Local-regional Disease Research Articles

Hypofractionated vs Conventionally Fractionated Postmastectomy Radiation After Implant-Based Reconstruction

Postmastectomy radiation therapy (PMRT) improves local-regional disease control and patient survival. Hypofractionation (HF) regimens have comparable efficacy and complication rates with improved quality of life compared with conventional fractionation (CF) schedules. However, the use of HF after mastectomy in patients undergoing breast reconstruction has not been prospectively examined. To compare HF and CF PMRT outcomes after implant-based reconstruction. This randomized clinical trial assessed patients 18 years or older undergoing mastectomy and immediate expander or implant reconstruction for breast cancer (Tis, TX, or T1-3) and unilateral PMRT from March 8, 2018, to November 3, 2021 (median [range] follow-up, 40.4 [15.4-63.0] months), at 16 US cancer centers or hospitals. Analyses were conducted between September and December 2023. Patients were randomized 1:1 to HF or CF PMRT. Chest wall doses were 4256 cGy for 16 fractions for HF and 5000 cGy for 25 fractions for CF. Chest wall toxic effects were defined as a grade 3 or higher adverse event. The primary outcome was the change in physical well-being (PWB) domain of the Functional Assessment of Cancer Therapy-Breast (FACT-B) quality-of-life assessment tool at 6 months after starting PMRT, controlling for age. Secondary outcomes included toxic effects and cancer recurrence. Of 400 women (201 in the CF arm and 199 in the HF arm; median [range] age, 47 [23-79] years), 330 patients had PWB scores at baseline and at 6 months. There was no difference in the change in PWB between the study arms (estimate, 0.13; 95% CI, -0.86 to 1.11; P = .80), but there was a significant interaction between age group and study arm (P = .03 for interaction). Patients younger than 45 years had higher 6-month absolute PWB scores if treated with HF rather than CF regimens (23.6 [95% CI, 22.7-24.6] vs 22.0 [95% CI, 20.7-23.3]; P = .047) and reported being less bothered by adverse effects (mean [SD], 3.0 [0.9] in the HF arm and 2.6 [1.2] in the CF arm; P = .02) or nausea (mean [SD], 3.8 [0.4] in the HF arm and 3.6 [0.8] in the CF arm; P = .04). In the as-treated cohort, there were 23 distant (11 in the HF arm and 12 in the CF arm) and 2 local-regional (1 in the HF arm and 1 in the CF arm) recurrences. Chest wall toxic effects occurred in 39 patients (20 in the HF arm and 19 in the CF arm) at a median (IQR) of 7.2 (1.8-12.9) months. Fractionation was not associated with chest wall toxic effects on multivariate analysis (HF arm: hazard ratio, 1.02; 95% CI, 0.52-2.00; P = .95). Fewer patients undergoing HF vs CF regimens had a treatment break (5 [2.7%] vs 15 [7.7%]; P = .03) or required unpaid time off from work (17 [8.5%] vs 34 [16.9%]; P = .02). In this randomized clinical trial, the HF regimen did not significantly improve change in PWB compared with the CF regimen. These data add to the increasing experience with HF PMRT in patients with implant-based reconstruction. ClinicalTrials.gov Identifier: NCT03422003.

Phase 1 study to evaluate safety and preliminary efficacy of padeliporfin vascular targeted photodynamic therapy (VTP) in patients with locally advanced (LA) unresectable pancreatic ductal adenocarcinoma (PDAC).

TPS4204 Background: Pancreatic cancer is the third most common cause of cancer death. Surgery offers the best survival rates however only a minority of patients are eligible. Approximately 15-20% of patients are deemed unresectable due to vascular involvement LA. Conversion of unresectable tumors, due to vascular involvement to resectable, is an unmet clinical need. Methods: A novel approach was developed to destroy the tumor encasing the artery combining padeliporfin, a photosensitive drug, locally activated by laser light illumination. The effectiveness of the strategy was confirmed in an orthotopic mouse model. A proof-of-concept study using 12 non-tumor pigs demonstrated an acceptable safety profile. A phase I dose escalation trial (NCT5918783) will be performed to evaluate the safety and maximal tolerated dose (MTD) of laser light dose of padeliporfin VTP. VTP will be delivered through an endovascular fiber integrated in a standard angioplasty balloon. The balloon will be advanced under fluoroscopy to the encased vascular segment of the superior mesenteric artery (SMA) and inflated. Following IV administration of padeliporfin, it will be activated by the laser light. Part A will be a classic 3+3 dose-escalation design to determine the MTD of laser light. The identified MTD will be applied in the Part B for preliminary efficacy evaluation. The primary objectives are to determine safety and MTD and/or recommended phase 2 laser light dose of VTP treatment. Secondary objectives are: rate of surgical conversion; evaluation of the pattern of disease progression (local regional and/or metastatic disease) after VTP based on CT. Standard of care surgery can be performed after 14 days post VTP. Key inclusion criteria: patients with histologically/cytologically confirmed stage III unresectable LA-PDAC in the head/uncinate process of the pancreas, with SMA solid tumor contact ˃180° with measurable disease per RECIST 1.1 and ECOG 0-1. Key exclusion criteria: metastatic disease, other malignancy, photosensitive skin diseases or porphyria, concurrent investigational therapy within past 30 days, medically uncontrolled moderate or severe ascites, previous radiation to pancreas, SMA variants. Recruitment begins in April 2024. Conversion of unresectable locally advanced pancreatic cancer to surgery is a critical unmet need. This phase I trial explores a novel approach to treat the tumor encasement enabling surgery. Clinical trial information: NCT5918783 .

Epidemiology of the non-head and neck sebaceous carcinoma and implications for distant metastasis screening.

Extraocular sebaceous carcinoma (SC), particularly those outside the head and neck region, is rare and not well-described. This study aimed to explore the epidemiology and identify the prognostic factors of non-head and neck SC, describe the possible relevant factors of distant metastasis, and provide implications for distant metastasis screening. Data from the 17 registries in the Surveillance, Epidemiology, and End Results database were retrospectively collected for patients with SC outside the head and neck from 2000 through 2020. Overall survival (OS) and disease-specific survival (DSS) were the primary endpoints. Survival analysis was conducted through Kaplan-Meier curves, and multivariate analysis was carried out using Cox proportional hazard models. A total of 1,237 patients with SC outside the head and neck were identified. The mean age at diagnosis of the entire patient cohort was 67.7 years (30 to 90+ years), and the mean tumor size was 2.2 cm (0.1-16 cm). Patients with distant disease experienced the lowest OS (mean, 29.5 months) than those with localized disease and regional disease (p < 0.0001). Multivariate analysis revealed that age, tumor size, and stage were independent determinants of OS; age, stage, and primary site were independent determinants of DSS. Tumor grade and lymph node status had less prognostic value for survival. Undifferentiated tumors have a trend toward distant metastasis, especially those at the primary site of the trunk. The prognosis of the non-head and neck SC is excellent, while the survival of distant disease is very poor. Distant metastasis screening can be considered for undifferentiated tumors, especially those located in the trunk region with large tumor sizes.

Proliferation Patterns of MCF-7 Breast Cancer Cells in Lipoaspirate Conditioned Media.

Autologous fat grafting (AFG) is a common technique used to enhance aesthetic outcomes in postmastectomy breast reconstruction patients. Adipokines are hormones secreted by adipose tissue that play a critical role in regulating metabolic processes and the immune system. However, dysregulated adipokine secretion and signaling can contribute to the development and progression of cancer by promoting angiogenesis, altering the immune response, and inducing the epithelial mesenchymal transition. We aimed to assess how breast cancer cells behave in conditioned media derived from fat grafting lipoaspirates and gain a better understanding of the potential interactions that may occur within the tumor microenvironment. Patients who were undergoing AFG as a part of breast reconstruction at NY-Presbyterian/Weill Cornell Medical Center between March 2021 and July 2023 were consented and enrolled in the study. This study was approved by the Weill Cornell Medicine Institutional Review Board (#20-10022850-14). Conditioned media is created using 20% of patient lipoaspirate secretome and 80% starving media. The growth of MCF-7, a human ER/PR+ breast cancer cell line, in conditioned media is assessed using CyQUANT. The breast cancer cells incubated in conditioned media displayed similar growth trends as those in complete media, which is enriched for cell growth (P > 0.05). MCF-7 cell behavior in conditioned media differed significantly from their proliferation patterns when serum starved in 100% starving media (P < 0.05). Our results suggest that there may be inherent factors within the lipoaspirate that may promote MCF-7 proliferation. One potential implication is that AFG used for breast reconstruction should be delayed until local-regional disease control has been established. In addition, based on the in vitro proliferation patterns of breast cancer cells in conditioned media, the safety profile of AFG may be enhanced if the procedure is performed after attaining negative margins and the completion breast cancer treatment.

Predictors of PSMA positivity at initial staging of prostate cancer.

283 Background: PSMA-based imaging improves detection of metastatic disease for initial staging of men diagnosed with prostate cancer (PCa) with higher accuracy compared to conventional imaging. PSMA imaging is now being increasingly adopted for initial local and distant metastatic staging. We sought to determine the contribution of clinical and pathological factors associated with PSMA positive nodal or metastatic disease. Methods: We retrospectively identified 404 men diagnosed with PCa who underwent initial staging with Gallium-68 or F-18 piflufolastat (DCFPyL) PSMA PET/CT across our eleven-hospital system from July 2021-December 2022. Patient characteristics, including demographic, clinical, pathologic, and imaging variables were obtained. PSMA positivity representing a suspicious nodal or distant lesion was determined based on radiology reports, histopathology, and other imaging modalities, and equivocal or likely benign lesions were counted as negative. Patients with prior diagnosis (&gt;6 months) of PCa (n=42) or incomplete clinical history (n=22) were excluded. Clinical variables were compared with Wilcoxon Rank Test, Chi square, and Fishers’ exact test as well as univariable and multivariable logistic regression. Number of risk factors for patients with unfavorable intermediate or very high risk disease was also examined. PSA was log transformed. Statistical significance was defined as p&lt;0.05. Results: 103/340 patients (30.3%) had PSMA imaging findings concerning for nodal or distant metastatic disease. Patients with positive finding were less likely to be Black, and had higher PSA, biopsy Gleason Grade Group, and higher presumptive NCCN risk. Stratifying by pre-scan NCCN risk group, PSMA positivity was observed in no patients with favorable intermediate risk PCa (n=17), 9.8% (12/123) with unfavorable intermediate risk PCa, 29% (25/86) with high risk PCa, and 58% (66/114) with very high risk PCa. Stratifying by number of risk factors, there were significant differences in scan positivity comparing unfavorable intermediate risk disease with 1 vs ≥2 risk factors (4.2% vs 17%, p=0.03) and very high risk disease with 1 risk vs ≥2 risk factors (49% vs 72%, p=0.01). On multivariable analysis, NCCN classification stratified by risk factors was associated with PSMA positivity while Black race was inversely associated (OR 0.32, 95% CI 0.11, 0.82, p=0.03). Conclusions: Initial staging with PSMA PET/CT identified local regional or metastatic disease in 30% of PCa patients. A substantial proportion of unfavorable intermediate risk men were N1 or M1 based on PSMA positivity, particularly those with multiple unfavorable intermediate risk features. The clinical benefit for PSMA PET/CT in patients with favorable intermediate risk PCa is low. Limitations include retrospective design (including possible selection bias for patients with equivocal lesions on conventional imaging) and a limited number of black men in the cohort.

Proton Therapy in the Treatment of Men with Breast Cancer

PurposeMale breast cancer treatment involves multimodality therapy, including radiation therapy; nevertheless, few men have received proton therapy (PT) for it. Further, heart disease is an established leading cause of death in men, and radiation therapy heart dose correlates with cardiac toxicity, highlighting the need for cardiac-sparing radiation techniques. Thus, we provide a descriptive analysis of PT in a male breast cancer cohort. Patients and MethodsMen who received PT for localized breast cancer between 2012 and 2022 were identified from a prospective database. Toxicities were prospectively recorded by using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. ResultsFive male patients were identified. All had estrogen receptor (ER)–positive, Her2neu-negative disease and received adjuvant endocrine therapy. One had genetic testing positive for BRCA2, one had a variant of unknown significance (VUS) in the APC gene, and one had a VUS in MSH2. Median age was 73 years (range, 41–80). Baseline comorbidities included obesity (n = 1), diabetes (n = 1), hypertension (n = 4), history of deep vein thrombosis (n = 1), personal history of myocardial infarction (n = 3; 1 with a pacemaker), and a history of lung cancer (n = 1). All received PT to the left chest wall and comprehensive regional lymphatics. One received passive-scattering PT, and 4 received pencil beam scanning. One patient received a boost to the mastectomy incision via electrons. Median heart dose was 1 GyRBE (range, 0–1.0), median 0.1-cm3 dose to the left anterior descending artery was 7.5 GyRBE (range, 0–14.2), and median follow-up was 2 years (range, 0.75–6.5); no patient experienced a new cardiac event, and all remain free from breast cancer recurrence and progression. ConclusionIn a small case series for a rare diagnosis, PT to the chest wall and regional lymphatics, including internal mammary nodes, resulted in low cardiac exposure, high local regional disease control rates, and minimal toxicity. Proton therapy should be considered for treating men with breast cancer to achieve cardiac sparing.

Early-onset pancreatic neuroendocrine neoplasms: A distinct disease with improved survival compared with old individuals.

The incidence, clinicopathologic characteristics, treatment patterns, and survival of early-onset pancreatic neuroendocrine neoplasms (EOPanNENs) have not been well explored. Patients diagnosed with PanNENs were identified from the SEER database between 2000 and 2018. EOPanNENs were defined as diagnosis in patients aged less than 50 years, while the remaining were defined as later-onset pancreatic neuroendocrine neoplasms (LOPanNENs). Incidence, clinical features, management, and prognosis were analyzed in our study. Multivariable analyses were performed to identify factors associated with overall survival (OS) in EOPanNENs and LOPanNENs, respectively. A total of 5172 patients with PanNENs were included: 1267 (24.5%) in the EOPanNENs cohort and 3905 (75.5%) in the LOPanNENs cohort. The age-adjusted incidence rate significantly increased among later-onset cases, while it remained relatively stable in early-onset cases. EOPanNENs were more frequently to be female, unmarried, and with better tumor differentiation compared with LOPanNENs. Of note, early-onset patients presented with a higher rate of lymph node involvement, and they were more likely to receive surgical treatment. For local-regional disease at presentation, surgery alone was the most frequently used regimen over the last two decades. With regard to distant stage, a combination of surgery and chemotherapy was more often utilized. Risk factors for PanNENs survival were more correlated with LOPanNENs compared with EOPanNENs. The OS and cancer-specific survival (CSS) were significantly better in the EOPanNENs group. Further analyses showed that EOPanNENs ≤ 2cm were associated with more favorable survival outcomes than EOPanNENs>2cm. EOPanNENs are a clinically rare and distinct entity from LOPanNENs. The advantages in survival for the EOPanNENs cohort over time were largely driven by the indolent clinical courses including better tumor differentiation and intensified surgical treatment. Further investigations are warranted to better understand the characteristics of this disease subgroup.

Multimodality Imaging Review of HER2-positive Breast Cancer and Response to Neoadjuvant Chemotherapy

Human epidermal growth factor receptor 2 (HER2/neu or ErbB2)-positive breast cancers comprise 15%-20% of all breast cancers. The most common manifestation of HER2-positive breast cancer at mammography or US is an irregular mass with spiculated margins that often contains calcifications; at MRI, HER2-positive breast cancer may appear as a mass or as nonmass enhancement. HER2-positive breast cancers are often of intermediate to high nuclear grade at histopathologic analysis, with increased risk of local recurrence and metastases and poorer overall prognosis. However, treatment with targeted monoclonal antibody therapies such as trastuzumab and pertuzumab provides better local-regional control and leads to improved survival outcome. With neoadjuvant treatments, including monoclonal antibodies, taxanes, and anthracyclines, women are now potentially able to undergo breast conservation therapy and sentinel lymph node biopsy versus mastectomy and axillary lymph node dissection. Thus, the radiologist's role in assessing the extent of local-regional disease and response to neoadjuvant treatment at imaging is important to inform surgical planning and adjuvant treatment. However, assessment of treatment response remains difficult, with the potential for different imaging modalities to result in underestimation or overestimation of disease to varying degrees when compared with surgical pathologic analysis. In particular, the presence of calcifications at mammography is especially difficult to correlate with the results of pathologic analysis after chemotherapy. Breast MRI findings remain the best predictor of pathologic response. The authors review the initial manifestations of HER2-positive tumors, the varied responses to neoadjuvant chemotherapy, and the challenges in assessing residual cancer burden through a multimodality imaging review with pathologic correlation. © RSNA, 2023 Quiz questions for this article are available through the Online Learning Center.

Comparison of clinicopathologic characteristics and survival outcomes between invasive IPMN and invasive MCN: A population-based analysis.

BackgroundIntraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN) are two main histological subtypes of pancreatic cystic neoplasms with rapidly increasing incidence recently. The natural histories, treatment patterns, and survival outcomes of invasive IPMN and invasive MCN have not been well explored.MethodsPatients with a diagnosis of invasive IPMN and invasive MCN in the SEER database from 2000 through 2018 were retrospectively identified. Multivariable Cox regression analysis was conducted to determine the independent risk factors associated with overall survival (OS). Subgroup analyses of survival outcomes for invasive IPMN and invasive MCN were conducted. The OS for invasive IPMN was compared between patients who underwent surgery alone and those who received surgery plus chemotherapy by propensity score matching (PSM).ResultsA total of 2,505 patients were included, of whom 2,300 were diagnosed with invasive IPMN and 205 were diagnosed with invasive MCN. Half of the invasive IPMN (48.4%) and three-quarters of the invasive MCN (76.1%) patients were female. Of all patients, both the OS and cancer-specific survival were significantly better in the invasive MCN cohort compared to the invasive IPMN cohort. In subgroup analyses, while invasive MCN experienced better OS compared to invasive IPMN in the subgroups of patients with local–regional disease, the survival advantages disappeared in patients at a distant stage. In addition, surgery plus chemotherapy in invasive IPMN patients was associated with significantly better survival compared to surgery alone after PSM.ConclusionWe examined the demographic and clinical characteristics between invasive IPMN and invasive MCN patients using a large-population-based analysis. Although the OS is significantly better for invasive MCN versus invasive IPMN, the difference disappeared in patients with distant disease. A combination of surgery and chemotherapy in selected invasive IPMN patients could confer survival benefits compared to surgery alone.

S3215 Improved Survival in Endoscopic Ultrasound-Guided Fine Needle Aspiration Compared to Percutaneous Aspiration in Pancreatic Cancer: A Propensity Score Analysis

Introduction: With the advent of endoscopic ultrasound, tissue sampling of suspicious pancreatic lesions is more routinely performed via endoscopic ultrasound guided fine needle aspiration (EUS-FNA) compared to percutaneous aspiration. Studies have not investigated whether either technique is associated with a mortality benefit, as both methods could lead to tumor seeding along the needle track. Methods: We identified patients >65 years who were diagnosed with pancreatic cancer between 2007-2015 using The Surveillance, Epidemiology and End RESULTS (SEER)- Medicare linked database. Patients who underwent EUS-FNA or percutaneous aspiration within three months of cancer diagnosis were included and patients who underwent both procedures were excluded. Survival was calculated using Kaplan Meier methods and inverse propensity-weighted adjusted Cox proportional hazard ratios (aHR), adjusted for clinical and demographic variables as well as chemotherapy, radiation, and surgery. Results: Between 2000-2015, 6,093 patients underwent EUS-FNA (44.8%) compared with 7,513 who underwent percutaneous biopsy (55.2%). Median survival (Q1-Q3) for patients who received EUS-FNA was 6.0 months (2.0-13.0) compared with 4.0 months (1.0-9.0) for those who underwent percutaneous biopsy (p < 0.0001). After adjusting for confounders, patients who received EUS-FNA had improved survival (aHR 0.81, 95%CI 0.79-0.84). In stratified analysis, improved survival with EUS-FNA was seen for patients with localized disease (aHR 0.78, 95% CI 0.72-0.84), regional disease (aHR 0.89, 95% CI 0.85-0.93), and distant disease (aHR 0.79, 95% CI 0.76-0.82). When limited to patients who underwent surgery and adjusted for confounders, there was no difference in survival between groups (aHR 0.92, 95%CI 0.83-1.00). Conclusion: Patients with pancreatic cancer who underwent EUS-FNA survived longer compared with those who underwent percutaneous aspiration, though no difference was seen when limited to patients who underwent surgery. Providers should be reassured that EUS-FNA can be used to safely diagnose pancreatic cancer. EUS-FNA may also serve as a surrogate for expert care, which may have led to improvement in survival.

Peritonectomy of the colonic mesentery. Case report of a new surgical technology.

Introduction and importanceMalignant peritoneal mesothelioma is a local-regional disease process that requires a comprehensive treatment plan including complete cytoreductive surgery and regional chemotherapy.Case presentationTreatments used in our patient began with a complete cytoreductive surgery. This required visceral resections, parietal peritonectomy, peritonectomy of the small bowel and its mesentery, and a peritoneal resection of the colonic mesentery with sparing of the major vasculature of the large bowel.Clinical discussionPeritoneal resection of the colonic mesentery and other treatments were performed in the absence of major complications. A 20-day hospitalization was required. The patient shows no internal hernias and no evidence of disease by CT follow-up at 4 years postoperatively. Her quality of life is excellent.ConclusionsMalignant peritoneal mesothelioma was in the past a disease of limited survival without effective treatment options. Peritoneal resection of the colonic mesentery may be required for complete cytoreduction. A sequence of cytoreductive surgical procedures and regional chemotherapy treatments has made long-term survival possible.

Patterns of recurrence after neoadjuvant chemoradiotherapy compared with surgery alone in esophageal cancer

Associated with improvement in survival, the neoadjuvant therapy had become the mainstay of therapy for patients with locally advanced esophageal cancer. Despite a significantly better survival, the recurrence risk after neoadjuvant therapy remains considerably high, with recurrence rate of>40%. Thus, it's important to gain a thorough understanding of the recurrence patterns for developing effective tertiary prevention and follow-up strategies. The aim of this review was to compare the patterns of recurrence in patients with esophageal cancer who received preoperative therapy followed by surgery or surgery alone. It is found that the most frequent recurrence pattern was distant metastasis in esophageal cancer regardless receipt of neoadjuvant therapy or not, and the major effect of neoadjuvant therapy appears to be an improvement in local regional disease control without a reduction in systemic. This frustrating fact may explain the poor survival of esophageal cancer patients receiving neoadjuvant therapy.

Epidemiology and outcomes of primary pediatric lung malignancies: Updates from the SEER database

BackgroundPrimary pediatric lung malignancies are rare tumors. We provide an updated analysis of the epidemiology and prognosis of these tumors since the last SEER series published in 2009. MethodsThe SEER 18 database from 1975 to 2016 was analyzed for patients ages 0–19 years with primary lung and/or bronchus neoplasms. Results348 patients met inclusion criteria. The majority were white and ≥12 years of age. The most common histologies were neuroendocrine (41.4%) and blastoma (16.4%). 75.4% of patients had local-regional disease and 81.4% underwent surgery. Significant differences between histologies were seen for age, year at diagnosis, tumor laterality and location, stage, and treatment type. Median survival was 36.6 years (95% CI 33.3–37.4). Blastoma (HR 3.47) and squamous cell (HR 6.26) carried a significantly higher risk of death than neuroendocrine cancer diagnosis. ConclusionPrimary pediatric lung malignancies are rare, long-term survival is favorable but histology-dependent. Surgery continues to be an important treatment modality.

DIPG-49. BRAINSTEM AND PONTINE VOLUMETRIC ANALYSIS AS A SURROGATE MEASURE OF LOCAL DISEASE CONTROL IN CHILDREN WITH DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)

INTRODUCTIONResponse-assessment in pediatric neuro-oncology (RAPNO) criteria designed to describe treatment outcomes are poorly implemented in diffuse intrinsic pontine glioma (DIPG), due to inter-observer variability in measurement of tumor volume, lack of tumor enhancement, and undefined relationships between radiographic parameters and survival. Given these issues, this study assessed whether anatomically defined brainstem and pontine volumes can serve as surrogate measures of local disease burden and response to therapy in DIPG.METHODSThirty-two consecutive patients with newly diagnosed DIPG were treated with standard definitive radiation therapy (RT) between 2010 and 2016 at a single institution. MRI brain scans throughout treatment course were analyzed using iPlan® Flow software (Brainlab AG, Munich, Germany). Semi-automated 3D measurements of the brainstem and pons were calculated using a built-in knowledge-based segmentation approach and manually adjusted.RESULTSMean age at diagnosis was 6.5+/-0.5 years (range 2–12 years). Median follow up time was 317 days. Average brainstem volume at diagnosis (Vdiag) was 52.7+/-2.1mL with subsequent decrease at first post-RT MRI to 41.4+/-2.0mL (p < 0.0001). By time of last follow up, brainstem volume increased to 51.9+/-3.3, no longer significantly different as compared to Vdiag (p=0.61). The same relationships were found for pontine volume.CONCLUSIONSVolumetric changes in the brainstem and pons occur in response to treatment and correlate with local disease burden and response to therapy. This surrogate may be a useful standardized measure in ongoing and future trials involving localized delivery of therapeutics in DIPG that require evaluation of local-regional disease control in addition to survival.

Presenting stage and risk group in men dying of prostate cancer.

Prostate cancer remains the 3rd leading cause of cancer-related mortality in Canadian men, and yet screening for prostate cancer continues to be controversial because the majority of men diagnosed with prostate cancer do not die of the disease. It also remains uncertain whether treatment of cases that can be treated with curative intent alters the mortality rate. There are very few studies describing the presenting stage, risk groups, and survival after diagnosis for men dying of prostate cancer in the literature. In this study, we explored these characteristics for all men who died of prostate cancer in British Columbia between 2013 and 2015. The population-based BC Cancer databases were used to identify all patients diagnosed between January 2013 and December 2015 who died of prostate cancer. Patient, tumour, and treatment characteristics were collected, and the risk grouping for each tumour was determined. The proportion of cases in each risk group at the time of diagnosis was determined. Survival time from diagnosis to death was calculated for all patients and for each risk group using the Kaplan-Meier method. A total of 1256 patients died of prostate cancer. Of patients who presented with metastatic disease, 57.2% presented with a Gleason score of 8 or more, compared with only 35.7% of patients who presented with nonmetastatic disease (p < 0.0001). The presenting stage and risk group of those dying of prostate cancer were as follows: 32% metastatic disease, 3% regional (defined as node-positive), 39% localized high risk, 9% localized intermediate risk, 4% localized low risk, 6% localized not otherwise specified, and 7% unknown. Therefore, 80.3% of those with a known risk group presented with either localized high-risk, regional, or metastatic disease at diagnosis. The median survival times from diagnosis to death were 12 years for localized low-risk, 10 years for localized intermediate-risk, 6.5 years for localized high-risk, 4 years for regional, and 1.7 years for metastatic disease at diagnosis. This population-based analysis demonstrates that patients with localized high-risk, regional, or metastatic disease at diagnosis constitute the overwhelming majority of patients who die of prostate cancer in British Columbia. Unless these disease states can reliably be identified at an earlier low- or intermediate-risk localized state in the future, it is unlikely that treatment of localized low- and intermediate-risk cancer will have an impact on survival. Furthermore, patients with de novo metastatic disease had identifiable risk factors of a higher prostate-specific antigen and Gleason score. Further studies are required to confirm these results.

Genomic Analyses for Predictors of Response to Chemoradiation in Stage III Non-Small Cell Lung Cancer

BackgroundRadiation with platinum-based chemotherapy is the standard of care for unresectable stage III non-small cell lung cancer (NSCLC). Despite aggressive treatment, progression-free survival and overall survival remain poor. It is unclear whether any tumor genetic mutations are associated with response to chemoradiation therapy. MethodsWe retrospectively reviewed clinical outcomes of patients with stage III NSCLC treated with definitive radiation who had undergone tumor molecular profiling through a next-generation DNA sequencing platform. Cox proportional hazards model was used to investigate associations between clinical outcomes and genetic mutations detected by next-generation sequencing. Results110 patients were identified with stage III NSCLC and underwent definitive radiation between 2013 and 2017 and tumor molecular profiling. Concurrent or sequential chemotherapy was given in 104 patients (95%). Unbiased genomic analyses revealed a significant association between AKT2 mutations and decreased local-regional tumor control and overall survival (hazard ratios [HR] 12.5 and 13.7, P = .003 and P = .003, respectively). Analyses restricted to loss-of-function mutations identified KMT2C and KMT2D deleterious mutations as negative prognostic factors for overall survival (HR 13.4 and 7.0, P < .001 and P < .001, respectively). Deleterious mutations in a panel of 38 DNA damage response and repair pathway genes were associated with improved local-regional control (HR 0.32, P = .049). ConclusionsThis study coupled multiplexed targeted sequencing with clinical outcome and identified mutations in AKT2, KMT2C, and KMT2D as negative predictors of local-regional control and survival, and deleterious mutations in damage response and repair pathway genes were associated with improved local-regional disease control after chemoradiation therapy. These findings will require validation in a larger cohort of patients with prospectively collected and detailed clinical information.

Su1032 IMPROVED SURVIVAL IN EUS GUIDED FNA COMPARED TO PERCUTANEOUS ASPIRATION IN PANCREATIC CANCER: A PROPENSITY SCORE ANALYSIS

Endoscopic ultrasound guided fine needle aspiration (EUS-FNA) is recognized as an effective and safe means of obtaining tissue to diagnosis pancreatic cancer. Previous studies have shown no mortality difference in patients undergoing EUS-FNA despite the initial concern that its use would lead to increased tumor dissemination. However, studies have not assessed if this held true when compared to percutaneous aspiration, as both methods could lead to tumor seeding along the needle track. We aimed to investigate if EUS-FNA conferred any mortality benefit compared to percutaneous aspiration. The Surveillance, Epidemiology and End Results (SEER)- Medicare linked database was used to identify patients >65 years diagnosed with pancreatic cancer between 2000-2011. We identified patients who underwent EUS-FNA or percutaneous aspiration within three months of cancer diagnosis as well as chemotherapy, radiation, and surgery from claims data. Demographic and clinical characteristics were compared using chi-squared tests. Kaplan Meier methods and inverse propensity-weighted adjusted Cox proportional hazard ratios (aHR) were used to evaluate survival. Between 2000-2011, 32,510 patients were diagnosed with pancreatic cancer. 4,137 underwent EUS-FNA (38.61%) compared with 6,578 who underwent percutaneous biopsy (61.39%). 1,786 (14.29%) underwent both EUS-FNA and percutaneous biopsy within 3 months of cancer diagnosis and were excluded. Mean survival (standard deviation) for patients who received EUS-FNA was 9.71 months (+/- 11.65), compared with 6.7 months (+/- 11.10) for those who underwent percutaneous biopsy (p<0.0001). After adjusting for confounders, patients who received EUS-FNA had improved survival (aHR 0.72, 95%CI 0.70-0.75). In stratified analysis, improved survival with EUS-FNA was seen for patients with localized disease (aHR 0.71, 95% CI 0.66-0.78), regional disease (aHR 0.77, 95% CI 0.74-0.80), and distant disease (aHR 0.69, 95% CI 0.66-0.73). When limited to patients who underwent surgery and adjusted for confounders, patients who received EUS-FNA continued to have improved survival (aHR 0.66, 95%CI 0.60-0.72). Improved pancreatic cancer survival was seen in patients who underwent EUS-FNA compared with those who underwent percutaneous aspiration. This survival advantage was seen for all stages of disease. Given that EUS-FNA may not be widely available, its use may be a surrogate for patients having had access to care at an expert center, which may thus lead to improvement in survival.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Lenvatinib (LEN) plus pembrolizumab (PEMBRO) for early-line treatment of advanced/recurrent endometrial cancer (EC).

6083 Background: As part of an ongoing phase Ib/II study (NCT02501096) in patients (pts) with selected solid tumors, LEN (20 mg PO QD) + PEMBRO (200 mg IV Q3W) displayed substantial and durable antitumor activity in advanced EC. In previously treated EC that was not microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR; n=94 pts), the objective response rate (ORR) by independent imaging review (IIR) per RECIST 1.1 was 38.3% (95% CI 28.5–48.9). In this post hoc analysis, we assessed 2 subgroups of pts with previously treated, advanced, non MSI-H or dMMR EC who received LEN + PEMBRO in an early-treatment setting. Methods: Pts were examined in 2 subgroups: (1) Pts with only 1 prior line of cytotoxic therapy regardless of surgical stage or setting (adjuvant treatment for local-regional disease or treatment for metastatic disease); and (2) pts from subgroup 1 with local-regional disease at diagnosis who received only adjuvant cytotoxic therapy. There were no restrictions on prior hormonal or chemoradiation therapies in either subgroup. Tumor responses were assessed by IIR per RECIST 1.1. Results: Subgroup 1 included 63 pts and subgroup 2 had 21 pts. ORR (95% CI) was 41.3% (29.0–54.4) for subgroup 1 and 57.1% (34.0–78.2) for subgroup 2. Additional efficacy outcomes are summarized in the table. In subgroup 1, treatment-related adverse events (TRAEs) occurred in 62 (98%) pts (42 [67%] ≥ grade 3). TRAEs led to study-drug interruption of one or both drugs in 43 (68%) pts and dose reductions of LEN in 42 (67%) pts; 12 (19%) pts discontinued one or both drugs due to a TRAE. Serious TRAEs occurred in 18 (29%) pts and 2 (3%) pts died from a TRAE. The safety profile for subgroup 2 was generally similar to the profile for subgroup 1. Conclusions: The efficacy of LEN + PEMBRO for early-line treatment of advanced non MSI-H or dMMR EC appears promising. No new safety signals have emerged. A phase III study of LEN + PEMBRO vs paclitaxel + carboplatin for first-line treatment in advanced or recurrent EC is underway. Clinical trial information: NCT02501096. [Table: see text]

Manejo de carcinomatosis peritoneal con citorreducción más quimioterapia hipertérmica intraoperatoria (HIPEC)

Introducción: la citorreducción más quimioterapia hipertérmica intraoperatoria (HIPEC) aborda la carcinomatosis peritoneal (CP) como una enfermedad locorregional, con respuesta adecuada en la supervivencia considerando la severidad de la patología. La agresividad del procedimiento se asocia con altos índices de morbimortalidad. Objetivo: evaluar la supervivencia global y libre de enfermedad a 1 año en pacientes con CP, en quienes se realizó tratamiento mediante citorreducción más HIPEC en el Hospital Infantil Universitario de San José entre enero 2016 y diciembre 2017. Metodología: estudio observacional de una cohorte con CP de diferentes etiologías que recibieron citorreducción más HIPEC, se obtuvo información a partir de las historias clínicas. Resultados: se incluyeron 10 casos con una mediana de edad de 49 años (RIC 43-54) y CP de origen primario en apéndice (60%, n=6), colon (20%, n=2) y ovario (20%, n=2). El índice de carcinomatosis peritoneal (ICP) presentó una mediana de 14.5 (RIC 6-24). Se observó recaída en 3 pacientes y 4 desenlaces fatales. Se estimó una supervivencia global de 54% y libre de enfermedad de 58% a un año. Conclusión: se encontraron mejores resultados en supervivencia global y libre de enfermedad a un año que los descritos en quimioterapia sistémica. Es importante la selección estricta de los pacientes, así como efectuar estudios con un mayor número para determinar con evidencia la relación entre el procedimiento y la supervivencia global y libre de enfermedad.

RADIOTHERAPY OF PROSTATE CANCER: PRIMARY RADIOTHERAPY AND RADIOTHERAPY IN DISEASE RELAPSE.

SUMMARYRadiotherapy presents one of the essential modes of treatment in patients with prostate cancer at almost any stage of the disease. It can be delivered as external beam radiotherapy, as brachytherapy or two methods combined. Higher radiation doses are proven to be more effective than low doses and moderate hypofractionation with doses up to 3.4 Gy per fraction is proven equivalent to standard fractionation using 1.8- 2 Gy per fraction. Stereotactic body radiotherapy (SBRT) with doses from 3.4 to 7.25 Gy per fraction presents valuable option in certain subgroups of patients. In case of local regional disease relapse, radiotherapy is used in curative setting.