Aspirin use is associated with improvement in distant metastases outcome in patients with residual disease after neoadjuvant chemotherapy.

PURPOSE: Aspirin (ASA) use has been correlated with improved outcomes in high-risk patients at risk for distant metastases. Breast cancer (BC) patients with residual disease, particularly nodal disease (ypN +) after neoadjuvant chemotherapy (NAC), are high-risk patients portending worse outcomes. We hypothesized that ASA use can reduce distant metastases and improve outcomes in these patients. METHODS: Patients at our institutions from 2005 to 2018, with BC who did not achieve complete response (pCR) after NAC were reviewed (IRB protocol STU- 052012-019). Data, including evidence of ASA use, and clinico-pathologic parameters were analyzed. Survival outcomes were obtained (Kaplan Meier analysis) and univariate (UVA) and multivariable (MVA) Cox proportional hazards regression analyses were performed. RESULTS: 637 did not achieve pCR (ypN+ = 422). 138 were ASA users. Median follow-up for the control and ASA group were 3.8 (IQR 2.2-6.3) and 3.8 (IQR 2.5-6.4) years, respectively. Majority were stage II/III. 387 were hormone receptor positive, 191 HER2 +, and 157 triple negative. On UVA, ASA use, PR status, pathologic and clinical stage showed significance for DMFS, and disease-free survival (DFS). On MVA, ASA use associated with improved 5-year DFS (p = .01, 87.0% vs 79.6%, adjusted HR = 0.48) and improved 5-year DMFS (p = .04, 92.8% vs 89.2%, adjusted HR = 0.57). In the ypN + patients, ASA use associated with improved 5-year DMFS (p = .008, 85.7% vs 70.7%, adjusted HR = 0.43) and DFS (p = .02, 86.8% vs 74.3%, adjusted HR = 0.48). CONCLUSION: For non-responders, particularly ypN + patients, ASA use associated with improved outcome. These hypotheses-generating results suggest for development of prospective clinical trials of augmented ASA use in selected very high-risk BC patients.

On the feasibility of improved target coverage without compromising organs at risk using online adaptive stereotactic partial breast irradiation (A-SPBI).

PURPOSE: Describe an early-adopting institution's experience with online adaptive radiation for stereotactic partial breast irradiation. METHODS AND MATERIALS: Retrospective review of 22 women treated between May 2021 and March 2022 with adaptive stereotactic partial breast irradiation. A total of 106 of 110 fractions were evaluated for dosimetric changes in target coverage and organ-at-risk (OAR) dose. Patient set up with stereotactic wooden frame and adapted per fraction. Treatment and planning times were collected prospectively by radiation therapists. RESULTS: Scheduled PTV30 Gy was <95% in 72.1% and <90% in 38.5% of fractions, and both PTV and CTV coverage were improved significantly after adaption, and 83.7% of fractions were delivered as adapted per physician choice. There was no difference in OAR coverage. Average adaptive treatment planning took 15 min and average time-on-couch was 34.4 min. CONCLUSIONS: Adaptive stereotactic breast irradiation resulted in improved target coverage with equivalent dosing to OARs in an efficient and tolerated treatment time. Improved target coverage allowed for decreased PTV margins compared to prior trial protocols that may improve acute and late toxicities.

Stereotactic Partial Breast Irradiation: What Does the Future Hold?

Breast irradiation has evolved significantly over the last several decades. Accelerated partial breast and stereotactic breast irradiation have evolved as strategies to reduce irradiated volumes, preserve appropriate oncologic control, and improve cosmetic outcome. The sequencing and/or combination of stereotactic partial breast irradiation with novel systemic agents is of great interest to the oncologic community. Here we explore the landscape of modern trials and opine on the future of partial breast irradiation.

Case Report: Adaptive radiotherapy in the radiation salvage of prostate cancer.

Adaptive radiotherapy has the potential to reduce margins, improve target coverage, and decrease toxicity to organs at risk (OARs) by optimizing radiation delivery to daily anatomic changes. Salvage for locally recurrent prostate cancer after definitive radiation remains a challenging clinical scenario given the risks to normal tissue in a setting of re-irradiation. Here, we present a case series of five patients with locally recurrent prostate cancer treated with an adaptive online linear accelerator or a 3-T MR-based linear accelerator to demonstrate excellent target coverage. All patients completed the planned treatment course with acceptable acute toxicities but a short follow-up time does not inform subacute/late toxicities.

Automated Text Message Reminders Improve Radiation Therapy Compliance.

PURPOSE: Protraction of radiation therapy courses can lead to lower cancer control and cancer-specific survival rates. The requirement for daily, consecutive radiation treatments coupled with the complexities of multimodality cancer care and quality assurance can occasionally lead to missed patient appointments or clinical inefficiency. To determine whether an automated text messaging (short message service [SMs]) platform could improve patient compliance with scheduled radiation therapy delivery, we created an automated SMS platform to send daily reminders of radiation therapy appointments. METHODS AND MATERIALS: An automated SMS text messaging program was used from July 2016 to January 2017 to deliver daily appointment time reminders to patients on an elective basis. Automated text messages were sent 2 hours before treatment appointments with appointment-specific information. We analyzed for compliance with radiation therapy appointments for patients who elected to receive SMS reminders versus those who did not. RESULTS: Multivariate analysis of >37,000 encounters involving ∼3400 patients demonstrated that of the factors considered, nonreceipt of SMS appointment reminders had a strong association with 15- to 60-minute tardiness (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.13-1.38; P < .0001), >60-minute tardiness (OR, 1.56; 95% CI, 1.34-1.82; P < .0001) and no-shows (OR, 6.77; 95% CI, 5.45-8.41; P < .0001). Other demographic factors associated with decreased compliance included being early in a radiation therapy course, having an appointment earlier in the day, younger age, and male sex. Receipt of an SMS message did not correlate with overall treatment package time. CONCLUSIONS: Receipt of text messages correlates with compliance for radiation therapy appointments. Prospective randomized trials would be required to determine conclusively whether SMS is an effective intervention for improving compliance in populations at risk for being late to or missing radiation therapy appointments.

Toward biocompatible dinitrosyl iron complexes: sugar-appended thiolates.

Both monomeric and dimeric tetraacetylglucose-containing {Fe(NO)2}9 dinitrosyl iron complexes (DNICs) were prepared and examined for NO release in the presence of both chemical NO-trapping agents and endothelial cells.

Rationale for RAS mutation-tailored therapies.

RAS mutations are among the most common genetic alterations found in cancerous tumors but rational criteria or strategies for targeting RAS-dependent tumors are only recently emerging. Clinical and laboratory data suggest that patient selection based on specific RAS mutations will be an essential component of these strategies. A thorough understanding of the biochemical and structural properties of mutant RAS proteins form the theoretical basis for these approaches. Direct inhibition of KRAS G12C by covalent inhibitors is a notable recent example of the RAS mutation-tailored approach that establishes a paradigm for other RAS mutation-centered strategies.

Metallodithiolates as ligands to dinitrosyl iron complexes: toward the understanding of structures, equilibria, and spin coupling.

Metallodithiolate ligands are used to design heterobimetallic complexes by adduct formation through S-based reactivity. Such adducts of dinitrosyl iron were synthesized with two metalloligands, namely, Ni(bme-daco) and V≡O(bme-daco) (bme-daco = bismercaptoethane diazacyclooctane), and, for comparison, an N-heterocyclic carbene, namely, 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene (Imes), by cleavage of the (µ-I)2[Fe(NO)2]2 dimer of electronic configuration {Fe(NO)2}(9) (Enemark-Feltham notation). With Fe(NO)2I as Lewis acid acceptor, 1:1 adducts resulted for both the IMes·Fe(NO)2I, complex 2, and V≡O(bme-daco)·Fe(NO)2I, complex 4. The NiN2S2 demonstrated binding capability at both thiolates, with two Fe(NO)2I addenda positioned transoid across the NiN2S2 square plane, Ni(bme-daco)·2(Fe(NO)2I), complex 3. Enhanced binding ability was realized for the dianionic vanadyl dithiolate complex, [Et4N]2[V≡O(ema)], (ema = N,N'-ethylenebis(2-mercaptoacetamide)), which, unlike the neutral (V≡O)N2S2, demonstrated reactivity with the labile tungsten carbonyl complex, cis-W(CO)4(pip)2, (pip = piperidine), yielding [Et4N]2[V≡O(ema)W(CO)4], complex 1, whose ν(CO) IR values indicated the dianionic vanadyl metalloligand to be of similar donor ability to the neutral NiN2S2 ligands. The solid-state molecular structures of 1-4 were determined by X-ray diffraction analyses. Electron paramagnetic resonance (EPR) measurements characterize the {Fe(NO)2}(9) complexes in solution, illustrating superhyperfine coupling via the (127)I to the unpaired electron on iron for complex 2. The EPR characterizations of 3 [Ni(bme-daco)·2(Fe(NO)2I)] and 4 [V≡O(bme-daco)·Fe(NO)2I] indicate these complexes are EPR silent, likely due to strong coupling between paramagnetic centers. Within samples of complex 4, individual paramagnetic centers with localized superhyperfine coupling from the (51)V and (127)I are observed in a 3:1 ratio, respectively. However, spin quantitation reveals that these species represent a minor fraction (<10%) of the total complex and thus likely represent disassociated paramagnetic sites. Computational studies corroborated the EPR assignments as well as the experimentally observed stability/instability of the heterobimetallic DNIC complexes.

Versatile N2S2 nickel-dithiolates as mono- and bridging bidentate, S-donor ligands to gold(I).

Development of square planar cis-dithiolate nickel complexes as metallo S-donor ligands focuses on the synthesis and structures of gold(I) heterometallic clusters derived from assemblage with three NiN2S2 complexes: Ni(bme-daco), Ni(bme-dach) and Ni(ema)(2-) (bme-daco = (bismercaptoethanediazacyclooctane); bme-dach = bismercaptoethanediazacycloheptane; and ema = N,N'-ethylenebis-2-mercaptoacetamide). With Ph3PAuCl as the gold source, examples of simple S-aurolation retaining the PPh3 on Au(+) were obtained for [{Ni(bme-daco)}AuPPh3](+)Cl(-) and [{Ni(ema)}2Au4(PPh3)4], where the latter complex demonstrated unsupported aurophilic interactions between [{Ni(ema)}Au2(PPh3)2] units in its X-ray crystal structure (Au-Au = 3.054 and 3.127 Å). Three compounds containing fully-supported digold units with Au-Au distances in the aurophilic range of 3.11 to 3.13 Å were found as stair-step structures in which planar NiN2S2 step treads are connected by planar S2Au2S2 risers at ca. 90°: [{Ni(bme-daco)}2Au2](2+)(Cl(-))2; [{Ni(bme-dach)}2Au2](2+)(Cl(-))2; and (Et4N(+))2[{Ni(ema)}2Au2](2-). Electrochemical data from cyclic voltammograms demonstrated a positive shift in Ni(II/I) couples for the [{NiN2S2}xAuy] complexes as compared to the NiN2S2 precursors and a ca. 700 mV decrease in communication between multiple NiN2S2 units as compared to [{NiN2S2}2Ni](2+) analogues in slant chair conformation. The analogy between NiN2S2 metallodithiolate ligands and diphosphine ligands holds here as in other examples of inorganic and organometallic complexes.