tbuckley/cabot-search huggingface dataset:
Validation of the pretreatment neutrophil-lymphocyte ratio as prognostic factor regarding cancer-specific, metastasis-free, and overall survival in a European cohort of patients with renal cell carcinoma.
Authors: Georg C. Hutterer, Martin Pichler, Caroline Stoeckigt, Thomas F. Chromecki, Tatjana Stojakovic, Silvia Golbeck, Armin Gerger, Karl Pummer, Richard Zigeuner
Journal: Journal of Clinical Oncology (2013)

410 Background: The neutrophil-lymphocyte ratio (NLR) has been proposed as an indicator of systemic inflammation response and data from previous studies report controversial results about its independent prognostic role in non-metastatic renal cell carcinoma (RCC). Thus, we decided to evaluate the prognostic significance of NLR in a large cohort of RCC patients. Methods: Data from 843 consecutive non-metastatic RCC patients, operated with radical nephrectomy or nephron sparing surgery between 2000 and 2010 at a single tertiary academic center, were evaluated retrospectively. Pre-treatment NLR was calculated one day before surgical intervention. Patients were categorized according to a NLR cut-off value of 3.2. Cancer-specific–, metastasis-free–, as well as overall survival were assessed using the Kaplan-Meier method. To evaluate NLR’s independent prognostic significance, a multivariate Cox regression model was performed for all three endpoints. Results: An increased NLR was associated with several well established prognostic factors including tumor size, tumor grade, and histologic tumor necrosis (all p&lt;0.05). Although an increased NLR was statistically significantly associated with poor outcome for all clinical endpoints (p&lt;0.001), multivariate analysis identified an increased NLR as an independent prognostic factor for overall (HR=1.58, 95% CI=1.12-2.20, p=0.008), but not for cancer-specific (HR=1.55, 95% CI=0.89-2.70, p=0.116), nor for metastasis-free survival (HR=1.37, 95% CI=0.88-2.14, p=0.160). Conclusions: Risk prediction for cancer-related endpoints using NLR does not seem to add independent prognostic information to other well established prognostic factors in patients with non-metastatic RCC. Regarding patients’ overall survival, an increased NLR represented an independent risk factor, which might reflect a higher risk for cardiovascular, infectious, as well as for gastrointestinal morbidities and mortalities.
A phase II study: Combination of sorafenib with docetaxel and cisplatin in the treatment of metastatic or advanced unresectable gastric and gastroesophageal junction (GEJ) adenocarcinoma (ECOG 5203)
Authors: W. Sun, M. E. Powell, P. O’Dwyer, R. H. Ansari, A. B. Benson
Journal: Journal of Clinical Oncology (2008)

4535 Background: Adenocarcinoma of the stomach and gastroesophageal junction (GEJ) is a highly virulent disease and remains a leading cause of death worldwide. Alterations of the ras/raf pathway may contribute to the pathogenesis of the disease. Sorafenib is a potent inhibitor of raf tyrosine kinase and of several receptor tyrosine kinases (RTKs) that are involved in tumor progression (e.g. VEGFR-2, VEGFR-3, PDGFR-β ). The combination of docetaxel and cisplatin is commonly used in the treatment of gastric cancer. This study tested the efficacy and tolerability of combining sorafenib with docetaxel and cisplatin in patients with metastatic or advanced unresectable gastric/GEJ adenocarcinoma. Methods: Sorafenib 400 mg bid orally, docetaxel 75 mg/m2 IV on day 1, cisplatin 75 mg/m2 IV on day 1, administerd on 21 day cycles. Results: Forty-four patients (35 pts [79.5%] with metastatic and 9 pts [20.5%] with locally advanced unresectable disease) were included with median age of 60 (28–86) and M/F of 37/7. The median number of treatment cycles was 4.5 (1–20+). The median PFS was 5.8 months (90% CI [5.4 - 7.2]), and the median OS 14.9 months (90% CI [8.6 - 15.2]). Seventeen pts have shown an objective response (RR 38.6%, 90% CI [26.3%, 52.2%]), including one complete response (CR 2.3%). The most common grade 3 or higher toxicity was neutropenia (26 pts, 90% CI [45.6%, 71.6%]). Two patients died on study with an event attributed to treatment as the ‘probable’ cause (one died from infection but with only mild [grade 1] neutropenia, the other died of GI hemorrhage). Other common grade 3 or higher toxicities were fatigue, anorexia, hand-foot reaction, nausea, diarrhea and dehydration. Conclusions: The results of the combination of sorafenib with docetaxel and cisplatin in metastatic/advanced gastric/GEJ adenocarcinoma are very encouraging. Further phase III study with the combination should be considered. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer/Onyx, sanofi-aventis sanofi-aventis Bayer, sanofi-aventis
Referral patterns to palliative care: An inpatient snapshot study.
Authors: Aaron Kee Yee Wong
Journal: Journal of Clinical Oncology (2016)

119 Background: Research suggests that palliative care referrals are not done as often or as early as required. In order to address potential barriers to referrals, current referral patterns need to be explored. We sought to identify the adequacy of palliative care referrals in hospital. Methods: We undertook a retrospective, cross-sectional study, censoring all inpatients on a single day from the largest tertiary hospital in the state. Each file was reviewed, and patients were identified as “palliative” based on the Gold Standards Framework criteria. Patients were followed for 3 months or until discharge, whichever was earlier. Results: Of the 873 inpatients, 134 patients were identified as palliative. Of the 95 patients who required formal palliative care input, only 28% were referred (27 patients). Specialty medical teams were the best at referring, whereas surgical teams were the worst. Only 50% of patients requiring terminal care and 10% requiring community palliative care (CPC) were referred. Conclusions: Alarmingly, most patients requiring palliative care were not referred (72% unreferred), most of these requiring CPC. Excluding CPC, still only 58% of patients requiring palliative care were referred. This is concerning, given data that shows that early integration of palliative care provides better quality of life, reduced depressive symptoms, and longer median survival. This suggests that either the severity of their illness is not recognised by treating teams, or that there is a lack of awareness in CPC, or possibly a lack of confidence in discussing it. There is a need for better referrals to palliative care, especially to CPC. Greater education is required, targeting the importance of early referrals. As used in this study, the Gold Standards Framework criteria can help identify patients who require referrals.
Prognostic factors in elderly patients with grade 3 gliomas.
Authors: A. Satra, N. Hashemi-Sadraei, H. S. Bawa, D. M. Peereboom, G. Stevens, L. A. Rybicki, J. H. Suh, M. A. Vogelbaum, R. Weil, G. Barnett, M. S. Ahluwalia
Journal: Journal of Clinical Oncology (2011)

2093 Background: Anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), and anaplastic oligoastrocytoma (AOA) are the major histological categories of WHO grade 3 gliomas. There is very limited data on specific prognostic factors in elderly patients (pts) with grade 3 gliomas, therefore we undertook this project to identify prognostic factors in elderly grade 3 glioma pts. Methods: After obtaining IRB approval, the Cleveland Clinic Brain Tumor and Neuro-Oncology Center’s database was used to identify pts with histologically confirmed grade 3 glioma ≥65 years of age at time of diagnosis. Multivariable analysis was conducted with use of a Cox proportional hazards model and a stepwise selection algorithm that used p<.10 as the criteria for entry and p<0.05 as retention in the model to identify independent predictors of survival. Results: Charts of 96 pts (52% of whom were men) diagnosed between 1994 and 2009 were reviewed. The median age at presentation was 71 years (range: 65-88 years). 65% of pts had biopsy only, 15 % had gross total resection (GTR), 1% had near total resection (NTR), and 19% had subtotal resection (STR). 92% of pts underwent radiation, 48% had concurrent chemotherapy. Median overall survival (OS) of AA, AOA, AO was 5.7 months, 22.5 months and 65.2 months respectively. Median OS for all pts was 6.7 months. On multivariable analysis, two factors were identified as independent predictors of overall survival, histology (AA vs. AO, p<.022) and Karnofsky Performance Status (p<.018). Conclusions: Poor performance status and AA were associated with higher risk of mortality. Risk factors for mortality Variable HR 95% CI P value Univariable analysis Gender Male vs female 0.84 0.53-1.34 0.47 Race (n=94) Caucasian vs Non-Caucasian 0.51 0.12-2.11 0.35 Age at diagnosis Per 10-year increase 1.14 0.76-1.70 0.53 KPS pre-RT (n=66) 30-60 vs. 90-100 2.44 1.15-5.18 0.021 70-80 vs. 90-100 2.22 1.11-4.42 0.023 Seizure at presentation Yes vs. No 0.53 0.31-0.90 0.018 Motor Signs Yes vs. No 1.43 0.90-2.27 0.13 Histology (n=94) Astro vs. Oligo 4.54 1.73-11.95 0.002 Mixed vs. Oligo 1.86 0.56-6.14 0.31 Type of surgery Biopsy vs. resection 1.82 1.10-3.00 0.020 Multivariable analysis KPS 30-60 vs. 90-100 2.57 1.18-5.61 <0.018 70-80 vs. 90-100 1.90 0.95-3.82 0.07 Histology Astro vs. Oligo 4.23 1.22-14.60 0.022 Mixed vs. Oligo 3.10 0.68-14.19 0.14
Safety profile of thoracoscopic esophagectomy for esophageal cancer compared with traditional thoracotomy from the results of JCOG0502: A randomized trial of esophagectomy versus chemoradiotherapy.
Authors: Isao Nozaki, Ken Kato, Hiroyasu Igaki, Yoshinori Ito, Hiroyuki Daiko, Masahiko Yano, Harushi Udagawa, Satoru Nakagawa, Masakazu Takagi, Hiroshi Okabe, Tetsuya Abe, Tetsu Nakamura, Jun Hihara, Yasushi Toh, Yasunori Akutsu, Yuichi Shibuya, Junki Mizusawa, Kenichi Nakamura, Haruhiko Fukuda, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2014)

82 Background: Esophagectomy for esophageal cancer via the thoracoscopic approach (TA) is expected to reduce the extent of trauma compared with traditional thoracotomy (TT). However, there have been few prospective studies comparing perioperative complications between TA and TT after esophagectomy. Therefore, this study aimed to clarify whether TA is a safe procedure with regard to morbidity and mortality using the data of patients (pts) who underwent esophagectomy in the JCOG0502 trial. Methods: The JCOG0502 trial is a currently on-going randomized trial including a patient preference arm of esophagectomy versus chemoradiotherapy for treatment of clinical stage I esophageal cancer. The primary analysis of overall survival is planned in 2018. In this trial, thoracic squamous cell carcinoma, adenosquamous carcinoma, and basaloid carcinoma of stage T1b/N0/M0 were eligible. When pts were randomized to surgery or selected surgery, esophagectomy with D2–3 lymphadenectomy was performed. TA or TT was selected at the surgeon’s discretion. Perioperative complications were defined as adverse events of grade 2 or greater as per CTCAE v3.0. Results: A total of 379 pts (11 randomized and 368 in the patient preference arm) were enrolled between December 2006 and February 2013 from 37 institutions, and 211 pts underwent surgery. Of these 211 pts, TA was performed in 101 pts while TT was performed in 110 pts. Blood loss was less in the TA group than in the TT group (median, 293 vs. 410 mL, respectively), and the surgical duration was longer in the TA group than in the TT group (median, 510 vs. 398 min). The proportion of intraoperative complications was similarly low in both groups. However, postoperative anastomotic leakage, pneumonia, and atelectasis were less common in the TA group than in the TT group (7%, 8%, and 11% vs. 14%, 17%, and 22%). Moreover, the proportion of recurrent nerve palsy was similar among both groups (15% vs. 16%). Each group had one in-hospital death. Conclusions: This study indicated that TA did not increase morbidity or mortality after esophagectomy and can be safely performed with risks comparable to those with TT. Clinical trial information: UMIN000000551.
Expression of pre B cell leukemia transcription factor (PBX) is correlated with prognosis and survival of patients with non-small cell lung carcinoma
Authors: Y. Qiu, Y. Tomita, E. Morii, K. Aozasa
Journal: Journal of Clinical Oncology (2008)

22222 Background: Pre B cell leukemia transcription factor 1 (PBX1) is a transcription factor for valosin-containing protein (VCP), which is involved in invasion and metastasis of cancers. To examine the prognostic significance of PBX1 and other PBX members, PBX2 and PBX3, in non-small cell lung cancer (NSCLC), the present study was designed. Methods: Expression of PBX1, PBX2, and PBX3 was immunohistochemically examined in 206 NSCLC patients (132 men and 74 women) with ages ranging from 35 to 78 (median, 62). Staining intensity of tumor cells was categorized as equal to or stronger expression than endothelial cells in less than 20% (score 1) or more than 20% (score 2). Results: PBX2 but not PBX1 and PBX3 nuclear expression correlated with high expression of VCP. Univariate analysis revealed score 1 PBX1 cytoplasmic expression, score 2 PBX2 nuclear expression, score 2 PBX2 cytoplasmic expression to be poor prognosticators for overall and disease-free survival. Multivariate analysis revealed that PBX1 cytoplasmic expression, visceral pleural invasion, and tumor size as independent prognostic factors for disease-free survival, and PBX1 cytoplasmic expression, PBX2 cytoplasmic expression, VCP expression, age, and visceral pleural invasion for overall survival. Conclusions: The present study showed that increased expression of PBX2 and decreased expression of PBX1 were poor prognosticators for NSCLC. Close correlation between PBX2 nuclear expression and VCP expression suggested the role of PBX2 as a transcription factor controlling VCP expression. No significant financial relationships to disclose.
Knowledge of and adherence to breast cancer screening guidelines in Hodgkin lymphoma survivors treated with mantle radiation.
Authors: L. L. Dietrich, M. K. Meinking, V. L. McHugh, M. A. Mathiason
Journal: Journal of Clinical Oncology (2011)

e19509 Background: Female Hodgkin Lymphoma (HL) survivors treated with mantle radiation have 3-10 times the risk of the general population for developing breast cancer. Forty percent are unaware of their increased risk and receive follow-up (f/u) care solely with a primary care provider (PCP) and may not receive the National Comprehensive Cancer Network (NCCN) recommended f/u. We aimed to assess the knowledge and practice of PCPs within the Gundersen Lutheran Health System (GLHS) toward breast cancer screening recommendations in this population. Methods: A review of medical records (MR) of female HL patients treated with mantle radiation from 1980-2005 was completed. Cancer and survival rates were calculated using Kaplan-Meier statistics. An email survey assessing knowledge on care for HL survivors was distributed to GLHS PCPs. Results: MR review of 61 patients found a mean age of diagnosis for HL of 34± 18 years (range, 6 to 82 years) and a mean f/u period of 11 years (range, 0.2-29.7years). Only 2 patients (3%) had received a breast MRI in follow-up care. Of those eligible for screening mammography per NCCN with 10 years f/u (n=23), 83% had one in the previous 2 years. Of those with >5 years of f/u, 5 (23.5%) were diagnosed with breast cancer. A survey of 87 PCPs found that 61% were aware that HL survivors had an increased risk of breast cancer, but only 36% were aware of complete recommended f/u care; 59% were aware of all but breast MRI recommendations and 66% stated they were “uncomfortable” treating female patients with a history of HL. Fewer than 50% of PCPs who care for female patients with HL inform these patients of increased breast cancer risk. Reasons for this included lack of awareness of the risk or assumption the risk was explained by an oncologist. Conclusions: We confirmed a high rate of breast cancer in female survivors of HL and lack of compliance with breast cancer screening guidelines. GLHS PCPs had average knowledge of the increased breast cancer risk and limited knowledge of the NCCN breast cancer screening guidelines in HL survivors. These results emphasize the need for cancer survivorship care that provides information for patients and PCPs in this and likely other aspects of long-term survivor f/u.
A first-in-class HDM2-inhibitor (JNJ-26854165) in phase I development shows potent activity against multiple myeloma (MM) cells <i>in vitro</i> and <i>ex vivo</i>
Authors: T. Stühmer, J. Arts, P. King, M. Page, K. Bommert, E. Leo, R. C. Bargou
Journal: Journal of Clinical Oncology (2008)

14694 Mutation of p53 in MM is often associated with refractory disease, indicating the important role of p53 in MM. HDM2 is a key regulator of p53, mediating its rapid degradation. Blockade of HDM2 provides an attractive treatment strategy to restore/enhance p53 activity. HDM2 binds also other partners (e.g. p73, E2F1, p21) and may thus affect MM growth through different mechanisms. Therefore, we explored the antitumoral/proapoptotic capacity of a novel first-in-class HDM2 inhibitor, JNJ-26854165, that recently entered Phase I development, In Vitro and Ex Vivo (primary MM samples) to assess its potential value for treatment of MM. Kill curves for JNJ-26854165 or Nutlin-3a were established for a panel of MM cell lines and apoptosis was measured by Annexin V-FITC/PI staining. Primary MM cells were prepared from diagnostic bone marrow (BM) aspirates by CD138-positive selection and kept in co-culture with BM stromal cells prior to challenge with either drug. MM cell lines showed different sensitivities for apoptosis induction by JNJ-26854165. 6 lines were sensitive (EC50 < 8 μM, EC90 < 20 μM) and 3 lines comparatively insensitive (EC50 > 15 μM, EC90 not reached at 25 μM). While all insensitive cell lines are known to express mutant p53, this was also true for two of the sensitive lines. In contrast, all p53 mutant cell lines were insensitive to Nutlin-3a. JNJ-26854165 (10 μM) reduced the viability of primary MM cells by over 50% in 9/18 samples. At 20 μM, 9/10 (JNJ- 26854165) vs. 6/9 (Nutlin-3a) MM samples showed less than 50% viability. Interestingly, two Nutlin-3a resistant samples were highly sensitive to JNJ-26854165. JNJ-26854165 was shown to be effective against MM In Vitro and Ex Vivo. This compound may represent a promising approach to restore p53 function and to potentially impact other HDM2 dependent pathways. While the activity pattern suggests a distinct role of p53 status for response, sensitivity of some p53 mutant and Nutlin-3a resistant samples points towards involvement of additional mechanisms, and allow for use in p53 mutated MM. JNJ-26854165 may open a novel treatment strategy for MM, specifically for aggressive disease with altered p53 status. Phase I development is currently ongoing in the clinics. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Ortho Biotech Ortho Biotech
Loco-regional outcomes of a population-based cohort of rectal neuroendocrine tumors.
Authors: Erica S Tsang, Yarrow Jean McConnell, David F. Schaeffer, Caroline Speers, Hagen F. Kennecke
Journal: Journal of Clinical Oncology (2016)

668 Background: Optimal management of rectal neuroendocrine tumors (NETs) is not well defined. We characterized the clinicopathologic features, loco-regional, and systemic management of a population-based cohort of rectal NETs. Methods: Patients diagnosed with rectal NETs from 1999-2011 were identified from British Columbia provincial databases. NETs were classified as G1 and G2 tumors with a Ki-67 ≤ 20% and/or mitotic count ≤ 20 per high power field. Results: Of 91 rectal NETs, median age was 58 (IQR 48-65) years and 35 (38%) were male. Median tumor size was 6 (IQR 4-8) mm. Median overall survival was 164.7 months, with 3 patients presenting with stage IV disease. Treatment included local excision (n = 79), surgical resection (n = 6), and pelvic radiation (n = 1; T3N1 tumor). Final margin status was positive in 17 (20%) cases. Local relapse occurred in 8 (9%) cases, and one relapse to bone 13 months after T3N1 tumor resection. Univariate analysis demonstrated an association between local relapse and T classification, Ki-67, mitotic count, grade, and perineural invasion (p&lt; 0.01), but not N or M classification, or lymphovascular invasion. Local relapse was not associated with surgical management or margin status. Of 3 patients with metastatic disease, two received systemic management, with capecitabine and temozolomide. Conclusions: Rectal NETs generally presented with small, early tumors and were treated with local excision or surgical resection without pelvic radiation. [Table: see text]
The prognostic impact of body mass index (BMI) in early breast cancer (BC) patients (pts)
Authors: M. S. Iyikesici, U. Kefeli, G. Basaran, F. Dane, M. Ekenel, P. F. Yumuk, N. S. Turhal
Journal: Journal of Clinical Oncology (2005)

882 Background: High BMI has been associated with poor outcome in breast cancer patients Methods: We analyzed the impact of BMI on the survival outcome of 273 pre and postmenopausal BC pts who received adjuvant systemic therapy between 1998–2004 in our department. We also recorded the clinical, pathological and treatment characteristics and analyzed the relation of these parameters with BMI. Results: The median age was 51(23–85). The median follow up was 29 months (3–107).The median height, weight and BMI were 159cm (145–175), 66kg (39–117), 26,6 (17,7–54,5) respectively. The BMI was <25 in 40%, between 25–30 (overweight) in 33% and >30 (obese) in 27% pts. Fifty-five (n=146) % of pts were postmenopausal, 55% pts had stage 3, 29% pts had stage 2 disease. Pathologically, 58% pts had node positive disease, 88% had grade 2–3 tms, 86% had invasive ductal carcinoma, 74% had ER and/or PgR positive tms. Seventy-six (26%) pts had breast conserving surgery, 96% pts received adjuvant chemotherapy (CT) (5% received CMF and the others received anthracycline-based CT), 68% received adjuvant radiotherapy (RT). Among 186 pts with ER and/or PgR, one pt received anastrozole and the rest received tamoxifen after completion of CT and RT. In univariate analysis, a high BMI (overweight and/or obese) was more frequent in postmenopausal pts (p=0.00). In multivariate analysis none of the clinical, pathological factors, BMI, height and weight were found to have a significant impact on DFS and OS. The 5yr-DFS was 82% and OS was 90%. There was no significant difference between the DFS and OS of pts who have high BMI (overweight and/or obese) and those with BMI <25. Conclusions: High BMI is known as an important risk factor for development of BC, particularly for postmenopausal pts. In our study even though the majority of the postmenopausal pts have a high BMI compared to premenopausal pts we could not detect a significant survival impact of high BMI. No significant financial relationships to disclose.