tbuckley/cabot-search huggingface dataset:
Neoadjuvant chemotherapy for locally advanced colon cancer patients: Long-term results from a single institutional experience.
Authors: Lucia Ceniceros, Carlos Pastor, Carlos Sanchez-Justicia, Carolina Arean, Jorge Baixauli, Ana Chopitea, Lucia Granero, Jorge Arredondo, Patricia Martinez, Jose Luis Hernandez-Lizoain, Javier Rodriguez
Journal: Journal of Clinical Oncology (2021)

e15598 Background: Neoadjuvant chemotherapy (NAC) is an emerging alternative in the management of patients with locally advanced colorectal cancer (LACRC), with promising results in terms of R0 resection rates, compliance, postoperative morbidity and a trend towards reduced risk of relapse. However, more mature data are required. We evaluated the long-term outcome of this strategy in our institution. Methods: We retrospectively analysed LACRC patients treated preoperatively with either biweekly FOLFOX or XELOX at standard doses as a follow-up of our previous experience with this neoadjuvant approach. Patients were identified from a prospectively collected tumor registry database from our institution. Clinical staging was based on colonoscopy and CT-scan. Only patients with radiological signs of lymph node involvement and/or extramural invasion &gt; 5 mm were included. The uracil/dihidrouracil ratio was calculated at baseline as a surrogate marker of DPD deficiency. Pathological tumor regression was graded according to the MSKCC and toxicity with the NCI-CTCAE 4.0. Results: From February 2006 to November 2019 91 pts with MSS LACRC (M/F: 62/29; median age 66. Clinical stage; T3: 60.4%, T4: 37.4%, N+: 75.8%; Sideness: 82.4% left located were analysed. Preoperative chemo was FOLFOX in 46 pts and CAPOX in 45 pts. Median number of preoperative cycles was 4 (range 1-10). Side effects profile included G3-4 diarrhea (3.3%), G2 sensitive neuropathy (12.1%) and G2 neutropenia (4.4%). 9 pts had a treatment delay due to haematological toxicity. No progressive disease was noted during neoadjuvant chemotherapy. All patients underwent surgery, most of them (63.7%) by a laparoscopic approach. pCR was found in 11 pts (12.1%). Grade 3, 3+ and 4 tumor regression according to MSKCC score was reached in 50.5% of the patients (Median number of harvested nodes was 17 (range 7-51), with 75.8% being ypN0. Lymphovascular and perineural invasion were found in 7.7% and 6.6% of the patients, respectively. The median hospital stay was 7 days (3-36) and 13 pts develop any surgical complication. 37.4% received adjuvant treatment. After a median follow-up of 63 months, median progression-free (PFS) and overall survival (OS) have not been reached. 5-year actuarial PFS for right and left LACRC was 77 and 87%, respectively. Conclusions: Our data add to the growing evidence suggesting that NAC may play a meaningful role in LACRC patients
EMBR-15. PRC2 COMPLEX ENFORCES NEURONAL LINEAGE AND SUPPRESSES TUMOR GROWTH IN SHH MEDULLOBLASTOMA
Authors: Abigail Cleveland, Daniel Malawsky, Mehal Churiwal, Timothy Gershon
Journal: Neuro-Oncology (2021)

Abstract Hyperactivation of Sonic Hedgehog (SHH) signaling pathway drives tumor progression in the largest medulloblastoma subgroup. During cerebellar development, promoters of SHH target genes show inhibitory trimethylation of histone H3 at lysine 27 (H3K27me3), mediated by the Polycomb Repressive Complex 2 (PRC2). Here, we explored the regulation of cerebellar growth and medulloblastoma tumorigenesis by PRC2 complex components EED and EZH2. For developmental studies, we conditionally deleted Eed or Ezh2 in the Atoh1 lineage that gives rise to the cerebellar granule neuron progenitors (CGNP) that are cells of origin for SHH medulloblastomas. For tumor studies, we bred the conditional Eed- or Ezh2-deleted mouse lines with mice genetically engineered to develop SHH medulloblastoma. Our developmental studies showed that Eed was absolutely required for cerebellar growth. Eed-deleted CGNPs underwent aberrant, myocyte-like differentiation and spontaneous apoptosis, resulting in cerebellar hypoplasia. In contrast, Ezh2 deletion produced no developmental phenotype, despite blocking all H3K27me3 in CGNPs. Our tumor studies showed that Eed-deleted medulloblastomas similarly showed aberrant, myocyte differentiation, but unlike CGNPs, did not undergo widespread apoptosis. Eed-deleted medulloblastomas progressed more rapidly than control tumors, indicating that the inappropriate, muscle-like differentiation did not slow tumor growth. Ezh2-deleted medulloblastomas similarly progressed more rapidly than controls. Our data show that the PRC2 complex acts to enforce neuronal lineage commitment in both development and tumorigenesis and to restrain tumor growth in SHH medulloblastoma. Myocyte differentiation in Eed-deleted tumors suggests that PRC2 loss of function may contribute to the medullomyoblastomas that have been observed in patients. The differences in developmental phenotype show that EZH2 and EED functions are non-identical and can be dissociated, while similar increase in tumor progression show tumor suppressive functions for both EED and EZH2.
Prospective Study of Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma on Waitlist for Liver Transplant
Authors: Tiffany Cho‐Lam Wong, Victor Ho‐Fun Lee, Ada Lai‐Yau Law, Herbert H. Pang, Ka‐On Lam, Vince Lau, Tracy Yushi Cui, Adrianna Sze‐Yin Fong, Sarah Wai‐Man Lee, Edwin Chun‐Yin Wong, Jeff Wing‐Chiu Dai, Albert Chi‐Yan Chan, Tan‐To Cheung, James Yan‐Yue Fung, Rebecca Mei‐Wan Yeung, Mai‐Yee Luk, To‐Wai Leung, Chung‐Mau Lo
Journal: Hepatology (2021)

Background and Aims There are no prospective data on stereotactic body radiation therapy (SBRT) as a bridge to liver transplantation for HCC. This study aimed to evaluate the efficacy and safety of SBRT as bridging therapy, with comparison with transarterial chemoembolization (TACE) and high‐intensity focused ultrasound (HIFU). Approach and Results Patients were prospectively enrolled for SBRT under a standardized protocol from July 2015 and compared with a retrospective cohort of patients who underwent TACE or HIFU from 2010. The primary endpoint was tumor control rate at 1 year after bridging therapy. Secondary endpoints included cumulative incidence of dropout, toxicity, and posttransplant survival. During the study period, 150 patients were evaluated (SBRT, n = 40; TACE, n = 59; HIFU, n = 51). The tumor control rate at 1 year was significantly higher after SBRT compared with TACE and HIFU (92.3%, 43.5%, and 33.3%, respectively; P = 0.02). With competing risk analysis, the cumulative incidence of dropout at 1 and 3 years after listing was lower after SBRT (15.1% and 23.3%) compared with TACE (28.9% and 45.8%; P = 0.034) and HIFU (33.3% and 45.1%; P = 0.032). Time‐to‐progression at 1 and 3 years was also superior after SBRT (10.8%, 18.5% in SBRT, 45%, 54.9% in TACE, and 47.6%, 62.8% in HIFU; P &lt; 0.001). The periprocedural toxicity was similar, without any difference in perioperative complications and patient and recurrence‐free survival rates after transplant. Pathological complete response was more frequent after SBRT compared with TACE and HIFU (48.1% vs. 25% vs. 17.9%, respectively; P = 0.037). In multivariable analysis, tumor size &lt;3 cm, listing alpha‐fetoprotein &lt;200 ng/mL, Child A, and SBRT significantly reduced the risk of dropout. Conclusions SBRT was safe, with a significantly higher tumor control rate, reduced the risk of waitlist dropout, and should be used as an alternative to conventional bridging therapies.
Outcomes of ER, PR, HER2, and triple-negative mutated breast cancer with brain metastasis.
Authors: Patrick Joseph O'Shea, Vineeth Tatineni, Yasmeen Rauf, Xuefei Jia, Erin Sennett Murphy, Samuel T. Chao, John H. Suh, David M. Peereboom, Manmeet Singh Ahluwalia
Journal: Journal of Clinical Oncology (2021)

e14009 Background: Breast cancer is the second most common cause of metastatic brain tumors. The presence of estrogen receptors (ER), and progesterone receptors (PR), and HER2 receptors have been used to guide both hormonal and targeted therapies for breast cancer. The presence or absence of these receptors may impact patient outcomes in breast cancer brain metastasis (BCBM). Methods: Patients with BCBM and known tumor marker status treated at our tertiary care center from 2010-2019 were evaluated. Overall Survival (OS) was measured from diagnosis of BCBM to date of death or last follow up. Many of these patients received multiple lines of treatment including hormonal and targeted therapies at some point during their care. The Cox proportional hazard model was used to determine differences in OS. Results: 137 patients with BCBM were included. Of these, 48 were ER or ER/PR positive (ER+), 3 were PR positive (PR+), and 47 were HER2, HER2/PR, HER2/ER, or HER2/ER/PR positive (HER2+), and 37 were triple-negative. For ER+ tumors the median age at diagnosis was 60 years (Interquartile range (IQR) 31-87) and 86% were white. For PR+ tumors the median age at diagnosis was 67 years (IQR 66-74) and 75% were white. For HER2+ tumors the median age at diagnosis was 55 years (IQR 31-84) and 79% were white. For triple-negative tumors the median age at diagnosis was 56 years (IQR 34-91) and 83% were white. OS for ER+, PR+, HER2+, and triple-negative patients had a median of 57.7, 19.8, 137.4, and 54.6 months and a 2-year rate of 76%, 33%, 82%, and 73%, respectively. With ER+ patients as a reference, PR+ patients had an OS hazard ratio of 1.49 (95% CI = 0.35 - 6.23, p = 0.59), HER2+ patients had an OS hazard ratio of 0.62 (95% CI = 0.36 - 1.06, p = 0.082), and triple-negative patients had an OS hazard ratio of 0.92 (95% CI = 0.54 - 1.57, p = 0.77). Conclusions: HER2+ tumors were associated with an increase in OS when compared to ER+, PR+, and triple-negative tumors in patients with BCBM. The OS of the other three tumor marker groups was not significantly different from one another. Further studies need to be done within tumor marker cohorts to determine the most effective treatments within those cohorts.[Table: see text]
Contemporary trends and survival outcomes of females with esophageal cancer in the United States.
Authors: Camille Baumrucker, Lindsay Remer, Dido Franceschi, Alan S Livingstone, Francis Igor Macedo
Journal: Journal of Clinical Oncology (2021)

e16100 Background: Esophageal cancer (EC) is historically a male dominant disease. Current evidence on the impact of gender on clinical presentation and survival outcomes of EC is limited by small sample size or single institution series. Methods: Patients with EC (stage I-III) were identified in the NCDB (2004-2016). Clinicopathologic and treatment characteristics of male and female patients were compared using Chi-square analysis. Kaplan-Meier and Cox multivariable regression were used to estimate overall survival (OS). Results: Of 62,893 patients included, most patients were male (77.7%). Adenocarcinoma was the most common subtype (66.7%). Squamous cell carcinoma was more predominant in females (57.1% vs. 26.5%, p&lt;0.001). Females were older (68.5 vs. 66.1 yrs; p&lt;0.001) and more likely African American (AA, 14% vs. 8.1%; p&lt;0.001). Females presented with more local disease (stage I, 19.6% vs. 18.2%; p&lt;0.001) while males presented with more locoregional disease (LRD, stage II/III, 80.4% vs 81.8%, p&lt;0.001). Of those with LRD, females less frequently received chemotherapy (CT, 75.4% vs. 82.9%, p&lt;0.001), radiation therapy (RT, 78.9% vs. 82.6%, p&lt;0.001), and esophagectomy (EG, 28% vs. 40.5%, p&lt;0.001). White females with LRD received less CT (76.2% vs. 83.9%, p&lt;0.001), RT (79.5% vs. 83.3%, p&lt;0.001), and EG (30.6% vs. 43.5%, p&lt;0.001). AA females with LRD received less CT (71.9% vs. 75.2%, p=0.013) and RT (77.4% vs. 80.5%, p=0.013) but had similar rates of EG as AA males (p=0.476). Females had worse OS than males (18.1 vs. 19.7mo, p=0.001; cI: 23.5 vs. 31.9mo, p&lt;0.001; LRD: 17.2 vs 18.3mo, p=0.473). White females had worse OS than white males (18.6 vs. 20.4mo, p&lt;0.001) while AA females had better OS (13.5 vs. 12.6mo, p=0.001). White females who underwent EG had improved OS over white males (47.6 vs 38mo, p&lt;0.001) while AA males and females who underwent EG had similar OS (p=0.473). Female gender, older age, AA race, high comorbidity score and clinical stage, and lack of access to CT, RT, and EG were independent predictors of mortality (Table 1). Conclusions: Females with EC seem to have less access to CT, RT, and EG with worse OS than males. Healthcare policies should focus on increasing access to standard treatments for female patients with EC.[Table: see text]
Efficacy of DAN-222, a novel investigational polymeric nanoparticle with topoisomerase I inhibitor, as monotherapy in breast cancer models and when combined with PARP inhibitor.
Authors: Ashley P Wright, Jodi D Bradley, Timothy Hagerty, Emily A Wyatt
Journal: Journal of Clinical Oncology (2021)

1081 Background: Patients with BRCA-positive HER2-negative breast cancer benefit from PARP inhibitor therapy, but additional benefit is still desired. PARP inhibition alone does not prevent all mechanisms for repairing damage to DNA such as homologous recombination repair. An attractive combination for treating such patients would be combining a topoisomerase I inhibitor with a PARP inhibitor given the dual mechanism this would provide for DNA damage and inhibited repair, leading to tumor cell death. This combination has been tried in multiple phase 1 studies, but myelotoxicity prevented the combination from being evaluated further. DAN-222 is a novel investigational polymeric nanoparticle conjugated with camptothecin, a topoisomerase I inhibitor, that provides significant accumulation of drug in tumor tissues via the enhanced permeability and retention (EPR) effect and significantly reduced bone marrow exposure compared to native chemotherapy. These observations underscore the potential advantages of DAN-222 alone as well as in combination with other agents such as PARP inhibitors in solid tumors. Here, we report the effects of DAN-222 monotherapy and in combination with a PARP inhibitor on the growth inhibition in an HRD+ TNBC breast cancer (MDA-MB-436) and an HRD- ovarian (OVCAR3) xenograft mouse model. Methods: HRD+ breast cancer tumor cells (MDA-MB-436) were implanted into female NCr nu/nu mice and HRD- ovarian cancer tumor cells (OVCAR3) were implanted into female CB.17 SCID mice. Mice were randomized to vehicle or treatment arms until tumors reached 2000 mm 3 or day 45 (MDA-MB-436) or 1000mm 3 or day 45 (OVCAR3). The groups evaluated include multiple dose levels of DAN-222 as monotherapy and those also combined with niraparib. Results: Results were consistent in both the HRD+ and HRD- tumor models with profound dose-response of DAN-222 monotherapy inhibiting tumor growth. Additionally, synergy was demonstrated when DAN-222 was combined with niraparib, clearly evident with low doses of both products when used in combination. The table below highlights the synergy of the combination of DAN-222 at 0.3 mg/kg and niraparib at 25 mg/kg above each agent alone on the tumor growth inhibition in the MDA-MB-436 xenograft. Conclusions: Combining a PARP inhibitor with a topoisomerase I inhibitor delivered via this polymeric nanoparticle delivery system (DAN-222) has synergistic efficacy in both HRD+ and HRD- xenograft tumor models. These data support continued development of DAN-222 to treat solid tumors and its combination use with PARP inhibitors.[Table: see text]
An analysis of the reasons and motives of patients seeking telehealth-based second opinion for cancer.
Authors: Rejil Rajan, Amit Kumar Jotwani, Thirtha Poovaiah, Rakesh Shankar Goud, Rama Waghmare, Shashidhar Gururao
Journal: Journal of Clinical Oncology (2021)

e13621 Background: Incidence of cancer is rising with each passing year in India and a majority number of patients get diagnosed in later stages of disease that leads to poor outcomes. Studies have reported that patients and their caregivers feel the need to get more information about their treatment options making them opt for second opinions due to need for reassurance or inadequate time for communication with their treating oncologists. We sought to analyse the primary concerns and motives of patients seeking second opinion services through onco.com. Methods: A cohort of 918 eligible patients who availed online multidisciplinary tumour board opinion through Onco.com was included in the study. We analysed the primary concerns of 918 eligible patients who availed online second opinion through onco.com between January 2019 &amp; December 2020. We looked at the specific questions they had for the multidisciplinary panel of oncologists. We also correlated the concerns with the stage of disease to understand if there was a variation for different stages of disease. Results: Of the total 918 patients, 864 had solid malignancies, out of which 16% had early (stage 1 &amp; 2) disease, 27% had locally advanced (stage III) disease, 47% had metastatic disease &amp; and 16% had recurrent disease. The most frequent motive for seeking a second opinion was the need for validation of ongoing treatment (72.5%) followed by enquiry for more advanced treatment options (37%), and to know any alternative treatment options (19%). Interestingly, only a minority of all patients were keen to know about clinical trials (3%). Conclusions: Our findings suggest that validation of ongoing treatment is the most frequent motive for patient driven second opinions in oncology. There was minimal interest to seek clinical trial options among patients, which could be due to general lack of awareness about clinical trials and some form of stigma associated with clinical trials due to negative perceptions and fears about adverse events. [Table: see text]
Outreach: Preliminary safety and efficacy results from a phase 2 study of lisocabtagene maraleucel (liso-cel) in the nonuniversity setting.
Authors: John E. Godwin, Bassam Ibrahim Mattar, Michael B. Maris, Carlos R. Bachier, Don A. Stevens, Daanish Hoda, Juan Carlos Varela, Mohamad Cherry, Suzanne R. Fanning, James H. Essell, Habte Aragaw Yimer, Jay G. Courtright, Jeff Porter Sharman, Nikolaus S. Trede, Marina Youssef, James Lymp, Paul Shaughnessy
Journal: Journal of Clinical Oncology (2021)

e19513 Background: Concerns about adverse events (AEs) related to CAR T cell therapy have resulted in administration of this therapy largely in an inpatient setting. OUTREACH (NCT03744676) evaluates safety and efficacy of liso-cel in patients (pts) with R/R large B-cell lymphoma (LBCL) across inpatient and outpatient settings at nonuniversity medical centers (NMCs). Methods: NMCs, including centers naïve to CAR T cell therapy, enrolled adults with R/R LBCL in this open-label, multicenter study. Eligible pts had R/R PET-positive disease after ≥2 lines of prior systemic therapy, ECOG PS ≤1, and adequate organ function. Prior autologous HSCT was allowed. Pts received sequential infusions of equal target doses of CD8 + and CD4 + cells at a total target dose of 100 × 10 6 CAR + T cells. Primary endpoint was incidence of grade (G) ≥3 cytokine release syndrome (CRS) graded per 2014 Lee criteria, neurological events (NEs), prolonged cytopenias (Day 29 G ≥3 lab values), and infections. Secondary endpoints were safety and overall response rate (ORR). Outpatient AE monitoring/management was managed by a multidisciplinary CAR T cell therapy team following standard operating procedures (SOPs). Results: At data cutoff, 46 pts (inpatients n = 16, outpatients n = 30) were treated with liso-cel. Inpatients and outpatients had similar demographics and baseline disease characteristics; median age was 63 y (range, 34–83), 63% had diffuse LBCL not otherwise specified, and 91% were refractory to last therapy. Safety data were similar across inpatients and outpatients (Table). Early (study Day ≤4) and overall hospitalization in outpatients was reported in 27% and 63%, respectively; median time to hospitalization was 5 (2–61) days and median length of stay was 6 (1–28) days. For efficacy-evaluable pts (n = 44), ORR was 75% for inpatients and 79% for outpatients; CR rates were 50% and 61%, respectively. Conclusions: Liso-cel was successfully administered to pts with R/R LBCL in the outpatient setting and pts were monitored for CAR T cell therapy–related toxicities by multidisciplinary teams using SOPs. The incidences of severe CRS and NEs and use of tocilizumab and/or corticosteroids were similar in inpatients and outpatients, and consistent with the pivotal study observations (Abramson, The Lancet 2020). Updated data with longer follow-up will be presented. Clinical trial information: NCT03744676. [Table: see text]
Validation of FOXM1 As a Therapeutic Target in Acute Myeloid Leukemia
Authors: Irum Khan, Anand Ashwin Patel, Marianna Halasi, Rachael Schultz, Yi-Hua Chen, Nathan Aardsma, Nandini Kalakota, Li C Liu, Nadim Mahmud, Peter Gann, Olga Frankfurt, Andrei Gartel
Journal: Blood (2017)
The role of Ki67 in involved lymph nodes as a predictive biomarker for response to neoadjuvant chemotherapy in patients with early breast cancer.
Authors: Cornelia Kolberg-Liedtke, Shady Hussein, Agnes Bankfalvi, Julia Steinborn, Saskia Ting, Ann-Kathrin Bittner, Oliver Hoffmann, Birgit Pott, Carla Verena Hannig, Sarah Wetzig, Hans-Christian Kolberg
Journal: Journal of Clinical Oncology (2021)

e12553 Background: Neoadjuvant chemotherapy (NACT) is a standard in early breast cancer (EBC) with an unfavorable tumor biology and pathologic complete remission (pCR) after NACT is indicating an improved prognosis. Ki67 is well established as a prognostic and predictive biomarker in early breast cancer and the association of high Ki67-results in breast tumors at the time of initial diagnosis and pCR after NACT is used for decision making for versus against NACT in daily routine in many countries. Data about associations of Ki67 in involved lymph nodes and response to NACT are missing. Methods: We conducted a retrospective analysis among patients in our database who had received NACT for EBC, had lymph node involvement verified by core cut biopsy and available data for pCR, age, estrogen and progesterone receptor (ER, PR) status, HER2neu status, Ki67 in the breast tumor and grading. Patients treated in clinical studies were excluded. Ki67 was measured in the archived material of biopsies from involved lymph nodes and the association between Ki67 in involved lymph nodes and response to neoadjuvant chemotherapy was analyzed. Results: 52 patients were included with regard to the criteria mentioned above, 21 had to be excluded because there was not enough lymph node biopsy material for Ki67 analysis. 7 (22.6) of the remaining 31 patients achieved a pCR and 11 (35.5%) achieved a nodal conversion to ypN0. Median Ki67 was 35% [3%, 85%] in involved lymph nodes and 40% [10%, 90%] in the breast. There was no significant correlation (Spearman Rho) between Ki67 in involved lymph nodes and pCR whereas there was for Ki67 in the breast (p = 0.046). The ROC-analysis resulted in a cut-off of 47% with the highest sensitivity for Ki67 in lymph nodes regarding prediction of nodal conversion. An analysis with a cut-off of Ki67 in involved lymph nodes of 47% predicted a nodal conversion in 60% of the cases (Chi-Square and Fisher’s Exact test; p = 0.0049). Conclusions: Our analysis supports Ki67 as a strong predictive biomarker regarding pCR after neoadjuvant chemotherapy. Although high Ki67 expression in involved lymph nodes is significantly associated with nodal conversion, it does not add clinically meaningful information to Ki67 in the breast.
Abstract 11391: Screening for Intracranial Aneurysms in Coarctation of the Aorta: A Decision and Cost-effectiveness Analysis
Authors: Sarah S Pickard, Ashwin Prakash, Jane W Newburger, Adel M Malek, John B Wong
Journal: Circulation (2019)

Introduction: Patients with coarctation of the aorta (CoA) have a high prevalence of intracranial aneurysms (IA) and suffer subarachnoid hemorrhage (SAH) at significantly younger ages than the gene...