tbuckley/cabot-search huggingface dataset:
Significance of lymph node metastasis in pancreatic neuroendocrine tumors.
Authors: Katsunobu Taki, Daisuke Hashimoto, Nobuyuki Ozaki, Shinjiro Tomiyasu, Risa Inoue, Kensuke Yamamura, Yuuki Kitano, Kota Arima, Takayoshi Kaida, Takaaki Higashi, Katsunori Imai, Akira Chikamoto, Toru Beppu, Hiroshi Takamori, Masahiko Hirota, Hideo Baba
Journal: Journal of Clinical Oncology (2016)

210 Background: Pancreatic neuroendocrine tumor (PNET) is uncommon, and its prognosis is generally better than that of pancreatic cancer. Although some PNET patients have lymph node metastasis, its effect on their prognosis is unclear, lymph node dissection for PNET is controversial. Our study aimed to clarify the significance of lymph node metastasis in PNET. Methods: We retrospectively examined 83 PNET patients who underwent pancreatic resections at Kumamoto University Hospital, Saiseikai Kumamoto Hospital and Kumamoto Regional Medical Center from April 2001 to December 2014. We excluded NET G3 from them. Their clinicopathological parameters were analyzed by the absence or presence of lymph node metastasis, and with regard to disease-free survival (DFS) and overall survival (OS). Results: Although 5-year DFS was lymph node metastasis group: 73.3%, and no lymph node metastasis group: 85.0% (P = 0.474); and 5-year OS was lymph node metastasis: 91.7% and no lymph node metastasis: 96.2% (P = 0.055), lymph node metastasis was not an independent risk factor for DFS or OS in multivariate analysis. However, tumors larger than 1.8 cm were found to be an independent prognostic factor. Conclusions: Although lymph node metastasis was not an independent prognostic factor, tumors larger than 1.8 cm were an independent prognostic factor, and warrant lymph node dissection for PNET patients with tumors of this size.
Dosimetric coverage of anal sphincter by 3D conformal fields in patients undergoing neoadjuvant chemoradiation for rectal cancer: An implication in the concept of sphincter-preserving radiation therapy.
Authors: Yi-Jen Chen, Michelle B. Chen, Alan Jianan Liu, Peter Tsung Wen Tsai, An Liu
Journal: Journal of Clinical Oncology (2013)

558 Background: Functional impact related to dosimetric coverage of the anal sphincter in rectal cancer patients treated with neoadjuvant chemoradiation (NCRT) remains unknown. We evaluated the anatomic location of the anal sphincter to pelvic bony landmarks related to 3D conformal radiotherapy (3DRT) and studied the dosimetric coverage of the anal sphincter in patients undergoing NCRT for rectal cancer. Methods: Between June 2006 and March 2012, 64 patients with rectal cancer treated with NCRT were included. All patients were treated in prone position on a bellyboard by 3DRT with 3 or 4-field setup up to 5,040 (86%) or 5,400 (14%) cGy. The inferior borders of the RT fields used were the lower of either at 3-5 cm inferior to the lowest gross tumorous volume (GTV) or at the inferior border of the obturator foramina (IBOF). The anal sphincters were contoured retrospectively and dose distributions were determined using dose volume histograms. Results: The mean anal sphincter volume was 5.1 cm 3 (range, 1.3 – 11.2 cm 3 ). On average, the center of anal sphincter was 18.6 mm inferior to the IBOF. In 53 cases (82.8%), the anal sphincter was completely inferior to the IBOF. In the remaining 11 cases (17.2%), the anal sphincter was either overlapping the IBOF (10 cases; 15.6%), or completely superior to the IBOF (1 case; 1.7%). On average, the center of anal sphincter was 39 mm inferior to the lowest edge of GTV. In 19 cases (30%), the anal sphincter was completely outside of the inferior border of the RT fields. In another 10 cases (16%), the sphincter was more than 4 cm away from the GTV inferior border but was partially treated. The mean dose delivered to anal sphincter was 2795 cGy (range, 245–5441 cGy). Lower mean doses delivered to the anal sphincters were noted for larger distances from the center of the anal sphincter to the GTV. Conclusions: Minimizing dose delivered to anal sphincter is possible, especially for upper or mid rectal cancer. However, meticulous planning to define the inferior border of RT fields is necessary. Future studies will focus on the correlation between RT dose distribution to the anal sphincter and anal-rectal dysfunction.
Prognostic Irrelevance of Vitamin D Insufficiency in Myeloproliferative Neoplasms and De Novo Myelodysplastic Syndromes
Authors: Animesh Pardanani, Matthew T. Drake, Christy Finke, Terra L Lasho, Shaina A Rozell, Thitina Jimma, Ayalew Tefferi
Journal: Blood (2011)
Prevalence of venous thromboembolism (VTE) among patients (pts) with acute leukemia (AL) prior to treatment.
Authors: N. V. Luong, S. Faderl, H. Kantarjian, K. Vu
Journal: Journal of Clinical Oncology (2011)

6595 Background: Cancer and cancer treatment increases the risk of VTE. However, the association of AL and VTE is unknown. Methods: We performed a retrospective chart review to determine the prevalence of VTE prior to treatment and recurrence of VTE. Medical records of 1295 pts [299 acute lymphoblastic leukemia (ALL) pts and 996 acute myelogenous leukemia (AML) pts] at MD Anderson Cancer Center between November 1999 and May 2005 were reviewed and analyzed. All computations were conducted using Stata version 11. Results: Of the 1295 pts with AL, the overall prevalence of VTE was 1.6% (22 VTE cases, median age: 63.5 yrs). The prevalence was 2.3 % (7/299) and 1.5% (15/996) among ALL and AML patients, respectively. Two of 14 AML pts were M3-AML. In the ALL group, 1 pt had VTE approximately 1 month prior to ALL diagnosis (dx), and 6 pts developed VTE at the time of ALL dx. In the AML group, 3 pts had VTE prior and 12 pts developed VTE at AML dx. Pulmonary embolism occurred in 4 pts [3 had associated lower extremity (LE) deep venous thrombosis (DVT)]. Nine pts (7 AML, 2 ALL) had upper extremity DVTs, and 9 pts (6 AML, 3 ALL) had LE DVTs. Recurrent VTE occurred in 5/22 (23%) pts. In a univariate model, pts with baseline platelet (plt) count ≤ 50 x 109/L or 50-99 x 109/L had a protective effect on VTE development, with 69% and 85% less likely to develop VTE than pts who had plt count 100-349x 109/L, respectively. Pts with prior history of VTE were 17.8 times (95%CI: 6.3-49.27) more likely to develop a VTE than pts without a prior VTE history. Pts with phlebitis were 4.8 times (95%CI: 1.07-21.9) more likely to develop VTE than pts without phlebitis. In a multivariate model, significant predictors of VTE were baseline plt count and prior history of VTE. Overall survival did not differ between pts who developed VTE prior to treatment versus others. Conclusions: Acute leukemia pts have a high prevalence of VTE. Occurrence of VTE prior to initiation of chemotherapy was not associated with poor prognosis. Further studies should be conducted to establish guidelines for the prevention and management of VTE in pts with leukemia.
Understanding causes for distress among cancer patients.
Authors: S. A. Taylor, M. A. Amin, L. Marzinski
Journal: Journal of Clinical Oncology (2011)

e19700 Background: While both cancer diagnosis and treatments are associated with substantial distress, the exact cause of distress is not well known. Understanding the specific cause for distress is the first step towards alleviating it and improving patient satisfaction and quality of care. Methods: From Feb 2 to Apr 7, 2007, office patients were asked to rate their distress objectively using the validated distress scale developed by the National Comprehensive Cancer Network (NCCN). Importantly, this scale quantifies distress by various domains (eg, emotional issues or physical symptoms). We now report the various causes of distress among cancer patients. Results: A total of 246 patients completed the distress questionnaire. We observed a wide variation in distress scores (ranging from 0 to 10), with a mean (± SD) score of 3.04 (± 2.71). We observed several common causes of distress: work or school or financial issues (15-25%), worry, depression, sadness (15-35%), physical symptoms (potentially related to chemotherapy) such as dry skin, dry nose, tingling in hands or feet, sleep difficulty, constipation or chronic pain (10-25%). (Table 1) Conclusions: Distress among cancer patients is very common. We identified several specific causes of distress related to emotional issues, or physical symptoms, which may be amenable to simple interventions such as anti-depressants, counseling, pain control, laxatives or anti-histamine agents. Use of the NCCN’s distress scale among cancer patients, helps identify specific causes of distress to direct simple interventions to alleviate distress among cancer patients and improve care. Domain Variable Percentage (%) Practical issues Insurance 10 Work/school 16 Transportation 7 Child care 2 Financial 22 Facility 5 Housing 10 Relationship Dealing with partner 8 Dealing with children 11 Other 7 Emotional Worry 31 Fears 17 Sadness 21 Depression 19 Nervousness 21 Spiritual Relating to God 3 Loss of faith 1 Physical symptoms Pain 25 Nausea 11 Sleep 25 Getting around 16 Bathing/ dressing 9 Breathing 8 Mouth sores 5 Eating 11 Indigestion 9 Constipation 11 Diarrhea 8 Changes in urination 7 Fevers 1 Skin dry/itchy 19 Nose dry/congested 15 Tingling in hands/feet 16 Feeling swollen 12 Sexual 7 Appearance 14
Phase I dose-escalation study of the investigational Aurora A kinase (AAK) inhibitor MLN8237 as an enteric-coated tablet (ECT) formulation in patients with nonhematologic malignancies.
Authors: S. Sharma, R. Kurzrock, L. Gouw, D. S. Hong, K. Jones, X. Zhou, H. Shi, H. Fingert, G. S. Falchook
Journal: Journal of Clinical Oncology (2011)

3094 Background: The investigational drug MLN8237 is an orally available, selective AAK inhibitor with early clinical trials using a powder in capsule (PIC) formulation in a range of tumor types. This phase I/II study was conducted in pts with nonhematologic malignancies using an ECT formulation. Safety and PK from phase I are reported. Methods: Eligible pts were age ≥18 y with advanced, nonhematologic malignancies, ECOG PS 0–1, measurable disease by RECIST and ≤2 prior cytotoxic chemotherapy regimens. MLN8237 ECT was administered orally BID for 7 d + 14 d of rest (21-d cycles). Doses were escalated in a 3+3 design based on dose-limiting toxicities in cycle 1 until maximum tolerated dose (MTD). AEs were graded according to NCI-CTCAE v4.0. Results: 17 pts were treated, 5 are ongoing, and enrollment is complete. Median age was 58 y (range 34–81), and frequent tumor types included sarcoma (n=4), and ovarian (n=2). Pts received a median of 2 cycles (range 1–8) at either 10 (n=1), 20 (n=3), 40 (n=4), 50 (n=6), or 60 mg (n=3) BID. The MTD was identified as 50 mg BID. A DLT of G4 febrile neutropenia was reported at 50 mg BID. No further DLTs were reported, but at 60 mg BID, 3 pts had G4 neutropenia. The most common AEs were neutropenia (47%) and fatigue (47%). Neutropenia was the most common G≥3 AE (41%), and was generally reversible. There were 17 treatment-emergent SAEs in 9 pts; neutropenia was the only SAE to occur in >1 pt (n=2). Preliminary PK data were available in 14 pts. Following oral administration, MLN8237 ECT was absorbed at a moderate rate with an overall median Tmax of 3 h and dose-related increase in exposure over 10–50 mg BID. Mean t½ was ~20 h following multiple dosing. Conclusions: In pts with advanced non-hematologic malignancies, the data suggest that the toxicity profile of MLN8237 was predictable, generally tolerable, and manageable, and these results support a recommended phase II dose of 50 mg BID for 7 days in a 21-day cycle using the ECT formulation. The ongoing phase II portion is investigating MLN8237 in lung, breast, head/neck and gastroesophageal malignancies.
Retrospective review of FOLFIRI with or without bevacizumab (bev) for patients (pts) with metastatic colorectal cancer (mCRC): Reviewing a single-center standard clinical practice.
Authors: Jean Alfred Maroun, Horia Marginean
Journal: Journal of Clinical Oncology (2014)

434 Background: Use of bev with FOLFIRI proved, in clinical trials, to be well tolerated and clinically effective in mCRC pts. In this single-center retrospective review we assess outcomes of mCRC pts on standard first-line treatment with FOLFIRI alone and FOLFIRI bev in routine care. Methods: Patients treated with FOLFIRI at TOHCC from Jan 1, 2004 to Aug 10, 2010 on a first-line mCRC were followed until August 10, 2012. According to bev availability three groups of pts can be identified: treated with FOLFIRI bev and treated with FOLFIRI alone before and after bev availability (Sept 5, 2005). Results: Of 526 pts, 470 (89%) were eligible; 176 (37%) treated with FOLFIRI with bev and 294 (63%) with FOLFIRI alone—127 (43%) before and 167 (57%) after bev availability. At the start of FOLFIRI therapy there was no significant difference among the 3 groups: median age 62 (range 36-83), 61 (32-81), 64 (28-85) years, male 54%, 72%, 64%, respectively. Pts treated with FOLFIRI bev received a median 19 cycles (range 2-78) of FOLFIRI and a median of 15 cycles (range 2-63) of bev; 89 (51%) discontinued bev before FOLFIRI. Pts treated with FOLFIRI alone received a median 12 cycles (range 3-35) before bev availability and 13 cycles (2-48) after. Toxicity was responsible for at least 1 dose adjustment in 146 (83%) pts on FOLFIRI bev and 215 (73%) pts on FOLFIRI alone. Bev was held in 95 (54%) pts; once 35%, twice 25%. The median time off bev was 37 days. Median PFS was 17 months (95%CI 13-20) for patients treated with FOLFIRI bev. When we consider patients treated with FOLFIRI before bev availability median PFS was 13 mo (95%CI 10-17) and 14 mo (95%CI 10-16) when we consider pts post bev availability. Over a period of 3 years the survival rates in three groups of pts (FOLFIRI bev, FOLFIRI alone before bev availability, FOLFIRI alone post bev availability) were 1 year 90%, 77%, and 78%; 2 years 67%, 49%, and 56%; 3 years 54% , 31%, and 44%. Conclusions: Pts treated with FOLFIRI bev received more cycles of chemotherapy however with more dose adjustments. There is a relevant benefit in terms of PFS and a more substantial advantage in terms of 1, 2 and 3 years survival rates with the addition of bev to FOLFIRI.
CYC202 (seliciclib or R-Roscovitine), a small molecule cyclin dependent kinase inhibitor, overcomes drug resistance via down-regulation of Mcl-1 in multiple myeloma (MM)
Authors: N. S. Raje, S. Kumar, T. Hideshima, A. Roccaro, K. Ishitsuka, D. Chauhan, N. C. Munshi, S. R. Green, K. C. Anderson
Journal: Journal of Clinical Oncology (2005)

6532 Background: Cell cycle is positively regulated by a family of proteins called cyclin dependent kinases (CDKs). CDK inhibitors have the potential to induce apoptosis in cancer cells. CYC202 is a potent inhibitor of CDKs currently undergoing phase II clinical testing in lung cancer, breast cancer, and B cell hematologic malignancies. Methods: We studied the in vitro activity of CYC202 in multiple myeloma (MM). MM cell lines and patient derived cells were used. Co-culture systems with patient derived bone marrow stromal cells (BMSCs) were used to recapitulate the in vivo host-tumor cell/BM interaction. Studies of cell cycle and apoptosis were performed and molecular mechanisms of drug activity were delineated. Results: Our data demonstrates that CYC202 has potent cytotoxicity against MM cells that are both sensitive (MM1.S, RPMI 8226, U266, OPM2) and resistant (MM1.R, Dox-40, LR5, MR 20) to conventional chemotherapy as well as primary MM patient cells. Cell cycle analysis demonstrated an increase in the apoptotic fraction of MM cells. Importantly, CYC202 triggered a rapid down-regulation of Mcl-1 transcription and protein expression independent of caspase cleavage. Co-culture experiments with BMSCs resulted in increased Mcl-1 expression associated with STAT3 phosphorylation, both of which were inhibited in a time and dose dependent manner with CYC202. To further characterize the molecular mechanism of Mcl-1 inhibition in our co-culture system, we demonstrate inhibition of interleukin-6 (IL-6) transcription and adhesion-mediated production of IL-6. Mcl-1 expression was only in part blocked by neutralizing antibody to IL-6, suggesting other possible mechanisms of Mcl-1 modulation by CYC202. CYC202 with Bortezomib and Doxorubicin demonstrated strong synergism in vitro, suggesting a role for combination therapies in MM. Conclusions: Our data demonstrates a molecular mechanism of activity of CYC202 in MM. Importantly, CYC202 overcomes drug resistance and is active even in the presence of BMSCs. These data provide the pre-clinical rationale for testing CYC202, alone and in combination, to treat patients with relapsed/refractory MM. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cyclacel Ltd.
Chronic myelomonocytic leukemia (CMML) associated with symptomatic pericardial effusion.
Authors: M. I. Ibrahim, P. G. Maslak, M. L. Heaney, M. S. George, R. J. Downey, M. S. Tallman
Journal: Journal of Clinical Oncology (2011)

6625 Background: CMML is a rare myeloid neoplasm which may possess the characteristics of both myelodysplastic and myeloproliferative disorders. Clinical manifestations may be protean. CMML is rarely associated with serous effusion in the pericardium, a phenomenon which is poorly understood. We report one patient with CMML with symptomatic pericardial effusion. Methods: Chart review of patient record including laboratory and pathology results. The retrospective chart review was approved by the MSKCC IRB. Results: Pt was a 63 y/o woman diagnosed with CMML in 7/2010, who presented with a white blood cell count (WBC) of 49,600/microliter, shortness of breath, and signs and symptoms consistent with impending cardiac tamponade. CT chest showed a large pericardial effusion and the pt was transferred to intensive care unit, where a subxiphoid pericardial window was formed. Approx. 700 cc of serosanguineous fluid was drained. Differential cell ct of the pericardial fluid showed 32% monocytes and 19% myeloid blasts. A review of the literature showed only 6 adult pts reported: a pt reported in 2000 (Corinna Strupp, Ulrich Germing et al. Pericardial Effusion in CMML: a case report and review of literature. Leuk Research 2000;24:1059); Mani et al. reported four patients with CMML and pericardial effusion (Sridhar Mani and Thomas P.Duffy. Pericardial Tamponade in CMML. Chest 1994;106;967-970); in 1993, Bradford et al. reported a single pt with CMML who also developed pericardial effusion (C R Bradford et al. Pericardial extramedullary haemopoiesis in CMML. J Clin Pathol 1993; 46: 674-675). Conclusions: CMML can be associated with isolated pericardial effusion, and in our pt who was previously untreated it was the first treatment-emergent disease manifestation. Patients with CMML who develop cardiopulmonary instability, should be evaluated for the presence of a pericardial effusion should be considered in the differential diagnosis. Extramedullary hematopoiesis has been documented in patients with CMML, most commonly in the skin and gingivae. However, the mechanisms involved in the development of extramedullary hematopoiesis, including pericardial effusion, are not well understood.
Validation of galectin-7 using backscattering interferometry.
Authors: Ian Roys Olmsted, Pierre P. Massion, Darryl J. Bornhop, Mohamed Hassanein, Megan Hoeksema
Journal: Journal of Clinical Oncology (2012)

15 Background: More than 60% of lung cancer patients are diagnosed with advanced disease due to a lack of early diagnosis tools. These patients are ineligible for surgical resection and have a poor prognosis. This situation could be avoided if we could quantify lung cancer specific biomarkers at sufficiently low concentrations, providing an indication of disease threat. Backscattering Inerferometry (BSI) is a label-free sensor with a simple optical train that is used to quantify biomarkers in complex matrices at picomolar to femtomolar levels. Here we demonstrate that BSI can enable lung cancer biomarker validation in complex, volume constrained samples and at detection limits significantly better than ELISA. Methods: A BSI dose response curve for Galectin-7 was constructed by incubating increasing concentrations (0-20 ng/mL) of recombinant galectin-7 with 100 ng/mL of polyclonal antibody. The samples were mixed at 300 RPM for 2 before being injected into the BSI instrument and measured in triplicate each day. All reagents used were obtained from a commercial ELISA kit. An ELISA dose response curve was similarly constructed using spiked serum and spiked plasma according to the manufacturer’s recommended procedure. Finally, 9 patient serum samples were quantified using BSI and ELISA for direct comparison of the two technologies. Results: BSI was used to quantify galectin-7 in spiked serum and patients samples. The lower limit of detection with standards was determined to be 0.5 ng/mL for ELISA in serum, 10 ng/mL for ELISA in plasma, and 0.04 ng/mL for BSI in serum. In the analysis of 9 patient serum samples, all were quantifiable using BSI, which enjoys low pg/mL detection limits, yet with ELISA only 5 samples contained a galectin-7 concentration high enough to be measured. In this small sample set there was a good correlation between disease state and galectin-7 concentration as measured by BSI. Conclusions: This study demonstrates that BSI is well-suited for biomarker detection and validation, having a greater dynamic operating range and much lower limits of detection than standard commercially available ELISA kits. Future work will focus on detecting other NSCLC biomarkers that are undetectable with currently available technology.
Robotic-assisted Ivor Lewis esophagectomy with or without neoadjuvant chemoradiation therapy for esophageal cancer.
Authors: Franz Omar Smith, Sarah Hoffe, Khaldoun Almhanna, Ravi Shridhar, Richard C. Karl, Kenneth Meredith
Journal: Journal of Clinical Oncology (2013)

117 Background: Neoadjuvant chemoradiation therapy (NT) has become standard of care for patients with locally advanced esophageal cancer. In selected patients, robotic-assisted Ivor Lewis esophagectomy (RAIL) is a safe and feasible operative strategy in the management of esophageal cancer. This study was designed to determine potential differences in peri-operative morbidity and short term outcomes in patients with esophageal cancer treated with RAIL with or without NT. Methods: A retrospective review of consecutive patients with esophageal cancer who underwent RAIL esophagectomy between October 2010 and June 2012 with and without NT was performed. Clinical and pathological variables were analyzed with two-sided student t-test assuming equal variance. Data were considered significant at a p-value &lt;0.05. Results: Eighty-nine patients underwent RAIL during the study period. Seventy-seven patients (87%) received NT and twenty-two patients did not (13%). The median age was 66 years (range 44 – 84) and the median BMI was 28 kg/m 2 (range 16.7 – 40.1). All patients had a R0 resection. There were no differences in the mean estimated blood loss (149 vs.153 mL; p = 0.52) and mean operative times (434 vs. 427 minutes; p = 1.0). There were no differences in the incidence of pneumonia or atrial fibrillation, lengths of stay in the ICU, or length of hospitalization. In total, there were two anastomotic leaks and one leak from the gastric conduit. The anastomotic leaks occurred in the group that did not receive NT and the gastric conduit leak occurred in the group that received NT. There were no mortalities in either group. There was no difference in the mean number of lymph nodes harvested in the NT group (22 ± 11 vs. 20 ± 8, p = 0.41). Conclusions: RAIL can be safely performed following neoadjuvant chemoradiation therapy.In this series there were similar perioperative, morbidity and short-term mortality outcomes in patients who received NT compared with RAIL alone. Longer follow-up is required in order to determine long term oncologic outcome.