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Shows the biodistribution data for [18F]αvβ6-BP in mice bearing paired αvβ6-expressing DX3puroβ6 and non-αvβ6-expressing DX3puro xenograft tumors at 1, 2 and 4 h p.i. and at 1 h p.i. after pre-administration of blocking peptide. Tissue uptake is expressed as decay-corrected percent injected dose per gram of tissue (dc % ID/g)

Purpose:The study was undertaken to develop and evaluate the potential of an integrin αvβ6-binding peptide (αvβ6-BP) for noninvasive imaging of a diverse range of malignancies with PET.Experimental Design:The peptide αvβ6-BP was prepared on solid phase and radiolabeled with 4-[18F]fluorobenzoic acid. In vitro testing included ELISA, serum stability, and cell binding studies using paired αvβ6-expressing and αvβ6-null cell lines. In vivo evaluation (PET/CT, biodistribution, and autoradiography) was performed in a mouse model bearing the same paired αvβ6-expressing and αvβ6-null cell xenografts. A first-in-human PET/CT imaging study was performed in patients with metastatic lung, colon, breast, or pancreatic cancer.Results:[18F]αvβ6-BP displayed excellent affinity and selectivity for the integrin αvβ6 in vitro [IC50(αvβ6) = 1.2 nmol/L vs IC50(αvβ3) >10 μmol/L] in addition to rapid target-specific cell binding and internalization (72.5% ± 0.9% binding and 52.5% ± 1.8%, respectively). Favorable tumor affinity and selectivity were retained in the mouse model and excretion of unbound [18F]αvβ6-BP was rapid, primarily via the kidneys. In patients, [18F]αvβ6-BP was well tolerated without noticeable adverse side effects. PET images showed significant uptake of [18F]αvβ6-BP in both the primary lesion and metastases, including metastasis to brain, bone, liver, and lung.Conclusions:The clinical impact of [18F]αvβ6-BP PET imaging demonstrated in this first-in-human study is immediate for a broad spectrum of malignancies.

Describes additional methods

Shows the in vivo stability of [18F]αvβ6-BP in human blood. Representative radio-HPLC of blood sample taken 30 min post injection. Top: Sample only; bottom: sample spiked with [18F]αvβ6-BP. X-axis: retention time [min]; Y-axis: detector response [volts].

Supplementary Methods, Table, Figures 1-4 from Targeted In vivo Imaging of Integrin αvβ6 with an Improved Radiotracer and Its Relevance in a Pancreatic Tumor Model

Background Volume of operative cases may be an important factor associated with improved survival for early-stage pancreatic cancer. Most high-volume pancreatic centers are also academic institutions, which have been associated with additional healthcare costs. We hypothesized that at high-volume centers, the value of the extra survival outweighs the extra cost. Study Design This retrospective cohort study used data from the California Cancer Registry linked to the Office of Statewide Health Planning and Development database from January 1, 2004 through December 31, 2012. Stage I-II pancreatic cancer patients who underwent resection were included. Multivariable analyses estimated overall survival and 30-day costs at low- vs high-volume pancreatic surgery centers. The incremental cost-effectiveness ratio (ICER) and incremental net benefit (INB) were estimated, and statistical uncertainty was characterized using net benefit regression. Results Of 2,786 patients, 46.5% were treated at high-volume centers and 53.5% at low-volume centers. There was a 0.45-year (5.4 months) survival benefit (95% CI 0.21–0.69) and a $7,884 extra cost associated with receiving surgery at high-volume centers (95% CI $4,074–$11,694). The ICER was $17,529 for an additional year of survival (95% CI $7,997–$40,616). For decision-makers willing to pay more than $20,000 for an additional year of life, high-volume centers appear cost-effective. Conclusions Although healthcare costs were greater at high-volume centers, patients undergoing pancreatic surgery at high-volume centers experienced a survival benefit (5.4 months). The extra cost of $17,529 per additional year is quite modest for improved survival and is economically attractive by many oncology standards.

Cancer cells are dysregulated and addicted to continuous supply and metabolism of nutritional glucose and amino acids (e.g., arginine) to drive the synthesis of critical macromolecules for uncontrolled growth. Recent studies have revealed that genome-derived microRNA (miRNA or miR)-1291-5p (miR-1291-5p or miR-1291) may modulate the expression of argininosuccinate synthase (ASS1) and glucose transporter protein type 1 (GLUT1). We also developed a novel approach to produce recombinant miR-1291 agents for research, which are distinguished from conventional chemo-engineered miRNA mimics. Herein, we firstly demonstrated that bioengineered miR-1291 agent was selectively processed to high levels of target miR-1291-5p in human pancreatic cancer (PC) cells. After the suppression of ASS1 protein levels, miR-1291 perturbed arginine homeostasis and preferably sensitized ASS1-abundant L3.3 cells to arginine deprivation therapy. In addition, miR-1291 treatment reduced the protein levels of GLUT1 in both AsPC-1 and PANC-1 cells, leading to a lower glucose uptake (deceased > 40%) and glycolysis capacity (reduced approximately 50%). As a result, miR-1291 largely improved cisplatin efficacy in the inhibition of PC cell viability. Our results demonstrated that miR-1291 was effective to sensitize PC cells to arginine deprivation treatment and chemotherapy through targeting ASS1- and GLUT1-mediated arginolysis and glycolysis, respectively, which may provide insights into understanding miRNA signaling underlying cancer cell metabolism and development of new strategies for the treatment of lethal PC. SIGNIFICANCE STATEMENT: Many anticancer drugs in clinical use and under investigation exert pharmacological effects or improve efficacy of coadministered medications by targeting cancer cell metabolism. Using new recombinant miR-1291 agent, we revealed that miR-1291 acts as a metabolism modulator in pancreatic carcinoma cells through the regulation of argininosuccinate synthase- and glucose transporter protein type 1-mediated arginolysis and glycolysis. Consequently, miR-1291 effectively enhanced the efficacy of arginine deprivation (pegylated arginine deiminase) and chemotherapy (cisplatin), offering new insights into development of rational combination therapies.

Background: Ductal carcinoma in situ (DCIS) now represents nearly a quarter of newly diagnosed breast cancers in the United States. Standard-of-care treatment for DCIS is aggressive local therapy consisting of either mastectomy or breast conserving surgery with radiation. However, DCIS mortality is low regardless of initial treatment, suggesting opportunities to explore a spectrum of treatment options. With these treatment options, there is the potential to create risk-adapted treatment plans, but the question of how to assess risk remains. Molecular tests can help to personalize treatment by stratifying disease sub-types and providing prognosis. One such tool is the Oncotype DX® Breast DCIS Score, a risk measure which was validated in a meta-analysis of 773 patients from the E5194 and Ontario DCIS Cohort studies. Along with calculating a Breast DCIS Score™ from the expression levels of 12 genes, the test provides a predicted 10-year risk of local recurrence from the score result, age, and tumor size for patients who receive breast conserving surgery alone. Understanding how such a tool might impact decision-making will inform its implementation. Eligibility & trial design: The ATHENA Breast Health Network is a consortium of the five University of California Medical centers. Through ATHENA, patients with histologically confirmed DCIS and no concurrent invasive cancer are approached to participate in the Athena DCIS Registry. Patients in the registry facing an active management decision are eligible to participate in the Oncotype DX® DCIS prospective study. Specific aims: The primary aim of the study is to determine whether the additional diagnostic information (i.e. the DCIS Score™) impacts patient treatment decisions and physician recommendation. Additional goals are to correlate the DCIS Score™ with mammographic findings, pathological variables, and treatment recommendations, and to estimate risk within each DCIS Score™ group. Participants and their physicians answer survey questions both before and after receiving the score to evaluate the impact of the DCIS Score™ on treatment recommendations and decisions. Statistical methods: The study will assess the percentage of patients who thought the DCIS risk score influenced their treatment decision. The study will also assess whether a significant proportion of physicians changed their recommendations after considering the DCIS Score™ using the chi-square test. Similarly, the patients’ preferred treatment option pre- and post- test surveys will be evaluated. In addition, the concordance between physicians’ and patients’ choices will be assessed by the Kappa statistic before and after the score. The patients’ and physicians’ confidence levels in their treatment recommendation and decision pre- and post- test will be compared using a Wilcoxon signed-rank test, as well as the percentage of patients and physicians who are glad they used the test. In addition, the study will assess whether the DCIS test influences a patient’s perception of their recurrence risk by comparing the self-reported 10-year breast cancer recurrence risk in their pre- and post- test questionnaires using a Wilcoxon signed-rank test. Current and target accrual: The current accrual across all sites in the Oncotype study is 94 patients. The target accrual for the initial pilot phase data is defined as the first 100 patients accrued. If interested in learning more about the study, please contact Rita Mukhtar, MD (Rita.Mukhtar@ucsf.edu). Citation Format: Jane M Wei, Paul Kim, Cheryl Ewing, Jasmine Wong, Laura J Esserman, Michael D Alvarado, Abimbola O Olusanya, Skye Stewart, Ashley Tydon, Parima Daroui, Jeffrey V Kuo, Hannah L Park, Karen T Lane, Eliza Jeong, Kelsey Brown, Ava Hosseini, Barbara A Parker, Sarah L Blair, Athena Breast Health Network Investigators, Frederick Baehner, Olivier Harismendy, Antonia Petruse, Carlie K Thompson, Helena R Chang, Alexander D Borowsky, Christina Yau, Gillian L Hirst, Richard J Bold, Rita A Mukhtar. Use of Oncotype DX DCIS for disease management in a prospective DCIS registry [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr OT3-09-01.

OBJECTIVES: Comorbid psychiatric illness has been associated with worse outcomes following some major surgical procedures. We hypothesized that patients with pre-existing mood disorders would have worse postoperative and oncologic outcomes after pancreatic cancer resection. METHODS: This retrospective cohort study analyzed Surveillance, Epidemiology, & End Results patients with resectable pancreatic adenocarcinoma. A pre-existing mood disorder was classified if a patient was diagnosed and/or treated with medication approved for depression/anxiety within 6 months before surgery. RESULTS: Of 1305 patients, 16% had a pre-existing mood disorder. Mood disorders had no impact on hospital length of stay (12.9 vs 13.2 days, P = 0.75), 30-day complications (26% vs 22%, P = 0.31), 30-day readmissions (26% vs 21%, P = 0.1), or mortality (30 days: 3% vs 4%, P = 0.35); only an increased 90-day readmissions rate (42% vs 31%, P = 0.001) was observed. No effect on adjuvant chemotherapy receipt (62.5% vs 69.2%, P = 0.06) or survival (24-months, 43% vs 39%, P = 0.44) was observed. CONCLUSIONS: Pre-existing mood disorders influenced 90-day readmissions after pancreatic resection, but not other postoperative or oncologic outcomes. These findings suggest that affected patients should be expected to have outcomes similar to patients without mood disorders.

Author(s): Bateni, Sarah B; Gingrich, Alicia A; Kirane, Amanda R; Sauder, Candice AM; Gholami, Sepideh; Bold, Richard J; Meyers, Frederick J; Canter, Robert J

Background Although malignant bowel obstruction (MBO) often is a terminal event, systemic therapies are advocated for select patients to extend survival. This study aimed to evaluate factors associated with receipt of chemotherapy after MBO and to determine whether chemotherapy after MBO is associated with survival. Methods This retrospective cohort study investigated patients 65 years of age or older with metastatic gastrointestinal, gynecologic, or genitourinary cancers who were hospitalized with MBO from 2008 to 2012 using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Fine and Gray models were used to identify factors associated with receipt of chemotherapy accounting for the competing risk of death. Cox models identified factors associated with overall survival. Results Of the 2983 MBO patients, 39% (n = 1169) were treated with chemotherapy after MBO. No differences in receipt of chemotherapy between the surgical and medical patients were found in the univariable analysis (subdistribution hazard ratio [SHR], 0.96; 95% confidence interval [CI], 0.86–1.07; p = 0.47) or multivariable analysis (SHR, 1.12; 95% CI, 1.00–1.26; p = 0.06). Older age, African American race, medical comorbidities, non-colorectal and non-ovarian cancer diagnoses, sepsis, ascites, and intensive care unit stays were inversely associated with receipt of chemotherapy after MBO (p < 0.05). Chemotherapy with surgery was associated with longer survival than surgery (adjusted hazard ratio [aHR], 2.97; 95% CI, 2.65–3.34; p < 0.01) or medical management without chemotherapy (aHR, 4.56; 95% CI, 4.04–5.14; p < 0.01). Subgroup analyses of biologically diverse cancers (colorectal, pancreatic, and ovarian) showed similar results, with greater survival related to chemotherapy (p < 0.05). Conclusions Chemotherapy plays an integral role in maximizing oncologic outcome for select patients with MBO. The data from this study are critical to optimizing multimodality care for these complex patients.

Background Secondary cancers account for 16% of all new cancer diagnoses, with breast cancer (BC) the most common secondary cancer. We have shown that secondary BC has unique characteristics and decreased survival compared with primary BC in adolescent and young adults (AYA; 15–39 years old). However, older BC populations are less well studied. Methods Females (age ≥ 15 years) diagnosed with primary BC during 1991–2015 (n = 377,167) and enrolled in the California Cancer Registry were compared with those with secondary BC (n = 37,625) by age (15–39, 40–64, ≥ 65 years). We examined BC-specific survival (BCSS) accounting for other causes of death as a competing risk using multivariable Cox proportional hazards regression. Results Most secondary BC patients were of older age (15–39, n = 777; 40–64, n = 15,848; ≥ 65, n = 21,000). Compared with primary BC treatment, secondary BCs were more often treated with mastectomy and less often with chemotherapy and/or radiation. BCSS was shorter in secondary BC patients than primary BC patients, but the survival difference between secondary and primary BC diminished with age [15–39 hazard ratio (HR): 2.09, 95% confidence interval (CI) 1.83–2.39; 40–64 HR: 1.51; 95% CI 1.44–1.58; ≥ 65 HR: 1.14; 95% CI 1.10–1.19]. Survival differences were most pronounced in women with hormone receptor positive disease and Hispanic and Asian/Pacific Islanders 40–64 years of age. Conclusions When BC is diagnosed following a prior cancer of any organ site, BCSS is worse than when compared with patients for whom BC is the primary diagnosis, suggesting that we may need to tailor our treatments for women with secondary BC.

BACKGROUND As the U.S. population ages, differences in oncologic outcomes among the elderly have been recognized. Our objective was to analyze the clinical, pathologic, and treatment outcomes for elderly soft tissue sarcoma (STS) patients, hypothesizing significant differences in the management and response to therapy. METHODS Using the National Cancer Database, we identified 33 859 patients with nonmetastatic extremity STS. We defined elderly as ≥74 years in age and compared patient and treatment variables between adult and elderly patients. Cox-proportional hazards analysis was used to determine predictors of overall survival (OS). RESULTS We identified 8504 elderly patients. Significant differences in histologic subtype, grade, and facility type between elderly and nonelderly patients (P

Background: Current consensus guidelines for the treatment of male breast cancer are driven by female-only clinical trials despite data suggesting distinct biologic, clinicopathologic, and prognostic differences between male and female breast cancer patients. This includes a recent retrospective multicenter analysis showing greater overall survival among male breast cancer patients who underwent lumpectomy with radiation therapy (RT), compared to total mastectomy or lumpectomy alone. In light of these findings and the CALGB 9343 trial performed in women, we sought to evaluate if survival was also equivalent in men ≥70 years old with early stage breast cancer treated with hormone therapy and lumpectomy with or without radiation therapy (RT), as shown in women. Methods: We performed a retrospective analysis of 752 stage I (T1N0M0), estrogen receptor (ER) positive male breast cancer patients ≥70 years of age who were treated with hormone therapy and underwent lumpectomy with or without RT or total mastectomy (without RT) from the National Cancer Database (NCDB) between the years 2004 to 2014. Chi-squared, Kruskal-Wallis, and analysis of variance tests were used to compare demographic and clinicopathologic differences between groups. Multivariable Cox proportional hazards regression analysis was used to compare overall survival between treatment groups, controlling for demographic and clinicopathologic differences. Results: Most patients underwent total mastectomy (67.4%), with only 32.6% treated with lumpectomy. Of those who underwent lumpectomy, 72.6% (n=178) underwent adjuvant RT. There were significant differences in age, tumor size, histology, grade, surgical margins, nodal surgery, and chemotherapy between patients who underwent lumpectomy without RT, lumpectomy with RT, and total mastectomy (p Conclusion: In this national sample of elderly ER positive male breast cancer patients with early disease on hormone therapy, lumpectomy alone was associated with equivalent survival compared to lumpectomy with RT and total mastectomy alone. These results suggest that breast conserving surgery without radiation therapy is appropriate for this subset of male breast cancer patients and greater adoption by breast surgeons should be considered. Citation Format: Bateni SB, Arora M, Daly ME, Bold RJ, Canter RJ, Sauder CA. The role of lumpectomy and radiation therapy in men 70 years of age and older with early breast cancer on hormone therapy: A NCDB analysis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-19-03.

BackgroundCurrent treatment guidelines for male breast cancer are predominantly guided by female-only clinical trials. With scarce research, it is unclear whether breast-conserving therapy (BCT) is equivalent to mastectomy in men. We sought to compare overall survival (OS) among male breast cancer patients who underwent BCT versus mastectomy.MethodsWe performed a retrospective analysis of 8445 stage I-II (T1-2 N0-1 M0) male breast cancer patients from the National Cancer Database (2004-2014). Patients were grouped according to surgical and radiation therapy (RT). BCT was defined as partial mastectomy followed by RT. Multivariable and inverse probability of treatment-weighted (IPTW) Cox proportional hazards models were used to compare OS between treatment groups, controlling for demographic and clinicopathologic characteristics.ResultsMost patients underwent total mastectomy (61.2%), whereas 18.2% underwent BCT, 12.4% underwent total mastectomy with RT, and 8.2% underwent partial mastectomy alone. In multivariable and IPTW models, partial mastectomy alone, total mastectomy alone, and total mastectomy with RT were associated with worse OS compared with BCT (p

PURPOSE: Reducing acute care use is an important strategy for improving value in cancer care. However, little information is available to describe and compare population-level hospital use across cancer types. Our aim was to estimate unplanned hospitalization rates and to describe the reasons for hospitalization in a population-based cohort recently diagnosed with cancer. MATERIALS AND METHODS: California Cancer Registry data linked with administrative inpatient data were used to examine unplanned hospitalization among individuals diagnosed with cancer between 2009 and 2012 (n = 412,850). Hospitalizations for maintenance chemotherapy, radiotherapy, or planned surgery were excluded. Multistate models were used to estimate age-adjusted unplanned hospitalization rates, accounting for survival. RESULTS: Approximately 67% of hospitalizations in the year after diagnosis were unplanned, 35% of newly diagnosed individuals experienced an unplanned hospitalization, and 67% of unplanned hospitalizations originated in the emergency department (ED). Nonmalignancy principal diagnoses most frequently associated with unplanned hospitalization included infection (15.8%) and complications of a medical device or care (6.5%). Unplanned hospitalization rates were highest for individuals with hepatobiliary or pancreatic cancer (2.08 unplanned hospitalizations per person-year at risk), lung cancer (1.58 unplanned hospitalizations), and brain or CNS cancer (1.47 unplanned hospitalizations), and were lowest among individuals with prostate cancer (0.18 unplanned hospitalizations) and melanoma (0.25 unplanned hospitalizations). CONCLUSION: The population burden of unplanned hospitalization among individuals newly diagnosed with cancer is substantial. Many unplanned hospitalizations originate in the ED and are associated with potentially preventable admission diagnoses. Efforts to reduce unplanned hospitalization might target subgroups at higher risk and focus on the ED as a source of admission.

PurposeCurrent treatment guidelines for male breast cancer are guided by female-only trials despite data suggesting distinct clinicopathologic differences between sexes. We sought to evaluate whether radiation therapy (RT) after lumpectomy was associated with equivalent survival among men > 70 years of age with stage I, estrogen receptor (ER) positive tumors, as seen in women from the Cancer and Leukemia Group B (CALGB) 9343 trial.MethodsWe performed a retrospective analysis of 752 stage I, ER-positive male breast cancer patients ≥70 years who were treated with hormone therapy and surgery, with or without RT, from the National Cancer Database between 2004 and 2014. Patients were categorized based on surgery and RT (lumpectomy alone, lumpectomy with RT, and mastectomy alone). Multivariable Cox proportional hazards regression analysis was used to compare overall survival between treatment groups.ResultsMost patients underwent total mastectomy, with only 32.6% treated with lumpectomy. Of those who underwent lumpectomy, 72.7% received adjuvant RT. In multivariate analysis, there was no statistical difference in overall survival when comparing lumpectomy alone and lumpectomy with RT (aHR 0.72 [95% CI 0.38-1.37], p=0.31) or when comparing lumpectomy (alone or with RT) and mastectomy (aHR 1.28 [95% CI 0.88-1.87], p=0.20).ConclusionsIn this national sample of elderly men with ER-positive early-stage disease treated with endocrine therapy, there were no significant differences in overall survival when comparing lumpectomy alone and lumpectomy with RT, or lumpectomy (alone or with RT) and mastectomy. These results suggest that less aggressive treatment may be appropriate for a subset of male breast cancer patients.

Although malignant bowel obstruction (MBO) often is a terminal event, systemic therapies are advocated for select patients to extend survival. This study aimed to evaluate factors associated with receipt of chemotherapy after MBO and to determine whether chemotherapy after MBO is associated with survival.This retrospective cohort study investigated patients 65 years of age or older with metastatic gastrointestinal, gynecologic, or genitourinary cancers who were hospitalized with MBO from 2008 to 2012 using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Fine and Gray models were used to identify factors associated with receipt of chemotherapy accounting for the competing risk of death. Cox models identified factors associated with overall survival.Of the 2983 MBO patients, 39% (n = 1169) were treated with chemotherapy after MBO. No differences in receipt of chemotherapy between the surgical and medical patients were found in the univariable analysis (subdistribution hazard ratio [SHR], 0.96; 95% confidence interval [CI], 0.86-1.07; p = 0.47) or multivariable analysis (SHR, 1.12; 95% CI, 1.00-1.26; p = 0.06). Older age, African American race, medical comorbidities, non-colorectal and non-ovarian cancer diagnoses, sepsis, ascites, and intensive care unit stays were inversely associated with receipt of chemotherapy after MBO (p0.05). Chemotherapy with surgery was associated with longer survival than surgery (adjusted hazard ratio [aHR], 2.97; 95% CI, 2.65-3.34; p0.01) or medical management without chemotherapy (aHR, 4.56; 95% CI, 4.04-5.14; p0.01). Subgroup analyses of biologically diverse cancers (colorectal, pancreatic, and ovarian) showed similar results, with greater survival related to chemotherapy (p0.05).Chemotherapy plays an integral role in maximizing oncologic outcome for select patients with MBO. The data from this study are critical to optimizing multimodality care for these complex patients.

Background Improving the quality of cancer care and reducing preventable health system use are goals of increasing importance to health practitioners and policy makers. Emergency department (ED) visits are often cited as a source of preventable health system use, however, few studies have described the incidence of ED use by recently diagnosed cancer patients in population-based samples, and no study has addressed the full spectrum of cancer types. Objective To describe ED use by recently diagnosed cancer patients. Methods California Office of Statewide Health Planning and Development data and the California Cancer Registry were used to describe ED use in the year after a cancer diagnosis (2009-2010). The incidence of ED use was tabulated by cancer type. Logistic regression and recycled predictions were used to examine ED use adjusting for confounding factors. Results Most ED visits (68%) occurred within 180 days of diagnosis. The incidence of ED use for all cancer types examined was 17% within 30 days, 35% within 180 days and 44% within 365 days of diagnosis. ED use varied by cancer type (5%-39% within 30 days of diagnosis; 14% -62% within 180 days; and 22%-69% within 365 days). Patterns of ED use by cancer type remained similar after accounting for demographic and socioeconomic factors. Limitations Those common to administrative and registry datasets. Specifically, we were unable to account for ED visits in relation to cancer treatment dates and comorbid conditions. Conclusions Cancer patients use EDs at higher rates than previously reported, with considerable variability by cancer type. Future research should examine reasons for ED visits by cancer type and identify predictors of ED use, including treatment and comorbid conditions.

The delivery of cancer care has never changed as rapidly and dramatically as we have seen with the coronavirus disease 2019 (COVID‐19) pandemic. During the early phase of the pandemic, recommendations for the management of oncology patients issued by various professional societies and government agencies did not recognize the significant regional differences in the impact of the pandemic. California initially experienced lower than expected numbers of cases, and the health care system did not experience the same degree of the burden that had been the case in other parts of the country. In light of promising trends in COVID‐19 infections and mortality in California, by late April 2020, discussions were initiated for a phased recovery of full‐scale cancer services. However, by July 2020, a surge of cases was reported across the nation, including in California. In this review, the authors share the response and recovery planning experience of the University of California (UC) Cancer Consortium in an effort to provide guidance to oncology practices. The UC Cancer Consortium was established in 2017 to bring together 5 UC Comprehensive Cancer Centers: UC Davis Comprehensive Cancer Center, UC Los Angeles Jonsson Comprehensive Cancer Center, UC Irvine Chao Family Comprehensive Cancer Center, UC San Diego Moores Cancer Center, and the UC San Francisco Helen Diller Family Comprehensive Cancer Center. The interventions implemented in each of these cancer centers are highlighted, with a focus on opportunities for a redesign in care delivery models. The authors propose that their experiences gained during this pandemic will enhance pre‐pandemic cancer care delivery.

The role of palliative surgery in the management of acute complications in patients with disseminated malignancy remains controversial given the complexity of assessing acute surgical risk and long-term oncologic outcome. With the emergence of checkpoint blockade immunotherapy, there appears to be an increasing role for historically palliative procedures as a bridge to systemic immunotherapy. This is especially evident in advanced microsatellite instability-high (MSI-H) colorectal cancer where malignant obstruction and fistula formation are more common and where immunotherapy with checkpoint blockade (anti-PD-1/PD-L1, anti-CTLA-4) has a high response rate with potential for favorable oncologic outcomes. We present a series of three patients with MSI-H metastatic colorectal cancer complicated by malignant bowel obstruction and fistula formation, who having progressed on standard chemotherapy, underwent palliative intervention as a bridge to immune checkpoint blockade with durable and clinically meaningful anti-cancer responses. These cases highlight the need to re-evaluate the role of historically palliative operations in the setting of disease progression for immunotherapy-responsive tumors.

BACKGROUND/AIM Competing mortality risks complicate treatment of elderly melanoma patients potentially leading to conservative management, including no sentinel lymph node biopsy. As systemic immunotherapy offers justification for nodal evaluation, we examined treatment trends among elderly melanoma patients. PATIENTS AND METHODS We performed a National Cancer Database analysis of melanoma patients from 2004-2015. Patients were categorized by age (elderly ≥80-years-old). Multivariable logistic regression analyses were performed comparing characteristics and treatment by age. RESULTS Of 187,814 patients, 2.7% were 1-25, 11.6% were 26-40, 46.6% were 41-64, 28.8% were 65-79, and 10.3% were ≥80-years-old with clinicopathologic and treatment differences between age cohorts. Nodal surgery was least common among elderly patients (43.1% vs. 60.7-69.8%, p

Real-time visualization of imaging data constitutes a critical part of surgical workflow. Augmented reality (AR) is a promising tool to assist in conventional surgical navigation systems. We have been developing an AR framework for clinical imaging and guidance using an optical see-through head-mounted display (OST-HMD) and fluorescence lifetime imaging (FLIm) instrumentation. This framework supports in vivo scanning of FLIm data and the real-time visualization of diagnostic information overlaid on the interrogated tissue area. With the high discriminative power of FLIm, our FLIm-AR concept has the potential for indicating tumor margins and assisting with tumor excision surgery.

Tumor-free surgical margins are critical in breast-conserving surgery. In up to 38% of the cases, however, patients undergo a second surgery since malignant cells are found at the margins of the excised resection specimen. Thus, advanced imaging tools are needed to ensure clear margins at the time of surgery. The objective of this study was to evaluate a random forest classifier that makes use of parameters derived from point-scanning label-free fluorescence lifetime imaging (FLIm) measurements of breast specimens as a means to diagnose tumor at the resection margins and to enable an intuitive visualization of a probabilistic classifier on tissue specimen. FLIm data from fresh lumpectomy and mastectomy specimens from 18 patients were used in this study. The supervised training was based on a previously developed registration technique between autofluorescence imaging data and cross-sectional histology slides. A pathologist’s histology annotations provide the ground truth to distinguish between adipose, fibrous, and tumor tissue. Current results demonstrate the ability of this approach to classify the tumor with 89% sensitivity and 93% specificity and to rapidly (∼ 20 frames per second) overlay the probabilistic classifier overlaid on excised breast specimens using an intuitive color scheme. Furthermore, we show an iterative imaging refinement that allows surgeons to switch between rapid scans with a customized, low spatial resolution to quickly cover the specimen and slower scans with enhanced resolution (400 μm per point measurement) in suspicious regions where more details are required. In summary, this technique provides high diagnostic prediction accuracy, rapid acquisition, adaptive resolution, nondestructive probing, and facile interpretation of images, thus holding potential for clinical breast imaging based on label-free FLIm.

Background: Radiotherapy is used to treat many adolescent and young adult (AYA) and childhood cancer patients and is a risk factor for secondary breast cancer. While premenopausal breast cancer is inherently more aggressive, no studies to date have evaluated the characteristics and breast cancer–specific survival (BCSS) of premenopausal secondary breast cancer after radiotherapy in AYA and childhood cancer survivors. Methods: Female patients ages 12 to 50 diagnosed with primary breast cancer from 1988 to 2014 (n = 107,751) were obtained from the California Cancer Registry and compared with similar aged patients with secondary breast cancer who were treated with radiotherapy for their primary tumor (n = 1,147) from ages 12 to 39. We examined BCSS using multivariable Cox proportional hazards regression. Results: The secondary breast cancer cohort was more likely to be Hispanic or Black, be 35 to 45 years of age, have earlier stage tumors, be higher grade, have no lymph node involvement, and be hormone receptor negative. All women showed worse BCSS for large tumor size, lymph node involvement, and hormone receptor–negative status. BCSS was worse for women with secondary breast cancer both overall (hazard ratio, 1.98; 95% confidence interval, 1.77–2.23) and in all subgroups considered. Associations were most pronounced in Hispanics, Asian/Pacific Islanders, and younger women, as well as those with earlier stage, lymph node–negative, and hormone receptor–positive disease. Conclusions: BCSS is significantly decreased among all survivors of childhood and AYA cancer treated with radiotherapy that develop a secondary breast cancer, including women with good prognostic features. Impact: Therefore, we may need to consider alternative and even more aggressive treatment in what were considered low-risk populations previously.

Pancreatic adenocarcinoma is the 9th most common cancer in the United States and the 4th most common cause of cancer-related death given its poor prognosis.The authors have performed a literature search for pertinent published clinical trials, ongoing Phase 3 clinical trials, and current treatment guidelines using PubMed, Clinicaltrials.gov, and NCCN, ASCO, ESMO, and JPS websites. The review itself discusses landmark studies and ongoing research into the chemotherapy regimens recommended by each oncologic society. The authors also examine drugs that were promising but failed in Phase 3 trials and those currently being investigated. Finally, the authors provide their expert opinion on the subject and provide their future perspectives.While advances in chemotherapy for pancreatic cancer have been limited in comparison to other cancers, there have been improvements in survival. Combination therapy and a goal of R0 resection are key elements to extend life. Novel agents directed at the unique properties of pancreatic cancer are promising.

© 2018, Society of Surgical Oncology. Background: Outcomes for pancreatic resection have been studied extensively due to the high morbidity and mortality rates, with high-volume centers achieving superior outcomes. Ongoing investigations include healthcare costs, given the national focus on reducing expenditures. Therefore, we sought to evaluate the relationships between pancreatic surgery costs with perioperative outcomes and volume status. Methods: We performed a retrospective analysis of 27,653 patients who underwent elective pancreatic resections from October 2013 to June 2017 using the Vizient database. Costs were calculated from charges using cost–charge ratios and adjusted for geographic variation. Generalized linear modeling adjusting for demographic, clinical, and operation characteristics was performed to assess the relationships between cost and length of stay, complications, in-hospital mortality, readmissions, and hospital volume. High-volume centers were defined as hospitals performing ≥ 19 operations annually. Results: The unadjusted mean cost for pancreatic resection and corresponding hospitalization was $20,352. There were no differences in mean costs for pancreatectomies performed at high- and low-volume centers [− $1175, 95% confidence interval (CI) − $3254 to $904, p = 0.27]. In subgroup analysis comparing adjusted mean costs at high- and low-volume centers, there was no difference among patients without an adverse outcome (− $99, 95% CI − $1612 to 1414, p = 0.90), one or more adverse outcomes (− $1586, 95% CI − $4771 to 1599, p = 0.33), or one or more complications (− $2835, 95% CI − $7588 to 1919, p = 0.24). Conclusions: While high-volume hospitals have fewer adverse outcomes, there is no relationship between surgical volume and costs, which suggests that, in itself, surgical volume is not an indicator of improved healthcare efficiency reflected by lower costs. Patient referral to high-volume centers may not reduce overall healthcare expenditures for pancreatic operations.

Immune checkpoint inhibitors represent a newly established standard of care in patients with refractory metastatic colorectal cancer with mismatch repair deficiency and microsatellite instability. However, the use of immunotherapy is unclear in recipients of liver transplants with or without concurrent liver function abnormalities. Clinical trials investigating immunotherapy have mostly excluded liver transplant recipients and patients with abnormal liver function. This report presents the first case, to our knowledge, of a liver transplant patient with mismatch repair–deficient colon adenocarcinoma with liver metastases and concurrent abnormal liver function who safely responded to immunotherapy. We also review the literature on checkpoint inhibitor use in patients with other metastatic solid tumors after liver transplant and those with baseline liver function abnormalities. An increasing body of evidence supports the safety of checkpoint inhibition in patients with cancer and solid organ transplants, but further prospective studies are warranted. Use of immunotherapy in liver transplant recipients who have metastatic colorectal cancer with microsatellite instability is feasible but should be performed in a multidisciplinary team setting.

BACKGROUND Cancer care coordination addresses the fragmented and inefficient care of individuals with complex care needs. The complexity of care coordination can be aided by innovative technology. Few examples of information technology-enabled care coordination exist beyond the conventional telephone follow-up. For this study, we implemented a custom-designed app, the Personal Health Network (PHN)—a Health Insurance Portability and Accountability Act-compliant social network built around a patient to enable patient-centered health and health care activities in collaboration with clinicians, care team members, caregivers, and others designated by the patient. The app facilitates a care coordination intervention for patients undergoing chemotherapy. OBJECTIVE This study aimed to understand patient experiences with PHN technology and assess their perspectives on the usability and usefulness of PHNs with care coordination during chemotherapy. METHODS A two-arm randomized clinical trial was conducted to compare the PHN and care coordination with care coordination alone over a 6-month period beginning with the initiation of chemotherapy. A semistructured interview guide was constructed based on a theoretical framework of technology acceptance addressing usefulness, usability, and the context of use of the technology within the participant’s life and health care setting. All participants in the intervention arm were interviewed on completion of the study. Interviews were recorded and transcribed verbatim. A summative thematic analysis was completed for the transcribed interviews. Features of the app were also evaluated. RESULTS A total of 27 interviews were completed. The resulting themes included the care coordinator as a partner in care, learning while sick, comparison of other technology to make sense of the PHN, communication, learning, usability, and usefulness. Users expressed that the nurse care coordinators were beneficial to them because they helped them stay connected to the care team and answered their questions. They shared that the mobile app gave them access to the health information they were seeking. Users expressed that the mobile app would be more useful if it was fully integrated with the electronic health record. CONCLUSIONS The findings highlight the value of care coordination from the perspectives of cancer patients undergoing chemotherapy and the important role of technology, such as the PHN, in enhancing this process by facilitating better communication and access to information regarding their illness.

OBJECTIVE The objective of the study is to understand potential differences in psychosocial outcomes from active treatment to survivorship. METHODS Using the Medical Expenditure Panel Survey Experiences with Cancer Survivorship Supplement (n = 1360), we examined and compared psychosocial outcomes among respondents in active treatment with survivors by year(s) since treatment ended. Survey-weighted regression models were used to test associations between year(s) since treatment and depressive symptoms (Patient Health Questionnaire-2), psychological distress (K6), and cancer-specific worry related to recurrence. RESULTS Unadjusted estimates showed no significant differences in depressive symptoms or psychological distress between those in active treatment and cancer survivors at any time posttreatment. In contrast, the prevalence of cancer-specific worry was lowest among survivors more than 5 years since treatment (10%), slightly higher among those with less than 1 year since treatment (15%), and highest among those in active treatment (32%). In models controlled for sociodemographic and health-related covariates, the year(s) since treatment ended was inversely associated with the odds of cancer-specific worry but was not associated with depressive symptoms or psychological distress. CONCLUSIONS In this population-based sample, worry about cancer recurrence may diminish with years since treatment ended, while depressive symptoms and distress are persistent across the trajectory. These findings highlight unmet psychosocial needs among cancer survivors and demonstrate the importance of targeted interventions across the survivorship continuum.

Background Operative resection can be associated with improved survival for selected patients with stage IV malignancies but may also be associated with prohibitive acute morbidity and mortality. We sought to evaluate rates of acute morbidity and mortality after lung resection in patients with disseminated malignancy with primary lung cancer and non–lung cancer pulmonary metastatic disease. Methods For 2011–2012, 6,360 patients were identified from the American College of Surgeons National Surgical Quality Improvement Program undergoing lung resections, including 603 patients with disseminated malignancy. Logistic regression analyses were used to compare outcomes between patients with and without disseminated malignancy. Results After controlling for preoperative and intraoperative differences, we observed no statistically significant differences in rates of 30-day overall and serious morbidity or mortality between disseminated malignancy and non–disseminated malignancy patients (P > .05). Disseminated malignancy patients were less likely to have a prolonged duration of stay and be discharged to a facility compared to non–disseminated malignancy patients (P

Background/purpose Reimbursement penalties for excess hospital readmissions have begun for the pediatric population. Therefore, research determining incidence and predictors is critical. Methods A retrospective review of University HealthSystem Consortium database (N=258 hospitals; 2,723,621 patients) for pediatric patients (age 0–17years) hospitalized from 9/2011 to 3/2015 was performed. Outcome measures were 7-, 14-, and 30-day readmission rates. Hospital and patient characteristics were evaluated to identify predictors of readmission. Results Readmission rates at 7, 14, and 30days were 2.1%, 3.1%, and 4.4%. For pediatric surgery patients (N=260,042), neither index hospitalization length of stay (LOS) nor presence of a complication predicted higher readmissions. Appendectomy was the most common procedure leading to readmission. Evaluating institutional data (N=5785), patients admitted for spine surgery, neurosurgery, transplant, or surgical oncology had higher readmission rates. Readmission diagnoses were most commonly infectious (37.2%) or for nausea/vomiting/dehydration (51.1%). Patients with chronic medical conditions comprised 55.8% of patients readmitted within 7days. 92.0% of patients requiring multiple rehospitalizations had comorbidities. Conclusions Readmission rates for pediatric patients are significantly lower than adults. Risk factors for adult readmissions do not predict pediatric readmissions. Readmission may be a misnomer for the pediatric surgical population, as most are related to chronic medical conditions and other nonmodifiable risk factors. Level of Evidence Level IV.

The incidence of complications for postchemotherapy (PC) resections is high. Severe intraoperative hemorrhage during retroperitoneal lymph node dissection is of significant concern. The safety and efficacy of endovascular technology in vascular surgery have been demonstrated, but no studies have incorporated endovascular stenting in preoperative planning. We present a case series of four patients with nonseminomatous germ cell tumors who underwent preoperative endovascular stenting to identify and protect major vascular structures encased by complex PC tumors. We measured operative time, estimated blood loss, intraoperative transfusion requirement, length of stay, and postoperative complications. In all cases, surgery progressed without full continuous identification of the major vascular structures and their branches because of the assurance that hemorrhage would be controlled should they be breached. Patient summary Preoperative endovascular stenting may be an effective approach for minimizing intraoperative hemorrhage and operative time in patients undergoing bulky postchemotherapy dissection. Additional studies are needed to better clarify patient selection criteria and quantify the efficacy and adverse consequences.

BACKGROUND Calls for multivisceral resection (MVR) of retroperitoneal sarcoma (RPS) are increasing, although the risks and benefits remain controversial. We sought to analyze current 30-day morbidity and mortality rates, and trends in utilization of MVR in a national database. METHODS Overall morbidity, severe morbidity, mortality rates, and temporal trends were analyzed utilizing the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). RESULTS From 2012 to 2015, a total of 564 patients underwent RPS resection with 233 patients (41%) undergoing MVR. The MVR group had a higher rate of preoperative weight loss and larger tumors overall. When comparing MVR to non-MVR, there was no significant difference in overall morbidity (22% vs 17%, P = .13), severe morbidity (11% vs 8%, P = .18), or mortality (

BACKGROUND:Surgical guidelines for soft tissue sarcoma (STS) emphasize pretreatment evaluation and reports of the perils of unplanned excision exist. Given the paucity of population-based data on this topic, our objective was to analyze clinical outcomes and costs of planned versus unplanned STS excisions in the Medicare population. METHODS:We analyzed 3913 surgical patients with STS ≥66y old from 1992 to 2011 using the Surveillance, Epidemiology, and End Results-Medicare datafiles. Planned excisions were classified based on preoperative MRI and/or biopsy, whereas unplanned excisions were classified by excision as the first procedure. Inverse probability of treatment weighting with propensity scores was used to adjust for clinicopathologic differences. Re-excisions, complications, and Medicare payments were compared with multivariate models. Overall survival and disease-specific survival were analyzed using Cox proportional hazards and competing risk models. RESULTS:Before the first excision, 24.3% had an MRI and biopsy, 27.3% had an MRI, 11.4% had a biopsy, and 36.9% were unplanned. Re-excision rates were highest for unplanned excisions: 46.3% compared to 18.1%, 36.4%, and 29.7% for other groups (P0.05). Planned excisions were associated with increased Medicare costs (P&nbsp

Purpose: The study was undertaken to develop and evaluate the potential of an integrin αvβ6-binding peptide (αvβ6-BP) for noninvasive imaging of a diverse range of malignancies with PET. Experimental Design: The peptide αvβ6-BP was prepared on solid phase and radiolabeled with 4-[18F]fluorobenzoic acid. In vitro testing included ELISA, serum stability, and cell binding studies using paired αvβ6-expressing and αvβ6-null cell lines. In vivo evaluation (PET/CT, biodistribution, and autoradiography) was performed in a mouse model bearing the same paired αvβ6-expressing and αvβ6-null cell xenografts. A first-in-human PET/CT imaging study was performed in patients with metastatic lung, colon, breast, or pancreatic cancer. Results: [18F]αvβ6-BP displayed excellent affinity and selectivity for the integrin αvβ6 in vitro [IC50(αvβ6) = 1.2 nmol/L vs IC50(αvβ3) >10 μmol/L] in addition to rapid target-specific cell binding and internalization (72.5% ± 0.9% binding and 52.5% ± 1.8%, respectively). Favorable tumor affinity and selectivity were retained in the mouse model and excretion of unbound [18F]αvβ6-BP was rapid, primarily via the kidneys. In patients, [18F]αvβ6-BP was well tolerated without noticeable adverse side effects. PET images showed significant uptake of [18F]αvβ6-BP in both the primary lesion and metastases, including metastasis to brain, bone, liver, and lung. Conclusions: The clinical impact of [18F]αvβ6-BP PET imaging demonstrated in this first-in-human study is immediate for a broad spectrum of malignancies.

© 2018 Elsevier B.V. Our recent studies have revealed that microRNA-1291 (miR-1291) is downregulated in pancreatic cancer (PC) specimens and restoration of miR-1291 inhibits tumorigenesis of PC cells. This study is to assess the efficacy and underlying mechanism of our bioengineered miR-1291 prodrug monotherapy and combined treatment with chemotherapy. AT-rich interacting domain protein 3B (ARID3B) was verified as a new target for miR-1291, and miR-1291 prodrug was processed to mature miR-1291 in PC cells which surprisingly upregulated ARID3B mRNA and protein levels. Co-administration of miR-1291 with gemcitabine plus nab-paclitaxel (Gem-nP) largely increased the levels of apoptosis, DNA damage and mitotic arrest in PC cells, compared to mono-drug treatment. Consequently, miR-1291 prodrug improved cell sensitivity to Gem-nP. Furthermore, systemic administration of in vivo-jetPEI-formulated miR-1291 prodrug suppressed tumor growth in both PANC-1 xenograft and PC patients derived xenograft (PDX) mouse models to comparable degrees as Gem-nP alone, while combination treatment reduced tumor growth more ubiquitously and to the greatest degrees (70–90%), compared to monotherapy. All treatments were well tolerated in mice. In conclusion, biologic miR-1291 prodrug has therapeutic potential as a monotherapy for PC, and a sensitizing agent to chemotherapy.