Eccrine spiroadenocarcinoma is an extremely rare malignant eccrine gland tumor which may masquerade as other more common malignancies such as poorly differentiated squamous carcinoma or metastatic breast cancer. We report a case of an ulcerated axillary skin lesion with bulky adenopathy in a 77 year-old female with a prior history of ipsilateral triple negative breast carcinoma. The clear transition of benign spiradenoma to malignant carcinoma was essential to establishing a definitive diagnosis and treatment plan.

Natural killer (NK) cells of the innate immune system are a key focus of research within the field of immuno-oncology based on their ability to recognize and eliminate malignant cells without prior sensitization or priming. However, barriers have arisen in the effective translation of NK cells to the clinic, in part because of critical species differences between mice and humans. Companion animals, especially dogs, are valuable species for overcoming many of these barriers, as dogs develop spontaneous tumors in the setting of an intact immune system, and the genetic and epigenetic factors that underlie oncogenesis appear to be similar between dogs and humans. Here, we summarize the current state of knowledge for dog NK cells, including cell surface marker phenotype, key NK genes and genetic regulation, similarities and differences of dog NK cells to other mammals, especially human and mouse, expression of canonical inhibitory and activating receptors, ex vivo expansion techniques, and current and future clinical applications. While dog NK cells are not as well described as those in humans and mice, the knowledge of the field is increasing and clinical applications in dogs can potentially advance the field of human NK biology and therapy. Better characterization is needed to truly understand the similarities and differences of dog NK cells with mouse and human. This will allow for the canine model to speed clinical translation of NK immunotherapy studies and overcome key barriers in the optimization of NK cancer immunotherapy, including trafficking, longevity, and maximal in vivo support.

11568 Background: Many Adolescent and Young Adult (AYA) Breast Cancer (BC) patients receive chemotherapy as part of their initial treatment. Long-term bone marrow suppression is a potential complication, but no studies have evaluated the impact of race/ethnicity on the development in AYA BC survivors. Methods: Female patients ages 15-39 diagnosed with BC during 1996-2012 and surviving ≥ 2 years were obtained from the California Cancer Registry and linked to statewide hospitalization data. We estimated the cumulative incidence of developing anemia, leukopenia, or major infection/sepsis (≥ 2 years after diagnosis), accounting for death as a competing risk, and examined the impact of race/ethnicity using multivariable Cox proportional hazards regression. Results: Of 14,729 patients, 48.8% were non-Hispanic white, 8.3% non-Hispanic black, 25.5% Hispanic, and 16.5% Asian/Pacific Islander. At diagnosis, 95.5% had local or regional disease (27.7% stage I, 49.4% stage II), and were mostly treated with surgery (96.2%) and chemotherapy (74.3%). The 10-year cumulative incidence of anemia (16.8% vs 11.7%), leukopenia (4.6% vs 2.1%), and major infection/sepsis (13.2% vs 7.9%) was greater following initial treatment with chemotherapy (p < 0.0001 for all vs no chemotherapy). In multivariable analyses controlling for sociodemographic factors, baseline comorbidities, treatment and stage, Blacks had the highest risk (vs. non-Hispanic whites) of medical late effects, including anemia [HR: 1.62, CI 1.41-1.86], leukopenia (HR: 1.53, CI 1.17-2.00), and major infection/sepsis (HR: 1.36, CI 1.16-1.60). Similarly, Hispanic and Asian/Pacific Islanders had a higher risk of developing anemia (HR: 1.16, CI 1.04-1.29; HR: 1.17, CI 1.03-1.33) and trended toward developing more leukopenia (HR: 1.24, CI 1.00-1.54; HR: 1.25, CI 0.98-1.61). Conclusions: AYAs of Black, Hispanic, and Asian/Pacific Islander race/ethnicity are at an increased risk of anemia and leukopenia after chemotherapy compared with non-Hispanic Whites. With improvements in prognostic testing resulting in potential decreased chemotherapy usage, there may be a decrease in long-term late effects for these young cancer survivors.

Background

Melanoma is the third most common cancer in the adolescent and young adult (AYA) population; however, no studies have addressed the occurrence of adverse health conditions following melanoma treatment in these survivors.

Methods

Data for patients ages 15 to 39 years diagnosed with cutaneous melanoma from 1996 to 2012 and surviving ≥2 years were obtained from the California Cancer Registry and linked to statewide hospitalization data. The influence of age at diagnosis, sex, race/ethnicity, neighborhood socioeconomic status (SES), health insurance, and surgery on the development of adverse health conditions was evaluated using Cox proportional hazards regression models.

Results

Of 8,259 patients, 35.3% were male, 83.3% were non-Hispanic White, 82.4% had private health insurance, and 60.5% were considered high SES. In Cox regression models, males had an increased risk of developing adverse health conditions across all systems, including cardiac [HR, 1.73, 95% confidence interval (CI), 1.47-2.03], lymphedema (HR, 1.56; 95% CI, 1.37-1.77), hematologic disorders (HR, 1.17; 95% CI, 1.03-1.33), major infection/sepsis (HR, 1.59; 95% CI, 1.39-1.82), and second cancers (HR, 1.51; 95% CI, 1.31-1.74). Patients with public/no insurance (vs. private) had a greater risk of developing all studied adverse health conditions, including subsequent cancers (HR, 2.34; 95% CI, 1.94-2.82). AYA patients residing in low SES neighborhoods had similar increased risk of developing adverse health conditions.

Conclusions

Of AYA melanoma survivors, males, those with public/no health insurance, and those living in low SES neighborhoods had a greater likelihood of developing adverse health conditions.

Impact

Strategies to improve surveillance and secondary prevention of these adverse health conditions are needed among AYA melanoma survivors, specifically for the at-risk populations identified.

Radiation therapy (RT) is advocated in the multimodal treatment of high-grade soft tissue sarcoma (STS), but its role may be less clear in chemotherapy-sensitive STS such as extraskeletal Ewing sarcoma (EES). The purpose of this study was to determine the role of RT on overall survival (OS) in localized EES adult patients treated with chemotherapy and surgery. Adult patients diagnosed with EES and reported to the National Cancer Database from 2004 to 2014 were evaluated. All patients were treated with surgical resection. Patient demographics, tumor characteristics, treatments received, resection margins, and survival were examined for the 232 patients identified. Using multivariate analysis and Cox proportional hazard analysis, predictors of OS were determined. In the overall cohort, 40 percent of patients received RT and 78 percent received chemotherapy, with 31 percent receiving both. The addition of RT to the patients receiving surgery + chemotherapy did not improve OS (p < 0.05). Twenty-four percent of patients who achieved R0 resection after surgery still received RT without any improvement in OS. Patients treated at community cancer centers were more likely to receive additional RT compared with Comprehensive Cancer Centers (p < 0.05). In adult EES patients with localized disease treated with chemotherapy and surgery, the addition of RT does not improve overall survival.

Background

Malignant bowel obstruction (MBO) is often a terminal event in end-stage cancer patients. The decision to intervene surgically is complex, given the risk of harm in patients with a limited lifespan. Therefore, we sought to compare clinically meaningful outcomes in MBO patients treated with surgical versus medical management using population-based data.

Methods

We performed a retrospective analysis of hospitalized patients with MBO from 2006 to 2010 using the California Office of Statewide Health Planning and Development dataset. Hospital-free days (HFDs) at 30-, 90-, and 180-days were calculated accounting for all hospitalization, emergency department visit, and skilled nursing facility lengths of stay. Adjusted regression models were used to compare HFDs, disposition, complications, in-hospital death, and survival for surgical versus medical MBO cohorts, using inverse probability of treatment weighting with propensity scores.

Results

Of 4576 MBO patients, 3421 (74.8%) were treated medically and 1155 (25.2%) were treated surgically. Surgical patients had higher rates of complications (44.0% vs. 21.3%, p < 0.0001) and in-hospital death (9.5% vs. 3.9%, p < 0.0001) with lower rates of disposition to home (76.3% vs. 89.8%, p < 0.0001). Surgical patients had fewer 30- and 90-day HFDs compared to medical patients (p < 0.01). However, at 180-days, there were no differences in HFDs between treatment groups. There was no difference in overall survival between surgical and medical patients (median 6.5 vs. 6.4 months).

Conclusion

In this population-based analysis, medical management was associated with less hospital utilization at 30- and 90-days, fewer in-hospital deaths, and more frequent discharges to home. These data underscore the potential benefits of medical management for MBO patients at the end-of-life.

Background/aim

The predictive value of serum C-reactive protein (CRP) and neutrophil/lymphocyte (N/L) ratio in soft tissue sarcoma (STS) patients receiving neoadjuvant radiotherapy (RT) has not been analyzed.

Patients and methods

From 2007 to 2015, we identified 98 STS patients from a prospective database. Using multivariate analysis, we analyzed CRP and N/L ratios as predictors of overall survival (OS).

Results

Mean age of patients was 59 years, 46% were female, and 55% of tumors were located at the extremity. A total of 15 histologies were represented. Fifty percent received preoperative RT. Except for extremity location, characteristics were similar between the preoperative RT and upfront surgery cohorts, including baseline CRP levels and N/L ratios. Multivariate analysis of upfront surgery revealed histological grade, tumor size, and baseline N/L ratio to be predictors of OS, while for preoperative RT, baseline CRP and N/L ratio were not predictive.

Conclusion

Baseline CRP and N/L ratio did not predict poor clinical outcome in STS patients receiving neoadjuvant RT.

Background

Neoadjuvant radiotherapy (RT) is increasingly advocated for the management of soft tissue sarcoma (STS). Therefore, this study sought to characterize the impact of neoadjuvant RT on rates of R0 resection and overall survival (OS) in extremity STS patients undergoing surgery.

Methods

From January 2003 to December 2012, the study identified patients with a diagnosis of extremity STS from the National Cancer Database. After exclusion of patients younger than 18 years, not treated by surgery, who had metastases at diagnosis, intraoperative RT, and missing or unknown data, 27,969 patients were identified. Logistic regression and Cox-proportional hazard analysis were used to compare rates of R0 resection among preoperative, postoperative, and no-RT cohorts and to determine predictors of R0 resection and OS.

Results

The mean age of the patients was 59.5 ± 17.1 years, and 45.9% were female. The median tumor size was 10.5 cm. The data showed that 51% of the patients did not receive RT, 11.8% received preoperative RT, and 37.2% received postoperative RT. The rates of R0 resection were 90.1% for the preoperative RT cohort, 74.9% for the postoperative RT cohort, and 79.9% for the no-RT cohort (P < 0.001). The independent predictors for achievement of R0 resection included academic facility type (odds ratio [OR] 1.36; 95% confidence interval [CI] 1.20-1.55), histologic subtype, tumor size (OR 0.99; 95% CI 0.99-0.99), Charlson score (OR 0.92; 95% CI 0.84-0.99), and preoperative RT (OR 1.83; 95% CI 1.61-2.07). Both R0 resection and RT (pre- or post-operative) were associated with increased OS.

Conclusions

Preoperative RT independently predicts higher rates of R0 resection for patients with extremity STS undergoing surgical resection. Negative surgical margins and pre- or postoperative RT are associated with improved OS.

Background

Unplanned excision of soft tissue sarcomas (STS) is an important quality of care issue given the morbidity related to tumor bed excision. Since not all patients harbor residual disease at the time of reexcision, we sought to determine predictors of residual STS following unplanned excision.

Methods

We identified 76 patients from a prospective database (January 1, 2008-September 30, 2014) who received a diagnosis of primary STS following unplanned excision on the trunk or extremities. We used univariable and multivariable analyses to evaluate predictors of residual STS as the primary endpoint. We calculated the sensitivity, specificity, and accuracy of interval magnetic resonance imaging (MRI) to predict residual sarcoma at reexcision.

Results

Mean age was 52 y, and 63.2% were male. 50% had fragmented unplanned excision. Among patients undergoing reexcision, residual STS was identified in 70%. On univariable analysis, MRI showing gross disease and fragmented excision were significant predictors of residual STS (odds ratio, 10.59; 95% CI, 2.14-52.49; P = 0.004 and odds ratio, 3.61; 95% CI, 1.09-11.94; P = 0.035, respectively). On multivariable analysis, tumor size predicted distant recurrence and overall survival. When we combined equivocal and positive MRI, the sensitivity and specificity of MRI for predicting residual STS were 86.7% (95% CI, 73.2%-95.0%) and 57.9% (95% CI, 33.5%-79.8%), with an overall accuracy of 78.1% (95% CI, 66.0%-87.5%).

Conclusions

About 70% of patients undergoing repeat excision after unplanned excision of STS harbor residual sarcoma. Although interval MRI and fragmented excision appear to be the most significant predictors of residual STS, the accuracy of MRI remains modest, especially given the incidence of equivocal MRI.

NK cells are a key focus in immuno-oncology, based on their ability to eliminate malignant cells without prior sensitization. Dogs are valuable models for translational immunotherapy studies, especially for NK cells, where critical species differences exist between mice and humans. Given that the mechanism for recognition of "self" by canine NK cells is currently unknown, we sought to evaluate expression of Ly49 in canine NK cells using in silico and high-throughput techniques. We interrogated the identified polymorphism/mutation in canine Ly49 and assessed the potential impact on structure using computational modeling of three-dimensional protein structure and protein-protein docking of canine Ly49 with MHC class I (MHC-I). Bulk and single-cell RNA-sequencing analysis was performed to detect gene expression of Ly49/KLRA1 in resting and activated NK cells. Tertiary protein structure demonstrated significant structural similarity to the known murine system. Molecular docking of canine Ly49 with MHC-I was favorable, converging at a single low-energy conformation. RNA sequencing revealed expression of Ly49/KLRA1 in both resting and activated NK cells and demonstrated almost exclusive expression of the gene in the NK cluster at the single-cell level. Despite prior reports of a mutated, nonfunctional canine Ly49, our data support that the protein product is predicted to bind to MHC-I in a comparable conformation to the murine system and is expressed in canine NK cells with upregulation following activation. Taken together, these data suggest that Ly49 is capable of recognizing MHC-I and therefore regulating NK cell function in dogs.