Citations

627 Background: With more centers using MRI to aid in initial staging, there is apprehension that the highly sensitive MRI exam may lead to “unnecessary” mastectomies. We evaluated whether a negative contralateral MRI could be used to rule out a synchronous contralateral carcinoma and hence avoid a prophylactic contralateral mastectomy (CPM) at initial breast cancer diagnosis. Methods: Data of women with a new diagnosis of breast cancer (invasive or DCIS) from February 2003-November 2007 at our institution were reviewed. Women who had a negative MRI of the contralateral breast and who subsequently underwent CPM were included. A CPM was one in which there was no histological confirmation of cancer in the contralateral breast before surgery. All mastectomy specimens were analyzed pathologically. True negatives were mastectomy samples which contained no cancer following pathologic examination. False negatives were mastectomy samples which were found to have cancer after pathologic review. Results: 538 women were identified. 51 women met the study criteria. Median patient age was 56 years (range, 33–77). Of the 51 women who underwent a CPM, 2 were found to have pathologic confirmation of cancer. One occult cancer was a 0.3 cm grade 1, invasive lobular carcinoma; the second a 0.5 cm, low grade DCIS. The overall prevalence of synchronous occult contralateral cancer after a negative MRI was 3.9% (95% CI 0.5 - 13.5%). The negative predictive value of MRI was 96.1% (95% CI 86.5 - 99.5%). Conclusions: This study provides pathologic data regarding the utility of a negative contralateral breast MRI in women with newly diagnosed breast cancer. The prevalence of a synchronous occult contralateral cancer after a negative MRI in women with newly diagnosed breast cancer is very low. Physicians and patients can be assured that the risk of occult cancer is low in the setting of a normal contralateral MRI, an important fact when considering CPM after a diagnosis of unilateral breast cancer. No significant financial relationships to disclose.

Background The aggressive clinical behavior of poorly differentiated and anaplastic thyroid cancers (PDTC and ATC) has proven challenging to treat, and survival beyond a few months from diagnosis is rare. Although 30%–60% of these tumors contain mutations in the BRAF gene, inhibitors designed specifically to target oncogenic BRAF have shown limited and only short-lasting therapeutic benefits as single agents, thus highlighting the need for improved treatment strategies, including novel combinations. Methods Using a BRAFV600E-driven mouse model of ATC, we investigated the therapeutic efficacy of the combination of BRAF inhibition and oncolytic herpes simplex virus (oHSV). Analyses of samples from tumor-bearing mice were performed to immunologically characterize the effects of different treatments. These immune data were used to inform the incorporation of immune checkpoint inhibitors into triple combination therapies. Results We characterized the immune landscape in vivo following BRAF inhibitor treatment and detected only modest immune changes. We, therefore, hypothesized that the addition of oncolytic virotherapy to BRAF inhibition in thyroid cancer would create a more favorable tumor immune microenvironment, boost the inflammatory status of tumors and improve BRAF inhibitor therapy. First, we showed that thyroid cancer cells were susceptible to infection with oHSV and that this process was associated with activation of the immune tumor microenvironment in vivo. Next, we showed improved therapeutic responses when combining oHSV and BRAF inhibition in vivo, although no synergistic effects were seen in vitro, further confirming that the dominant effect of oHSV in this context was likely immune-mediated. Importantly, both gene and protein expression data revealed an increase in activation of T cells and natural killer (NK) cells in the tumor in combination-treated samples. The benefit of combination oHSV and BRAF inhibitor therapy was abrogated when T cells or NK cells were depleted in vivo. In addition, we showed upregulation of PD-L1 and CTLA-4 following combined treatment and demonstrated that blockade of the PD-1/PD-L1 axis or CTLA-4 further improved combination therapy. Conclusions The combination of oHSV and BRAF inhibition significantly improved survival in a mouse model of ATC by enhancing immune-mediated antitumor effects, and triple combination therapies, including either PD-1 or CTLA-4 blockade, further improved therapy.

Abstract Background: Lung cancer remains the leading cause of cancer death worldwide, with 15% to 20% occurring in never smokers. To assess genetic determinants for prognosis among never smokers, we conducted a genome-wide investigation in the International Lung Cancer Consortium (ILCCO). Methods: Genomic and clinical data from 1,569 never-smoking patients with lung cancer of European ancestry from 10 ILCCO studies were included. HRs and 95% confidence intervals of overall survival were estimated. We assessed whether the associations were mediated through mRNA expression–based 1,553 normal lung tissues from the lung expression quantitative trait loci (eQTL) dataset and Genotype-Tissue Expression (GTEx). For cross-ethnicity generalization, we assessed the associations in a Japanese study (N = 887). Results: One locus at 13q22.2 was associated with lung adenocarcinoma survival at genome-wide level, with carriers of rs12875562-T allele exhibiting poor prognosis [HR = 1.71 (1.41–2.07), P = 3.60 × 10−8], and altered mRNA expression of LMO7DN in lung tissue (GTEx, P = 9.40 × 10−7; Lung eQTL dataset, P = 0.003). Furthermore, 2 of 11 independent loci that reached the suggestive significance level (P < 10−6) were significant eQTL affecting mRNA expression of nearby genes in lung tissues, including CAPZB at 1p36.13 and UBAC1 at 9q34.3. One locus encoding NWD2/KIAA1239 at 4p14 showed associations in both European [HR = 0.50 (0.38–0.66), P = 6.92 × 10−7] and Japanese populations [HR = 0.79 (0.67–0.94), P = 0.007]. Conclusions: Based on the largest genomic investigation on the lung cancer prognosis of never smokers to date, we observed that lung cancer prognosis is affected by inherited genetic variants. Impact: We identified one locus near LMO7DN at genome-wide level and several potential prognostic genes with cis-effect on mRNA expression. Further functional genomics work is required to understand their role in tumor progression.

Breast cancer treatment-related lymphedema (BCRL) is a common comorbidity in breast cancer survivors. Although magnetic resonance imaging (MRI) is widely used to evaluate therapeutic response of patients with various medical conditions, it is not routinely used to evaluate lymphedema patients. We conducted a systematic review of the literature to identify studies on the use of MRI to evaluate therapy for BCRL. We hypothesized that MRI could provide information otherwise not possible through other examinations. On October 21, 2019, we conducted a systematic review on the PubMed/MEDLINE and Scopus databases, without time frame or language limitations, to identify studies on the use of MRI to evaluate therapy for BCRL. We excluded studies that investigated other applications of MRI, such as lymphedema diagnosis and surgical planning. Of 63 potential articles identified with the search, three case series fulfilled the eligibility criteria. In total, 53 patients with BCRL were included and quantitatively evaluated with MRI before and after manual lymphatic drainage. Authors used MRI or MR lymphagiography to investigate factors such as lymphatic vessel cross-sectional area, tissue water relaxation time (T2), and chemical exchange saturation transfer. The only study that compared MRI measurement with standard examinations reported that MRI added information to the therapy evaluation. MRI seems to be a promising tool for quantitative measurement of therapeutic response in patients with BCRL. However, the identified studies focused on only manual lymphatic drainage and were limited by the small numbers of patients. More studies are necessary to shed light on the topic.

Pneumatosis intestinalis, or air within the wall of the gastrointestinal tract, has been documented from the esophagus to the rectum. Its presence can suggest gangrenous changes of the stomach or colon and represents a surgical emergency. However, pneumatosis intestinalis can also occur as a result of a benign, nongangrenous condition. We report the conservative management of a patient with nongangrenous gastric and esophageal pneumatosis.

Adrenal masses have varying presentations. Most commonly, adrenal masses are discovered incidentally on CT or MRI during an evaluation for an unrelated complaint. Although the majority of these are nonfunctional cortical adenomas, hormonally active tumors and adrenocortical carcinoma must also be considered in the differential diagnosis. Rarely, retroperitoneal tumors may mimic an adrenal mass. We report a case of a 49-year-old man with anemia and weight loss who was found to have a large retroperitoneal mass arising from the adrenal gland. Surgical treatment involved en bloc resection of the right kidney, adrenal gland, segments 7 and 8 of the liver, and a portion of the right hemidiaphragm. Final pathology revealed a low-grade myofibrosarcoma. We believe that this is the first case report of a myofibrosarcoma of the adrenal gland. Myofibrosarcomas are rare malignant tumors composed of myofibroblasts that arise from the deep soft tissues. These tumors have a predilection for the head and neck, trunk, or extremities. Myofibrosarcomas can be differentiated from other sarcomas by immunohistochemical staining and pathologic features. We will briefly discuss the workup of an adrenal mass and focus on the diagnosis of myofibrosarcoma.

AbstractPurposeStudy objectives were to examine: (a) biomarker trajectories (change from presurgical baseline values of Lymphedema index (L‐Dex) units and arm volume difference) and symptom cluster scores 24 months after breast cancer surgery and (b) associations of these objective biomarkers and symptom cluster scores. Patient/treatment characteristics influencing trajectories were also evaluated.MethodsA secondary analysis of data from the published interim analysis of a randomized parent study was undertaken using trajectory analysis. Five hundred and eight participants included in the prior analysis with 24 months of postsurgical follow‐up were initially measured with bioelectric impedance spectroscopy (BIS) and tape measure (TM) and completed self‐report measures. Patients were reassessed postsurgery for continuing eligibility and then randomized to either BIS or TM groups and measured along with self‐report data at regular and optional* visits 3, 6,12,15*,18, 21*, and 24‐months.ResultsThree subclinical trajectories were identified for each biomarker (decreasing, stable, increasing) and symptom cluster scores (stable, slight increase/decrease, increasing). Subclinical lymphedema was identified throughout the 24‐month period by each biomarker. An L‐Dex increase at 15 months in the BIS group was noted. The self‐report sets demonstrated contingency coefficients of 0.20 (LSIDS‐A soft tissue, P = .031) and 0.19 (FACTB+4, P = .044) with the L‐Dex unit change trajectories.ConclusionsThese data support the need for long‐term (24 months) prospective surveillance with frequent assessments (every 3 months) at least 15 months after surgery. Statistically significant convergence of symptom cluster scores with L‐Dex unit change supports BIS as beneficial in the early identification of subclinical lymphedema.