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Currently, there are multiple breast dosimetry estimation methods for mammography and its variants in use throughout the world. This fact alone introduces uncertainty, since it is often impossible to distinguish which model is internally used by a specific imaging system. In addition, all current models are hampered by various limitations, in terms of overly simplified models of the breast and its composition, as well as simplistic models of the imaging system. Many of these simplifications were necessary, for the most part, due to the need to limit the computational cost of obtaining the required dose conversion coefficients decades ago, when these models were first implemented. With the advancements in computational power, and to address most of the known limitations of previous breast dosimetry methods, a new breast dosimetry method, based on new breast models, has been developed, implemented, and tested. This model, developed jointly by the American Association of Physicists in Medicine and the European Federation for Organizations of Medical Physics, is applicable to standard mammography, digital breast tomosynthesis, and their contrast-enhanced variants. In addition, it includes models of the breast in both the cranio-caudal and the medio-lateral oblique views. Special emphasis was placed on the breast and system models used being based on evidence, either by analysis of large sets of patient data or by performing measurements on imaging devices from a range of manufacturers. Due to the vast number of dose conversion coefficients resulting from the developed model, and the relative complexity of the calculations needed to apply it, a software program has been made available for download or online use, free of charge, to apply the developed breast dosimetry method. The program is available for download or it can be used directly online. A separate User's Guide is provided with the software., (© 2023 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Purpose: Because of the negative impact of cancer treatment on female sexual function, effective treatments are warranted. The purpose of this multisite study was to evaluate the ability of two dose levels of extended-release bupropion, a dopaminergic agent, to improve sexual desire more than placebo at 9 weeks, measured by the desire subscale of the Female Sexual Function Index (FSFI), and to evaluate associated toxicities., Methods: Postmenopausal women diagnosed with breast or gynecologic cancer and low baseline FSFI desire scores (< 3.3), who had completed definitive cancer therapy, were eligible. Women were randomly assigned to receive 150 mg or 300 mg once daily of extended-release bupropion or a matching placebo. t -tests were performed on the FSFI desire subscale to evaluate whether there was a significantly greater change from baseline to 9 weeks between placebo and each bupropion arm as the primary end point. Sixty-two patients per arm provided 80% power using a one-sided t -test., Results: Two hundred thirty women were randomly assigned from 72 institutions through the NRG Oncology NCORP network. At 9 weeks, there were no statistically significant differences in change of the desire subscale scores between groups; participants in all three arms reported improvement. The mean changes for each arm were placebo 0.62 (standard deviation [SD] = 1.18), 150-mg once daily bupropion 0.64 (SD = 0.95), and 300-mg once daily bupropion 0.60 (SD = 0.89). Total and subscale scores on the FSFI were low throughout the study, indicating dysfunction in all groups., Conclusion: Bupropion was not more effective than placebo in improving the desire subscale of the FSFI. Subscale and total scores of the FSFI demonstrated dysfunction throughout the 9 weeks of the study. More research is needed to support sexual function in female cancer survivors., Competing Interests: Debra L. BartonResearch Funding: Merck Stephanie L. PughResearch Funding: Pfizer (Inst), Millennium (Inst) Patricia A. GanzLeadership: Intrinsic LifeSciences (I)Stock and Other Ownership Interests: Xenon Pharma (I), Intrinsic LifeSciences (I), Teva, Novartis, Merck, Johnson & Johnson, Pfizer, GlaxoSmithKline, Abbott LaboratoriesConsulting or Advisory Role: InformedDNA, Vifor Pharma (I), Ambys Medicines (I), Global Blood Therapeutics (I), GlaxoSmithKline (I), Ionis Pharmaceuticals (I), Protagonist Therapeutics (I), Akebia Therapeutics (I), Regeneron (I), Sierra Oncology (I), Rockwell Medical Technologies Inc (I), Astellas Pharma (I), Gossamer Bio (I), American Regent (I), Disc Medicine (I), Blue Note Therapeutics (I), Grail (I)Research Funding: Blue Note Therapeutics (Inst)Patents, Royalties, Other Intellectual Property: Related to iron metabolism and the anemia of chronic disease, UpToDate royalties for section editor on survivorshipTravel, Accommodations, Expenses: Intrinsic LifeSciences (I) Steven C. PlaxeStock and Other Ownership Interests: Pfizer, Merck, Zimmer Biomet, GlaxoSmithKline, AstraZeneca, Bristol Myers Squibb/Pfizer, Johnson & Johnson/JanssenResearch Funding: Endocyte, Incyte, MedImmune, Novartis, Pfizer, Janssen Oncology, BIND Therapeutics, PharmaMar, AstraZeneca, Kevelt, Millennium, Tesaro Bridget F. KoontzEmployment: GenesisCareLeadership: GenesisCareConsulting or Advisory Role: Blue Earth Diagnostics, Myovant Sciences, Rythera TherapeuticsResearch Funding: Janssen, Merck, Blue Earth DiagnosticsPatents, Royalties, Other Intellectual Property: Demos Publishing Matthew L. HillStock and Other Ownership Interests: AstraZeneca, Newlink Genetics, Kazia Therapeutics, Leap Therapeutics, OncoSec, MEI Pharma, PLx Pharma, Radius Health, Crispr Therapeutics, Cassava SciencesOpen Payments Link: https://openpaymentsdata.cms.gov/physician/820072 Carolyn Y. MullerResearch Funding: AstraZeneca, Genmab, VBL Therapeutics, Roche/Genentech, TapImmune Inc, Linnaeus Therapeutics, Agenus, Incyte, MerckPatents, Royalties, Other Intellectual Property: Have a pending patent on the cancer use for R-ketorolac—not yet its own new drugOther Relationship: NCI, Department of Defense Lisa A. KachnicConsulting or Advisory Role: New B InnovationResearch Funding: Varian Medical SystemsPatents, Royalties, Other Intellectual Property: UpToDateNo other potential conflicts of interest were reported.

Purpose: Contrast-Enhanced Mammography (CEM) produces a dual-energy subtracted (DES) image that demonstrates iodine uptake (neovascularity) in breast tissue. We aim to review a range of artifacts on DES images produced using equipment from two different vendors and compare their incidence and subjective severity., Methods: We retrospectively reviewed CEM studies performed between September 2013 and March 2017 using GE Senographe Essential (n = 100) and Hologic Selenia Dimensions (n = 100) equipment. Artifacts were categorized and graded in severity by a subspecialist breast radiologist and one of two medical imaging technologists in consensus. The incidence of artifacts between vendors was compared by calculating the relative risk, and the severity gradings were compared using a Wilcoxon rank-sum test., Results: Elephant rind, corrugations and the black line on chest wall artifact were seen exclusively in Hologic images. Artifacts such as cloudy fat, negative rim around lesion and white line on pectoral muscle were seen in significantly more Hologic images (p < 0.05) whilst halo, ripple, skin line enhancement, black line on pectoral muscle, bright pectorals, chest wall high-lighting and air gap were seen in significantly more GE images (p < 0.05). The severity gradings for cloudy fat had a significantly higher mean rank in Hologic images (p < 0.001) whilst halo and ripple artifacts had a significantly higher mean rank in GE images (p < 0.001 and p = 0.028 respectively)., Conclusion: The type, incidence and subjective severity of CEM-specific artifacts differ between vendors. Further research is needed, but differences in algorithms used to produce the DE image are postulated to be a significant contributor., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: Preclinical studies report that trastuzumab (T) can boost radiotherapy (RT) effectiveness. The primary aim of the B-43 trial was to assess the efficacy of RT alone vs concurrent RT plus T in preventing recurrence of ipsilateral breast cancer (IBTR) in women with ductal carcinoma in situ (DCIS)., Patients and Methods: Eligibility: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, DCIS resected by lumpectomy, known estrogen receptor (ER) and/or progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) status by centralized testing. Whole-breast RT was given concurrently with T. Stratification was by menopausal status, adjuvant endocrine therapy plan, and nuclear grade. Definitive intent-to-treat primary analysis was to be conducted when either 163 IBTR events occurred or all accrued patients were on study ≥ 5 years., Results: There were 2,014 participants who were randomly assigned. Median follow-up time as of December 31, 2019, was 79.2 months. At primary definitive analysis, 114 IBTR events occurred: RT arm, 63 and RT plus T arm, 51 (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.17; P value = .26). There were 34 who were invasive: RT arm, 18 and RT plus T arm, 20 (HR, 1.11; 95% CI, 0.59 to 2.10; P value = .71). Seventy-six were DCIS: RT arm, 45 and RT plus T arm, 31 (HR, 0.68; 95% CI, 0.43 to 1.08; P value = .11). Annual IBTR event rates were: RT arm, 0.99%/y and RT plus T arm, 0.79%/y. The study did not reach the 163 protocol-specified events, so the definitive analysis was triggered by all patients having been on study for ≥ 5 years., Conclusion: Addition of T to RT did not achieve the objective of 36% reduction in IBTR rate but did achieve a modest but statistically nonsignificant reduction of 19%. Nonetheless, this trial had negative results. Further exploration of RT plus T is needed in HER2-positive DCIS before its routine delivery in patients with DCIS resected by lumpectomy., Competing Interests: Melody A. CobleighConsulting or Advisory Role: Roche/Genentech, Immunomedics, Genomic Health, Puma Biotechnology, Seattle GeneticsResearch Funding: Macrogenics, Radius Health, Genentech/Roche, Seattle Genetics, Zymeworks, SynthonPatents, Royalties, Other Intellectual Property: Genomic HealthTravel, Accommodations, Expenses: Genentech, Immunomedics, Puma Biotechnology, Seattle Genetics Stewart J. AndersonConsulting or Advisory Role: Jazz Pharmaceuticals Kalliopi P. SiziopikouHonoraria: Ventana Medical Systems, Lilly, Merck Douglas W. ArthurStock and Other Ownership Interests: Advanced Radiation Therapy Rachel RabinovitchStock and Other Ownership Interests: Abbott Laboratories, Bristol-Myers Squibb, Intuitive Surgical, IDEXX LaboratoriesResearch Funding: Prelude Therapeutics Dennis L. CarterEmployment: Rocky Mountain Cancer Centers Melissa S. DillmonStock and Other Ownership Interests: Johnson & JohnsonConsulting or Advisory Role: Puma Biotechnology Vivek S. KavadiEmployment: US Oncology Network Matthew L. HillStock and Other Ownership Interests: AstraZeneca, Newlink Genetics, Kazia Therapeutics, Leap Therapeutics, OncoSec, MEI Pharma, PLx Pharma, Radius Health, Crispr Therapeutics, Cassava Sciences Sushil BeriwalHonoraria: Varian Medical Systems, XOFT Eleftherios P. MamounaHonoraria: Genentech/Roche, Genomic Health, PreciscaConsulting or Advisory Role: Genomic Health, BioTheranostics, Roche/Genentech, Merck, Daiichi Sankyo, Puma Biotechnology, PreciscaSpeakers' Bureau: Genomic Health, Genentech/RocheTravel, Accommodations, Expenses: Genomic Health, Genentech/RocheNo other potential conflicts of interest were reported.

Despite molecular biological advances in understanding human cancers, translation into therapy has been less forthcoming; targeting neoplastic cells still requires that tumor-specific markers, preferably those on the cell surface, be identified. The epidermal growth factor receptor (EGFR) exists in a deletion-mutant form, EGFRvIII, which has been identified by genetic and immunological means in a subset of gliomas and non-small cell lung carcinomas. Specific polyvalent antisera to the extracellular portion of the variant were readily induced, but immunization using a synthetic linear peptide representing the unique EGFRvIII primary sequence has been unsuccessful in mice or macaques. We report here five specific monoclonal antibodies (mAbs) developed through long-term immunization protocols using the EGFRvIII-specific synthetic peptide and the intact variant in different formats that maintained secondary and tertiary conformation. These mAbs identify the EGFRvIII on the cell surface with relatively high affinity (KA range, 0.13 to 2.5 x 10(9) M-1) by live cell Scatchard analysis. These mAbs are specific for EGFRvIII as determined by RIA, ELISA, Western blot, analytical flow cytometry, autophosphorylation, and immunohistochemistry. Isolating specific mAbs enabled us to analyze normal and neoplastic human tissue and establish that EGFRvIII is truly tumor specific for subsets of breast carcinomas and for previously reported non-small cell lung carcinomas and gliomas. Also, this receptor is not expressed by any normal human tissues thus far examined, including elements of the peripheral, central nervous, and lymphoid systems. With mAbs, we identified a higher incidence of EGFRvIII positivity in gliomas than previously described and identified an EGFRvIII-positive subset of breast tumors; also, we observed that the EGFRvIII epitope is not expressed in normal tissues, and we demonstrated the localizing and therapeutic potential of the mAbs for tumors expressing this epitope. Our observations strongly warrant development of this mAb-antigen system as therapy for breast, lung, and central nervous system tumors.