October 2022. Median age was 64 years-old, (range 40-77). Forty-three patients had invasive cancers and 5 had DCIS. Median clinical tumor size was 13 mm, (range 5-26). Grade 3 wound dehiscence requiring surgical revision occurred in one patient (2%). There were no other grade 3 adverse events. Three patients (6%) had grade 2 infections requiring antibiotics. The target boost volume was significantly lower that the mock post-operative volume (11cc vs. 56 cc; p <.001) Cosmetic outcome at 1st follow up was very good or excellent in 87% of patients and none had poor cosmetic outcome.
CONCLUSIONS: The use of a pre-operative RT boost followed by whole breast RT as administered here resulted in an acceptable primary outcome with a similar rate of post-operative wound complications and smaller boost volume compared to standard postoperative RT. This approach is currently under consideration for cooperative group Phase III trial.

PARVAX is a genetic vaccine platform based on an adeno-associated vector that has demonstrated to elicit potent, durable, and protective immunity in nonhuman primates (NHPs) after a single dose. Here, we assessed vaccine immunogenicity following a PARVAX prime-boost regimen against SARS-CoV-2. In mice, a low-dose prime followed by a higher-dose boost elicited potent neutralizing antibody responses and distinct cross-reactivity profiles, depending on the antigen used in the booster vaccine. However, the potent neutralizing anti-vector antibody responses developed in mice limited the dose that could be administered as a prime. We further explored the re-administration efficacy in NHPs primed with a SARS-CoV-2 Delta vaccine and boosted with an Omicron BA.1 vaccine at week 15, after the primary response peak antibody levels were reached. The boost elicited an increase in antibodies against several Omicron variants, but no increase was detected in the antibody titers for other variants. The anti-vector responses were low and showed some increased subsequent boosts but generally declined over time. The potent prime vaccination limited the detection of the boosting effect, and therefore, the effect of anti-vector immunity was not fully elucidated. These data show that PARVAX can be effectively re-administered and induce a novel antigenic response.

The usage and safety of the Boost and Ease-off features in the CamAPS FX hybrid closed-loop system were analyzed in a retrospective analysis of real-world data from 7,464 users over a 12-month period. Boost was used more frequently than Ease-off, but for a shorter duration per use. Mean starting glucose was above range for Boost (229 ± 51 mg/dL), and within range for Ease-off (114 ± 29 mg/dL). Time spent below 70 mg/dL was low during Boost periods [median (interquartile range; IQR) 0.0% (0.0, 0.5%)], and lower than during no Boost periods [2.1% (1.2, 3.4%)], while time spent above 180 mg/dL was lower during Ease-off periods (15 ± 14%) compared with no Ease-off periods (25 ± 12%). There were no episodes of severe hypoglycemia or diabetic ketoacidosis attributed to Boost or Ease-off use. Boost and Ease-off allow users to engage safely with CamAPS FX to manage their glucose levels during periods of more-than-usual and less-than-usual insulin needs.

BACKGROUND: Locally advanced recurrent rectal cancer (RRC) requires a multimodal approach. Intraoperative high-dose-rate brachytherapy (HDR-BT) may reduce the risk of local recurrence. However, the optimal therapeutic regimen remains unclear. The aim of this retrospective monocentric study was to evaluate the toxicity of HDR-BT after resection of RRC.
METHODS: Between 2018 and 2022, 17 patients with RRC received resection and HDR-BT. HDR-BT was delivered alone or as an anticipated boost with a median dose of 13 Gy (range 10-13 Gy) using an 192iridium microSelectron HDR remote afterloader (Elekta AB, Stockholm, Sweden). All participants were followed for assessment of acute and late adverse events using the Common Terminology Criteria for Adverse Events version 5.0 and the modified Late Effects in Normal Tissues criteria (subjective, objective, management, and analytic; LENT-SOMA) at 3‑ to 6‑month intervals.
RESULTS: A total of 17 patients were treated by HDR-BT with median dose of 13 Gy (range 10-13 Gy). Most patients (47%) had an RRC tumor stage of cT3‑4 N0. At the time of RRC diagnosis, 7 patients (41.2%) had visceral metastases (hepatic, pulmonary, or peritoneal) in the sense of oligometastatic disease. The median interval between primary tumor resection and diagnosis of RRC was 17 months (range 1-65 months). In addition to HDR-BT, 2 patients received long-course chemoradiotherapy (CRT; up to 50.4 Gy in 1.8-Gy fractions) and 2 patients received short-course CRT up to 36 Gy in 2‑Gy fractions. For concomitant CRT, all patients received 5‑fluorouracil (5-FU) or capecitabine. Median follow-up was 13 months (range 1-54). The most common acute grade 1-2 toxicities were pain in 7 patients (41.2%), wound healing disorder in 3 patients (17.6%), and lymphedema in 2 patients (11.8%). Chronic toxicities were similar: grade 1-2 pain in 7 patients (41.2%), wound healing disorder in 3 patients (17.6%), and incontinence in 2 patients (11.8%). No patient experienced a grade ≥3 event.
CONCLUSIONS: Reirradiation using HDR-BT is well tolerated with low toxicity. An individualized multimodality approach using HDR-BT in the oligometastatic setting should be evaluated in prospective multi-institutional studies.

Sequencing the tyrosine phosphoproteome using MS-based proteomics is challenging due to the low abundance of tyrosine phosphorylation in cells, a challenge compounded in scarce samples like primary cells or clinical samples. The broad-spectrum optimisation of selective triggering (BOOST) method was recently developed to increase phosphotyrosine sequencing in low protein input samples by leveraging tandem mass tags (TMT), phosphotyrosine enrichment, and a phosphotyrosine-loaded carrier channel. Here, we demonstrate the viability of BOOST in T cell receptor (TCR)-stimulated primary murine T cells by benchmarking the accuracy and precision of the BOOST method and discerning significant alterations in the phosphoproteome associated with receptor stimulation. Using 1 mg of protein input (about 20 million cells) and BOOST, we identify and precisely quantify more than 2000 unique pY sites compared to about 300 unique pY sites in non-BOOST control samples. We show that although replicate variation increases when using the BOOST method, BOOST does not jeopardise quantitative precision or the ability to determine statistical significance for peptides measured in triplicate. Many pY previously uncharacterised sites on important T cell signalling proteins are quantified using BOOST, and we identify new TCR responsive pY sites observable only with BOOST. Finally, we determine that the phase-spectrum deconvolution method on Orbitrap instruments can impair pY quantitation in BOOST experiments.

OBJECTIVE: Whether brachytherapy based microboosting of the dominant intraprostatic lesion (DIL) improves outcomes over standard approaches is not known. The purpose of this study is to perform a systematic review on brachytherapy microboosting of the DIL to evaluate clinical outcomes and toxicities with this treatment approach.
METHODS: This review was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Databases including Pubmed, Embase, and Google Scholar were queried. About 16 studies met our inclusion criteria. These studies reported PSA control and/or toxicities based on standardized scales.
RESULTS: There were 10 studies (two monotherapy, eight combination) that used HDR microboosting on a total of 516 patients. HDR dose (EQD2 assuming alpha/beta of 1.5) to the DIL ranged from 90 to 180 Gy. Most patients were low/intermediate risk. PSA control rates at 5-8 years ranged from 69% to 100%. Acute/late G3-G4 GU/GI toxicities ranged from 0% to 12%. There were six studies (five monotherapy, one combination) that used LDR microboosting on a total of 1041 patients. Studies performed a microboost of 130-150% of the whole gland prescription to the DIL. Most patients were low/intermediate risk. PSA control rates at 5 years ranged from 69% to 98%. Acute/late G3-4 GU/GI toxicities ranged from 0% to 4%.
CONCLUSIONS: Over 1000 patients have been treated with a brachytherapy based microboost in published series. Severe acute/late toxicities appear limited. PSA control rates with more than 5 years of follow-up are limited. Longer-term follow-up is needed to determine ideal utilization of this approach.

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.

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.

BACKGROUND: A surge of human influenza A(H7N9) cases began in 2016 in China from an antigenically distinct lineage. Data are needed about the safety and immunogenicity of 2013 and 2017 A(H7N9) inactivated influenza vaccines (IIVs) and the effects of AS03 adjuvant, prime-boost interval, and priming effects of 2013 and 2017 A(H7N9) IIVs.
METHODS: Healthy adults (n = 180), ages 19-50 years, were enrolled into this partially blinded, randomized, multicenter phase 2 clinical trial. Participants were randomly assigned to 1 of 6 vaccination groups evaluating homologous versus heterologous prime-boost strategies with 2 different boost intervals (21 vs 120 days) and 2 dosages (3.75 or 15 μg of hemagglutinin) administered with or without AS03 adjuvant. Reactogenicity, safety, and immunogenicity measured by hemagglutination inhibition and neutralizing antibody titers were assessed.
RESULTS: Two doses of A(H7N9) IIV were well tolerated, and no safety issues were identified. Although most participants had injection site and systemic reactogenicity, these symptoms were mostly mild to moderate in severity; injection site reactogenicity was greater in vaccination groups receiving adjuvant. Immune responses were greater after an adjuvanted second dose, and with a longer interval between prime and boost. The highest hemagglutination inhibition geometric mean titer (95% confidence interval) observed against the 2017 A(H7N9) strain was 133.4 (83.6-212.6) among participants who received homologous, adjuvanted 3.75 µg + AS03/2017 doses with delayed boost interval.
CONCLUSIONS: Administering AS03 adjuvant with the second H7N9 IIV dose and extending the boost interval to 4 months resulted in higher peak antibody responses. These observations can broadly inform strategic approaches for pandemic preparedness. Clinical Trials Registration. NCT03589807.