tbuckley/cabot-search huggingface dataset:
Positive radial resection margin after esophagectomy for esophageal cancer patients treated at a tertiary center and its impact on survival.
Authors: Parth Kishore Shah, Miles Cameron, Jessica M. Frakes, Jacques Fontaine, Domenico Coppola, Sarah E. Hoffe, Khaldoun Almhanna, Jose Mario Pimiento
Journal: Journal of Clinical Oncology (2017)

162 Background: Although residual tumor at the radial margin can be expected to have a significant impact on the recurrence or overall survival of patient with node negative esophageal cancer (EC), its impact on recurrence and overall survival of patients with node positive EC has not been well characterized. Methods: A retrospective review of patients who underwent esophagectomy for EC at a single institution over a 16 year period (1999-2015) was performed. Pre-operative clinical parameters, stage as well as oncologic management were reviewed as well as the impact of positive radial margin on overall survival of pre-treatment node positive tumors was analyzed using descriptive statistics. Results: The study group consisted of 437 patients (46%) with pre-treatment stage IIB or III out of 945 patients with EC undergoing esophagectomy. The mean age of patients was 63 years with male predominance (85%). Neoadjuvant therapy (NAT) was administered to 87% of patients. Trans-thoracic surgery was performed in 86% of patients and trans-hiatal in 14%. Positive radial margin on final pathology was identified in 14 patients (3.2%); none of these had squamous histology. Neither the surgical approach nor the use of NAT was associated with radial margin positivity (p = 0.6). The median overall survival was significantly lower in the patients with positive radial margin when compared to the rest of the cohort (13.6 months v/s 41.2 months, p = 0.004). Moreover, when focused only on patients with post treatment pathologic T3 and T4 disease, margin positive disease remained associated with worse survival (p = 0.04). However, when final N status is included in multivariate analysis margin positivity loses significance. Conclusions: Radial margin positive disease after surgical resection for EC is associated with worse overall survival. This finding was significant regardless of the pathologic T stage; however, pathologic nodal staging was the most important factor for prognostication in locally advanced EC. Adenocarcinoma is the predominant pathology identified in patients with positive radial margin and concurrent node positivity.
A phase 1 multicenter open-label dose-escalation study of BMS-936561 (MDX-1203) in clear cell renal cell carcinoma (ccRCC) and B-cell non Hodgkin lymphoma (B-NHL).
Authors: Taofeek Kunle Owonikoko, Arif Hussain, Walter Michael Stadler, David C. Smith, Mario Sznol, Ana M. Molina, Parul Gulati, Aadhar Shah, Christoph Matthias Ahlers, Josephine Cardarelli, Lewis J. Cohen
Journal: Journal of Clinical Oncology (2014)

2558 Background: BMS936561 is a fully human monoclonal anti-body conjugate targeting the CD70 transmembrane cell-surface protein highly expressed in ccRCC and B-NHL. The study was designed to determine the safety profile and maximum tolerated dose (MTD) of BMS-936561 in this patient population. Methods: This phase 1 study employed an accelerated titration design followed by a 3+3 dose escalation to evaluate the safety, maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of BMS-936561. Patients with advanced ccRCC or B-NHL, ≤ 3 prior chemotherapy regimens, ECOG performance status 0-2 were treated with escalating doses of BMS-936561 (0.5mg/kg, 1mg/kg, 2mg/kg, 4mg/kg, 8mg/kg, 15mg/kg) by IV infusion every 21 days in a 42 day cycle up to 17 cycles. Dose limiting toxicity (DLT) was defined as any of the following adverse events (AEs): ≥ Grade 4 anemia, leukopenia, thrombocytopenia, neutropenia or any other ≥ Grade 3 events according to NCI CTCAE 3.0 during the first cycle. Results: There were 26 patients enrolled into the escalation (16) and expansion cohorts (10): median age: 63 y, range 48-74; gender: 18M/8F; race: 25W/1AA. BMS-936561 was tested at doses ranging from 0.1 to 15 mg/kg without a defined MTD. There was DLT of grade 3 hypersensitivity in 2/16 (13%) subjects treated at the 15 mg/kg dose cohort. The most commonly reported AEs included fatigue (85%), nausea (54%), decreased appetite (39%), anemia, dyspnea (35% each), constipation, peripheral edema (31% each), vomiting (27%), cough, skin hyperpigmentation, thrombocytopenia (23% each). Delayed toxicities characterized by facial edema and/or pleural or pericardial effusions were observed in 6/16 (38%) subjects treated at the 15mg/kg dose. All treatment emergent grades 3-4 serious AEs occurred in subjects treated at the 15 mg/kg dose. No deaths were attributed to BMS-936561. Exploratory efficacy analysis by investigator assessment showed a best response of stable disease in 18 of 26 patients (69%) without any apparent correlation with the administered dose. Conclusions: BMS936561 is well tolerated over a wide range of doses in patients with advanced ccRCC and B-NHL. Clinical trial information: NCT00944905.
Bloodless transplants for multiple myeloma are feasible and yield similar results as matched controls.
Authors: Chikaodili Olusola Obidike, Ajay K. Nooka, Jonathan L. Kaufman, Leonard T. Heffner, Amelia A. Langston, Sagar Lonial
Journal: Journal of Clinical Oncology (2015)

e19538 Background: High dose therapy-autologous stem cell transplant (HDT-ASCT) prolongs progression free survival (PFS) and overall survival (OS) in multiple myeloma (MM). The use of myelo-ablative HDT regimens is expected to significantly decrease hematopoiesis and replacement transfusions are given until engraftment. Thus, patients that cannot receive blood products during pancytopenic phase may not be offered HDT-ASCT. We evaluated the safety, feasibility, and efficacy of HDT-ASCT in Jehovah’s Witness (JW) patients that cannot be transfused due to religious beliefs. Methods: This is a retrospective case-control evaluation of patients that underwent HDT-ASCT for MM at Emory University Hospital from August 2006 until October 2014. Each JW patient was compared with three controls (non-JW patients) that underwent ASCT in the same period, matched by age (±5 years), sex, race and risk stratification. Non-parametric Mann-Whitney U test compared engraftment parameters and log-rank test compared PFS and OS between two groups. Results: Twelve JW patients and 36 non-JW patients were analyzed. Median ages at time of ASCT for JW and non-JW were 50.5 years (range 33-66) and 50.5 years (range 34-64); p=0.924, respectively. Median times from diagnosis to HDT-ASCT for JW and non-JW were 8.5 months (range 4-47) and 10.5 months (range 4-45); p=0.353, respectively. Median times to neutrophil engraftment between JW and non-JW were 12 days (range 8-17) and 13 days (range 11-20), respectively, p=0.45; median times to platelet engraftment were 13 days (range 8-17) and 12.5 days (range 7-26), respectively, p=0.990; and median hospital stays were 16 days (range 13-22) and 16 days (range 12-24), respectively, p=0.656. Median PFS for JW and non-JW was 39 months (95% CI 31.93-46.07) and 56 months (range 13.8-98.17), respectively, p=0.593. At a median follow up of 48 months after ASCT, median OS has not been reached. There was no transplant-related mortality in either group. Conclusions: Bloodless transplants are safe, feasible, and can yield similar survival benefits to those attained with blood products. Noting the younger age range in our series, our data suggests carefully selected patients can safely have a bloodless transplant for MM.
Recurrent glioblastoma: Stratification of patient survival using tumor volume before and after antiangiogenic treatment.
Authors: Raymond Huang, Rifaquat Rahman, Alhafidz Hamdan, Caroline Kane, Christina Chen, Andrew David Norden, David A. Reardon, Srinivasan Mukundan, Patrick Y. Wen
Journal: Journal of Clinical Oncology (2013)

2075 Background: Although antiangiogenic therapies can induce a dramatic clinical and imaging response in patients with recurrent glioblastoma, their benefit on overall survival is less pronounced. We assessed whether tumor volume based on magnetic resonance imaging (MRI) before and after treatment with bevacizumab can stratify patients in terms of progression-free survival (PFS) and overall survival (OS). Methods: Baseline and post-treatment MRI scans of 93 patients with recurrent glioblastoma treated with bevacizumab were evaluated for volume of the enhancing tumor, as well as volume of the T2/FLAIR hyperintensity. The Cox proportional hazards model was used in univariate and multivariate settings to identify volume parameters prognostic and predictive for PFS and OS. Results: Our results show that baseline enhancing tumor volume were predictive of PFS (p = 0.047) and OS (p = 0.011). Specifically, patients with pretreatment enhancing tumor volume less than 18 cm 3 have a median OS of 45 weeks, while patients with tumor volume greater than 18 cm 3 have a median OS of 26 weeks. In addition, enhancing tumor volume 3 to 6 weeks after treatment, as well as percentage change in volume, are independent predictors of PFS and OS. Neither T2/FLAIR volume nor percentage change in T2/FLAIR volume was associated with survival. Conclusions: These results indicate that measurement of enhancing tumor volume can help identify patients more likely to benefit from bevacizumab therapy.
Preoperative chemotherapy as a new strategy of treatment for low-grade gliomas in eloquent areas: A phase II study.
Authors: Roberta Ruda, Lorenzo Bello, Antonella Castellano, Luca Bertero, Elisa Trevisan, Marco Riva, Andrea Falini, Riccardo Soffietti
Journal: Journal of Clinical Oncology (2014)

2080 Background: Total/near total resection has been associated with increased survival and reduced risk of malignant transformation in low grade gliomas (LGGs). This study is aimed to evaluate whether preoperative chemotherapy with temozolomide can reduce tumor infiltration and improve the surgical resectability of LGGs in eloquent areas. Methods: Patients with LGG after biopsy or partial resection at a previous surgery, who progressed with increasing seizures and/or radiologically, received 1 week on/1 week off temozolomide to a maximum of 12 cycles. Response on MRI-FLAIR images was evaluated every 3 months based on RANO and volumetric criteria. Changes on diffusion tensor imaging (DTI) were assessed by histogram analysis and Functional Diffusion Maps and compared with RANO and volumetric criteria, and response of seizures. Results: 24 patients with an histological diagnosis of LGG according to WHO 2007 were enrolled from 2008 to 2013. Reasons for chemotherapy were either a large residual tumor in 15/24 (seizures in 13/15) or tumor progression in 9/24 (seizures in 3/9). Nineteen of 24 patients are evaluable for response so far. Best response according to RANO was: MR in 3/19 (16%), SD in 14/19 (74%) and PD in 2/19 (10%). Among patients with response or stable disease according to RANO, tumor volume reduction on FLAIR images ranged between 4.3% and 42.7% (median: 26.6%). In all patients significant changes in diffusion patterns, suggestive of a reduced tumor infiltration, were observed after 3 cycles (p<0.05) and became more significant (p<0.01) after 6 cycles. Twelve out of 15 patients had a significant reduction of seizure frequency concurrent with significant changes on DTI despite a volumetric stability. Seventeen out of 19 patients underwent reoperation: overall, a near-total resection (≥ 95%) was achieved in 9/19 (47%) patients of the whole series. In 4 patients total resection was confirmed by the absence of IDH1 mutated cells in tumor margins. Conclusions: Preoperative chemotherapy in patients with LGG in “eloquent” areas can allow a total near-total resection at reoperation in a significant subset of patients. DTI could improve the evaluation of feasibility and timing of reoperation.
LUX head and neck 2: A randomized, double-blind, placebo-controlled, phase III study of afatinib as adjuvant therapy after chemoradiation in primarily unresected, clinically high-risk, head and neck cancer patients.
Authors: Barbara Burtness, Jean Bourhis, Jan Baptist Vermorken, Luyan Dai, Charlotte Lind, Eva Ehrnrooth, Ezra E. W. Cohen
Journal: Journal of Clinical Oncology (2012)

TPS5599 Background: Locally advanced squamous cell cancer of the head and neck (SCCHN) is treated with curative intent, but recurrence and death are common. SCCHN frequently over-expresses EGFR (ErbB1). Co-expression of other HER family members such as HER2 (ErbB2) may contribute to resistance to EGFR inhibition, which is the only validated targeted therapy in SCCHN. Methods: The trial investigates if adjuvant afatanib, an irreversible ErbB family blocker, which has shown preclinical activity against all ErbB dimers including EGFR and HER2, reduces the risk of recurrence in high-risk patients who have no evidence of disease following platinum-based chemoradiation with or without neck dissection. Patients are eligible who have received definitive chemoradiation to a minimum of 66 Gy, with concurrent cisplatin (≥200 mg/m 2 ) or carboplatin (≥AUC 9), for SCC of the oral cavity, oropharynx, or hypopharynx or larynx. Patients with base of tongue or tonsil cancer and ≤10 pack years of tobacco use, as well as those with nasopharynx, sinus or salivary gland cancer, are excluded. Adequate bone marrow, liver and kidney function is required. Prior therapy with investigational agents or EGFR inhibitors is not permitted. Randomization must take place within 16 weeks of the completion of chemoradiation with or without subsequent neck dissection. Patients are randomized 2:1 to afatinib 40 mg po qd or placebo, and treatment continues for 18 months in the absence of disease recurrence, second primary tumors, or intolerance to the study medication. Dose escalation to 50 mg qd is undertaken in patients with no side effects, and stepwise dose reduction to 30 or 20 mg po qd for diarrhea, skin toxicity or other adverse events is permitted. The primary endpoint is disease-free survival (DFS). The study is planned to accrue approximately 669 patients worldwide, with a 90% power to detect a hazard ratio of 0.72. Secondary endpoints are DFS at 2 years, overall survival, health-related quality of life, and safety.
Signet ring cell (SRC) histology of localized gastric adenocarcinoma (LGAC) to predict response to preoperative chemoradiation.
Authors: Nikolaos Charalampakis, Graciela M. Nogueras-Gonzalez, Elena Elimova, Roopma Wadhwa, Hironori Shiozaki, Yusuke Shimodaira, Mariela A. Blum, Jane Elizabeth Rogers, Jeana Garris, Aurelio Matamoros, Tara L. Sagebiel, Prajnan Das, Jeannelyn Estrella, Brian D. Badgwell, Jaffer A. Ajani
Journal: Journal of Clinical Oncology (2015)

4067 Background: Patients with LGAC, when treated with preoperative therapy, have heterogeneous and unpredictable outcomes. Currently, there are no clinical variables or biomarkers that can predict response to therapy. Methods: We analyzed 107 LGAC patients who were treated with chemoradiation followed by surgery. LGAC were grouped into categories based on: (1) presence of SRC (yes-SRC) or absence of SRC (no-SRC). LGACs with yes-SRC were further grouped by the % of SRC(s): 0%, 1-10%, 11-49%, and 50-100% and (2) histologic grade: moderately (G2) or poorly (G3) differentiated. These variables were correlated with pathologic complete response (pathCR) or < pathCR in the resected specimens. Descriptive statistics and survival analyses were utilized. Results: The patients were primarily males (60%), had clinical stage III LGAC (50%), and had received chemotherapy before chemoradiation (93%). Most had G3 tumors (78%) and yes-SRC (58%). Patients with yes-SRC had a lower rate of pathCR (11%) compared to no-SRC (36%, p = 0.004) and the association remained statistically significant even for a low percentage of SRC (1-10%) (p = 0.014). Higher the fraction of yes-SRC, the lower was pathCR (p = 0.03). The pathCR rate tended to be lower (18%) in G3 LGACs compared to G2 LGCAs (33%; p = 0.125). Patients with G3 tumors and yes-SRC had shorter overall survival (OS) (p = 0.046 and p = 0.038, respectively). Post-therapy pathologic stage was the only prognostic factor independently associated with OS and recurrence-free survival (p < 0.001). Conclusions: Our data suggest that yes-SRC LGACs are relatively chemoradiation resistant compared to no-SRC LGACs. A higher fraction of yes-SRC is associated with higher LGAC resistance. Validation and biomarker evaluation are warranted. From U. T. M. D. Anderson Cancer Center (UTMDACC), Houston, Texas, USA. (Supported in part by UTMDACC, and CA 138671 and CA172741 from the NCI). Dr. Nikolaos Charalampakis has been awarded a scholarship from the Hellenic Society of Medical Oncology.
Combined inhibition of β-catenin and Bcr–Abl synergistically targets tyrosine kinase inhibitor-resistant blast crisis chronic myeloid leukemia blasts and progenitors in vitro and in vivo
Authors: H Zhou, P Y Mak, H Mu, D H Mak, Z Zeng, J Cortes, Q Liu, M Andreeff, B Z Carter
Journal: Leukemia (2017)
Result of <i>Arid1a</i> deletion on intraductal papillary mucinous neoplasm formation.
Authors: Sam C. Wang
Journal: Journal of Clinical Oncology (2017)

328 Background: ARID1A, a member of the SWI/SNF chromatin-remodeling complex, is mutated in up to 30% of pancreatic ductal adenocarcinoma (PDAC). Here, we studied the effect of Arid1a loss in pancreatic tumorigenesis in the setting of a constitutively activated Kras allele ( Kras G12D ), which is the basis of a well-established mouse model of pancreas cancer. Methods: Arid1a was deleted during embryogenesis in acinar, duct, and islet cells in Ptf1a-Cre; Arid1a f/f (CA) and Kras G12D ; Ptf1a-Cre; Arid1a f/f (KCA) mice. Arid1a was inducibly deleted in adult mice specifically in duct or acinar cells with Kras G12D ; Sox9-Cre ER ; Arid1a f/f (KS ER A), and Kras G12D ; Ptf1a-Cre ER ; Arid1a f/f (KP ER A) mice, respectively. Tamoxifen was given at 4 weeks of age. Results: Genotyping of CA mice toes and pancreata showed Arid1a loss only in the latter confirming pancreas-specific recombination. Western blot confirmed decreased protein expression and immunohistochemistry (IHC) demonstrated Arid1a loss in most of the acini and half of the ducts. ~35% of CA mice developed benign appearing cysts by 4 months. KCA mice had macroscopic cysts by 3 weeks. The cyst fluid was thick and amylase rich. These cysts resembled intraductal papillary mucinous neoplasm (IPMN) as they had papillary features and stained for Alcian blue, confirming the presence of mucin. Muc protein staining pattern was consistent with pancreaticobiliary type IPMN. The stroma was negative for estrogen and progesterone receptors. KS ER A mice developed large mucin producing ductal lesions by 12 weeks while only pancreatic intraepithelial neoplasias were seen in KP ER A mice. Conclusions: Arid1a loss in the pancreas leads to pancreaticobiliary IPMN that appear to arise from the duct cells. Future directions include aging studies to determine if these cysts transform to frank PDAC, determining the status of ARID1A in human IPMN, and elucidating the mechanisms for cyst formation. Finally, this model may be useful as a platform to test therapeutic interventions to treat IPMN.
Impact of a pre- and postoperative chemotherapy (Ctx) on overall survival (OS) and progression free survival (PFS) in locally advanced gastric cancer (LAGC).
Authors: Ricarda Manth, H Schaefer, J Schroeder, G Spiessl, N Nuessler, Meinolf Karthaus
Journal: Journal of Clinical Oncology (2017)

156 Background: Perioperative Ctx has become standard of care for LAGC. Duration of pre- and post-op Ctx is a matter of debate. Our study evaluated effects of varying durations of pre- and post-op Ctx on PFS and OS. Secondary endpoints were toxicity, reasons for cessation of Ctx and response. We compared the outcome to a group of pts receiving no perioperative Ctx as an internal control. Methods: Pts with LAGC were included in a prospective cohort trial from a single institution from 2007 to 2015. Inclusion criteria were T1-T4, N0-3, M0, AEG (n=27) or gastric cancers (n=65). Initial therapy decisions were made by an interdisciplinary tumor board for all pts. Pts received DDP/5-FU (qw d28 mod FFCD-Protocol, Ychou et al. JCO 2011) for 2 mo, and a 3rd mo of pre-op Ctx in case of non-progression after 2 mo and proceeded to Ctx after surgery for a planned total of six mo of Ctx. Results: 92 pts (53 m; 39 f pts) with a median age of 69 ys (range 33-96) were included. A total of 74 pts were recommended periop Ctx and 18 primary surgery (S). A total of 67 (91%) of the periop Ctx received pre-op Ctx (NA) of which 47 (64%) received 3 mo of pre-op Ctx, 19 (26%) two mo, 1 pt (1%) one mo, and 7 pts refused preop Ctx (9%) of which only 3 proceeded to surgery. Only 53 pts (72 %) received post-op Ctx; 25 pts (34%) received three mo, 9 pts (12 %) two mo, and another 10 pts (14 %) one mo of postop Ctx. Nine pts (13%) in the NA group and 20 pts (39%) in the post-op Ctx group had to stop Ctx due to toxicity after 1 (n=11) and &lt;2 (n=9) mo of Ctx. Only 23 pts (31%) received the planned pre- and postop Ctx of 6 mo in total. Up to 07/2016 a total of 36 deaths were observed (39%). 5 yr PFS was 49% in the group of periop Ctx vs 14% in the S group. PFS in pts receiving a total of &lt; 4 mo of Ctx was 36% vs. 61% in pts receiving 6 mo of Ctx. 3 yr OS was 19% in the S group vs 48% in the Ctx group. The OS in pts receiving &lt; 4 mo was 34% vs.43% in pts with 6 mo Ctx. A pCR after preop Ctx was observed in 2 pts, a PR in 47 pts, a SD in 12 pts, while a PD occurred in 3 pts only. Conclusions: Pre-op Ctx was considerably better tolerated than post-op Ctx and led to fewer Tx cessations. We found a better PFS for pts with &gt;4 mo of periop Ctx, as well as OS was affected by a shorter duration of periop Ctx.