Breast Cancer Presenting With Intravascular Tumor Emboli in Axillary Soft Tissue: Recurrence Risk and Radiation Therapy Outcomes.

Purpose: Intravascular tumor emboli in axillary soft tissue (ITE) is a rare pathologic finding in breast cancer and is associated with higher axillary nodal disease burden. The independent prognostic and predictive value of this entity is unknown, as is the role of radiation therapy for ITE. Methods and Materials: We analyzed a prospectively maintained database of breast cancer patients treated from 1992 to 2020. Patients with ITE were matched to those without (1:2) based on propensity scores to control for potential confounding factors. Locoregional (LRR) and distant recurrence (DR) were evaluated using competing risks methods accounting for death as a competing event. Overall survival (OS) and disease-free survival (DFS) were evaluated by Cox regression models. Among patients with ITE, we also evaluated whether RT improved outcomes. Results: Among 2377 total patients, 129 had ITE, of whom 126 were propensity score matched to 252 without ITE. Median follow-up from time of surgery was 5.5 years (IQR 2.3, 9.7). There were no statistically significant differences in the 5-year incidence of LRR between groups (5.4% [95% CI, 1.6%-13%] with ITE vs 10% [95% CI, 6.7%-15%] without, P = .53) or DR (24% [95% CI, 15% 35%] with ITE vs 21% [95% CI, 16%-27%] without, P = .51). Five-year OS and DFS did not differ between groups (P > .9 for both comparisons, patients with ITE vs without ITE). In analyzing the effect of RT among patients with ITE, receipt of RT was associated with significantly improved DFS (HR, 0.34, 95% CI, 0.12-0.93, P = .04). Conclusions: Patients with ITE do not exhibit significantly worse LRR, DR, DFS, or OS compared with a propensity-score-matched cohort without ITE. However, among patients with ITE, those who received RT demonstrated significantly improved DFS. Larger studies with longer follow-up are needed to evaluate the prognostic and predictive implications of ITE.

The presence of extensive lymphovascular invasion (LVI) is associated with higher risks of local-regional recurrence compared to usual LVI in curatively treated breast cancer patients.

PURPOSE/OBJECTIVES: Several datasets have demonstrated a correlation between lymph-vascular invasion (LVI) and local-regional recurrence (LRR). Whether the observation of "extensive LVI" is a further and incremental determinant of LRR risk is unknown. We describe clinical outcomes in women with invasive breast cancer stratified by: 1) absence of LVI (neg), 2) LVI focal or suspicious (FS-LVI), 3) usual (non-extensive) LVI (LVI) and 4) extensive LVI (E-LVI). MATERIALS/METHODS: Between 12/2009 and 8/2021, 8837 patients with early-stage breast cancer were treated with curative intent and were evaluable. Clinical-pathological details were abstracted by retrospective review. The description of LVI was abstracted from pathology reports. Recurrence and survival outcomes were compared based on the extent of LVI. A matched propensity score analysis compared outcomes between patients with LVI vs. E-LVI. RESULTS: Of the 8837 patients studied, 5584 were neg, 461 had FS-LVI, 2315 had LVI, and 477 had E-LVI. Patient with E-LVI had an adverse risk profile compared to the other groups. The 5- and 10-year local regional recurrence (LRR) cumulative incidence estimates in patients with E-LVI were 9.6% (95% CI: 7.1-13) and 13% (95% CI: 10-17), which were significantly higher than observed in the usual LVI group (6.8% [5.7-7.9] and 10% [8.8-12], respectively). A statistically significant difference in LRR was demonstrated on univariable (HR 1.4, 95% CI [1.03-1.89], p-value 0.029) and multivariable regression analysis (HR 1.62, 95% CI [1.15-2.27], p-value 0.005) when compared to non-extensive LVI. In an alternative approach, we performed a 2:1 propensity-matched analysis comparing LVI to E-LVI patients. The hazard ratio for LRR (HR 1.47 (CI 1.02-2.14, p=0.041) was suggestive of a higher risk with E-LVI. CONCLUSIONS: Our work suggests that patients with E-LVI are at a higher risk for LRR than those with usual LVI. For patients who are borderline candidates for regional nodal irradiation or PMRT, the finding of E-LVI might be decisive in favor of intensified treatment.

Statistical design and optimization of nano-transfersomes based chitosan gel for transdermal delivery of cefepime.

OBJECTIVES: This research aimed to overcome challenges posed by cefepime excessive elimination rate and poor patient compliance by developing transdermal delivery system using nano-transfersomes based chitosan gel. METHODS: Rotary evaporation-sonication method and the Box-Behnken model were used to prepare cefepime loaded nano-transfersomes (CPE-NTFs). The physiochemical characterization of CPE-NTFs were analyzed including DLS, deformability index, DSC and antimicrobial study. Optimized CPE-NTFs loaded into chitosan gel and appropriately characterized. In vitro release, ex vivo and in vivo studies were performed. RESULTS: The CPE-NTFs were physically stable with particle size 222.6 ± 1.8 nm, polydispersity index 0.163 ± 0.02, zeta potential -20.8 ± 0.1 mv, entrapment efficiency 81.4 ± 1.1% and deformability index 71 ± 0.2. DSC analysis confirmed successful drug loading and thermal stability. FTIR analysis showed no chemical interaction among the excipients of CPE-NTFs gel. The antibacterial activity demonstrated a remarkable reduction in the minimum inhibitory concentration of cefepime when incorporated into nano-transfersomes. CPE-NTFs based chitosan gel (CPE-NTFs gel) showed significant physicochemical properties. In vitro release studies exhibited sustained release behavior over 24 h, and ex vivo studies indicated enhanced permeation and retention compared to conventional cefepime gel. In vivo skin irritation studies confirmed CPE-NTFs gel was nonirritating and biocompatible for transdermal delivery. CONCLUSION: This research showed nano-transfersomes based chitosan gel is a promising approach for cefepime transdermal delivery and provides sustained release of cefepime.

Real-World Use of Hypofractionated Radiotherapy for Primary CNS Tumors in the Elderly, and Implications on Medicare Spending.

BACKGROUND: For elderly patients with high-grade gliomas, 3-week hypofractionated radiotherapy (HFRT) is noninferior to standard long-course radiotherapy (LCRT). We analyzed real-world utilization of HFRT with and without systemic therapy in Medicare beneficiaries treated with RT for primary central nervous system (CNS) tumors using Centers for Medicare & Medicaid Services data. METHODS: Radiation modality, year, age (65-74, 75-84, or ≥85 years), and site of care (freestanding vs hospital-affiliated) were evaluated. Utilization of HFRT (11-20 fractions) versus LCRT (21-30 or 31-40 fractions) and systemic therapy was evaluated by multivariable logistic regression. Medicare spending over the 90-day episode after RT planning initiation was analyzed using multivariable linear regression. RESULTS: From 2015 to 2019, a total of 10,702 RT courses (ie, episodes) were included (28% HFRT; 65% of patients aged 65-74 years). A considerable minority died within 90 days of RT planning initiation (n=1,251; 12%), and 765 (61%) of those received HFRT. HFRT utilization increased (24% in 2015 to 31% in 2019; odds ratio [OR], 1.2 per year; 95% CI, 1.1-1.2) and was associated with older age (≥85 vs 65-74 years; OR, 6.8; 95% CI, 5.5-8.4), death within 90 days of RT planning initiation (OR, 5.0; 95% CI, 4.4-5.8), hospital-affiliated sites (OR, 1.4; 95% CI, 1.3-1.6), conventional external-beam RT (vs intensity-modulated RT; OR, 2.7; 95% CI, 2.3-3.1), and no systemic therapy (OR, 1.2; 95% CI, 1.1-1.3; P<.001 for all). Increasing use of HFRT was concentrated in hospital-affiliated sites (P=.002 for interaction). Most patients (69%) received systemic therapy with no differences by site of care (P=.12). Systemic therapy utilization increased (67% in 2015 to 71% in 2019; OR, 1.1 per year; 95% CI, 1.0-1.1) and was less likely for older patients, patients who died within 90 days of RT planning initiation, those who received conventional external-beam RT, and those who received HFRT. HFRT significantly reduced spending compared with LCRT (adjusted ß for LCRT = +$8,649; 95% CI, $8,544-$8,755), whereas spending modestly increased with systemic therapy (adjusted ß for systemic therapy = +$270; 95% CI, $176-$365). CONCLUSIONS: Although most Medicare beneficiaries received LCRT for primary brain tumors, HFRT utilization increased in hospital-affiliated centers. Despite high-level evidence for elderly patients, discrepancy in HFRT implementation by site of care persists. Further investigation is needed to understand why patients with short survival may still receive LCRT, because this has major quality-of-life and Medicare spending implications.

A Phase II Study Evaluating the Effect of Intensity Modulated Postmastectomy Radiation Therapy on Implant Failure Rates in Breast Cancer Patients With Immediate, 2-Stage Implant Reconstruction With an MRI Imaging Correlative Substudy.

PURPOSE: Postmastectomy radiation therapy is a mainstay in the adjuvant treatment of node-positive breast cancer, but it poses risks for women with breast reconstruction. Multibeam intensity-modulated radiation therapy improves dose conformality and homogeneity, potentially reducing complications in breast cancer patients with implant-based reconstruction. To investigate this hypothesis, we conducted a single-arm phase 2 clinical trial of breast cancer patients who underwent mastectomy/axillary dissection and prosthesis-based reconstruction. METHODS AND MATERIALS: The primary endpoint was the rate of implant failure (IF) within 24 months of permanent implant placement, which would be considered an improvement over historical controls if below 16%. IF was defined as removal leading to a flat chest wall or replacement with another reconstruction. Patients were analyzed in 2 cohorts. Cohort 1 (RT-PI) received radiation therapy to the permanent implant. Cohort 2 (RT-TE) received radiation therapy to the TE. IF rates, adverse events, and quality of life were analyzed. Follow-up/postradiation therapy assessments were compared with the baseline/preradiation therapy assessments at 3 to 10 weeks after exchange surgery. A subgroup underwent serial magnetic resonance imaging (MRI) sessions to explore the association between MRI-detected changes and capsular contracture, a known adverse effect of radiation therapy. RESULTS: Between June 2014 and March 2017, 119 women were enrolled. Cohort 1 included 45 patients, and cohort 2 had 74 patients. Among 100 evaluable participants, 25 experienced IF during the study period. IF occurred in 8/42 (19%) and 17/58 (29%) in cohorts 1 and 2, respectively. Among the IFs, the majority were due to capsular contracture (13), infection (7), exposure (3), and other reasons (2). Morphologic shape features observed in longitudinal MRI images were associated with the development of Baker grade 3 to 4 contractures. CONCLUSIONS: The rate of IF in reconstructed breast cancer patients treated with intensity-modulated radiation therapy was similar to, but not improved over, that observed with conventional, 3-dimensional-conformal methods. MRI features show promise for predicting capsular contracture but require validation in larger studies.

Comparative Evaluation of Proton Therapy and Volumetric Modulated Arc Therapy for Brachial Plexus Sparing in the Comprehensive Reirradiation of High-Risk Recurrent Breast Cancer.

Purpose: Recurrent or new primary breast cancer requiring comprehensive regional nodal irradiation after prior radiation therapy (RT) to the supraclavicular area and upper axilla is challenging due to cumulative brachial plexus (BP) dose tolerance. We assessed BP dose sparing achieved with pencil beam scanning proton therapy (PBS-PT) and photon volumetric modulated arc therapy (VMAT). Methods and Materials: In an institutional review board-approved planning study, all patients with ipsilateral recurrent breast cancer treated with PBS-PT re-RT (PBT1) with at least partial BP overlap from prior photon RT were identified. Comparative VMAT plans (XRT1) using matched BP dose constraints were developed. A second pair of proton (PBT2) and VMAT (XRT2) plans using standardized target volumes were created, applying uniform prescription dose of 50.4 per 1.8 Gy and a maximum BP constraint <25 Gy. Incidence of brachial plexopathy was also assessed. Results: Ten consecutive patients were identified. Median time between RT courses was 48 months (15-276). Median first, second, and cumulative RT doses were 50.4 Gy (range, 42.6-60.0), 50.4 Gy relative biologic effectiveness (RBE) (45.0-64.4), and 102.4 Gy (RBE) (95.0-120.0), respectively. Median follow-up was 15 months (5-33) and 18 months for living patients (11-33) Mean BP max was 37.5 Gy (RBE) for PBT1 and 36.9 Gy for XRT1. Target volume coverage of V85% (volume receiving 85% of prescription dose), V90%, and V95% were numerically lower for XRT1 versus PBT1. Similarly, axilla I-III and supraclavicular area coverage were significantly higher for PBT2 than XRT2 at dose levels of V55%, V65%, V75%, V85%, and V95%. Only axilla I V55% did not reach significance (P = .06) favoring PBS-PT. Two patients with high cumulative BPmax (95.2 Gy [RBE], 101.6 Gy [RBE]) developed brachial plexopathy symptoms with ulnar nerve distribution neuropathy without pain or weakness (1 of 2 had symptom resolution after 6 months without intervention). Conclusions: PBS-PT improved BP sparing and target volume coverage versus VMAT. For patients requiring comprehensive re-RT for high-risk, nonmetastatic breast cancer recurrence with BP overlap and reasonable expectation for prolonged life expectancy, PBT may be the preferred treatment modality.

Accelerated Partial Breast Irradiation for HER2-Positive Early-Stage Breast Cancer.

PURPOSE: HER2-positive (HER2+) breast cancer historically exhibited the most adverse local outcomes and, consequently, has had limited representation among trials of partial breast irradiation (PBI). We hypothesized that with contemporary HER2-targeted agents, patients may now exhibit excellent disease control outcomes after adjuvant PBI. METHODS AND MATERIALS: Using a prospectively maintained institutional database, we identified patients with HER2+ breast cancer treated with breast conserving surgery (BCS) and PBI from 2000 to 2022. Salient clinicopathologic and treatment parameters were collected. All patients received external beam PBI to 40 Gy in 10 daily fractions. Cumulative incidence functions were calculated to estimate the incidence of local recurrence (LR) with the competing risk of death. RESULTS: We identified 1248 patients who underwent PBI at our institution, of whom the study cohort comprised 52 (4%) with HER2+ breast cancer (median age, 64 years; range, 44-87). Nearly all had T1 tumors (98%; median size, 12 mm [range, 1-21 mm]). Most had estrogen receptor positive disease (88%), and all patients had negative surgical margins. Nearly all underwent sentinel node biopsy (94%), with the remainder undergoing no surgical axillary evaluation. Forty-two (81%) received chemotherapy; 40 (77%), hormone therapy; and 42 (81%), HER2-directed therapy, most commonly trastuzumab. At 143.8 person-years of follow-up (range, 7-226 months for each patient), we observed 2 LR events at 14 and 26 months, respectively, yielding a 2-year LR rate of 3.8%. No regional or distant recurrences were observed, nor were any breast-specific mortality events. Two deaths were observed, both without evidence of disease. CONCLUSIONS: Among a cohort of patients with HER2+ early-stage breast cancer managed with BCS and PBI, we observed a 2-year LR rate of 3.8%, with no regional or distant recurrences and excellent overall survival. These findings require confirmation with longer follow-up among larger cohorts but appear consistent with the excellent results of contemporary randomized trials of PBI unselected for HER2 status.

Evaluation of ChatGPT pathology knowledge using board-style questions.

OBJECTIVES: ChatGPT is an artificial intelligence chatbot developed by OpenAI. Its extensive knowledge and unique interactive capabilities enable its use in various innovative ways in the medical field, such as writing clinical notes and simplifying radiology reports. Through this study, we aimed to analyze the pathology knowledge of ChatGPT to advocate its role in transforming pathology education. METHODS: The American Society for Clinical Pathology Resident Question Bank 2022 was used to test ChatGPT, version 4. Practice tests were created in each subcategory and answered based on the input that ChatGPT provided. Questions that required interpretation of images were excluded. We analyzed ChatGPT performance and compared it with average peer performance. RESULTS: The overall performance of ChatGPT was 56.98%, lower than that of the average peer performance of 62.81%. ChatGPT performed better on clinical pathology (60.42%) than on anatomic pathology (54.94%). Furthermore, its performance was better on easy questions (68.47%) than on intermediate (52.88%) and difficult questions (37.21%). CONCLUSIONS: ChatGPT has the potential to be a valuable resource in pathology education if trained on a larger, specialized medical data set. Those relying on it (in its current form) solely for the purpose of pathology training should be cautious.

Proton Reirradiation for High-Risk Recurrent or New Primary Breast Cancer.

Radiotherapy is an integral component of multidisciplinary breast cancer care. Given how commonly radiotherapy is used in the treatment of breast cancer, many patients with recurrences have received previous radiotherapy. Patients with new primary breast cancer may also have received previous radiotherapy to the thoracic region. Curative doses and comprehensive field photon reirradiation (reRT) have often been avoided in these patients due to concerns for severe toxicities to organs-at-risk (OARs), such as the heart, lungs, brachial plexus, and soft tissue. However, many patients may benefit from definitive-intent reRT, such as patients with high-risk disease features such as lymph node involvement and dermal/epidermal invasion. Proton therapy is a potentially advantageous treatment option for delivery of reRT due to its lack of exit dose and greater conformality that allow for enhanced non-target tissue sparing of previously irradiated tissues. In this review, we discuss the clinical applications of proton therapy for patients with breast cancer requiring reRT, the currently available literature and how it compares to historical photon reRT outcomes, treatment planning considerations, and questions in this area warranting further study. Given the dosimetric advantages of protons and the data reported to date, proton therapy is a promising option for patients who would benefit from the added locoregional disease control provided by reRT for recurrent or new primary breast cancer.

Non-cell-autonomous cancer progression from chromosomal instability.

Chromosomal instability (CIN) is a driver of cancer metastasis1-4, yet the extent to which this effect depends on the immune system remains unknown. Using ContactTracing-a newly developed, validated and benchmarked tool to infer the nature and conditional dependence of cell-cell interactions from single-cell transcriptomic data-we show that CIN-induced chronic activation of the cGAS-STING pathway promotes downstream signal re-wiring in cancer cells, leading to a pro-metastatic tumour microenvironment. This re-wiring is manifested by type I interferon tachyphylaxis selectively downstream of STING and a corresponding increase in cancer cell-derived endoplasmic reticulum (ER) stress response. Reversal of CIN, depletion of cancer cell STING or inhibition of ER stress response signalling abrogates CIN-dependent effects on the tumour microenvironment and suppresses metastasis in immune competent, but not severely immune compromised, settings. Treatment with STING inhibitors reduces CIN-driven metastasis in melanoma, breast and colorectal cancers in a manner dependent on tumour cell-intrinsic STING. Finally, we show that CIN and pervasive cGAS activation in micronuclei are associated with ER stress signalling, immune suppression and metastasis in human triple-negative breast cancer, highlighting a viable strategy to identify and therapeutically intervene in tumours spurred by CIN-induced inflammation.

Is Likert better than PI-RADS at predicting prostate cancer on MRI and can a mathematical algorithm achieve similar results?

BACKGROUND: Prostate Imaging Reporting & Data System (PI-RADS) is an internationally recognized system to quantify risk of prostate cancer on magnetic resonance imaging (MRI). However, studies have suggested methods to improve predictive accuracy. PURPOSE: To assess two different methods that aim to improve the accuracy of PI-RADS scores: a subjective Likert score given by experienced reporters, and an objective Calculated Adjustment of PI-RADS Equivocal Score (CAPES). MATERIAL AND METHODS: Five experienced reporters in a quaternary referral unit used a standardized reporting template to prospectively collect PI-RADS and Likert scores for 1467 multiparametric MRI (mpMRI) scans between January 2021 and June 2022. Histology results were recorded for patients who underwent trans-perineal biopsy. The CAPES tool was retrospectively applied to the cases scoring PI-RADS 3. A theoretical standardized biopsy protocol (assuming all patients scoring ≥3 were referred for biopsy) was used to compare the three scoring systems for sensitivity, specificity, and positive predictive value (PPV). RESULTS: Across all reporters, significantly fewer equivocal "3" scores were given using Likert (15.7%) or CAPES (2.2%) compared to PI-RADS (24.1%). Assuming a protocol where all patients scoring ≥3 were biopsied, Likert had a higher specificity (69.0% vs. 54.4%), sensitivity (98.3% vs. 97.7%), and PPV (49.9% vs. 40.3%) than PI-RADS for identifying ISUP ≥2 cancer. The CAPES tool had an even higher specificity (81.4%) and PPV (61.2%) with only a slightly lower sensitivity (93.4%) resulting in 37.1% (n = 316) fewer biopsies than PI-RADS, and 22.4% (n = 155) fewer biopsies than Likert across 1467 patients. CONCLUSIONS: Compared to PI-RADS scoring, Likert scoring or CAPES can result in fewer equivocal scores, greater PPV, and fewer unnecessary biopsies.

Regional nodal irradiation for breast cancer using volumetric modulated arc therapy: Echocardiographic functional outcomes.

Introduction: Regional nodal irradiation (RNI) for breast cancer yields improvements in disease outcomes, yet comprehensive target coverage often increases cardiac radiation (RT) dose. Volumetric modulated arc therapy (VMAT) may mitigate high-dose cardiac exposure, although often increases the volume of low-dose exposure. The cardiac implications of this dosimetric configuration (in contrast to historic 3D conformal techniques) remains uncertain. Methods: Eligible patients receiving adjuvant RNI using VMAT for locoregional breast cancer were prospectively enrolled on an IRB-approved study. Echocardiograms were performed prior to RT, at the conclusion of RT, and 6-months following RT. Echocardiographic parameters were measured by a single reader (AY) and measures were compared pre- and post-RT via the Wilcoxon rank sum test. Changes in echocardiographic parameters over time were compared to mean and max heart doses via the Spearman correlation test. Results: Among 19 evaluable patients (median age 38), 89% (n=17) received doxorubicin and 37% (n=7) received trastuzumab/pertuzumab combination therapy. All patients received VMAT-based whole-breast/chest-wall and regional nodal irradiation. Average mean heart dose was 456cGy (range 187-697cGy) and average max heart dose was 3001cGy (1560-4793cGy). Among salient echocardiographic parameters, no significant decrement in cardiac function was observed when comparing pre-RT to 6-months post-RT: mean left ventricular ejection fraction (LVEF) was 61.8 (SD 4.4) pre-RT and 62.7 (SD 3.8) 6-months post-RT (p=0.493); mean global longitudinal strain (GLS) was -19.3 (SD 2.2) pre-RT and -19.6 (SD 1.8) 6-months post-RT (p=0.627). No individual patient exhibited reduced LVEF or sustained decrement in GLS. No correlations were observed for changes in LVEF or GLS when compared to mean or maximum heart doses (p>0.1 for all). Conclusions: VMAT for left-sided RNI yielded no significant early decrement in echocardiographic parameters of cardiac function, including LVEF and GLS. No patient exhibited significant LVEF changes, and none exhibited sustained decrements in GLS. VMAT may be a reasonable approach to cardiac avoidance in patients requiring RNI, including those receiving anthracyclines and HER2-directed therapy. Larger cohorts with longer follow-up will be needed to validate these findings.

Locoregional Control Benefit of a Tumor Bed Boost for Ductal Carcinoma In Situ.

Purpose: Radiation therapy (RT) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) reduces invasive and in situ recurrences. Whereas landmark studies suggest that a tumor bed boost improves local control for invasive breast cancer, the benefit in DCIS remains less certain. We evaluated outcomes of patients with DCIS treated with or without a boost. Methods and Materials: The study cohort comprised patients with DCIS who underwent BCS at our institution from 2004 to 2018. Clinicopathologic features, treatment parameters, and outcomes were ascertained from medical records. Patient and tumor characteristics were evaluated relative to outcomes using univariable and multivariable Cox models. Recurrence-free survival (RFS) estimates were generated using the Kaplan-Meier method. Results: We identified 1675 patients who underwent BCS for DCIS (median age, 56 years; interquartile range, 49-64 years). Boost RT was used in 1146 cases (68%) and hormone therapy in 536 (32%). At a median follow-up of 4.2 years (interquartile range, 1.4-7.0 years), we observed 61 locoregional recurrence events (56 local, 5 regional) and 21 deaths. Univariable logistic regression demonstrated that boost RT was more common among younger patients (P < .001) with positive or close margins (P < .001) and with larger tumors (P < .001) of higher grade (P = .025). The 10-year RFS rate was 88.8% among those receiving a boost and 84.3% among those without a boost (P = .3), and neither univariable nor multivariable analyses revealed an association between boost RT and locoregional recurrence. Conclusions: Among patients with DCIS who underwent BCS, use of a tumor bed boost was not associated with locoregional recurrence or RFS. Despite a preponderance of adverse features among the boost cohort, outcomes were similar to those of patients not receiving a boost, suggesting that a boost may mitigate risk of recurrence among patients with high-risk features. Ongoing studies will elucidate the extent to which a tumor bed boost influences disease control rates.

Three-Fraction Accelerated Partial Breast Irradiation (APBI) Delivered With Interstitial Brachytherapy Is Safe: First Results From the Tri-fraction Radiation Therapy Used to Minimize Patient Hospital Trips (TRIUMPH-T) Trial.

PURPOSE: Shorter courses of breast radiotherapy are offered as an alternative to 4 weeks of whole-breast irradiation after lumpectomy, including brachytherapy. A prospective phase 2multi-institution clinical trial to study 3-fraction accelerated partial breast irradiation delivered by brachytherapy was conducted. METHODS AND MATERIALS: The trial treated selected breast cancers after breast-conserving surgery with brachytherapy applicators that delivered 22.5 Gy in 3 fractions of 7.5 Gy. The planning treatment volume was 1 to 2 cm beyond the surgical cavity. Eligible women were age ≥45 years with unicentric invasive or in situ tumors ≤3 cm excised with negative margins and with positive estrogen or progesterone receptors and no metastases to axillary nodes. Strict dosimetric parameters were required to be met and follow up information was collected from the participating sites. RESULTS: Two hundred patients were prospectively enrolled; however, a total of 185 patients who were enrolled were followed for a median of 3.63 years. Three-fraction brachytherapy was associated with low chronic toxicity. There was excellent or good cosmesis in 94% of patients. There were no grade 4 toxicities. Grade 3 fibrosis at the treatment site was present in 1.7% and 32% percent had grades 1 or 2 fibrosis at the treatment site. There was 1 rib fracture. Other late toxicities included 7.4% grade 1 hyperpigmentation, 2% grade 1 telangiectasias, 1.7% symptomatic seromas, 1.7% abscessed cavities, and 1.1% symptomatic fat necrosis. There were 2 (1.1%) ipsilateral local recurrences, 2 (1.1%) nodal recurrences and no distant recurrences. Other incidents included one contralateral breast cancer and 2 second malignancies (lung). CONCLUSIONS: Ultra-short breast brachytherapy is feasible and has excellent toxicity and could be an alternative to standard 5-day, 10 fraction accelerated partial breast irradiation in eligible patients. Patients from this prospective trial will continue to be followed to evaluate long-term outcomes.

Roman Urdu Hate Speech Detection Using Transformer-Based Model for Cyber Security Applications.

Social media applications, such as Twitter and Facebook, allow users to communicate and share their thoughts, status updates, opinions, photographs, and videos around the globe. Unfortunately, some people utilize these platforms to disseminate hate speech and abusive language. The growth of hate speech may result in hate crimes, cyber violence, and substantial harm to cyberspace, physical security, and social safety. As a result, hate speech detection is a critical issue for both cyberspace and physical society, necessitating the development of a robust application capable of detecting and combating it in real-time. Hate speech detection is a context-dependent problem that requires context-aware mechanisms for resolution. In this study, we employed a transformer-based model for Roman Urdu hate speech classification due to its ability to capture the text context. In addition, we developed the first Roman Urdu pre-trained BERT model, which we named BERT-RU. For this purpose, we exploited the capabilities of BERT by training it from scratch on the largest Roman Urdu dataset consisting of 173,714 text messages. Traditional and deep learning models were used as baseline models, including LSTM, BiLSTM, BiLSTM + Attention Layer, and CNN. We also investigated the concept of transfer learning by using pre-trained BERT embeddings in conjunction with deep learning models. The performance of each model was evaluated in terms of accuracy, precision, recall, and F-measure. The generalization of each model was evaluated on a cross-domain dataset. The experimental results revealed that the transformer-based model, when directly applied to the classification task of the Roman Urdu hate speech, outperformed traditional machine learning, deep learning models, and pre-trained transformer-based models in terms of accuracy, precision, recall, and F-measure, with scores of 96.70%, 97.25%, 96.74%, and 97.89%, respectively. In addition, the transformer-based model exhibited superior generalization on a cross-domain dataset.

Accuracy and Efficiency of Patient Setup Using Surface Imaging versus Skin Tattoos for Accelerated Partial Breast Irradiation.

Purpose: Skin tattoos represent the standard approach for surface alignment and setup of breast cancer radiation therapy, yet permanent skin markings contribute to adverse cosmesis and patient dissatisfaction. With the advent of contemporary surface-imaging technology, we evaluated setup accuracy and timing between "tattoo-less" and traditional tattoo-based setup techniques. Methods and Materials: Patients receiving accelerated partial breast irradiation (APBI) underwent traditional tattoo-based setup (TTB), alternating daily with a tattoo-less setup via surface imaging using AlignRT (ART). Following initial setup, position was verified via daily kV imaging, with matching on surgical clips representing ground truth. Translational shifts (TS) and rotational shifts (RS) were ascertained, as were setup time and total in-room time. Statistical analyses used the Wilcoxon signed rank test and Pitman-Morgan variance test. Results: A total of 43 patients receiving APBI and 356 treatment fractions were analyzed (174 TTB fractions and 182 using ART). For tattoo-less setup via ART, the median absolute TS were 0.31 cm in the vertical (range, 0.08-0.82), 0.23 cm in the lateral (0.05-0.86), and 0.26 cm in the longitudinal (0.02-0.72) axes. For TTB setup, the corresponding median TS were 0.34 cm (0.05-1.98), 0.31 cm (0.09-1.84), and 0.34 cm (0.08-1.25), respectively. The median magnitude shifts were 0.59 (0.30-1.31) for ART and 0.80 (0.27-2.13) for TTB. ART was not statistically distinguishable from TTB in terms of TS, except in the longitudinal direction (P = .154, .059, and .021, respectively), and was superior to TTB for magnitude shift (P < .001). The variance of each TS variable was significantly narrower for ART compared with TTB (P ≤ .001 vertical, P = .001 lateral, P = .005 longitudinal). The median absolute RS for ART was 0.64° rotation (range, 0.00-1.90), 0.65° roll (0.05-2.90), and 0.30° pitch (0.00-1.50). The corresponding median RS for TTB were 0.80° (0.00-2.50), 0.64° (0.00-3.00), and 0.46° (0.00-2.90), respectively. ART setup was not statistically different from TTB in terms of RS (P = .868, .236, and .079, respectively). ART showed lower variance than TTB in terms of pitch (P = .009). The median total in-room time was shorter for ART than TTB (15.42 vs 17.25 minutes; P = .008), as was the median setup time (11.12 vs 13.00 minutes; P = .001). Moreover, ART had a narrower distribution of setup time with fewer lengthy outliers versus TTB. Conclusions: These findings suggest that a tattoo-less setup approach with AlignRT may be sufficiently accurate and expeditious to supplant surface tattoos for patients receiving APBI. Further analyses with larger cohorts will determine whether tattoo-based approaches can be replaced by noninvasive surface imaging.

Metaplastic carcinoma of the breast: matched cohort analysis of recurrence and survival.

PURPOSE: Metaplastic breast carcinoma (MBC) is a rare subtype of breast cancer, defined as mammary carcinoma with squamous or mesenchymal differentiation, that may include spindle cell, chondroid, osseous, or rhabdomyoid differentiation patterns. The implications of MBC recurrence and survival outcomes remains unclear. METHODS: Cases were ascertained from a prospectively maintained institutional database of patients treated from 1998 to 2015. Patients with MBC were matched 1:1 to non-MBC cases. Cox proportional-hazards models and Kaplan-Meier estimates were used to evaluate outcome differences between cohorts. RESULTS: 111 patients with MBC were matched 1:1 with non-MBC patients from an initial set of 2400 patients. Median follow-up time was 8 years. Most patients with MBC received chemotherapy (88%) and radiotherapy (71%). On univariate competing risk regression, MBC was not associated with locoregional recurrence (HR = 1.08; p = 0.8), distant recurrence (HR = 1.65; p = 0.092); disease-free survival (HR = 1.52; p = 0.065), or overall survival (HR = 1.56; p = 0.1). Absolute differences were noted in 8-year disease-free survival (49.6% MBC vs 66.4% non-MBC) and overall survival (61.3% MBC vs 74.4% non-MBC), though neither of these reached statistical significance (p = 0.07 and 0.11, respectively). CONCLUSION: Appropriately-treated MBC may exhibit recurrence and survival outcomes that are difficult to distinguish from those of non-MBC. While prior studies suggest that MBC has a worse natural history than non-MBC triple-negative breast cancer, prudent use of chemotherapy and radiotherapy may narrow these differences, although studies with more power will be required to inform clinical management. Longer follow-up among larger populations may further elucidate the clinical and therapeutic implications of MBC.

Does including histological outcomes in a multiparametric MRI report improve prostate biopsy decision making?

OBJECTIVES: To see if inserting audited histological outcome data for each Likert score into prostate mpMRI reports was helpful for clinicians counselling patients and influenced prostate biopsy uptake. METHODS: A single radiologist reported 791 mpMRI scans for query prostate cancer between 2017 and 2019. A structured template which included histological outcome data from this cohort was devised and included in 207 mpMRI reports between January and June 2021. The outcomes of the new cohort were compared with the historical cohort, and with 160 contemporaneous reports without histological outcome data from the four other radiologists in the department. The opinion of this template was sought from referring clinicians who counselled patients. RESULTS: The proportion of patients biopsied fell from 58.0 to 32.9% overall between the n = 791 cohort and the n = 207 cohort. This was most noticeable in those scoring Likert 3, where the proportion biopsied fell from 78.4 to 42.9%. This reduction was also seen when comparing the biopsy rates of patients scored Likert 3 by other reporters in a contemporaneous n = 160 cohort without the audit information (65.2%) with the n = 207 cohort (42.9%). 100% of counselling clinicians were in favour and 66.7% said it gave them greater confidence to advise the patient when they did not need a biopsy. CONCLUSION: Fewer low-risk patients choose unnecessary biopsies when audited histological outcomes for the radiologist's Likert scores are included in mpMRI reports. ADVANCES IN KNOWLEDGE: Clinicians welcome reporter-specific audit information in mpMRI reports which could result in fewer biopsies.

Early effectiveness and toxicity outcomes of reirradiation after breast conserving surgery for recurrent or new primary breast cancer.

PURPOSE: Breast reirradiation (reRT) after breast conserving surgery (BCS) has emerged as a viable alternative to mastectomy for women presenting with recurrent or new primary breast cancer. There are limited data on safety of different fractionation regimens. This study reports safety and efficacy among women treated with repeat BCS and reRT. METHODS AND MATERIALS: Patients who underwent repeat BCS followed by RT from 2015 to 2021 at 2 institutions were analyzed. Univariate logistic regression models were used to identify predictors of acute and late toxicities. Kaplan-Meier estimates were used to evaluate overall survival (OS), distant metastasis-free survival (DMFS) and locoregional recurrence-free survival (LR-RFS). RESULTS: Sixty-six patients were reviewed with median follow-up of 16 months (range: 3-60 months). At time of first recurrence, 41% had invasive carcinoma with a ductal carcinoma in situ (DCIS) component, 41% had invasive carcinoma alone and 18% had DCIS alone. All were clinically node negative. For the reirradiation course, 95% received partial breast irradiation (PBI) (57.5% with 1.5 Gy BID; 27% with 1.8 Gy daily; 10.5% with hypofractionation), and 5% received whole breast irradiation (1.8-2 Gy/fx), all of whom had received PBI for initial course. One patient experienced grade 3 fibrosis, and one patient experienced grade 3 telangiectasia. None had grade 4 or higher late adverse events. We found no association between the fractionation of the second course of RT or the cumulative dose (measured as EQD2) with acute or late toxicity. At 2 years, OS was 100%, DMFS was 91.6%, and LR-RFS was 100%. CONCLUSION: In this series of patients with recurrent or new primary breast cancer, a second breast conservation surgery followed by reirradiation was effective with no local recurrences and an acceptable toxicity profile across a range of available fractionation regimens at a median follow up of 16 months. Longer follow up is required.