Citations

Background: Paclitaxel-treated patients can suffer from years of peripheral neuropathy with pain, numbness, and tingling. Promising preclinical data with poly (ADP-ribose) polymerase (PARP) inhibitors led us to explore this class of agents to palliate this neuropathy. Methods: We relied on a completed trial that tested the antineoplastic effects of veliparib (NCT01012817). Data from patients who had been enrolled on NCT01012817, who previously received paclitaxel, and who had completed a validated pain assessment instrument were evaluated for improvement in their pain scores. Results: All 34 eligible patients were women, and all had a metastatic gynecological malignancy. On a 10-point scale (higher numbers indicative of worse pain), the average baseline score was 3.6 (range: 0-7). Seven patients (21%; 95% confidence interval: 9%-38%) manifested a drop in pain score (1 score lower than baseline followed by at least one consecutive value also below baseline). Of note, no patients initiated other therapy for neuropathy while on NCT01012817. Conclusion: The PARP inhibitors merit further study for chemotherapy-induced peripheral neuropathy. For patients suffering from peripheral neuropathy, these putative palliative effects might prompt earlier consideration of a PARP inhibitor as part of cancer treatment.

ObjectiveThe primary aim of this study was to determine the inter‐ and intrarater reliability of ultrasound (US) measurements of the ischiofemoral space (IFS) following a brief training session. A secondary aim was to determine if reliability correlated with sonographer experience.DesignProspective cohort study.SettingPhysical medicine and rehabilitation department within a tertiary care institution.ParticipantsSeven male and 3 female individuals were recruited to serve as models. Nine physician sonographers (3 postgraduate year [PGY]‐2 residents, 3 PGY‐4 residents, 3 physicians) were recruited to serve as sonographers.Methods or InterventionsSonographers received a 15‐minute educational session on identifying the IFS with US, followed by 20 minutes of practice. Models were then placed in a prone position and secured to prevent hip movement. All operators measured bilateral IFSs in each model twice with a washout period between measurements. Operators were blinded to all measurements.Main Outcome MeasuresPrimary outcomes were inter‐ and intrarater reliability interclass coefficients (ICCs) of IFS measurements among the groups with different levels of US experience. Secondary outcomes included comparisons of inter‐ and intrarater reliability ICCs of IFS measurements between groups, and the difference of mean IFS measurements between groups.ResultsIntrarater reliability ICCs were 0.829, 0.680, and 0.596 for physician, PGY‐4, and PGY‐2 groups, respectively. Interrater reliability ICCs were 0.722, 0.427, and 0.558 for physician, PGY‐4, and PGY‐2 groups, respectively. No statistically significant differences in reliability were identified between groups. Mean IFS measurements were 31.2, 33.4, and 34.0 mm for physician, PGY‐4, and PGY‐2 groups, respectively. Physician measurements were significantly smaller than the PGY‐4 and PGY‐2 measurements (P < .049 and P < .01).ConclusionsFollowing a brief training session, experienced sonographers demonstrated excellent IFS measurement intrarater reliability, whereas PGY‐4 and PGY‐2 sonographers demonstrated fair intrarater reliability. All sonographers demonstrated fair interrater reliability.Level of EvidenceII

A national conversation regarding the price and affordability of drugs exists, where concern for value and benefits of medications is challenged by the increasing price of both injectable and oral medications, including the cost of care of myeloma. At the same time, we have seen unprecedented improvements in the overall survival of patients with myeloma, mostly because of the availability of these new drugs. Here, we present data to assert that these medications and associated expenses are of direct benefit to patients and society. The entrepreneurial reward for drug development in the United States has fueled vigorous drug development efforts that have culminated in the approval of 11 new drugs for the treatment of myeloma by the U.S. Food and Drug Administration (FDA) since 1999. These patented drugs are available to patients in the United States usually at a higher price than in the rest of the world. Nevertheless, the majority of patients, via direct copay assistance or through indirect support via third parties, have access to these drugs irrespective of their socioeconomic status. One of the major regulatory hurdles that prevents access to these drugs is the legal impossibility that pharmaceutical companies have in directly supporting copay assistance for patients with government-funded health care. Moreover, assessments of value should include formal pharmacoeconomic analyses performed by experts. Interference with market forces and coercive action, such as price controls, or exercising eminent domain in the quest for cheaper medications will stymie innovation and rob us of the cures of the future.

Abstract In high resolution imaging of biologic structure, atomic lorce microscopy (AFM) has been prevailing over scanning tunneling microscopy (STM). This is primarily because biologic materials do not conduct electricity, and STM requires that electrons flow to or from the surface of the specimen, whereas electron flow is not required for AFM. Microscopists intent on using STM have compensated by coating specimens with a thin coat of metal. However, the presence of metal atoms on the surface degrades the resolution. A new development may make STM more useful to biologists than ever before.

Abstract OBJECTIVE: Neoadjuvant endocrine therapy (NET) is increasingly used for the treatment of low and intermediate grade, hormone receptor positive, HER2 negative breast cancer. Several MRI phenotypes that may predict response to neoadjuvant chemotherapy (NAC) have been identified, but little data exists for phenotypes associated with response to NET. This study analyzed imaging phenotypes for all patients treated with NET with the aim to identify specific features that can be predictive of response to therapy. MATERIALS AND METHODS: The study was retrospective and included 21 patients with clinical stage I, II, and III breast cancer. The tumors were grade 1 or 2, estrogen receptor (ER) positive in &gt;20% of cells, and HER2 non-amplified. MRI examinations were performed in all women before NET. MRI interpretation included mass shape, non-mass enhancement (NME) pattern, background parenchymal enhancement, and MRI phenotype (I well-defined unicentric mass; II well defined multilobulated mass; III area enhancement with nodularity; IV area enhancement without nodularity; V septal spreading). Type of neoadjuvant endocrine therapy included: tamoxifien alone, an aromatase inhibitor (AI) alone, AI + ovarian suppression, and AI + a non-chemotherapeutic agent. Patients received NET for a total duration ranging between 3 - 6 months, with one patient receiving therapy for 18 months. Clinically meaningful response was defined as stable or decreased tumor size by clinical exam and confirmed at resection by comparing final pathologic T stage with clinical T stage. RESULTS: Twenty-one patients were identified. Median age was 62 (range 36-84) years. Most were post-menopausal 17 (81%). Pre-neoadjuvant meadian tumor size on MRI was 3.9 (range 1.0-7.5) cm and comprised T1 3 (14.3%), T2 8 (38.1%), T3/4 10 (47.6%). Pre-treatment N stage was N0 14 (66.7%), N1 7 (33.3%) and pre-NET stage was I in 3 (14.3%), II in 8 (38.1%), and III in 10 (47.6%) patients. The majority 17 (81%) had some tumor reduction, and 4 (19%) had no response. No one achieved a complete response. Of the 17 responders, 7 (41%) had a good response defined as &gt;25% decrease in tumor size. Median tumor size after NET was 3.1 (range 0.6-11) cm and the distribution of T stage was T1 7 (33.3%), T2 9 (42.9%), and T3/4 5 (23.8%). Eleven of 12 (92%) patients with well-defined phenotypes had a response as compared to 6 of 9 (67%) patients with non-well defined phenotypes. Phenotype was not predictive of a good response to therapy, 4 were in the well-defined phenotype and 3 were in the non-well defined phenotype groups. All 4 non-responders had moderate or marked background enhancement as compared to 5 of 17 responders (p = 0.02). CONCLUSION: A well-defined pre treatment MRI phenotype was significantly predictive of a positive response to NET, while a non well-defined MRI phenotype and higher degree of background enhancement was significantly predictive of negative response to NET. This warrants further prospective evaluation, especially in association with Ki-67 levels. If validated, pre treatment MRI phenotype can be applied in the clinical decision to either initiate NET or referral for upfront surgical resection. Citation Format: Hilal T, Covington M, Pockaj B, Northfelt D, Wu T, Zwart C, Li J, Patel BK. Pre-neoadjuavnt therapy MRI phenotype can predict response to neoadjuvant endocrine therapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-02-03.