tbuckley/cabot-search huggingface dataset:
EMBR-05. THE TENTATIVE APPLICATION OF EN BLOC CONCEPT IN THE PEDIATRIC BRAIN TUMOR: EXPERIENCE FROM A LARGE PEDIATRIC CENTER IN CHINA
Authors: Liangliang Cao, Jie Ma
Journal: Neuro-Oncology (2021)

Abstract Background The less allowable blood loss and tolerance of intraoperative blood loss of children lead to the high rate of massive blood transfusion in the treatment of brain tumor. The surgical concepts of en bloc resection may contribute to the improvement of brain tumor resection. Objective To investigate the effects of en bloc concept on short outcomes of pediatric brain tumors and factors associated with the application of en bloc concept. Methods According to the surgical concept involved, the patients were divided into three subgroups-complete en bloc concept, partial en bloc concept and piecemeal concept. The matching-comparison (piecemeal group and en bloc group formed from the first two subgroups) was conducted based on age, tumor location, lesion volume, and pathological diagnosis to investigate effect of the en bloc concept on the short-term outcomes. Then the patient data after January 2018, when the en bloc concept was routinely integrated into brain tumor surgery in our medical center, were reviewed and analyzed to find out the predictors associated with the application of en bloc concept. Results In the en bloc group, the perioperative outcomes, including hospital stay (p=0.001), PICU stay (p=0.003), total blood loss(p=0.015), transfusion rate(p=0.005) and complication rate(p=0.039), were all significantly improved. The multinomial logistic regression analysis showed that tumor volume and imaging features, like bottom vessel, encasing nerve or pass-by vessel, finger-like attachment, ratio of “limited line” and ratio of “clear line” remained independent factors for the application of en bloc concept in our medical center. Conclusion This study supports the application of complete or partial en bloc concept in the pediatric brain tumor surgery referring to the preoperative imaging features, and compared with piecemeal concept, en bloc concept can improve the short outcomes without significant increases in neurological complication. Large series and Additional supportive evidence are still warranted.
A multicenter analysis of treatment and outcomes in neuroendocrine carcinoma of the uterine cervix (NCUC).
Authors: Ashley Deanelle Hickman, Patrick Walsh McGarrah, Gretchen Glaser, Boris Naraev, Andrea Elisabeth Wahner Hendrickson, Thorvardur Ragnar Halfdanarson
Journal: Journal of Clinical Oncology (2021)

e17518 Background: Morbidity and mortality for patients with cervical cancer has improved significantly over the past few decades with modern multimodal therapy. However, neuroendocrine carcinoma of the uterine cervix (NCUC), which accounts for 1-2% of cervical cancers, remains a deadly subtype. In this study, we combine data from Mayo Clinic (MC) and the University of Iowa Hospitals and Clinics (UIHC) to provide information on tumor characteristics, treatment, and outcomes. Methods: The electronic medical record was reviewed for patients with NCUC from MC and UIHC. Data on diagnosis, treatment, and outcomes were collected through chart review. Primary endpoints included progression-free survival (PFS) and overall survival (OS). Secondary endpoints included median survival, survival at 1 year after surgery, and survival at 1 year by first line chemotherapy agent. Kaplan-Meier survival analysis was used to estimate median PFS, median survival, and OS. Fisher’s test analysis was used to calculate survival at 1 year after surgery and by first line chemotherapy agent. Results: There were 62 patients (MC: 26, UIHCC: 36) with NCUC stage I-IV (stage I: 29, stage II: 9, stage III: 7, stage IV: 14, unknown: 3). Median age of diagnosis was 47 years (range 21-77 years). By subtype, 47 were small cell (76%), 9 were large cell (15%), and 6 were unknown/undetermined (9%). The initial treatment modalities for each patient are outlined in the table. 28 patients had complete/partial response or stable disease from first line treatment, while 10 patients had disease progression. Of the patients who initially responded or had stable disease, 16 later progressed (57%) with a median time to progression of 15 months. Median follow up was 65.1 months with a median OS of 28.5 months. Median survival for those with stage I was 40.9 months, stage II: 54.6 months, stage III: 8.75 months, and stage IV: 11.7 months. There was a significant difference in overall survival at 1 year between those who received surgery and those who did not in stage I/II ( p = 0.01). There was no significant difference in overall survival at 1 year for those who received surgery in stage III/IV. There was no statistical difference in survival at 1 year for carboplatin or cisplatin in combination with etoposide as first line chemotherapy agent. Conclusions: NCUC is an aggressive malignancy that is usually progressive despite multimodal therapy. Our study demonstrated a median overall survival of 28.5 months and 5-year survival rate of 21%. Our study showed a survival benefit at 1 year for those who receive surgery with stage I/II NCUC. There was no significant survival benefit at 1 year between carboplatin or cisplatin in combination with etoposide as first line agent.[Table: see text]
Enhancing myelin renewal reverses cognitive dysfunction in a murine model of Alzheimer’s disease
Authors: Jing-Fei Chen, Kun Liu, Bo Hu, Rong-Rong Li, Wendy Xin, Hao Chen, Fei Wang, Lin Chen, Rui-Xue Li, Shu-Yu Ren, Lan Xiao, Jonah R. Chan, Feng Mei
Journal: Neuron (2021)
Gastric subcentimeter subepithelial tumor: successful resection with an over-the-scope padlock clip
Authors: Hsu-Heng Yen, Hui-Ting Hsu
Journal: Endoscopy (2021)

A 60-year-old woman was referred for endoscopic resection of two 5-mm gastric subepithelial lesions ([Fig. 1]) incidentally found during a screening endoscopy. Abdominal computed tomography (CT) revealed no lesions. The lesions were hypoechoic and originated from the muscle layer on endoscopic ultrasonography and were undetected on the endoscopy performed 5 years before. Follow-up was advised owing to the small lesions, but the patient requested an endoscopic resection to further clarify the nature of the tumor.
Role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC).
Authors: Pooja Ghatalia, Elizabeth A. Handorf, Mengying Deng, Matthew R. Zibelman, Philip Abbosh, Fern Anari, Richard E. Greenberg, Rosalia Viterbo, David Chen, Marc C. Smaldone, Alexander Kutikov, Daniel M. Geynisman, Robert Guy Uzzo
Journal: Journal of Clinical Oncology (2021)

4582 Background: The role of CN in mRCC was challenged by the results of the CARMENA trial in the targeted therapy (TT) era. We sought to evaluate the role of both upfront and deferred CN in pts receiving modern IO-based and TT regimens. Methods: Pts with synchronous mRCC who received systemic therapy (tx) for mRCC after 2011 were included from the de-identified nationwide Flatiron Health database. We evaluated 3 groups: systemic tx alone, systemic-&gt; CN, and CN-&gt; systemic tx. Overall survival (OS) was calculated from the time of initiation of first therapy – systemic or CN. Patient characteristics were compared using chi-squared tests or t-test. Weighted Kaplan-Meier curves, log-rank tests, and Cox proportional hazards regressions with time-varying covariates were used to assess the effect of tx on survival. Adjustment was conducted via inverse probability of treatment weighing based on the generalized propensity score, estimated via Bayesian Additive Regression Trees. Covariates in the model were age, gender, race, insurance at mRCC diagnosis, and IMDC risk group. Results: Of 1719 pts with mRCC, 972 (56.5%) received systemic tx alone, 605 (35.1%) received CN-&gt; systemic tx, and 142 (8.2%) received systemic-&gt;CN. 310 pts received IO or IO/IO, 123 pts received IO+TT and 1152 pts received only TT. The median follow-up was 37.1 months. In adjusted analyses using propensity score weighting and time-varying covariates, CN-&gt; systemic was significantly associated with improved OS compared with systemic tx alone (Table). When stratifying groups by type of systemic treatment (IO and TT), there was improvement of OS in the CN groups compared to systemic tx alone, although we lacked power to reach statistical significance. Among CN-treated patients, the order of systemic tx relative to CN did not change OS (hazard ratio [HR] = 1.00, 95% CI 0.76-1.32, p=0.96). Conclusions: Using a national, EHR-based cohort, which includes a large number of IO treated pts, our findings support an oncologic role for CN in select mRCC pts. The timing of CN, for pts who were able to receive both systemic therapy and CN, may not affect overall outcome. The associated improvement in survival of CN is seen in pts receiving IO and TKI based systemic tx.[Table: see text]
Retrospective study to assess the impact of hepatitis C virus infection on the prognosis and management of multiple myeloma.
Authors: David Kaldas, Andrew Wahba, Radwa Hamdy Azab, Ehab Mostafa Elnakoury, Nagla Fawzy Abdel Karim, Raafat Abdel-Malek
Journal: Journal of Clinical Oncology (2021)

e20001 Background: Multiple Myeloma (MM) is a neoplasm of the post-germinal center, terminally differentiated B-cells. MM accounts for 1% of all types of cancer and 10% for all hematologic malignancies. Chronic hepatitis C virus (HCV) is an infection that affects over 71 million patients worldwide. Cytotoxic agents and immunosuppressive therapy as steroids are the main line of therapy in lymphoid malignancies, but these drugs may exacerbate chronic viral hepatitis and cause uncontrolled replication of hepatitis viruses. The impact of HCV infection on MM patients remains unclear. Objective: To assess the impact of HCV infection on the prognosis and management of MM patients. Methods: A 10-year retrospective study of MM patients was conducted at Cairo University Clinical Oncology Department from January 2009 to April 2019. Results: During this time, 150 patients were diagnosed with MM, 109 (72.7%) were HCV negative, 24 (16%) were HCV positive, and 17 (11.3%) with unknown HCV status. The median age was 51 and 54 years for HCV negative and positive groups respectively, with a statistically insignificant difference (p-value &gt; 0.2). In the multivariate analysis, HCV infection was not an independent factor related to overall survival (OS), however age, creatinine and hemoglobin levels correlated significantly with OS (p &lt; 0.009, 0.008, 0.031 respectively). The median OS for the HCV negative group was 31.11 months (95% CI: 22.62 - 39.61) compared to 37.66 months (95% CI: 7.19 - 68.13) for the HCV positive group. The median progression-free survival (PFS) for all patients was 18.9 months, for HCV positive patients was 15.36 months (95% CI: 13.18 – 17.54), and for HCV negative patients was 20.49 months (95% CI: 14.13 – 26.85). Age below 60 years and creatinine level less than 2 mg/dL were statistically significant for favorable disease-free survival (DFS) (p &lt; 0.030, 0.034 respectively). Conclusions: Age, creatinine and hemoglobin levels are significant prognostic factors in MM but HCV status doesn’t affect the overall survival or progression-free survival. HCV infection should not contraindicate MM therapy.
CCTG CO.28 primary endpoint analysis: Neoadjuvant chemotherapy, excision and observation for early rectal cancer, the NEO trial.
Authors: Hagen Fritz Kennecke, Carl J Brown, Jonathan M. Loree, Husein Moloo, Derek J. Jonker, Manoj Raval, Reilly Musselman, Grace Ma, Antonio Caycedo-Marulanda, Val Simianu, Sunil Patel, Lacey D. Pitre, Ramzi Helewa, Vallerie Lynn Gordon, Katerina Neumann, Max Sherry, Dongsheng Tu, Christopher J. O'Callaghan
Journal: Journal of Clinical Oncology (2021)

3508 Background: CO.28 (NCT03259035) is a phase II study designed to determine if patients with cT1-T3a/bN0 rectal cancer can be treated with induction chemotherapy (FOLFOX/CAPOX) and organ-preserving surgery. Methods: Patients with MRI staged cT1-3a/bN0 tumors and no pathologic (p) high risk features received 6/4 cycles of FOLFOX/CAPOX, repeat sigmoidoscopy/pelvic MRI and subsequent Transanal Endoscopic Surgery (TES) in the absence of tumor progression. ypT0/T1N0 tumors were treated with observation while ypT2+ or ypN+ stage were recommended Total Mesorectal Excision (TME). The primary endpoint was protocol specified Organ Preservation Rate (psOPR = ypT0/T1N0, no p high risk features) and actual Organ Preservation Rate (aOPR = ypT0/T1N0 stage plus higher yp stage patients who declined TME surgery). The study would be considered negative with an psOPR of 50% or lower (H0) and as promising if it is 65% or higher (H1). Results: Between 08/2017 to 05/2020, 58 eligible patients were accrued in Canada and the United States, median age was 67 years, 71% male. All had well-moderately differentiated, non-mucinous rectal adenocarcinoma and median tumor height was 6 cm (range 0-18). Median follow-up was 15.4 months. Chemotherapy with FOLFOX (32) or CAPOX (26) was administered, 90% completed all planned cycles. A total of 56/58 (97%) proceeded to TES, while one patient was ineligible due to tumor progression (1.7%) and one declined. In the intention to treat analysis, the psOPR was 57% (95% CI 43-70%) while the aOPR was 79% (95% CI 67% to 89%) due to 13/23 declining recommended TME surgery. Of 10 patients who proceeded to recommended TME, a complete R0 TME was performed in 9/10, and no p residual carcinoma was found in 7/10. Crude loco-regional (LR) and distant recurrence rates were 3.5% (95% CI 0.4 to 12%) and 0%, respectively. A recurrence occurred in 1/13 patients who initially declined TME surgery. Conclusions: In select patients with early stage rectal cancer, three months of induction CAPOX/FOLFOX followed by TES resulted in a high OPR without the use of pelvic irradiation. The observed high rate of pathologic downstaging may point to high chemo-responsiveness in early rectal adenocarcinoma with no p high risk features. Further trials to evaluate this approach are justified and updated results will be presented. Clinical trial information: NCT03259035. [Table: see text]
Simultaneous Targeting of PARP1 and RAD52 Triggers Dual Synthetic Lethality in BRCA-Deficient Leukemia Cells
Authors: Katherine Sullivan, Elisabeth Bolton-Gillespie, Yashodhara Dasgupta, Samantha Langer, Micheal Siciliano, Margaret Nieborowska-Skorska, Huaqing Zhao, Peter Valent, Tomasz Skorski
Journal: Blood (2017)
Association of cell-free DNA dominant clone allele frequency with poor outcomes in advanced biliary cancers treated with platinum-based chemotherapy.
Authors: Umair Majeed, Pedro Luiz Serrano Uson Junior, Jun Yin, Mohamad Bassam Sonbol, Daniel H. Ahn, Tanios S. Bekaii-Saab, Jason S. Starr, Jeremy C Jones, Samantha R Inabinett, Natasha Wylie, Ashton WR Boyle, Mitesh J. Borad, Kabir Mody
Journal: Journal of Clinical Oncology (2021)

4079 Background: Cell-free circulating tumor DNA (ctDNA) holds significant promise and is being used for clinical decision making in multiple tumors. This study aimed to evaluate the prognostic value of pre-treatment ctDNA in metastatic biliary tract cancers (BTC) treated with platinum based first-line chemotherapy treatment. Methods: We performed a retrospective analysis of 67 patients who underwent ctDNA testing before platinum-based chemotherapy for first-line treatment for metastatic BTC. For analysis we considered the detected gene with highest variant allele frequency (VAF). Results of ctDNA analysis were correlated with patients’ demographics, progression-free survival (PFS) and overall survival (OS). Results: The median age of patients was 67 y/o (27-90). 54 (80.6%) of 67 patients evaluated had intrahepatic cholangiocarcinoma; seven had extrahepatic cholangiocarcinoma and six gallbladder cancer. 46 (68.6%) of the patients were treated with cisplatin plus gemcitabine, 14 (21%) patients received gemcitabine and other platinum (carboplatin or oxaliplatin) combinations while 7 (10.4%) patients were treated on a clinical trial with gemcitabine and cisplatin plus additional targeted agents (CX4945 or PEGPH20). TP53, KRAS, APC, FGFR2 and IDH1 were the genes with highest frequency as dominant clone. The median dominant clone allele frequency (DCAF) was 3% (0-97%). DCAF &gt;3% was associated with statistically significant worse PFS (median PFS: 4.05 vs. 7.70 months, p=0.046) and OS (median OS: 10.8 vs. 18.8 months, p=0.056). Each 1% increase in DCAF is associated with a hazard ratio of 26.21 in OS when adjusting for subtypes, age, treatment type, and CA19-9 [Table]. Conclusions: Patients with metastatic BTC with DCAF &gt; 3% at diagnosis have worse PFS and OS compared to patients with low ctDNA when treated with upfront platinum-based chemotherapy.[Table: see text]
Isatuximab plus carfilzomib and dexamethasone in relapsed multiple myeloma patients with high-risk cytogenetics: IKEMA subgroup analysis.
Authors: Ivan Spicka, Philippe Moreau, Thomas G. Martin, Thierry Facon, Gracia Martinez, Albert Oriol, Youngil Koh, Andrew Lim, Gabor Mikala, Laura Rosiñol, Münci Yağci, Michele Cavo, Marie-Laure Risse, Gaëlle Asset, Sandrine Macé, Helgi Van De Velde, Kwee Yong
Journal: Journal of Clinical Oncology (2021)

8042 Background: A prespecified interim efficacy analysis of the Phase 3 IKEMA study (NCT03275285) demonstrated that isatuximab (Isa) + carfilzomib (K) and dexamethasone (d) (Isa-Kd) significantly improved progression-free survival (PFS) compared with Kd in patients (pts) with relapsed multiple myeloma (RMM) (HR 0.531; 99% CI, 0.318–0.889; P= 0.0007), with a clinically meaningful increase in minimal residual disease negativity (MRD-) (29.6% vs 13.0%) and complete response (CR) (39.7% vs 27.6%) rates, and a manageable safety profile. This subgroup analysis of IKEMA examined efficacy and safety in pts with high-risk cytogenetics [t(4;14), del(17p), and t(14;16)] and/or gain(1q21). Methods: Pts with 1–3 prior lines of therapy were randomized 3:2 to receive Isa-Kd (n = 179) or Kd (n = 123). High-risk cytogenetics was assessed by central laboratory analysis and defined as ≥1 of the following: del(17p): 50% cutoff; t(4;14) or t(14;16): 30% cutoff. Assessment of gain(1q21) was prespecified as ≥3 copies: 30% cutoff. Results: Of the randomized pts, 23.5% (Isa-Kd) and 25.2% (Kd) had ≥1 high-risk cytogenetic abnormality (CA); 26.3% (Isa-Kd) and 25.2% (Kd) had isolated gain(1q21). The addition of Isa to Kd improved PFS for pts with ≥1 high-risk CA and standard-risk pts (Table); pts with t(4;14) (HR 0.549; 95% CI, 0.232–1.301) had a more pronounced treatment effect than pts with del(17p) (HR 0.837; 95% CI, 0.281–2.496). A clear PFS benefit with Isa-Kd was also seen for pts with isolated gain(1q21) and gain(1q21) combined with other high-risk CA (Table). The trend toward improved CR, ≥very good partial response (VGPR), and MRD- rates with the addition of Isa was more pronounced in pts with gain(1q21) than in pts with high-risk CA alone. Grade ≥3 treatment-emergent adverse events (TEAEs) were more common with Isa-Kd vs Kd, but the incidence of serious and fatal TEAEs was similar with both arms for high-risk pts (Table). Conclusions: The addition of Isa to Kd improved PFS in pts with high-risk CA and disease response in pts with gain(1q21) isolated or combined with high-risk CA, with a manageable safety profile, consistent with the benefit observed in the overall IKEMA population. Isa-Kd is a potential new treatment option for the difficult-to-treat subgroup of pts with RMM and high-risk cytogenetics. Funding: Sanofi. Clinical trial information: NCT03275285. [Table: see text]
Risk and distribution of venous thromboembolic events during treatment for advanced endometrial cancer.
Authors: Julia Rose Salinaro, Emily Goins, Laura J Havrilesky, Brittany Anne Davidson
Journal: Journal of Clinical Oncology (2021)

e17565 Background: Understanding the incidence and timing of venous thromboembolic (VTE) events among patients receiving treatment for advanced endometrial cancer (EC) may help to inform VTE risk stratification and consideration of thromboprophylaxis. We aimed to describe the rate of VTE at each stage of primary treatment for advanced EC as well as the baseline Khorana Score (KS) distribution in this population. Methods: This was a retrospective cohort study of patients diagnosed with stage IVB EC from January 2001 to July 2020 at a single academic institution. The primary outcome was VTE incidence at each stage of primary treatment (at diagnosis, during neoadjuvant chemotherapy [NACT] if applicable, post-operatively [&lt; 30 days from surgery], or during adjuvant chemotherapy). Subjects who were anticoagulated at EC diagnosis were excluded. Khorana score was calculated according to established parameters (1 point each for gynecologic malignancy, pre-chemotherapy platelet count ≥ 350, hemoglobin &lt; 10 or use of red blood cell growth factors, leukocyte count &gt;11, and BMI ≥ 35). Descriptive statistics were used for analysis. Results: There were 76 patients diagnosed with stage IVB EC, 2 of whom were excluded for anticoagulation at cancer diagnosis. Of the remaining 74 patients, 58 underwent primary surgery (78%) and 16 received NACT (22%). A total of 59 received adjuvant chemotherapy after either primary or interval debulking surgery. The two predominant tumor histologies were serous (48%) and endometrioid (20%).A total of 16 VTE occurred during the primary treatment course (22%), 11 among the cohort receiving primary surgery (19%) and 5 among the cohort receiving NACT (31%). The distribution of VTE by stage of primary treatment is shown in Table. The rate of VTE was highest during adjuvant chemotherapy. There were 62 patients for whom a Khorana score could be calculated either before NACT or adjuvant chemotherapy. The distribution of KS was: 17 (27%) with KS 1 (low risk) and 45 (73%) with KS ≥ 2 (intermediate – high risk). Of the 11 non-postoperative VTE, 3 patients (27%) had KS 1 and 8 (73%) had KS ≥ 2. Conclusions: The incidence of VTE among patients with advanced EC was high regardless of whether treatment was initiated with NACT or primary surgery. The majority of VTE occurred among patients with a high KS, but those with a low KS remained at risk. Thromboprophylaxis among all patients with advanced EC may be warranted, and larger studies are needed to determine the performance of KS as a VTE predictor in advanced EC.[Table: see text]