National Cancer Center Network Research Articles

Large cohort analysis of incidental CDH1 PVs among patients undergoing MGPT.

10618 Background: Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant condition caused by a heterozygous pathogenic variant (PV) in CDH1.HDGC is associated with an increased risk for DGC (33-70%) and invasive lobular breast cancer (LBC) (~64%) [1]. The National Cancer Center Network (NCCN) and International Gastric Cancer Linkage Consortium (IGCLC) recommend consideration of CDH1 germline testing based on personal and family history of DGC and LBC. However, with the advent of next generation sequencing and the inclusion of CDH1 in multigene panels (MGP), several cohort studies have identified CDH1+ patients who do not meet criteria [2,3,4,5]. Our group previously analyzed a cohort of patients with a personal or family history of BC who had CDH1 testing through MGPT and did not observe a significant association between CDH1 PVs and suspicion for HDGC (p-value=0.2066) [6]. In this expanded study, we aim to evaluate a larger cohort of patients of all cancer histories to gain a more comprehensive picture of the prevalence of incidental CDH1 PV among patients undergoing MGPT. Methods: 14,891 individuals who underwent CDH1 testing within MGPT were seen at MD Anderson’s Clinical Cancer Genetics (CCG) program between August 2013 and January 2024. This cohort was obtained from a prospectively maintained patient database within MD Anderson’s CCG program. Individuals were stratified based on CDH1 germline status (PV vs. negative or variant of uncertain significance) and meeting modified criteria for HDGC. Results: Within our expanded cohort, 1,716 individuals (11.5%) met criteria for suspicion for HDGC, while 13,715 did not meet criteria. Of the 70 individuals who tested positive for CDH1 (0.47%), 39 (0.28%) met criteria while 31 (0.23%) did not. We observed a statistically significant relationship between meeting our modified criteria for suspicion for HDGC and testing positive for a pathogenic variant in CDH1 (p-value <0.0001). Conclusions: Among patients who underwent CDH1 testing within MGPT, we observed a correlationbetween having a CDH1PV and meeting criteria for suspicion for HDGC. This contrasts with prior findings from our breast cancer cohort, potentially due to the limited number of CDH1 positive patients (n=3). These results suggest that while perhaps not robustly capturing HDGC families within a sub-population of patients undergoing MGPT, overall, NCCN and IGCLC guidelines closely reflect the clinical picture of a significant number of HDGC families. Meanwhile, the presence of incidental CDH1 PVs in this cohort portrays the variable expressivity and incomplete penetrance among patients with HDGC, including the detection of occult signet ring cell carcinomas during endoscopies or total gastrectomies [7]. We seek to expand this analysis by comparing these findings to rates of incidental CDH1 PVs in a subset of patients who meet NCCN guidelines for CDH1 testing based on suspicion for hereditary breast cancer syndromes.

Does structural racism impact receipt of NCCN guideline-concordant breast cancer treatment?

Disparities in breast cancer survival remain a challenge. We aimed to analyze the effect of structural racism, as measured by the Index of Concentration at the Extremes (ICE), on receipt of National Cancer Center Network (NCCN) guideline-concordant breast cancer treatment. We identified patients treated at two institutions from 2005 to 2017 with stage I-IV breast cancer. Census tracts served as neighborhood proxies. Using 5-year estimates from the American Community Survey, 5 ICE variables were computed to create 5 models, controlling for economic segregation, non-Hispanic Black (NHB) segregation, NHB/economic segregation, Hispanic segregation, and Hispanic/economic segregation. Multi-level logistic regression models were used to determine the association between individual and neighborhood-level characteristics on receipt of NCCN guideline-concordant breast cancer treatment. 5173 patients were included: 55.2% were Hispanic, 27.5% were NHW, and 17.3% were NHB. Regardless of economic or residential segregation, a NHB patient was less likely to receive appropriate treatment [(OR)Model1 0.58 (0.45-0.74); ORModel2 0.59 (0.46-0.78); ORModel3 0.62 (0.47-0.81); ORModel4 0.53 (0.40-0.69); ORModel5 0.59(0.46-0.76); p < 0.05]. To our knowledge, this is the first analysis assessing receipt of NCCN guideline-concordant treatment by ICE, a validated measure for structural racism. While much literature emphasizes neighborhood-level barriers to treatment, our results demonstrate that compared to NHW patients, NHB patients are less likely to receive NCCN guideline-concordant breast cancer treatment, independent of economic or residential segregation. Our study suggests that there are potential unaccounted individual or neighborhood barriers to receipt of appropriate care that go beyond economic or residential segregation.

Single instillation intravesical chemotherapy after radical nephroureterectomy for upper tract urothelial carcinoma: current evidence and future directions.

Upper urinary tract urothelial carcinoma (UTUC) accounts for 5% to 10% of urothelial carcinomas and two-thirds are high-grade at the time of diagnosis. The gold standard management of high-grade UTUC is radical nephroureterectomy (RNU). Despite primary treatment, disease recurrence involves the bladder in 22% to 47% of cases. Single dose, postoperative intravesical chemotherapy (pIVC) is an adjunct to RNU to decrease bladder recurrences that is currently recommended in guidelines from the European Association of Urology, National Cancer Center Network, and American Urological Association. Two clinical trials, using single dose, postoperative intravesical mitomycin C or pirarubicin, have provided level 1 evidence to support the formation of these guidelines. Despite this evidence, pIVC utilization is reportedly low among urologists, ranging from 12% to 55% among three studies, with non-utilizers citing lack of supporting evidence, safety concerns, and clinical infrastructure as leading rationale. In the past 10 years, no additional trials on single dose pIVC have been completed and validated in systematic reviews or meta-analyses. Utilization of pIVC still has room for improvement and further studies on this subject are warranted to overcome the barriers to implementation. Herein, we describe the critical literature that supports guideline recommendations for single dose pIVC after RNU to understand efficacy, safety, practice patterns, and discuss the future directions of this treatment adjunct.

CDH1 incidental findings in patients with personal or family history of breast cancer.

10524 Background: Pathogenic variants in CDH1 ( CDH1+) are associated with hereditary diffuse gastric cancer (HDGC), with an increased risk for DGC (~40-83%) and lobular breast cancer (BC) (~64%) [1]. The National Cancer Center Network recommends the inclusion of CDH1 in multi-gene panel testing (MGPT) for patients with significant history of BC, given its classification as a high-risk BC gene [2]. Management includes prophylactic gastrectomy or consideration of annual endoscopic biopsies and high-risk breast screening, with consideration of prophylactic mastectomy. Several studies have identified CD H1+ patients who do not meet the International Gastric Linkage Consortium’s diagnostic criteria for HDGC [3.4,5,6]. These studies have brought concerns of CDH1 pathogenic variants in patients with low risk phenotypes, given the potential for total gastrectomy to reduce DGC risk. Our study aims to investigate our cohort of patients with a personal and/or family history of BC to determine if there is a significant number of CDH1+ patients with a non-classical presentation of HDGC. Methods: 17,208 families with a history of BC who underwent MGPT were seen in a Clinical Cancer Genetics (CCG) high-risk breast clinic between August 2013 and July 2022. They were identified using a prospectively maintained MD Anderson Cancer Center CCG database. Families were categorized by their history of GC and CDH1 status. Results: Among the families, 10,202 (59%) had a proband with a personal history of BC, with a mean age of onset of 51 years. 49 families (0.28%) were CDH1+. 21 CDH1+ families (43%) had no personal and/or family history of GC. Overall, 0.12% of families within the cohort were CDH1+ and had no family history of GC. A chi-square goodness of fit test was performed comparing observed (O) versus expected frequencies (E) (O/E) of families that were: 1) CDH1+ and had a history of GC (28/28), 2) CDH1+ and no history of GC (21/21), 3) CDH1 – (benign variant or variant of unknown significance (VUS)) and a history of GC (180/164), and 4) CDH1- and no history of GC (16,979/16,995). O was determined by using a general population risk of GC (0.81%) and estimated risk of DGC for CDH1+ individuals (58.2%). The X2 was determined to be 1.576, with a p-value of 0.66483. Conclusions: In comparison to the expected frequency of incidental CDH1+ families identified via MGPT, we found that there was not a significant difference in expected and observed frequencies of families based on CDH1 status and presence of GC. These results likely reflect the incomplete penetrance and variable expressivity of HDGC, in addition to reported cases of occult signet ring cell carcinomas in biopsy samples or surgical pathology that has been reported in low risk presenting families [7]. We seek to validate these results with cohort of patients in which the diffuse gastric cancer pathology is known and to expand the analysis in patients specifically with a personal history of lobular breast cancer.

Health behaviors among head and neck cancer survivors

PurposeTo determine to what extent head and neck cancer (HNC) survivors participate in health behaviors (HBs) recommended by the National Cancer Center Network (NCCN®).MethodsParticipants identified through the tumor registries at the Abramson Cancer Center (ACC), University of Pennsylvania and affiliated sites. Eligibility: (a) diagnosis and treatment HNC; (b) aged 18 to 70 years; (c) ≥ 1-year post-diagnosis; (d) human papillomavirus (HPV) status confirmed; (e) ability to understand written English. Potential participants received an explanation of the study, informed consent, self-reported questionnaire, and self-addressed stamped envelope.Results451 individuals eligible, 102 (23%) agreed to participate, HPV positive (74%). Current smoking rare (7%), historical use common (48%). Current alcohol use common (65%), average 2.1 drinks/day, 12 days/month. 22% binge drank with an average of 3.5 binge-drinking sessions per month. Nutritional behavior mean 7.1 (range 0–16), lower scores indicating better nutrition. Body mass index (BMI) 59% overweight/obese. Adequate aerobic exercise 59%, adequate strength and flexibility 64%. Leisure time activity, 18% sedentary, 19% moderately active, 64% active. All participants reported having a primary care physician, 92% seen in the previous 12 months.ConclusionsMost HNC survivors participated in some HBs. Current smoking rarely reported, binge drinking and high BMI most common negative HBs. Opportunities remain to improve dietary and exercise behaviors.Implications for cancer survivorsThe NCCN® has outlined HBs that decrease likelihood of cancer survivors developing comorbidities that could impact overall survival. It is incumbent on healthcare providers to educate and encourage cancer survivors to participate in these HBs.

Gender equality in leading cancer centers

Background: Gender equality policy has been instituted in institutions across the European Union and the United States. Based on landscapes drawn over a decade ago about gender inequalities in health management. Oncology is projected to be a significant burden for healthcare systems very soon. Aim: to record leadership gender status in most prominent oncology institutions in 2022. Materials and methods: We searched the Organisation of European Cancer Institute website and the National Cancer Center Network Member Institutions website. We recorded the gender of the legal representative of the center (CEO/director). Results: The Organisation of the European Cancer Institute has a membership of 123 cancer centers, seven outside the European Union. Those situated in the EU have 17 leaders of the female sex (out of 116; 14,66%). While in the US, there are seven leaders of the female gender (out of 32; 21,88%). Conclusion: The introduction of gender equality policy in recent years slowly impacts the predominance of the male gender in leading positions of oncology centers.

A Novel Use for Pelvic MRI Scans to Estimate Lean Body Mass and Screen for Sarcopenia in Patients With Rectal Cancer.

Sarcopenia, the combination of low lean body mass and decreased muscle strength, is associated with significant morbidity and mortality among patients with colorectal cancer. Standard methods for assessing lean body mass and muscle strength, such as bioelectric impedance analysis and handgrip dynamometry, are rarely obtained clinically. Per National Cancer Center Network recommendations, pelvic MRI is routinely collected for staging and surveillance among patients with rectal cancer. However, there are no data assessing the relationship of pelvic MRI lean body mass measurements at the fifth lumbar vertebrae with bioelectric impedance analysis, handgrip strength, or abdominal CT in patients with rectal cancer. Therefore, we aimed to assess whether pelvic MRI lean body mass correlates with a standard for lean body mass measurement (bioelectric impedance analysis), muscle function (handgrip strength), and an imaging modality frequently used in the literature to identify sarcopenia (abdominal CT at the third lumbar vertebrae). Lean body mass measurements from routinely collected pelvic MRI at the fifth lumbar vertebrae accurately and reproducibly estimate lean body mass and modestly correlate with handgrip strength. Rectal cancer pelvic MRI may be repurposed for identifying sarcopenia without increasing inconvenience, ionizing radiation exposure, or expenditure to patients with rectal cancer. Patients with locally advanced rectal cancer with pretreatment bioelectric impedance analysis and handgrip strength measurements within 3 months of their staging pelvic MRI were eligible. Axial skeletal muscle areas were segmented using T1-weighted series pelvic MRI at the fifth lumbar vertebrae and abdominal CT at the third lumbar vertebrae using Slice-O-Matic (Tomovision, Montreal, Canada). Lean body mass (kilograms) was derived from skeletal muscle area with standard equations. Handgrip strength (kilograms) was the maximum of 3 dominant hand attempts in the standing anatomical position. The primary outcome was the agreement between lean body mass measured by pelvic MRI (at the fifth lumbar vertebrae) and bioelectric impedance analysis. Secondary outcomes included the concordance of pelvic MRI lean body mass (at the fifth lumbar vertebrae) with abdominal CT (at the third lumbar vertebrae) and handgrip strength. Additionally, the intra- and interobserver validity, internal consistency, and the mean difference (bias) between lean body mass measurements by pelvic MRI and bioelectric impedance analysis were evaluated. Sixteen patients were eligible. The average lean body mass was similar and consistent across 2 observers between bioelectric impedance analysis and pelvic MRI. There was a strong correlation between lean body mass measured on pelvic MRI, bioelectric impedance analysis, and abdominal CT. The reliability of 2 pelvic MRI lean body mass measurements (2 weeks apart by blinded observers) and the correlation of lean body mass between pelvic MRI and bioelectric impedance analysis was strong. Inter- and intraobserver correlation, reliability, and internal consistency were strong for the entire cohort. There was a moderate correlation between pelvic MRI lean body mass and handgrip strength. Lean body mass measured at the fifth lumbar vertebrae on pelvic MRI is reproducible and correlates strongly with measurements from bioelectric impedance analysis (standard) and abdominal CT at the third lumbar vertebrae and modestly with handgrip strength. These data suggest that MRI lean body mass measurements may be a method to screen patients with rectal cancer for sarcopenia. Future studies may evaluate changes in lean body mass on serial pelvic MRI studies among patients with rectal cancer.

A Case Report on a Chemotherapy Treatment to a SARSCOV2 PCR Positive, Non-Hodgkins Lymphoma Filipino Patient

SARSCOV2 causing the COVID-19 infection has spread to a pandemic scale and putting the vulnerable population at risk of infection such as those with malignancies. Cancer treatment remains to be controversial in this time of pandemic such that recommendations were either delay treatment, reduce hospital exposure, or to balance the risk of disease progression(e.g. malignancy) and acquiring the disease (COVID-19). Information on COVID-19 positive cancer patients receiving chemotherapy remains to be limited. Thus, this case is reported. The case is a 64 year old male, newly diagnosed, Non-Hodgkins lymphoma who presented with severe anemia and weight loss. He was diagnosed through the bone marrow findings of CD20, Ki67, BCL2 positive B cell Non-Hodgkins lymphoma, NOS. He underwent induction chemotherapy with Prednisone, Cyclophosphamide and Vincristine. Thereafter he diagnosed to have COVID-19 infection, moderate. He remained to be PCR positive but with noted negative IgM Antibody. He showed signs of worsening anemia thus was given succeeding chemotherapy while admitted in the COVID unit of the hospital. Malignancy in general poses greater risk of severe infection with COVID-19 and possibly a worse outcome.8 The decision to proceed with chemotherapy treatment at the time when cases in the Philippines were not clear due to few testing capacity in the different institutions was based on the symptomatic persistence of severe anemia and weight loss as well as reduction in the functional capacity of the patient. The focus of efforts of oncologists and hematologists as recommended by their respective societies was on the reduction of the possibility of acquiring COVID-19 infection. There is paucity of data among those patients who have been diagnosed with COVID-19 and was given chemotherapy. Although, several studies have shown that among patients with COVID-19 and cancer as co-morbidity, the mortality can reach as high as 21% to 33% or can present with severe type of infection. Recommendations given by National Cancer Center Network(NCCN), American Society of Clinical Oncology(ASCO), European Society for Medical Oncology(ESMO, National Institute for Health and Care Excellence(NICE), World Health Organization(WHO), and Center for Disease Control(CDC) consistently revolve around the shifting of follow-up consults via teleconsultation to reduce travel to the hospital, delay or reduction of immunosuppressive treatments if possible, careful and holistic, multidisciplinary individualized approach in chemotherapeutic treatment, and withholding chemotherapy once positive with SARSCOV2 PCR positive test. In this case, the patient remained to be asymptomatic, non-oxygen requiring but remained to be positive on his 3rd PCR test done (20 days from initial positive test). The infectious disease service considered this as a false positive test and only a reflection of SARSCOV2 RNA remnants in the patient's upper airway. The clinical presentation of this cancer patient to the COVID infection is contradictory to those seen in most studies reviewed. Based on the limited knowledge on the pathophysiology of COVID-19, hyperinflammatory response occur in a robust immune system that causes Systemic inflammatory response syndrome(SIRS) and cytokine storm or hypoinflammatory response leading to multiple secondary bacterial infection.10 But neither was seen in this case. It is therefore possible that details of the mechanism of COVID-19 infection and its association with co-morbidities (malignancy) to severity are yet to be elucidated. All of the knowledge that is learned in this time of pandemic stems from a continuous trial and error efforts of clinicians who, through a sound theoretical foundation, first hand clinical experience and outcome endlessly refine approaches to produce the best outcome for those who are infected with the virus, most importantly, to the vulnerable population, such as those who is burdened by malignancies and COVID-19 infection. The treatment of COVID-19 positive patients with hematologic malignancy should be individualized and should focus on the balance between disease severity and risk of worsening COVID-19 infection.

Current Clinical Practice of Precision Medicine Using Comprehensive Genomic Profiling Tests in Biliary Tract Cancer in Japan.

With the recent advances of next generation sequencing technologies, comprehensive genomic profiling (CGP) tests, which are designed to measure more than hundreds of cancer-related genes at a time, have now been widely introduced into daily clinical practice. For the patients whose tumor samples are not fit for tissue-based CGP tests, a blood-based CGP test (liquid biopsy) is available as an alternative option. Three CGP tests, “OncoGuide NCC™Oncopanel System (124 genes)”, “FoundationOne®CDx (324 genes)”, and “Founda-tionOne®CDx Liquid (324 genes)”, are now reimbursed by public insurance in 233 hospitals designated for cancer genomic medicine in Japan. In biliary tract cancer, the prevalence of druggable variants is relatively higher compared to other cancer types and the European Society for Medical Oncology recommends routine use of CGP tests for advanced biliary tract cancer to guide treatment options. The latest National Cancer Center Network guideline lists eight druggable markers (NTRK fusion, MSI-H, TMB-H, BRAF V600E, FGFR2 fusions/rearrangement, IDH1 mutations, RET fusion, and HER2 overexpression) and matched therapies. In Japan, matched therapies for four markers (NTRK, MSI-H, TMB-H, and FGFR2) are reimbursed by public insurance (as of September 2022). The progress of genomic profiling technology will contribute to the improvement of the dismal clinical outcomes of this disease in the future.

Breast Implant-Associated Anaplastic Large-Cell Lymphoma: Updated Systematic Review and Analysis of Treatment Strategies.

Although guidelines have been published on treatment of breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL), there has been no comprehensive analysis of BIA-ALCL treatment variation based on the available literature. The authors sought to assess current treatment strategies of BIA-ALCL relative to current guidelines. Database searches were conducted in June of 2020. Included articles were case reports and case series with patient-level data. Collected variables included clinicopathologic features, implant characteristics, diagnostic tests, ALCL characteristics, treatment, and details of follow-up and outcome. Treatment data from before and after 2017 were compared with National Cancer Center Network guidelines. A total of 89 publications were included and 178 cases of BIA-ALCL were identified. Most patients presented with seroma ( n = 114, 70.4 percent), followed by a mass ( n = 14, 8.6 percent), or both ( n = 23, 14.2 percent). Treatment included en bloc capsulectomy of the affected implant in 122 out of 126 cases with treatment details provided (96.8 percent). Radiation therapy was given in 38 cases (30.2 percent) and chemotherapy was given in 71 cases (56.3 percent). Practitioners used less chemotherapy for local disease after treatment guideline publication in 2017 ( p < 0.001), whereas treatment for advanced disease remained unchanged ( p = 0.3). There were 10 recurrences and eight fatalities attributable to BIA-ALCL, which were associated with advanced presentation (29 versus 2.1 percent; OR, 19.4; 95 percent CI, 3.9 to 96.3; p < 0.001). BIA-ALCL remains a morbid but treatable condition. Current guidelines focus treatment for local disease and reduce nonsurgical interventions with radiation or chemotherapy. Patients presenting with advanced BIA-ALCL experience higher rates of recurrence and mortality.

Prostate cancer therapy personalization via multi-modal deep learning on randomized phase III clinical trials

Prostate cancer is the most frequent cancer in men and a leading cause of cancer death. Determining a patient’s optimal therapy is a challenge, where oncologists must select a therapy with the highest likelihood of success and the lowest likelihood of toxicity. International standards for prognostication rely on non-specific and semi-quantitative tools, commonly leading to over- and under-treatment. Tissue-based molecular biomarkers have attempted to address this, but most have limited validation in prospective randomized trials and expensive processing costs, posing substantial barriers to widespread adoption. There remains a significant need for accurate and scalable tools to support therapy personalization. Here we demonstrate prostate cancer therapy personalization by predicting long-term, clinically relevant outcomes using a multimodal deep learning architecture and train models using clinical data and digital histopathology from prostate biopsies. We train and validate models using five phase III randomized trials conducted across hundreds of clinical centers. Histopathological data was available for 5654 of 7764 randomized patients (71%) with a median follow-up of 11.4 years. Compared to the most common risk-stratification tool—risk groups developed by the National Cancer Center Network (NCCN)—our models have superior discriminatory performance across all endpoints, ranging from 9.2% to 14.6% relative improvement in a held-out validation set. This artificial intelligence-based tool improves prognostication over standard tools and allows oncologists to computationally predict the likeliest outcomes of specific patients to determine optimal treatment. Outfitted with digital scanners and internet access, any clinic could offer such capabilities, enabling global access to therapy personalization.

Efficacy of Brentuximab Vedotin and Bendamustine Combination in Relapsed/Refractory Hodgkin Lymphoma: Experience from a Tertiary Care Hospital

Background:Hodgkin lymphoma (HL) is an uncommon B-cell malignant neoplasm, with high curable rate for patients with localized disease or advanced.However, up to 30% of patients with HL are either refractory or relapsed after primary treatment. Salvage chemotherapy followed by autologous hematopoietic stem cell transplant (HSCT) is the standard of care for eligible patients in relapsed setting. Brentuximab vedotin and Bendamustine (BvB) combination have been recommended by National Cancer Center Network (NCCN) as one of the salvage regimens for patients with relapsed or refractory HL prior to transplant or who relapsed after hematopoietic stem cell transplant (HSCT). Evidence from retrospective and prospective studies in regards of BvB have shown remarkable progression free survival (PFS) with 2-years PFS ranging from 62.2% up to 93.7%, and overall survival (OS) ranging from 88.1% up to 95%, and complete remission (CR) rates ranging from 43% to 90%. The objective of this study is to assess patient response to BvB in the treatment of relapsed/refractory HL especially for patients beyond first salvage therapy unlike many other studies.Methods:A retrospective study was conducted in patients with relapsed/refractory Hodgkin lymphoma treated with BvB chemotherapy at single tertiary hospital from January 2016 until July of 2021. Data collection was done including patient demographics data, comorbidities, disease stage, lines of chemotherapy regimens taken, and PET scan response with Deauville score. Brentuximab was given as 1.8mg/kg on day 1, and bendamustine was given as 90mg/m 2 on day 1 and day 2. Cycle was repeated every three weeks.Result:A total of 16 patients with relapsed/refractory HL whom treated with BvB chemotherapy were analyzed. Median age is 29 years (22-70 years), 5 patients were female, and median number of lines of therapy prior to starting BvB is 2 (0-5). The median number of cycles of BvB was 5.5 (3-8 cycles). 2 out of 16 patients had a prior autologous HSCT (12.5%).15 patients were assessed for response and one patient died before disease assessment. The overall response rate was 80% with 50% of patients achieving complete metabolic response on PET scan. After median follow up of 14.5 months, the median PFS was 13.4 months (Figure 1), and the median OS was not reached (Figure 2). 4 patients underwent HSCT (3 autologous, and 1 allogeneic).Conclusion:BvB combination is an effective outpatient-based salvage regimen for heavily pretreated patients with multiple lines chemotherapy in relapsed/refractory HL, as majority of patients in our study were beyond first salvage. As there is no standard salvage regimen in this setting, randomized trials are needed to compare efficacy and safety BvB with other established regimens. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Long-Term Survival Following Definitive Radiation Therapy for Oligometastases in Gynecological Malignancies: A Landmark Analysis

Radiation therapy (RT) has been shown to prolong survival for patients with select oligometastatic cancers. Limited long-term follow-up data exist to determine if the prolonged survival correlates with cure versus a delayed relapse. To investigate this, we evaluated the clinical and disease characteristics of long-term survivors treated with definitive RT for oligometastatic gynecological cancer at our institution.We performed a landmark analysis in patients with oligometastatic gynecological cancer (OMGC) who survived for at least 5 years following treatment of their metastasis. OMGC was defined as metastasis (maximum of 5 total and 3 per site) present at a distant site at time of diagnosis or at a regional or distant site at time of recurrence. All patients received definitive RT between 2000 and 2015. Demographic and clinical variables were extracted from the medical record. Disease-free survival (DFS) after treatment of the first ROMGC was modeled using Kaplan Meier curves.48 patients with OMGC were analyzed; 20 (41.7%) had ovarian cancer, 16 (33.3%) had uterine cancer, 11 (22.9%) had cervical cancer, 1 (2.1%) had vaginal cancer. Median age was 52 years. A majority (45.8%) were stage III at primary diagnosis. The most common histology was adenocarcinoma (35.4%). The most common site of OMGC was in the pelvic lymph nodes (LN) (40.7%), with the following other sites: para-aortic LN (38.9%), supraclavicular LN (7.4%), lung (5.6%), mediastinal LN (3.7%), and axillary LN (3.7%). The median size was 2 cm. The median [interquartile range (IQR)] total RT dose and fractionation was 62.1 [52.5-64.5] Gy and 2.1 [2-2.2] Gy/fraction. The majority (70.8%) were treated with intensity-modulated RT. 25 (52.1%) patients received concurrent chemoRT (CRT) for their OMGC. After a median follow-up of 9.9 years after OMGC treatment, median [range] DFS for all patients was 73 [4-212] months (mo). 5-year DFS for cervical, uterine, and ovarian cancers was 82% (95% confidence interval [CI], 45-95%), 69% (CI, 41-86%), and 35% (CI, 16-55%), respectively. Patients who received CRT had better median DFS than those treated with RT alone (103 vs. 65 mo, P = 0.18). Patients with nodal OMGC had similar median DFS as those with non-nodal OMGC (73 vs. 66 mo, P = 0.86). During the first OMGC course, patients treated for 1 site had worse median DFS than those treated for 2+ sites (65 vs. 103 mo, P = 0.61). Of all 48 patients, 8 (16.7%) died of gynecologic cancer, 11 (22.9%) died of other causes, 3 (6.3%) had progression of disease. The remaining 26 (54.2%) patients were disease free at long-term follow up.Cure is possible for patients treated definitively for OMGC. Patients with cervical cancer, a greater number of treated OMGC sites, and treated with CRT had the longest DFS among this selected cohort. A randomized trial in oligometastatic gynecologic cancer is needed to determine if RT increases overall survival.K.L. Corrigan: None. A.K. Yoder: None. L.L. Lin: Employee; VA Hospital. Research Grant; Astra Zeneca. Travel Expenses; Astra Zeneca. A. Jhingran; American Board of Radiology. M.M. Joyner: Consultation with executive management and participation in board meetings; Frontline Bioenergy. P.J. Eifel: Travel Expenses; National Cancer Center Network. Stock; Apple Computer. L. Colbert: None. K.H. Lu: None. A.H. Klopp: Research Grant; MD Anderson Cancer Center SPORE Grant.

Circulating and Tumor-Associated Neutrophils Function as a Powerful Biomarker for Response to Chemoradiation in Locally Advanced Cervical Cancer

The role of the immune system in mediating the cytotoxic effects of chemoradiotherapy, remains incompletely understood. The integration of immunotherapies into treatment will require insight into features and timing of immune microenvironment associated with treatment response. Here, we investigate the role of circulating and tumor-associated neutrophils (TANs) as potential agents and biomarkers for disease-related outcomes in LACC.Hematologic parameters for two patient cohorts, a retrospective clinical and a prospective translational cohort, were obtained at baseline, weekly during chemoradiation, and at first follow up visit. Baseline, mean and lowest on-treatment values for platelets, hemoglobin, absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) were correlated with disease-related outcomes using univariate (UVA) and multivariable analyses (MVA). Circulating neutrophils were isolated from peripheral blood mononuclear cells (PBMCs) and TANs were isolated from tumor tissue via a novel serial cytobrush sampling assay. The samples were analyzed by flow cytometry and correlated via linear regression analysis.A total of 151 patients were included in the retrospective cohort with a median follow up of 33 months. Of the tested hematologic parameters elevated on-treatment mean ANC (mANC) was associated with lower rate of local control on UVA (HR 1.314; 95% CI, 1.102-1.567, P = 0.002) and MVA (HR 1.369; 95% CI, 1.104-1.697, P = 0.004). mANC was the only hematologic factor associated with lower survival on MVA (HR 1.255; 95% CI, 1.048-1.502, P = 0.013). mANC was not associated with a difference in distant metastases (HR 1.002; 95% CI, 0.810-1.241, P = 0.984). In an independent, prospectively-accrued cohort, mANC was similarly associated with lower OS (HR 1.636, 95% CI, 1.172-2.285, P = 0.004) on UVA. Analysis of the tumor-associated neutrophils (TAN) demonstrated that neutrophils constituted 22.4% (standard error [SE] 3.96%) of all live leukocytes in the tumor at baseline, which steadily increased and peaked at 41.3% (SE 7.8%) at week 5 of treatment (P = 0.027). Neutrophils constituted of 78.2% (SE 4.6%) of live leukocytes in PBMCs at baseline, and steadily decreased with a nadir of 65.7% (SE 8.5%) at week 5 of treatment (P = 0.137). Regression analysis showed an inverse relationship between circulating neutrophils and TANs, with the strongest correlation observed at week 5 of chemoradiation (R2 = 0.29).These findings implicate neutrophils in chemoradiation treatment resistance, identify on-treatment mean neutrophil count as a robust and optimal predictor of disease-related outcomes, and establish an inverse relationship between circulating and tumor-associated neutrophils.O. Gjyshi: None. A. Grippin: Student; University of Florida. D. Boyce-Fappiano: None. A. Jhingran: American Board of Radiology. L.L. Lin: Employee; VA Hospital. Research Grant; AstraZeneca. Travel Expenses; AstraZeneca. P.J. Eifel: Travel Expenses; National Cancer Center Network. Stock; Apple Computer. M.M. Joyner: Consultation with executive management and participation in board meetings; Frontline Bioenergy. J. Sastry: None. K. Court: None. T. Solley: None. V. Hegde: None. L. Colbert: None. A.H. Klopp: Research Grant; MD Anderson Cancer Center SPORE Grant.

Bone Mineral Density Changes Within and Outside of RT Fields Used to Treat Cervical Cancer

Pelvic insufficiency fractures and decreased bone mineral density (BMD) can occur in women treated with radiotherapy (RT) for gynecologic cancers. The purpose of this study was to compare the magnitude of BMD changes inside and outside of the radiation field in patients treated with radiation +/- chemotherapy for cervical cancer.In an IRB-approved prospective study, women (N = 78) with cervical cancer were assessed with serial tomographic scans and dual-energy x-ray absorptiometry (DXA) scans to evaluate the incidence of pelvic fractures (previously reported) and post-treatment BMD changes. Patients were treated with definitive RT or chemoradiation (CRT) at a single institution between 09/2008 and 07/2015. DXA scans were obtained at baseline (before CRT), 3 months, 1 year, and 2 years after completion of therapy. Serial BMD values at L1, L2, L3 and L4 were extracted from DXA reports. Patients with a pre-treatment history of pelvic fractures, bone metastases, or pelvic RT were excluded. The current analysis focused on a subset of 78 patients whose RT fields had upper borders below L1 and above L4, permitting a comparison of BMD changes in the field (L4) with those in a vertebral body outside the field (L1). Linear mixed models (LMM) were performed to examine the impact of radiotherapy on BMD change over time, and were adjusted for covariates (age, menopausal status, BMI, number of chemotherapy cycles).The median age of 78 patients was 45.5 years (range 23-88); all received RT and 76/78 (97.5%) received concurrent CRT. Treatment was associated with a significant decline in BMD in all 4 lumbar vertebral bodies over time, P < 0.05 with nadir at 3 months (L4) and 1 year (L1). By pairwise comparisons at 3 months and 2 years after treatment, BMD in L4 (inside RT field, P = 0.037) significantly improved while BMD in L1 (outside RT field) did not significantly change. After controlling for covariates noted above, there was no significant difference in BMD between 3 months and 2 years. Levels of C-terminal telopeptide of type I collagen (P = 0.018), bone alkaline phosphatase (P < 0.001), and number of chemotherapy cycles (P = 0.031) were significant predictors of L1 BMD loss. A trend of higher BMD at all time points was found for patients who were premenopausal versus postmenopausal at study entry. At 1- and 2-years of follow-up, trends towards BMD at levels higher than baseline were seen for patients who received hormone replacement therapy (HRT) after RT.Significant BMD loss following radiation treatment in all lumbar vertebrae (both in and out of field) was observed. On multivariate analysis, in-field vertebral bodies experienced no additional significant BMD decline earlier than those out-of-field, suggesting multifactorial contributors to bone density loss. HRT may improve BMD recovery and emphasizes the need for HRT after radiotherapy in appropriate premenopausal women.J. Wu: None. D.S. Lakomy: None. B. Fellman: None. M.P. Salcedo: IGCS-International Gynecologic Cancer Society, Brazilian Federation of Gynecology and Obstetricians (FEBRASGO)/BRAZIL (Federação Brasileira de Ginecologia e Obstetricia, FEBRASGO). A. Sood: Consultant; Kiyatec, Astra Zeneca. Stock; BioPath. sponsored research; M-Trap. A. Jhingran: American Board of Radiology. A.H. Klopp: Research Grant; MD Anderson Cancer Center SPORE Grant. R.B. Iyer: None. C. Jimenez: None. L. Colbert: None. K. Schmeler: None. P.J. Eifel: Travel Expenses; National Cancer Center Network. Stock; Apple Computer. L.L. Lin: Employee; VA Hospital. Research Grant; AstraZeneca. Travel Expenses; AstraZeneca.

Association of Gut Microbiome Characteristics With the Late Gastrointestinal Toxicities After Pelvic Receiving Radiation Treatment for Cervical, Vaginal, and Anal Cancers

Radiation therapy is curative for treating cervical, vaginal, and anal cancers, but can lead to gut toxicities that reduce quality of life in recovering patients. Previously, higher gut microbiome diversity was shown to be positively correlated with less severe acute gastrointestinal (GI) toxicities per patient-reported assessments of bowel function. The goal of this study was to explore effects of gut microbiome diversity and composition on late GI toxicities. We hypothesized that the occurrence of late GI toxicities in patients that receive abdominal radiation therapy correlates with gut microbiome diversity.We collected and analyzed rectal swabs from 66 patients with cervical, anal, and vaginal cancer receiving standard of care treatment. Samples from baseline and week 5 of treatment were sequenced using 16Sv4 ribosomal RNA (rRNA) gene sequencing. We also retrospectively evaluated the late (occurring after 3 months) radiation induced GI toxicities of patients who had completed their treatment 2 years prior using the RTOG/EORTC Late Radiation Morbidity Scoring Schema and the Common Terminology Criteria for Adverse Events (CTCAE) v.5. The gut microbial diversity of the patients was then characterized by indexes of richness, evenness and diversity. 59 patients were included in the analysis; exclusion criteria were lack of either follow-up or microbiome data and receiving additional radiation therapy or chemotherapy. Independent students t-tests were used to compare the alpha diversity metrics between patients who experienced late toxicities and those who did not. Beta diversity was evaluated using linear discriminant analysis effect size (LEfSe) to identify bacteria taxa that were differentially enriched in groups of patients with no toxicity against those with toxicity, and independent t-tests were used to compare the relative abundances of these taxa between patients with and without late toxicities.37.3% of patients per RTOG/EORTC criteria and 42.4% per CTCAE criteria experienced late GI toxicities (RTOG > = 1, CTCAE > = 1). Overall, neither the alpha diversity at baseline nor at week 5 was significantly different in patients who experienced late toxicities compared with those who didn't. Of the 22 taxa identified in the LEFse analysis, Sutterella species were higher at baseline in patients who did not experience late GI toxicities (0.21% vs. 0.72%, respectively, P = 0.01 for RTOG/EORTC criteria; 0.19% vs. 0.79%, respectively, P = 0.004 per CTCAE criteria).The presence of Sutterella was significantly associated with late toxicity, consistent with prior observations of acute toxicity. Overall, is no strong association between gut microbiome diversity and the presence of late GI toxicities in patients who have received radiation therapy for cervical, vaginal, and anal cancers. The observation has implications in the ongoing search for gut microbiome-targeted treatments for mitigating side effects of radiation.E.J. Lynn: None. M.B. El Alam: None. T. Karpinets: None. D. Lin: None. R. Kouzy: None. K. Court: None. X. Wu: None. M.P. Mezzari: None. N. Ajami: None. T. Solley: None. L.L. Lin: Employee; VA Hospital. Research Grant; AstraZeneca. Travel Expenses; AstraZeneca. L. Ramondetta: None. A. Jhingran: American Board of Radiology. P.J. Eifel: Travel Expenses; National Cancer Center Network. Stock; Apple Computer. K. Schmeler: None. B.D. Minsky: None. E.J. Koay: Research Grant; PANCAN-AACR, MD Anderson Cancer Center, Philips, National Institutes of Health, General Electric, Elekta, Stand Up 2 Cancer, Project Purple. Royalty; Taylor and Francis LLC. Patent/License Fees/Copyright; Pending Patent. I help coordinate scientific and advocacy activities for this Foundation, focused on radiation oncology. P. Das: Honoraria; MD Anderson Cancer Center Madrid, National Cancer Institute/Leidos, ASTRO. Consultant; Adlai Nortye. C.M. Taniguchi: Research Grant; NIH, Reaumond Foundation, Mark Foundation. Consultant; Phebra Pty, Ltd, Xerient Pharmaceuticals. Advise on various radiation products; Accuray. A.H. Klopp: Research Grant; MD Anderson Cancer Center SPORE Grant. L. Colbert: None.

Genetics in prostate cancer: implications for clinical practice.

Recent advances in our understanding of prostate cancer genetics have transformed the field. However, challenges in implementation and clinical application remain. The aim of this review is to discuss recent noteworthy publications in prostate cancer germline testing, genetically informed treatment, and polygenetic risk. The recent U.S. Food and Drug Administration approval of two poly adenosine diphosphate-ribose inhibitors (olaparib and rucaparib) for the treatment of men with metastatic castration-resistant prostate cancer with mutations in DNA damage repair genes and updates to the National Cancer Center Network testing guidelines that expand the eligibility criteria for germline and somatic genetic testing in men with prostate cancer provide an opportunity for a larger portion of the prostate cancer population to access genetic testing and targeted therapies. Due to this, clinicians have needed to rapidly adapt their clinical workflows. Further, the field has renewed efforts to evaluate polygenetic risk profiles to better understand the complex genetic landscape beyond single genes. This review highlights advances in the understanding of prostate cancer genetics, and areas that remain less well defined. Collaboration between multidisciplinary team members is necessary to move this field forward and provide quality, optimal care.

Analysis of hematology and oncology fellowship website content and diversity representation.

11004 Background: Fellowship in hematology and oncology (HO) is widely sought after but lags behind all other internal medicine subspecialties in attracting applicants underrepresented in medicine (URM). An approach to appealing to URMs involves preexisting in-person strategies but also adapting virtual tools to promote inclusion. Specifically, program websites serve as the first impressions of a program, as well as influence the perception of diversity and inclusion. We evaluated the content and diversity representation of HO program websites to facilitate a generally more informed and URM-considerate recruitment. Methods: The websites of 2019-2020 ACGME accredited HO programs were assessed between June 1st to July 1st, 2020. Data focused on 30 informational categories, derived from published methodology, along with three additional categories concerning diversity, based on suggestions for inclusive graduate medical education recruitment strategies, were compared using two-tailed t tests. We defined websites with 70% or more of the 30 informational categories as “comprehensive websites.” Affiliation with a National Cancer Institute (NCI) Designated Cancer Center, NCI Designated Cancer Center + National Cancer Center Network (NCCN) member institution, and a top 50 ranked cancer hospital by U.S. News was also considered in the analysis. Results: A total of 156 program websites were analyzed: 37.2% NCI; 19.9% NCCN; 29.5% U.S. News ranked. Only 31 (19.9%) were “comprehensive websites,” and 34 (21.8%) had information pertaining to at least one of the diversity categories. There was a significant association between inclusion of diversity content and being a “comprehensive website” (p = 0.001). Compared to those that were neither designated nor ranked, programs designated by NCI, NCCN, or ranked by U.S. News were more likely to have more complete information available (p &lt; 0.001, = 0.008, and &lt; 0.001, respectively). However, only programs ranked by U.S. News were more likely to include information about diversity on their websites (p = 0.006). Conclusions: The vast majority of HO fellowship program websites were not comprehensive, including a lack of diversity and inclusivity content. NCI designation, NCCN participation, and US News ranking were significantly associated with more complete fellowship websites. Given the context of the COVID-19 pandemic in which institution visitation is restricted, program websites may have elevated importance in recruitment. HO programs should direct resources to offering more complete and inclusive websites to better inform applicants, including URM residents.

Analytical and clinical performance of chromosomal microarrays compared with FISH panel and conventional karyotyping in patients with chronic lymphocytic leukemia

In this single center retrospective analysis on 102 CLL patients, we assessed analytical and clinical performance of CMA against a targeted FISH panel (ATM, TP53, CEP12, D13S319 and LAMP1 loci) and karyotyping. CMA yielded additional information compared to karyotype in 39 cases (38 %). On the other hand, while CMA detected aberrations were also detected by FISH in all 31 cases (30 %), aberrations with low clonal size (<30 %) detected by FISH were missed by CMA. When evaluated with National Cancer Center Network (NCCN) guidelines, the capture rate of prognostic relevant cytogenetic information for FISH only, FISH + Chromosomes and FISH + CMA analyses were 95, 96 and 100 % respectively. With Cancer Cytogenomics Consortium (CGC) Criteria, these figures for FISH only, FISH + Chromosomes and FISH + CMA were 88 %, 92 and 100 % respectively. In conclusion, CMA provides additional analytical information to FISH and karyotyping, but this information has a clinical utility only in a small number of patients. Limit of detection (LOD) issues preclude replacement of FISH by CMA, but CMA may be a viable alternative to karyotyping. Further research is warranted.

The impact of race, comorbid conditions and obesity on survival endpoints in women with high grade endometrial carcinoma

ObjectiveTo estimate overall survival, disease-specific survival, and progression-free survival among high grade endometrial carcinoma cases and to determine factors impacting survival for non-Hispanic white and non-Hispanic black women. MethodsWe identified high grade endometrial carcinoma cases among non-Hispanic white and non-Hispanic black women from ongoing institutional studies, and determined eligibility through medical record and pathologic review. We estimated effects of demographic and clinical variables on survival outcomes using Kaplan Meier methods and Cox proportional hazards modelling. ResultsNon-Hispanic Black women with BMI <25.0 had poorest overall survival compared to non-Hispanic white women with BMI <25.0 (HR 3.03; 95% CI [1.35, 6.81]), followed by non-Hispanic black women with BMI 25.0+ (HR 2.43; 95% CI [1.28, 4.60]). A similar pattern emerged for disease-specific survival. Non-Hispanic black women also had poorer progression-free survival than non-Hispanic white women (HR 1.40; 95% CI [1.01, 1.93]). Other significant factors impacting survival outcomes included receipt of National Cancer Center Network (NCCN) guideline-concordant treatment (GCT), earlier stage at diagnosis, and fewer comorbid conditions. ConclusionsBMI and race interact and modify the association with high grade endometrial carcinoma survival. Other potentially modifiable factors, such as reducing comorbidities and increasing access to GCT will potentially improve survival after diagnosis of high grade endometrial carcinomas. A better understanding of the molecular drivers of these high grade carcinomas may lead to targeted therapies that reduce morbidity and mortality associated with these aggressive tumors.