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In a prospective multicenter study, gemcitabine monotherapy followed by stereotactic body radiation therapy (SBRT) was well tolerated with outcomes comparable to chemoradiation for locally advanced pancreatic cancer (LAPC). Recent trials have reported improved survival with multiagent chemotherapy (MA-CTX) alone. This prospective trial explored whether SBRT could be safely delivered after MA-CTX. Herein, we report the long-term outcomes of adding SBRT after MA-CTX in LAPC patients and evaluate whether genetic profiles of specimens obtained before SBRT influence outcomes.This prospective nonrandomized controlled phase 2 trial enrolled 44 LAPC and 4 locally recurrent patients after multidisciplinary evaluation between 2012 and 2015 at a high-volume pancreatic cancer center. For induction CTX, most received modified FOLFIRINOX (mFFX), or gemcitabine and nab-paclitaxel (GnP) followed by 5-fraction SBRT for all. During fiducial placement, biopsies were obtained with DNA extracted for targeted sequencing using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets platform.Median induction CTX duration was ≥4 months, and 31 patients received mFFX (65%). Among 44 LAPC patients, 17 (39%) were surgically explored, and 12 of 16 (75%) achieved a R0 resection. Median overall survival (mOS) was 20.2 and 14.6 months from diagnosis and SBRT, respectively. One- and 2-year OS from SBRT was 58% and 28%. The mOS after resection was 28.6 and 22.4 months from diagnosis and SBRT, respectively. Median local progression-free survival was 23.9 and 15.8 months from diagnosis and SBRT, respectively. The mOS for pre-SBRT CA 19-9 ≤180 U/mL versus180 was 23.1 and 11.3 months, respectively (hazard ratio, 0.53; P = .04). Only 1 patient (2.1%) had late grade ≥2 gastrointestinal toxic effects attributable to SBRT. Despite significant pretreatment with chemotherapy, 88% of tumor specimens were effectively sequenced; survival outcomes were not significantly associated with specific mutational patterns. Quality of life was prospectively collected pre- and post-SBRT with the EORTC QLQ-C30 and PAN26 questionnaires showing no significant change.SBRT was safely administered with MA-CTX with minimal toxicity. A high proportion of LAPC patients underwent R0 resection with favorable survival outcomes.

Treatment regimens, platinum-sensitivity and BRCA status of ovarian and fallopian tube cancer patients.

Sites of disease and progression of all patients.

Quality of life (QoL) t-tests for all patients (A), GYN versus non-GYN patients (B) and patients who completed cycle 2 and those who did not (C).

Supplemental Figure Legend from A Phase I Study of Veliparib (ABT-888) in Combination with Low-Dose Fractionated Whole Abdominal Radiation Therapy in Patients with Advanced Solid Malignancies and Peritoneal Carcinomatosis

Purpose: The combination of low-dose radiotherapy with PARP inhibition has been shown to enhance antitumor efficacy through potentiating DNA damage. We combined low-dose fractionated whole abdominal radiation (LDFWAR) with escalating doses of veliparib (ABT-888), a small-molecule PARP inhibitor, in patients with peritoneal carcinomatosis from advanced solid tumor malignancies.Experimental Design: Patients were treated with veliparib (80–320 mg daily) for a total of 3 cycles. LDFWAR consisted of 21.6 Gy in 36 fractions, 0.6 Gy twice daily on days 1 and 5 for weeks 1–3 of each cycle. Circulating tumor cells (CTC) were collected and evaluated for γ-H2AX. Quality of life (QoL) was assessed using the EORTC-QLQ-C30 questionnaire.Results: Twenty-two patients were treated. Treatment-related grade 3 and 4 toxicities included lymphopenia (68%), anemia (9%), thrombocytopenia (14%), neutropenia (4%), leukopenia (9%), ascites (4%), vomiting (4%), and dyspnea (4%). No objective responses were observed. Disease stabilization (≥24 weeks) was observed in 7 patients (33%). Median progression-free survival (mPFS) was 4.47 months and median overall survival (mOS) was 13.04 months. In the subset of 8 ovarian and fallopian cancers, mPFS was 6.77 months and mOS was 17.54 months compared with mPFS 2.71 months and mOS 13.01 months in others. Patients with ovarian and fallopian cancers had better QoL over time than those with other cancers. An increased percentage of γ-H2AX–positive CTCs was observed in a subset of patients (3/6 with >2 CTCs at baseline).Conclusions: Combined veliparib and LDFWAR is a well-tolerated regimen that resulted in prolonged disease stability for some patients with advanced solid tumors and carcinomatosis, particularly in the ovarian and fallopian cancer subpopulation. Clin Cancer Res; 21(1); 68–76. ©2014 AACR.

CTC number and ɣ-H2AX-positive CTC changes during treatment with radiotherapy and veliparib.

Background Patients with borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC) are at high risk of margin-positive resection. Neoadjuvant stereotactic body radiation therapy (SBRT) may help sterilize margins, but its additive benefit beyond neoadjuvant chemotherapy (nCT) is unclear. The authors report long-term outcomes for BRPC/LAPC patients explored after treatment with either nCT alone or nCT followed by five-fraction SBRT (nCT-SBRT). Methods Patients with BRPC or LAPC from 2011 to 2016 who underwent resection after nCT alone or nCT-SBRT were retrospectively reviewed. Baseline characteristics were compared, and the propensity score with inverse probability weighting (IPW) was used to compare pathologic/survival outcomes. Results Of 198 patients, 76 received nCT, and 122 received nCT-SBRT. The nCT-SBRT cohort had a higher proportion of LAPC (53% vs 22%; p p = 0.03), but adjuvant chemotherapy was less frequently administered (53% vs 67.1%; p p p p = 0.02). In the multivariate analysis, nCT-SBRT remained associated with R0 resection (p p = 0.81). Conclusions Despite having more advanced disease, the nCT-SBRT cohort was still more likely to undergo an R0 resection and experienced similar survival outcomes compared with the nCT alone cohort.

Purpose: The purpose of this study was to determine if somatic mutations are associated with clinical and pathologic outcomes in patients with borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC) who were treated with neoadjuvant chemotherapy and stereotactic body radiotherapy (SBRT). Materials and Methods: Patients treated with neoadjuvant chemotherapy and SBRT followed by surgical resection from August 2016 to January 2019 and who underwent next generation sequencing of their primary tumor were included in the study. Next-generation sequencing was performed either in-house with a Solid Tumor Panel or with FoundationOne CDx. Univariate (UVA) and multivariable analyses (MVA) were performed to determine associations between somatic mutations and pathologic and clinical outcomes. Results: Thirty-five patients were included in the study. Chemotherapy consisted of modified FOLFIRINOX, gemcitabine and nab-paclitaxel, or gemcitabine and capecitabine. Patients were treated with SBRT in 33 Gy in 5 fractions. On UVA and MVA, tumors with KRAS G12V mutation demonstrated better pathologic tumor regression grade (TRG) to neoadjuvant therapy when compared to tumors with other KRAS mutations (odds ratio = 0.087; 95% confidence interval [CI], 0.009–0.860; p = 0.036). On UVA and MVA, mutations in NOTCH1/2 were associated with worse overall survival (hazard ratio [HR] = 4.15; 95% CI, 1.57–10.95; p = 0.004) and progression-free survival (HR = 3.61; 95% CI, 1.41–9.28; p = 0.008). On UVA, only mutations in NOTCH1/2 were associated with inferior distant metastasis-free survival (HR = 3.38; 95% CI, 1.25–9.16; p = 0.017). Conclusion: In BRPC and LAPC, the KRAS G12V mutation was associated with better TRG following chemotherapy and SBRT. Additionally, NOTCH1/2 mutations were associated with worse overall survival, distant metastasis-free survival, and progression-free survival.

PURPOSE Genetic alterations in many components of the homologous recombination, DNA damage response, and repair (HR-DDR) pathway are involved in the hereditary cancer syndromes, including familial pancreatic cancer. HR-DDR genes beyond BRCA1, BRCA2, ATM, and PALB2 may also mutate and confer the HR-DDR deficiency in pancreatic ductal adenocarcinoma (PDAC). METHODS We conducted a study to examine the genetic alterations using a companion diagnostic 15-gene HR-DDR panel in PDACs. HR-DDR gene mutations were identified and characterized by whole-exome sequencing and whole-genome sequencing. Different HR-DDR gene mutations are associated with variable homologous recombination deficiency (HRD) scores. RESULTS Eight of 50 PDACs with at least one HR-DDR gene mutation were identified. One tumor with BRCA2 mutations is associated with a high HRD score. However, another tumor with a CHEK2 mutation is associated with a zero HRD score. Notably, four of eight PDACs in this study harbor a RAD51B gene mutation. All four RAD51B gene mutations were germline mutations. However, currently, RAD51B is not the gene panel for germline tests. CONCLUSION The finding in this study thus supports including RAD51B in the germline test of HR-DDR pathway genes.

Purpose: Immunotherapy is currently ineffective for nearly all pancreatic ductal adenocarcinomas (PDAC), largely due to its tumor microenvironment (TME) that lacks antigen-experienced T effector cells (Teff). Vaccine-based immunotherapies are known to activate antigen-specific Teffs in the peripheral blood. To evaluate the effect of vaccine therapy on the PDAC TME, we designed a neoadjuvant and adjuvant clinical trial of an irradiated, GM-CSF-secreting, allogeneic PDAC vaccine (GVAX). Patients and Methods: Eighty-seven eligible patients with resectable PDAC were randomly assigned (1:1:1) to receive GVAX alone or in combination with two forms of low-dose cyclophosphamide. Resected tumors following neoadjuvant immunotherapy were assessed for the formation of tertiary lymphoid aggregates (TLA) in response to treatment. The clinical endpoints are disease-free survival (DFS) and overall survival (OS). Results: The neoadjuvant treatment with GVAX either alone or with two forms of low-dose cyclophosphamide is safe and feasible without adversely increasing the surgical complication rate. Patients in Arm A who received neoadjuvant and adjuvant GVAX alone had a trend toward longer median OS (35.0 months) than that (24.8 months) in the historical controls who received adjuvant GVAX alone. However, Arm C, who received low-dose oral cyclophosphamide in addition to GVAX, had a significantly shorter DFS than Arm A. When comparing patients with OS > 24 months to those with OS < 15 months, longer OS was found to be associated with higher density of intratumoral TLA. Conclusions: It is safe and feasible to use a neoadjuvant immunotherapy approach for PDACs to evaluate early biologic responses. In-depth analysis of TLAs is warranted in future neoadjuvant immunotherapy clinical trials.

Recent research on genomic profiling of pancreatic ductal adenocarcinoma (PDAC) has identified many potentially actionable alterations. However, the feasibility of using genomic profiling to guide routine clinical decision making for PDAC patients remains unclear. We retrospectively reviewed PDAC patients between October 2013 and December 2017, who underwent treatment at the Johns Hopkins Hospital and had clinical tumor next-generation sequencing (NGS) through commercial resources. Ninety-two patients with 93 tumors tested were included. Forty-eight (52%) patients had potentially curative surgeries. The median time from the tissue available to the NGS testing ordered was 229 days (interquartile range 62–415). A total of three (3%) patients had matched targeted therapies based on genomic profiling results. Genomic profiling guided personalized treatment for PDAC patients is feasible, but the percentage of patients who receive targeted therapy is low. The main challenges are ordering NGS testing early in the clinical course of the disease and the limited evidence of using a targeted approach in these patients. A real-time department level genomic testing ordering system in combination with an evidence-based flagging system for potentially actionable alterations could help address these shortcomings.

The unprecedented impact of the Sars-CoV-2 pandemic (COVID-19) has strained the healthcare system worldwide. The impact is even more profound on diseases requiring timely complex multidisciplinary care such as pancreatic cancer. Multidisciplinary care teams have been affected significantly in multiple ways as healthcare teams collectively acclimate to significant space limitations and shortages of personnel and supplies. As a result, many patients are now receiving suboptimal remote imaging for diagnosis, staging, and surgical planning for pancreatic cancer. In addition, the lack of face-to-face interactions between the physician and patient and between multidisciplinary teams has challenged patient safety, research investigations, and house staff education. In this study, we discuss how the COVID-19 pandemic has transformed our high-volume pancreatic multidisciplinary clinic, the unique challenges faced, as well as the potential benefits that have arisen out of this situation. We also reflect on its implications for the future during and beyond the pandemic as we anticipate a hybrid model that includes a component of virtual multidisciplinary clinics as a means to provide accessible world-class healthcare for patients who require complex oncologic management.

368 Background: Pancreas cancer (PC) survival is among the lowest of all malignancies. While limited advances in treatment are a major driver of this reality, ample opportunity exists to improve outcomes by reducing care variation, providingcoordinated, comprehensive care, and accelerating research. Learning health networks (LHNs) improve outcomes in pediatric diseases through such mechanisms, yet are not widely implemented in adult care. We aimed to develop, implement, and collect initial outcomes of the first oncology LHN, the Canopy Cancer Collective (CCC). Methods: In 2019, we established CCC to apply to PC the LHN model, including core tenets of continuous quality improvement (QI), data-sharing, empowered interdisciplinary teams and a stakeholder community including individuals with PC, and focus on community-defined improvable “outcomes that matter”. Six care centers were selected to join the LHN, and engaged in a collaborative design process to co-create a set of improvement aims and change ideas. Center team members received training in basic QI methods/tools guided by the IHI Model for Improvement and were coached to apply these to local improvement efforts. LHN infrastructure and technology enabled sharing of new ideas, best practices, and results amongst centers. Eight more centers joined in 2021, and an outcomes database built and implemented. Results generated by this database will inform center-specific and Network-wide improvement efforts and allow the LHN to undertake research. Results: Currently, 14 care centers are active participants in the CCC LHN. Five key outcomes have been defined as key targets, and centers have co-created and tested change ideas organized around key drivers of excellent PC care including proactive, timely care, aligned/prepared multidisciplinary teams, informed, activated patients, and accurate diagnosis and disease classification. 100% of care centers are trained in QI methods and actively testing change ideas. For example, in May 2022, 11 centers reporting on monthly QI activities met on average 4 times to advance QI projects, deploying a mean of 2.9 plan-do-study-act (PDSA) cycles (range, 0-5) focused on key drivers and outcomes, including reduced time to treatment, increased trial enrollment, assessment of patient experience, and improved data capture. Conclusions: Building a sustainable LHN for PC centers is feasible and has set the stage for improving patient and provider outcomes through iterative community-building, continuous improvement, and sharing of data and multidisciplinary best practices. Results lay the foundation for expansion not only in PC, but translation to other complex malignancies that will benefit from transformative, system-based approaches to outcome improvement.

63 Background: Patients with localized pancreatic adenocarcinoma (PDAC) generally benefit from multi-modality therapy, which may be best coordinated through a pancreas multi-disciplinary clinic (PMDC). Whether treatment practice patterns vary based on whether a patient was seen through PMDC versus individual specialty-specific clinics is unclear. Methods: Using institutional Pancreatic Cancer Registry, we identified patients who came to Johns Hopkins Hospital through either PMDC or one of the individual surgical, medical, or radiation oncology clinics for localized PDAC between 2018-2020 and eventually underwent resection. During this time, it was standard practice for borderline resectable (BRPC) patients to undergo at least 4 months of neoadjuvant chemotherapy, with or without radiation, before transitioning to exploration, while locally advanced (LAPC) patients were treated with 4-6 months of chemotherapy, followed by radiation, followed by potential exploration. The primary outcome was completion of neoadjuvant therapy as per the above stage-specific institutional standards. Multivariable analyses were performed to find association between PMDC visit and completion of neoadjuvant therapy, controlling for age, sex, race, stage, baseline performance status and type of chemotherapy. Results: A total of 240 patients met inclusion criteria. Of these, 157 (65.4%) had PMDC visits. Distribution of stage across the cohort included 81 (34.3%), 91 (38.5%), and 64 (27.1%) patients with resectable PDAC, BRPC and LAPC, respectively. Patients in the PMDC group received radiation therapy more commonly (59.7% vs 34.9%, p = 0.004), as compared to patients seen through individual specialty-specific clinics. Mean duration of chemotherapy was higher for patients seen through PMDC (4.4 (SD: 1.7) vs 3.9 (SD: 2.0) months) compared with individual clinics. Completion of neoadjuvant therapy per institutional stage-specific standards was seen in 46% (n = 24) of the patients visiting individual specialty-specific clinics compared to 71% (n = 85) of patients who were seen through PMDC (p = 0.002). The adjusted odds ratio of completion of neoadjuvant therapy per institutional standards for patients seen through PMDC visit was 3.35 times the odds for patients seen through individual clinics (95% CIs 1.46-7.07; p = 0.004). Of note, a higher proportion of patients who were seen through PMDC enrolled in a clinical trial (n = 26, 16.6%) compared with patients seen through individual clinics (n = 6; 7.2%) (p = 0.043). Conclusions: Provision of care through a multi-disciplinary clinic was associated with significantly higher odds of completing neoadjuvant therapy per institutional standards as compared to care through individual specialty-specific clinics. In addition, care through a PMDC may also be associated with increased trial enrollment.

A cancer diagnosis not only affects multiple aspects of a patient's life, but can also have a significant impact on the caregiver, who is often the spouse as well. Beginning in 2012, the Johns Hopkins Gastrointestinal Oncology group has organized a couples' retreat program to help address the concerns of oncology patients as well as their caregivers in a safe and closed environment. These retreats are disease-site specific and include 10 to 12 couples with metastatic or locally advanced pancreatic or colorectal cancer. The program includes a multidisciplinary approach over 3 days and includes meals, activities, and lodging. Couples are encouraged to engage with each other as well as other couples enduring a similar journey in an effort to help them relate and express concerns and questions they may have. Sessions include topics by medical professions such as treatments and symptom management as well as sessions by additional professionals to address other practical needs related to the diagnosis, such as finances and advance directives. These retreats have shown that both patients and caregivers appreciate the opportunity to discuss their feelings with others and subsequently feel less uncertainty about their future. They have also been beneficial to the health-care professionals participating to gain knowledge on which activities as a whole are important to these populations. Data are extremely limited for programs such as these, but we are hopeful they will continue to help support these populations of oncology patients and their caregivers through a very difficult portion of their lives.

Trials studying additional solid cancers, such as pancreatic cancer, head and neck cancer, glioblastoma, and glioma are reviewed in this section and accompanied by advanced practitioner commentaries. In addition, a study exploring the benefits of proton therapy over photon therapy is discussed.

Purpose For patients with localized pancreatic cancer (PC) with vascular involvement, prediction of resectability is critical to define optimal treatment. However, the current definitions of borderline resectable (BR) and locally advanced (LA) disease leave considerable heterogeneity in outcomes within these classifications. Moreover, factors beyond vascular involvement likely affect the ability to undergo resection. Herein, we share our experience developing a model that incorporates detailed radiologic, patient, and treatment factors to predict surgical resectability in patients with BR and LA PC who undergo stereotactic body radiation therapy (SBRT). Methods and materials Patients with BR or LA PC who were treated with SBRT between 2010 and 2016 were included. The primary endpoint was margin negative resection, and predictors included age, sex, race, treatment year, performance status, initial staging, tumor volume and location, baseline and pre-SBRT carbohydrate antigen 19-9 levels, chemotherapy regimen and duration, and radiation dose. In addition, we characterized the relationship between tumors and key arteries (superior mesenteric, celiac, and common hepatic arteries), using overlap volume histograms derived from computed tomography data. A classification and regression tree was built, and leave-one-out cross-validation was performed. Prediction of surgical resection was compared between our model and staging in accordance with the National Comprehensive Care Network guidelines using McNemar’s test. Results A total of 191 patients were identified (128 patients with LA and 63 with BR), of which 87 patients (46%) underwent margin negative resection. The median total dose was 33 Gy. Predictors included the chemotherapy regimen, amount of arterial involvement, and age. Importantly, radiation dose that covers 95% of gross tumor volume (GTV D95), was a key predictor of resectability in certain subpopulations, and the model showed improved accuracy in the prediction of margin negative resection compared with National Comprehensive Care Network guideline staging (75% vs 63%; P Conclusions We demonstrate the ability to improve prediction of surgical resectabiliy beyond the current staging guidelines, which highlights the value of assessing vascular involvement in a continuous manner. In addition, we show an association between radiation dose and resectability, which suggests the potential importance of radiation to allow for resection in certain populations. External data are needed for validation and to increase the robustness of the model.

4134 Background: Management of locally advanced pancreas cancer (LAPC) standardly involves chemotherapy with consolidative radiation and surgery in selected pts. Checkpoint inhibitors have shown limited benefit alone in pancreas cancer but may be primed by radiation and GM-CSF secreting allogeneic pancreatic cancer vaccine (GVAX). We present data from a phase 2 study for LAPC pts who have not developed metastases after standard of care chemotherapy treated with combination cyclophosphamide (CY), GVAX, pembrolizumab (pembro), and stereotactic body radiation therapy (SBRT). Methods: This is a single-arm, single institution, open-label study for pts with LAPC at diagnosis (as per NCCN guidelines, arterial involvement > 180°, or unreconstructible SMV/PV) who remained without metastatic disease after 4-8 28-day cycles FOLFIRINOX or gemcitabine/abraxane based therapy. Pts received CY (200mg/m2 IV) and pembro (200mg IV) on day 1, followed by GVAX (6 intradermal inj) on day 2 q3 wk x 2 cycles, with cycle 2 initiating concurrently with 5 days SBRT. Pts were restaged 4-6 weeks after SBRT, and if non-metastatic, pts underwent surgical resection, irreversible electroporation (IRE), or biopsy (if not undergoing surgical resection). Pts received two cycles of chemotherapy, and if metastasis free, received q3 wk CY/pembro/GVAX x 6 cycles with restaging scans q3 mos. In 5/2017, the protocol was addended to include an extended phase with q3 wk pembro x 9 cycles and q6 mo CY/GVAX x 4. Primary endpoint was distant metastasis free survival (DMFS) defined as C1D1 to distant metastases or death. Results: From Jul 2016-Jan 2021, 58 pts with LAPC were enrolled at the Johns Hopkins Hospital, 54 completed 2 cycles CY/pembro/GVAX and SBRT and were evaluable for response (2 dropouts due to thrombocytopenia, 2 due to irAE (DKA and hepatitis)), median followup was 15.8 mos. Demographics: median age 66 (range 42-84), 53% male, 84% White, 12% African American. At first restaging (N = 54), 8 (15%) had metastatic disease, 9 (17%) were unresectable, 37 (69%) were eligible for surgical resection. 35 pts proceeded to the OR (1 died of cholangitis prior to surgery and 1 declined surgery), 24 had tumors resected (44% of evaluable pts, 10 (42%) had grade 1 (marked) pathologic response), 1 IRE, 2 were unresectable, 8 were metastatic. Common related AEs were vaccine site reactions; grade 3 irAE included 1 case each of dermatitis, colitis, DKA, nephritis, and pneumonitis. DMFS was 9.7 mos [95% CI 6.3-19.3 mos]. Conclusions: We present data from a ph II study of 54 pts w LAPC treated w CY/GVAX/pembro and SBRT. Primary endpoint of DMFS > 13.6 mos not reached, however 44% of pts underwent surgical resection of whom 42% had grade 1 path response rate. Additional correlative studies are underway. Clinical trial information: NCT02648282.

A standardized treatment regimen for unresectable isolated local recurrence (ILR) of pancreatic ductal adenocarcinoma has not been established. This study evaluated the outcomes for patients with ILR who underwent stereotactic body radiation therapy (SBRT). The records of patients with ILR who underwent SBRT between 2010 and 2016 were retrospectively reviewed. Symptom palliation and treatment-related toxicity were recorded. Associations between patient or treatment characteristics and overall survival (OS), progression-free survival (PFS), and local progression-free survival (LPFS) were assessed. The study identified 51 patients who received SBRT for ILR. Of the 51 patients, 26 (51%) had not received radiation therapy before SBRT. The median OS was 36 months after diagnosis. From the first day of SBRT, the median OS, PFS, and LPFS were respectively 16, 7, and 10 months. Patients with a recurrence-free interval of 9 months or longer after surgery had superior OS (P = 0.019). Maintenance chemotherapy after SBRT was associated with superior OS (P

The use of neoadjuvant chemotherapy or radiation for borderline resectable pancreatic adenocarcinoma (BL‐PDAC) is increasing. However, the impact of neoadjuvant chemotherapy and radiation therapy on the outcome of BL‐PDAC remains to be elucidated. We performed a retrospective analysis of 93 consecutive patients who were diagnosed with BL‐PDAC and primarily followed at Johns Hopkins Hospital between February 2007 and December 2012. Among 93 patients, 62% received upfront neoadjuvant chemotherapy followed by chemoradiation, whereas 20% received neoadjuvant chemoradiation alone and 15% neoadjuvant chemotherapy alone. Resectability following all neoadjuvant therapy was 44%. Patients who underwent resection with a curative intent had a median overall survival (mOS) of 25.8 months, whereas those who did not undergo surgery had a mOS of 11.9 months. However, resectability and overall survival were not significantly different between the three types of neoadjuvant therapy. Nevertheless, 22% (95% CI, 0.13–0.36) of the 58 patients who received upfront chemotherapy followed by chemoradiation remained alive for a minimum of 48 months compared to none of the 19 patients who received upfront chemoradiation. Among patients who underwent curative surgical resection, 32% (95% CI, 0.19–0.55) of those who received upfront chemotherapy remained disease free at least 48 months following surgical resection, whereas none of the eight patients who received upfront chemoradiation remained disease free beyond 24 months following surgical resection. Neoadjuvant therapy with upfront chemotherapy may result in long‐term survival in a subpopulation of patients with BL‐PDAC.

// Lauren M. Rosati 1,* , Megan N. Kummerlowe 1,* , Justin Poling 2 , Amy Hacker-Prietz 1 , Amol K. Narang 1 , Eun J. Shin 3 , Dung T. Le 4 , Elliot K. Fishman 5 , Ralph H. Hruban 2 , Stephen C. Yang 6 , Matthew J. Weiss 6 and Joseph M. Herman 1,7 1 Department of Radiation Oncology & Molecular Radiation Sciences, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA 2 Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA 3 Department of Gastroenterology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA 4 Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA 5 Department of Radiology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA 6 Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD, USA 7 Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA * These authors have contributed equally to this manuscript Correspondence to: Joseph M. Herman, email: // Keywords : pancreatic cancer, pancreatic ductal adenocarcinoma, metastatic, esophagus, esophageal metastasis Received : April 28, 2017 Accepted : May 20, 2017 Published : June 12, 2017 Abstract Purpose: We report a very unique case of an esophageal metastasis from a pancreatic ductal adenocarcinoma (PDAC) primary. Methods: After obtaining consent from the patient, all relevant records of the case were obtained and retrospectively reviewed. Results: At presentation, the patient was diagnosed with synchronous pancreatic and esophageal cancer. He received six months of neoadjuvant therapy including FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) and stereotactic body radiation therapy (SBRT) to the pancreatic tumor followed by a combined pancreaticoduodenectomy and Ivor Lewis esophagectomy. Review of the final esophageal specimen revealed normal overlying squamous mucosa with an underlying focus of metastatic PDAC. The patient remains alive with no evidence of disease 17 months from surgery and 25 months from diagnosis. Conclusions: Differentiating an esophageal metastasis from a PDAC primary versus a synchronous esophageal carcinoma is very difficult despite state-of-the-art diagnostic techniques performed at a high-volume tertiary cancer center. Extensive evaluation and continued follow-up of PDAC patients presenting with a synchronous esophageal lesion in a multidisciplinary setting may help ensure efficient and accurate management. In our case, neoadjuvant FOLFIRINOX and SBRT to the primary PDAC tumor followed by surgery has been an effective approach for this patient.

Endoluminal brachytherapy (EBT) has been shown to be an effective neoadjuvant monotherapy for rectal adenocarcinoma. Radiographic predictors of response are used to guide treatment in rectal cancer; however, no predictors of response to EBT have been identified. This is a single-institutional prospective study from 2010 to 2013. Analysis included 17 patients undergoing EBT and 13 patients undergoing conventional external beam chemoradiation (CRT). Clinical response to therapy was assessed with serial MRI and PET/CT variables. Pathological response to therapy was assessed using tumor regression grade (TRG) and compared with clinical response. EBT and CRT patients did not differ with respect to age, sex, race, carcinoembryonic antigen, or clinical stage of disease. There was a similar rate of pathologic complete response for both groups, with a trend towards more TRG 0 with EBT compared with CRT (35.3% vs. 7.7%, p = 0.08). Four days of EBT resulted in a significantly greater reduction in tumor volume on MRI than did CRT (92.7% vs. 63.1%, p = 0.004). Using receiver operating characteristic analysis, change in peak standardized uptake value was the best predictor for complete pathologic response in EBT patients (sensitivity 67%, specificity 82%). False-positive findings for nodal disease on MRI were seen in 59% of EBT patients and 23% of CRT patients. This study demonstrates that EBT is an effective alternative with similar response rates to CRT. However, the inability of MRI and PET/CT to discern reactive from malignant tumor and nodes may pose limitations in their use for guiding further therapy. Larger randomized studies are needed.

Background The combination of low-dose radiation therapy with PARP inhibition enhances anti-tumor efficacy through potentiating DNA damage. We combined low-dose fractionated whole abdominal radiation (LDFWAR) with ABT-888 in patients with peritoneal carcinomatosis with a dose escalation in ovarian and fallopian cancer patients (OV). Methods Patients were treated with veliparib, 40–400mg orally BID on days 1–21 of 3 28-day cycles on 6 dose levels. Dose levels 5 and 6 included only OV patients. LDFWAR consisted of 21.6Gy in 36 fractions, 0.6Gy twice daily on days 1 and 5 for weeks 1–3 of each cycle. Circulating tumor material and quality of life were serially assessed. Results 32pts were treated. Median follow-up was 45months (10–50). The most common treatment-related grade 3 and 4 toxicities were lymphopenia (59%), anemia (9%), thrombocytopenia (12%), neutropenia (6%), leukopenia (6%), nausea (6%), diarrhea (6%), anorexia (6%), vomiting (6%) and fatigue (6%). The maximum tolerated dose was determined to be 250mg PO BID. Median PFS was 3.6months and median OS was 9.1months. In OV patients, OS was longer for platinum-sensitive patients (10.9mo) compared to platinum-resistant patients (5.8mo). QoL decreased for all groups during treatment. Germline BRCA status was known for 14/18 patients with OV cancers, 5 of whom were BRCA mutation carriers. One objective response (3%) was observed. Conclusion ABT-888 plus LDFWAR is tolerable with gastrointestinal symptoms, fatigue and myelosuppression as the most common toxicities. The single observed objective response was in a germline BRCA mutated, platinum-sensitive patient.

Purpose We previously reported clinical outcomes and physician-reported toxicity of gemcitabine and hypofractionated stereotactic body radiation therapy (SBRT) in locally advanced pancreatic cancer (LAPC). Here we prospectively investigate the impact of gemcitabine and SBRT on patient-reported quality of life (QoL). Methods and materials Forty-nine LAPC patients received 33 Gy SBRT (6.6 Gy daily fractions) upfront or after ≤3 doses of gemcitabine (1000 mg/m 2 ) followed by gemcitabine until progression. European Organization for Research and Treatment of Cancer QoL core cancer (QLQ-C30) and pancreatic cancer-specific (European Organization for Research and Treatment of Cancer QLQ-PAN26) questionnaires were administered to patients pre-SBRT and at 4 to 6 weeks (first follow-up [1FUP]) and 4 months (2FUP) post-SBRT. Changes in QoL scores were deemed clinically relevant if median changes were at least 5 points in magnitude. Results Forty-three (88%) patients completed pre-SBRT questionnaires. Of these, 88% and 51% completed questionnaires at 1FUP and 2FUP, respectively. There was no change in global QoL from pre-SBRT to 1FUP ( P = .17) or 2FUP ( P > .99). Statistical and clinical improvements in pancreatic pain ( P = .001) and body image ( P = .007) were observed from pre-SBRT to 1FUP. Patients with 1FUP and 2FUP questionnaires reported statistically and clinically improved body image ( P = .016) by 4 months. Although pancreatic pain initially demonstrated statistical and clinical improvement ( P = .020), scores returned to enrollment levels by 2FUP ( P = .486). A statistical and clinical decline in role functioning ( P = .002) was observed in patients at 2FUP. Conclusions Global QoL scores are not reduced with gemcitabine and SBRT. In this exploratory analysis, patients experience clinically relevant short-term improvements in pancreatic cancer-specific symptoms. Previously demonstrated acceptable clinical outcomes combined with these favorable QoL data indicate that SBRT can be easily integrated with other systemic therapies and may be a potential standard of care option in patients with LAPC.

Background There is continued debate regarding the optimal combinations of radiation therapy and chemotherapy in the preoperative treatment of locally advanced rectal adenocarcinomas. We report our single-institution experience of feasibility and early oncologic outcomes of short-course preoperative radiation therapy (5 Gy X 5 fractions) followed by consolidation neoadjuvant chemotherapy. Methods We reviewed the records of 26 patients with locally advanced rectal adenocarcinoma. All patients underwent short course radiotherapy (5 Gy X 5 fractions) followed by chemotherapy [either modified infusional and bolus 5-fluorouracail and oxalipatin (mFOLFOX6) or capecitabine and oxaliplatin] prior to consideration for surgery. A full course of chemotherapy was defined as at least 8 weeks of chemotherapy. Results There were five clinical (c) T2, 16 cT3, and five cT4 rectal tumors, with 88% cN+. Twenty-five patients received a median of 4 cycles (range 3 to 8) of mFOLFOX6 (with one cycle defined as a two-week period); one patient received 3 cycles of capecitabine and oxaliplatin. All patients completed SCRT; 81% completed the full course of neoadjuvant chemotherapy with 19% requiring dose reductions in chemotherapy, most commonly due to neuropathy. Nineteen patients underwent post-treatment endoscopic evaluation, and nine patients were noted to achieve a complete clinical response (CCR). Six of the nine patients who achieved CCR opted for a non-operative approach of watch-and-wait. Twenty patients underwent surgical resection; pathologic complete response was observed in seven (35%) of these twenty. The main radiation-associated toxicity was proctitis with CTCAE Grade 2 proctitis observed in seven patients (27%). Post-operative Clavien-Dindo Grade 3 complications within 30 days of surgery were identified in six patients (30%), with no Grade 4 or 5 adverse events. Median length of hospital stay was 4.5 days (range 2–16 days); three patients were readmitted within a 30 day period. Conclusions Short course preoperative radiotherapy followed by neoadjuvant chemotherapy was well-tolerated and achieved oncologic outcomes that compare favorably with short-course radiation therapy alone or long-course chemoradiotherapy. This regimen is associated with high rates of clinical and pathologic complete response.

444 Background: The benefit of stereotactic body radiation therapy (SBRT) in the neoadjuvant setting for patients with localized pancreatic adenocarcinoma (PDAC) remains an area of active investigation. Herein, we report on surgical, pathologic, and survival outcomes in a modern cohort of borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) patients (pts) who were treated at a high-volume institution with upfront chemotherapy (CTX) followed by SBRT. Methods: A prospectively collected institutional IRB-approved database was reviewed to identify PDAC pts diagnosed between 2015-2018. All pts were seen in our multidisciplinary clinic and treated with multiagent induction CTX followed by 5-fraction SBRT. In general, it was our institutional preference that ECOG 0-1 pts were recommended modified FOLFIRINOX (mFFX), whereas others were recommended gemcitabine/abraxane. Pathological outcomes by stage were characterized. Kaplan-Meier analysis was used to generate survival curves, and factors prognostic for survival were identified. Results: Our cohort consisted of 156 pts, including 92 LAPC pts (59%) and 63 BRPC pts (41%). Median follow-up from diagnosis was 21.0 months (range 4-49 mos). Of the entire cohort, 117 (75%) received mFFX and 37 (24%) received gemcitabine/abraxane. Median duration of upfront CTX before SBRT was 4.0 months, with 126 pts (80.8%) receiving greater than 4 months. After SBRT, 130 pts (84%) were surgically explored with 106 pts (68%) successfully resected. Of 106 pts who were resected, 97 pts (92%) achieved negative margins, 63 pts (59%) were node-negative, and eight pts (8%) achieved a pathological complete response (pCR). Among 63 BRPC pts, 49 pts (78%) underwent resection, of whom 47 pts (96%) achieved margin negative resection. Among 92 LAPC pts, 57 pts (62%) underwent resection, of whom 50 pts (88%) achieved margin negative resection. For the entire cohort, median overall survival (mOS) from diagnosis was 25.4 mos (95% CI: 22.2 to NR) and 17.6 mos from SBRT (95% CI: 16.1 to NR). ECOG 0-1, initial biopsy grade (well-to-moderately differentiated), duration of neaodjuvant CTX (≥ 4 mos), surgical resection, and receipt of adjuvant CTX were all associated with improved survival from diagnosis (all p < 0.05), but stage (BR vs. LAPC) was not ( p = 0.43). Conclusions: In a modern cohort of patients receiving mFFX (75%) followed by SBRT, a high proportion of pts were successfully resected with favorable pathologic outcomes. Interestingly, OS was not significantly different for BRPC vs LAPC. Factors that proved to be important with respect to OS included duration of neoaduvant CTX, performance status, initial biopsy grade, and receipt of adjuvant CTX, After maximal multiagent CTX, factors other than stage should be considered in determining which pts will benefit from SBRT and/or subsequent surgery.

440 Background: We previously reported a multi-center study in which gemcitabine and stereotactic body radiation therapy (SBRT) were shown to be safe with outcomes comparable to chemoradiation in locally advanced pancreatic cancer (LAPC). This prospective clinical trial was developed to evaluate the efficacy of adding SBRT to multi-agent chemotherapy in LAPC. Herein, we report on the long-term survival outcomes. Methods: From 2012 to 2015, 48 patients (pts) were prospectively enrolled after multidisciplinary evaluation at a single high-volume pancreatic center. Pts received multi-agent chemotherapy (CTX) with modified mFOLFIRINOX (mFFX) or gemcitabine/abraxane followed by 5 fractions of SBRT (median 33 Gy; range, 25-33 Gy). At the time of fiducial placement, biopsies were obtained and DNA extracted for targeted sequencing using MSK-IMPACT. Kaplan-Meier curves were generated to compare survival outcomes by sub-group. Multivariate analysis (MVA) was performed to identify factors prognostic for survival. Results: 44 pts (91.7%) had LAPC disease and 4 (8.3%) had locally recurrent disease. The median follow-up interval was 21.5 months (mo) from diagnosis. CTX consisted of mFFX in 25 pts (52.1%) with 24 pts (50.0%) receiving therapy for a duration ≥4 mo. Of 44 pts with LAPC, 15 (34.1%) were surgically explored, and 11 (73.3%) achieved a margin-negative resection. From diagnosis and after completion of SBRT, respectively, the median overall survival (OS) was 21.6 (95% CI 16-29.7 mo) and 14.6 mo (95% CI: 11.6-23.0 mo); median progression free survival (PFS) was 13.2 (95% CI 11.9-18.1mo) and 6.4 mo (95% CI: 5-12.7 mo); median local PFS (LPFS) was 23.9 (95% CI 18.9-56.9 mo) and 15.8 mo (95% CI: 12.9-27.6 mo); and median distant metastasis free survival (DMFS) was 18.4 (95% CI 12.6-29.3 mo) and 8.5 mo (95% CI: 6.3-17.2 mo). Resected pts experienced better DMFS at 1-year (78% vs. 34%, p= 0.004) with an improved trend for 1-year OS (73% vs. 52%, p= 0.331). If CTX duration was ≥4 mo, 1-year OS (75% vs. 42%, p= 0.018), PFS (50% vs. 21%, p= 0.022), and DMFS (72% vs. 29%, p= 0.031) were significantly improved. In 44 LAPC pts, MVA confirmed ≥4 mo duration of CTX was associated with OS, PFS, and DMFS. Surgical resection was associated with improved DMFS, and CA19-9 level prior to SBRT was associated with PFS and LPFS. The most common mutations detected from biopsy specimens were KRAS (64.3%) , TP53 (50%), and SMAD4 (16.7%). Conclusions: In a prospective trial of pts with LAPC receiving multiagent CTX and SBRT, clinical outcomes were improved with longer durations of CT ( > 4 mo). A high proportion of LAPC pts underwent margin negative resection with favorable outcomes. Future studies should focus on which pts are most likely to benefit from SBRT and surgery following multiagent CTX. In pts who cannot undergo resection, escalated doses of SBRT may be indicated. Clinical trial information: NCT01781728.

443 Background: Patients (pts) withborderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC) are at high risk of margin positive resection with upfront surgery. Pre-operative stereotactic body radiation therapy (SBRT) may help sterilize vascular margins, but its additive benefit beyond multi-agent chemotherapy (CTX) is unclear. We report on long-term outcomes from a high-volume institution of BRPC/LAPC pts who were reviewed by a multidisciplinary team and explored after either multi-agent CTX alone or multi-agent CTX followed by SBRT. Methods: Consecutive BRPC/LAPC pts diagnosed 2011-2016 who underwent resection following CTX alone or CTX followed by 5-fraction SBRT (CTX-SBRT) were retrospectively reviewed. Baseline demographic, clinical, and treatment factors were compared between cohorts, and survival analysis was conducted to compare pathologic and survival outcomes. Results: Of 199 pts, 77 received CTX alone and 122 received CTX-SBRT. There was no significant difference between cohorts in age, gender, performance status, tumor location, CA19-9 at diagnosis, or post-CTX CA19-9 values (all p > 0.05). The CTX-SBRT cohort had a higher proportion of pts with LAPC as compared to the CTX cohort (53% vs 22%, p< 0.001). Modified FOLFIRINOX (mFFX) was administered to 55% of pts, while 70% of pts received either mFFX or gemcitabine/abraxane, with no difference between cohorts. Duration of CTX was longer in the CTX-SBRT cohort as compared to the CTX cohort (median 4.6 vs. 2.9 mos, p= 0.03), but adjuvant CTX was not given as often in the CTX-SBRT arm (60.4% vs. 86.4%, p= < 0.001). Notably, 30% of the CTX cohort also received adjuvant chemoradiation. Pathologic response was significantly improved in the CTX-SBRT cohort vs the CTX cohort, specifically negative margins (92% vs 70%, p< 0.001), node negative (59% vs. 42%, p< 0.001), and pathologic complete response (7% vs. 0%, p= 0.02). On multivariable analysis, after controlling for prognostic factors, CTX-SBRT remained significantly associated with margin negative resection ( p< 0.001). Despite having more advanced stage and less adjuvant therapy administration in the CTX-SBRT cohort, there was no significant difference in overall survival after surgery (median OS: 24.6 vs. 22.2 mo, p= 0.79), local progression free survival (14.0 vs. 13.6 mo, p= 0.33), or distant metastasis free survival (16.4 vs. 11.8 mo, p= 0.33). Conclusions: Despite more advanced disease at presentation, BRPC/LAPC pts treated with CTX-SBRT were more likely to undergo margin negative resection and experienced similar survival outcomes, as compared to CTX alone. More data are needed to refine which patients benefit from neoadjuvant SBRT and how RT administration can be optimized to impact survival outcomes.

Radiation-induced lymphopenia (RIL) is associated with inferior survival in patients with glioblastoma, lung cancer, and pancreatic cancer. We asked whether stereotactic body radiation therapy (SBRT) decreases severity of RIL compared to conventional chemoradiation therapy (CRT) in locally advanced pancreatic cancer (LAPC).Serial total lymphocyte counts (TLCs) from patients enrolled in a prospective trial of SBRT for LAPC were compared to TLCs from an existing database of LAPC patients undergoing definitive CRT. SBRT patients received 33 Gy (6.6 Gy × 5 fractions). CRT patients received a median dose of 50.4 Gy (1.8 Gy × 28 fractions) with concurrent 5-fluorouracil (77%) or gemcitabine (23%) therapy. Univariate and multivariate analyses (MVA) were used to identify associations between clinical factors and post-treatment TLC and between TLC and survival.Thirty-two patients received SBRT and 101 received CRT. Median planning target volume (PTV) was smaller in SBRT (88.7 cm(3)) than in CRT (344.6 cm(3); P.001); median tumor diameter was larger for SBRT (4.6 cm) than for CRT (3.6 cm; P=.01). SBRT and CRT groups had similar median baseline TLCs. One month after starting radiation, 71.7% of CRT patients had severe lymphopenia (ie, TLC500 cells/mm(3) vs 13.8% of SBRT patients; P.001). At 2 months, 46.0% of CRT patients remained severely lymphopenic compared with 13.6% of SBRT patients (P=.007). MVA demonstrated that treatment technique and baseline TLCs were significantly associated with post-treatment TLC at 1 but not 2 months after treatment. Higher post-treatment TLC was associated with improved survival regardless of treatment technique (hazard ratio [HR] for death: 2.059; 95% confidence interval: 1.310-3.237; P=.002).SBRT is associated with significantly less severe RIL than CRT at 1 month in LAPC, suggesting that radiation technique affects RIL and supporting previous modeling studies. Given the association of severe RIL with survival in LAPC, further study of the effect of radiation technique on immune status is warranted.

Multidisciplinary clinics for pancreatic cancer such as one established at Johns Hopkins offer advantages in the care of patients with pancreatic cancer. Advanced practitioners can play a role in multidisciplinary care, providing symptom management and acute care, and clinical trial enrollment/consent process.

Stereotactic body radiation therapy (SBRT) is a promising option for patients with pancreatic cancer (PCA); however, limited data support its efficacy. This study reviews our institutional experience of SBRT in the treatment of locally advanced (LAPC) and borderline resectable (BRPC) PCA. Charts of all PCA patients receiving SBRT at our institution from 2010 to 2014 were reviewed. Most patients received pre-SBRT chemotherapy. Primary endpoints included overall survival (OS) and local progression-free survival (LPFS). Patients received a total dose of 25–33 Gy in five fractions. A total of 88 patients were included in the analysis, 74 with LAPC and 14 with BRPC. The median age at diagnosis was 67.2 years, and median follow-up from date of diagnosis for LAPC and BRPC patients was 14.5 and 10.3 months, respectively. Median OS from date of diagnosis was 18.4 months (LAPC, 18.4 mo; BRPC, 14.4 mo) and median PFS was 9.8 months (95 % CI 8.0–12.3). Acute toxicity was minimal with only three patients (3.4 %) experiencing acute grade ≥3 toxicity. Late grade ≥2 gastrointestinal toxicity was seen in five patients (5.7 %). Of the 19 patients (21.6 %) who underwent surgery, 79 % were LAPC patients and 84 % had margin-negative resections. Chemotherapy followed by SBRT in patients with LAPC and BRPC resulted in minimal acute and late toxicity. A large proportion of patients underwent surgical resection despite limited radiographic response to therapy. Further refinements in the integration of chemotherapy, SBRT, and surgery might offer additional advancements toward optimizing patient outcomes.

Background This phase 2 multi-institutional study was designed to determine whether gemcitabine (GEM) with fractionated stereotactic body radiotherapy (SBRT) results in acceptable late grade 2 to 4 gastrointestinal toxicity when compared with a prior trial of GEM with single-fraction SBRT in patients with locally advanced pancreatic cancer (LAPC). Methods A total of 49 patients with LAPC received up to 3 doses of GEM (1000 mg/m2) followed by a 1-week break and SBRT (33.0 gray [Gy] in 5 fractions). After SBRT, patients continued to receive GEM until disease progression or toxicity. Toxicity was assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0] and the Radiation Therapy Oncology Group radiation morbidity scoring criteria. Patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) and pancreatic cancer-specific QLQ-PAN26 module before SBRT and at 4 weeks and 4 months after SBRT. Results The median follow-up was 13.9 months (range, 3.9-45.2 months). The median age of the patients was 67 years and 84% had tumors of the pancreatic head. Rates of acute and late (primary endpoint) grade ≥2 gastritis, fistula, enteritis, or ulcer toxicities were 2% and 11%, respectively. QLQ-C30 global quality of life scores remained stable from baseline to after SBRT (67 at baseline, median change of 0 at both follow-ups; P>.05 for both). Patients reported a significant improvement in pancreatic pain (P = .001) 4 weeks after SBRT on the QLQ-PAN26 questionnaire. The median plasma carbohydrate antigen 19-9 (CA 19-9) level was reduced after SBRT (median time after SBRT, 4.2 weeks; 220 U/mL vs 62 U/mL [P

Purpose To explore seromarker levels for associations with outcomes in locally advanced pancreatic cancer (LAPC) patients who received chemotherapy and stereotactic body radiation therapy (SBRT). Methods and Materials Serum from LAPC patients in 2 prospective trials of hypofractionated SBRT (5-6.6 Gy × 5) was collected before SBRT. Proximity ligation assay quantified the expression levels of 36 pancreatic cancer–specific candidate seromarkers: Axl, BMP2, CA 125, CA 19-9, CEA, CXCL-1/6/9/10, EGFR, Gas6, Her2, IGF-2, IGFBP-2/3/7, IL-6/6Ra/7/8/12, mesothelin, MMP-1/2/3/7, osteopontin, PDGFRa, PDK1, PF4, RegIV, SPARC, TGF-β, VEGF-A/D, and YKL40. Seromarker values were log transformed owing to log-normal distribution of the values, and Cox regression analysis was performed to assess for any association with overall survival. The Benjamini-Hochberg method was used to control for a false discovery rate (FDR) of only 10%. Results Sixty-four patients with LAPC were included. No clinical factors (including surgical resection, receipt of pre-SBRT chemotherapy, receipt of post-SBRT chemotherapy, performance status, and age) or potential biomarkers in the panel were associated with improved survival in this cohort after application of the FDR correction. Potential prognostic factors for improved survival for future investigation included surgical resection (P=.007, adjusted P=.153) and the serum expression of IL-8 (P=.006, adjusted P=.153), CA 19-9 (P=.031, adjusted P=.377), and MMP-1 (P=.036, adjusted P=.377). Conclusions These data explore the expression of a panel of proteins in pre-SBRT serum of LAPC patients in the context of a conservative FDR correction. None of the clinical factors or expression levels of the serum proteins were found to be associated with survival; however, IL-8, CA 19-9, and MMP-1 were highlighted as possible candidates warranting inclusion in future seromarker studies in the ongoing efforts to identify tools for risk stratification and treatment allocation in LAPC.

Neoadjuvant therapy increases rates of margin-negative resection of borderline resectable pancreatic ductal adenocarcinoma (BL-PDAC). Criteria for BL-PDAC resection following neoadjuvant chemotherapy and radiation therapy (NCRT) have not been clearly defined.Fifty consecutive patients with BL-PDAC who received NCRT from 2007 to 2012 were identified. Computed tomography (CT) scans pre- and post-treatment were centrally reviewed.Twenty-nine patients (58 %) underwent resection following NCRT, while 21 (42 %) remained unresected. Patients selected for and successfully undergoing resection were more likely to have better performance status and absence of the following features on pre- and post-treatment CT: superior mesenteric vein/portal vein encasement, superior mesenteric artery involvement, tumor involvement of two or more vessels, and questionable/overt metastases (allApparent radiographic extent of vascular involvement does not change significantly after NCRT. Patients without metastatic disease should be chosen for surgical exploration based on adequate performance status and lack of disease progression.

BACKGROUND Intraoperative radiotherapy (IORT) has advantages over external beam radiation therapy (EBRT). Few studies have described side effects associated with its addition. We evaluated our institution's experience with abdominopelvic IORT to assess safety by postoperative complication rates. METHODS Prospectively collected IRB-approved database of all patients receiving abdominopelvic IORT (via high dose rate brachytherapy) at Johns Hopkins Hospital between November 2006 and May 2014 was reviewed. Patients were discussed in multidisciplinary conferences. Those selected for IORT were patients for whom curative intent resection was planned for which IORT could improve margin-negative resection and optimize locoregional control. Perioperative complications were classified via Clavien-Dindo scale for postoperative surgical complications. RESULTS A total of 113 patients were evaluated. Most common diagnosis was sarcoma (50/113, 44%) followed by colorectal cancer (45/113, 40%), most of which were recurrent (84%). There were no perioperative deaths. A total of 57% of patients experienced a complication Grade II or higher: 24% (27/113) Grade II; 27% (30/113) Grade III; 7% (8/113) Grade IV. Wound complications were most common (38%), then gastrointestinal (25%). No radiotherapy variables were significantly associated with complications on uni/multi-variate analysis. CONCLUSIONS Our institution's experience with IORT demonstrated historically expected postoperative complication rates. IORT is safe, with acceptable perioperative morbidity.

Objective Yttrium-90 (Y-90) radioembolization is an emerging treatment option for unresectable neuroendocrine liver metastases (NELM). However, the data regarding this treatment are currently limited. This study evaluates the efficacy and tolerability of Y-90 radioembolization and identifies prognostic factors for radiographic response and survival. Methods and materials Thirty-eight patients underwent Y-90 radioembolization for NELM at our institution between April 2004 and February 2012. Patients were assessed radiographically (RECIST criteria, enhancement), serologically, and clinically at 1 month, and then at every 3 months after treatment for tumor response, toxicity, and survival outcomes. Results Median length of follow-up was 17.0 months (IQR, 9.0–37.0). Median survival was 29.2 months. Three patients (9%) had a radiographic complete response to treatment, 6 (17%) had a partial response, 21 (60%) had stable disease, and 5 (14%) developed progressive disease. Two factors were significantly associated with a good radiographic response (complete/partial response): islet cell histological subtype (p = 0.043) and hepatic tumor burden ≥ 33% (p = 0.031). Multivariate analysis revealed that patients requiring multiple Y-90 treatments (HR 2.9, p = 0.035) and patients who had previously failed systemic therapy with octreotide/chemotherapy (HR 4.4, p = 0.012) had worse survival. Grade 3 serologic toxicity was observed in 2 patients (5%; hyperbilirubinemia, elevated alkaline phosphatase) after treatment. Grade 3 non-serologic toxicities included abdominal pain (11%), fatigue (11%), nausea/vomiting (5%), ascites (5%), dyspnea (3%), diarrhea (3%), and peripheral edema (3%). No grade 4 or 5 toxicity was reported. Conclusions Y-90 radioembolization is a promising treatment option for inoperable NELM and is associated with low rates of grade ≥ 3 toxicity.

This study seeks to: (a) quantify radiologic-pathologic discrepancy for pancreatic adenocarcinoma by comparing tumor size on conventional computed tomography (C-CT) and 3-dimensional CT (3D-CT) to corresponding pathologic specimens; and (b) to identify clinico-pathologic characteristics predictive of radiologic-pathologic discrepancy to assist radiotherapy planning.Sixty-three patients with pancreatic adenocarcinoma and preoperative C-CT and volume-rendered 3D-CT imaging within 6 weeks of resection were identified. Maximum tumor diameter (MTD) was measured on pathology, C-CT, and 3D-CT and compared for each patient as well as among different clinico-pathologic subgroups.There was a trend toward C-CT underestimation of MTD compared to final pathology (p=0.08), but no significant difference between 3D-CT MTD and pathology (p=0.54). Pathologic tumor size was significantly underestimated by C-CT in patients with larger pathologic tumor size (3.0 cm, p=0.0001), smaller tumor size on C-CT (3.0 cm, p=0.003), higher CA19-9 (90 U/mL, p=0.008), and location in the pancreatic head (p=0.015). A model for predicting pathologic MTD using C-CT MTD and CA19-9 level was generated.3D-CT may allow for more accurate contouring of pancreatic tumors than C-CT. Patients with the above clinico-pathologic characteristics may require expanded margins relative to tumor size estimates on C-CT during radiotherapy planning.

PURPOSE: We report on a novel preclinical pancreatic cancer research model that uses bioluminescence imaging (BLI)-guided irradiation of orthotopic xenograft tumors, sparing of surrounding normal tissues, and quantitative, noninvasive longitudinal assessment of treatment response. MATERIALS AND METHODS: Luciferase-expressing MiaPaCa-2 pancreatic carcinoma cells were orthotopically injected in nude mice. BLI was compared to pathologic tumor volume, and photon emission was assessed over time. BLI was correlated to positron emission tomography (PET)/computed tomography (CT) to estimate tumor dimensions. BLI and cone-beam CT (CBCT) were used to compare tumor centroid location and estimate setup error. BLI and CBCT fusion was performed to guide irradiation of tumors using the small animal radiation research platform (SARRP). DNA damage was assessed by γ-H2Ax staining. BLI was used to longitudinally monitor treatment response. RESULTS: Bioluminescence predicted tumor volume (R = 0.8984) and increased linearly as a function of time up to a 10-fold increase in tumor burden. BLI correlated with PET/CT and necropsy specimen in size (P < .05). Two-dimensional BLI centroid accuracy was 3.5 mm relative to CBCT. BLI-guided irradiated pancreatic tumors stained positively for γ-H2Ax, whereas surrounding normal tissues were spared. Longitudinal assessment of irradiated tumors with BLI revealed significant tumor growth delay of 20 days relative to controls. CONCLUSIONS: We have successfully applied the SARRP to a bioluminescent, orthotopic preclinical pancreas cancer model to noninvasively: 1) allow the identification of tumor burden before therapy, 2) facilitate image-guided focal radiation therapy, and 3) allow normalization of tumor burden and longitudinal assessment of treatment response.