tbuckley/cabot-search huggingface dataset:
Polymorphisms of interleukin (IL)-1β and the risk of epithelial ovarian cancer
Authors: H. P. Lee, W. Ju, J. W. Kim, N. H. Park, Y. S. Song, S. B. Kang, H. S. Saw, S. C. Kim
Journal: Journal of Clinical Oncology (2005)

5036 Background: The aim of this investigation was to analyze the association between a single nucleotide polymorphism (SNP) in the interleukin (IL)-1β-511 and ovarian cancer risk. Methods: The blood samples of 98 epithelial ovarian cancer patients and 321 non-cancer control subjects who managed at Seoul National University Hospital from 1999 to 2002 were collected. Polymorphisms in IL1β-511 were determined using TaqMan method. Allele frequency and genotype distribution in the ovarian cancer group were compared with those of the control group to determine whether this polymorphism elevates the susceptibility to ovarian cancer. Thereafter association between this polymorphism and the survival in patients with epithelial ovarian cancer was evaluated. Results: There was significantly elevated risk of ovarian cancer among women IL1β-C511T polymorphism (TT + CT) compared with CC genotype (OR:1.12, 95% CI:1.05∼1.20). In subgroup analysis within the cancer group, the frequency of epithelial ovarian cancers over that of borderline malignancies was higher in TT+CT group with marginal significance (OR: 1.07 95% CI:1.01∼1.13). However the survival analysis showed no difference between two groups which means this polymorphism does not affect the prognosis. Conclusions: In conclusion, this study shows that polymorphism in IL-1β-C511T is significantly associated with susceptibility to ovarian cancer. No significant financial relationships to disclose.
Prediction of survival in patients with muscle-invasive bladder cancer (MIBC) by neutrophil (NTP) infiltration in benign lymph nodes (LNs).
Authors: Sumanta Kumar Pal, Wei Liang, Richard Jove, Bertram E. Yuh, Kevin Chan, Timothy G. Wilson, David James McConkey, Seth P. Lerner
Journal: Journal of Clinical Oncology (2013)

273 Background: In preclinical models, NTPs appear to establish a pre−metastatic niche that fosters the invasion of metastases (Kowanetz et al PNAS 2010). This observation still requires clinical validation in MIBC. Methods: Benign LN tissue was obtained from patients (pts) who had undergone cystectomy and LN dissection for documented MIBC. Immunohistochemical (IHC) staining for CD15, a NTP marker, was performed for the entire cohort. Phosphorylated signal transducer and activator of transcription 3 (pSTAT3), vascular endothelial growth factor receptor−1 (VEGFR1), and CD68 (a macrophage marker) were further assessed in an initial cohort (detailed subsequently) via IHC. Positively staining cells were counted and averaged over 8 high power fields (hpfs). Pts were stratified by the median cell count for each biomarker. Analyses of overall survival (OS) were performed using the Kaplan−Meier method and log−rank test. Results: In an initial cohort of 19 pts who had received no neoadjuvant chemotherapy (NC), a median CD15 count of 284/hpf was noted. Median OS was higher in those pts with low CD15 as compared to high CD15 (158.7 mos v 36.9 mos, P=0.02). Median OS was also improved in those with high pSTAT3 v low pSTAT3 (not reached v 106.4 mos, P=0.04), but no difference was noted in OS in groups stratified by clinical stage, VEGFR1 staining, or CD68 staining. To determine if the prognostic value of CD15 staining was retained in pts with exposure to NC, the cohort was expanded to include an additional 36 pts who had received either preoperative GC (n=17) or MVAC (n=19) chemotherapy. In this group, no significant difference in OS was noted based using the previously applied CD15 cutoff. Conclusions: NTP recruitment to benign LNs may be prognostic of OS in pts with MIBC who have not received NC. pSTAT3, a putative mediator of NTP recruitment, may play a role in this phenomenon. VEGFR1 and CD68, which may mediate pre−metastatic niche through a different mechanism, do not predict OS in our dataset (Kaplan et al Nature 2005). Bolstered by these findings, the prognostic value of NTP recruitment will be examined prospectively in SWOG 1011, a trial comparing limited v extended LN dissection in pts with MIBC.
Thymidylate synthase expression and pemetrexed therapy in NSCLC.
Authors: A. G. E. Silva, J. T. Cole
Journal: Journal of Clinical Oncology (2011)

e18068 Background: Pemetrexed was the first chemotherapy to demonstrate histology dependance in the treatment of metastatic non-small lung cancer (NSCLC). These is thought to be influenced by the expression of thymidylate synthase (TS). Our objective was to analyze patients diagnosed with metastatic NSCLC at our institution from 2005 to 2007 that were treated with Pemetrexed, and identify the role of TS expression in predicting responses. Methods: Patients diagnosed with NSCLC were identified and data was extracted and analyzed. Patients who received pemetrexed as part of the treatment had their specimen studied for TS expression by immunohistochemistry (IHC). A TS score was given based on its intensity x extent of cells (J Int Med Res 2010, 38:484-497). Scores equal to and below 5 were considered negative while those above were considered positive. Results: Four hundred and thirty charts were reviewed and 70 identified patients received palliative chemotherapy, of those, 28 received pemetrexed. Median age was 65 (46-81). Seventy five percent of patients had definitive histology, adenocarcinoma being the most common. The overall response rate (ORR) for first line therapy was 40%, with a median time to progression (TTP) of 5 months. The general response rate for patients receiving Pemetrexed as second or third line was 28% (8/28). Of the 28 patients, only 16 had tissue available for staining. The response rate was 20% (2/10) in the TS overexpressed group and 50% (3/6) in the TS negative group. Conclusions: Despite the small number of cases, TS expression appears to predict response rates in patient with NSCLC treated with pemetrexed. Larger controlled trials are needed to support this data. Responders Nonresponders RR TS overexpressed 2 8 20% TS negative 3 3 50%
Comparative analysis of neoadjuvant chemotherapy versus primary debulking surgery in advanced epithelial ovarian cancer
Authors: S. J. Sirop, S. Saha, D. Iddings, M. Ghanem, N. Dutt, J. Metz, D. Wilson, D. Weise, M. L. Arora, T. Singh, D. Eilender
Journal: Journal of Clinical Oncology (2008)

16596 Background: Primary debulking surgery (DS) has been used to achieve Optimal CytoReduction (OCR) in advanced epithelial ovarian cancer (OvCa). Survival has been directly related to the residual disease after surgery. The impact of neoadjuvant chemotherapy (NAC) is controversial, hence, a study was undertaken to evaluate impact of NAC on the surgical outcome, survival and recurrence of the disease compared to primary DS followed by adjuvant chemotherapy (AdjC). Methods: A retrospective analysis was undertaken in 86 consecutive patients (pts) diagnosed with advanced OvCa (stage IIIC and IV). Forty six pts had bulkier disease and were treated with NAC followed by DS and AdjC and 40 pts were treated with primary DS followed by AdjC. Carboplatin and Paclitaxel based chemotherapy was used in 89% of pts treated with NAC and in 79% of pts treated with primary DS. Data were collected regarding demographics, survival, recurrence and surgical outcome. Results: There was no difference in the percentage of stage IIIC and IV pts between the two groups (table 1). The median CA125 level at the time of diagnosis was 867 for pts treated with NAC vs 145 for pts treated with PDS (p=0.008). NAC was associated with decreased length of stay (8 vs 10 days) and less intra-operative blood loss (400 vs 700 cc, p=0.003). OCR was achieved in 93% of pts treated with NAC versus only 63% of pts treated with primary DS (p=0.001, table 1). Rates of recurrent/persistent disease were similar in both groups (63% vs 62%). There was improvement in the disease free survival (DFS) in both stage IIIC pts (22 vs 19 months) and stage IV pts (22 vs 16 months) treated with NAC as compared to pts treated with primary DS. Conclusions: NAC was associated with significantly higher rates of OCR, possibly leading to improved DFS despite having more extensive disease. Additionally, pts treated with NAC had less intra-operative blood loss and shorter length of stay Table 1: NAC versus PDS in advanced Epithelial Ovarian Cancer Variable NAC PDS P value Stage IIIC (# of pts/percentage) 38/82% 35/87% 0.56 IV (# of pts/percentage) 8/18% 5/13% 0.56 Surgery OCR (percentage) 93% 63% 0.001 LOS (days) 8 10 0.58 Blood loss (ml) 400 700 0.003 BR (# of pts/percentage) 26 (56%) 21 (53%) 0.82 CA 125 at diagnosis 867 145 0.008> Recurrence disease/Persistence disease (# of pts) 19/10 17/8 1 IIIC DFS (months) 22 19 0.25 IV DFS (months) 22 16 0.1 Recurrence sites Liver (# of pts) 5 2 Peritonium (# of pts) 8 9 Pelvic mass (# of pts) 5 4 Others (# of pts) 1 2 NAC, neoadjuvant chemotherapy; PDS, primary debulking surgery; LOS, length of stay; OCR, optimal cytoreduction; DFS, disease free survival; BR, bowel resection. No significant financial relationships to disclose.
Receipt of inguinal lymph node dissection in patients with T2 penile cancer: Results from the National Cancer Database.
Authors: Mohammed Haseebuddin, Elizabeth Handorf, Nikhil Waingankar, Yu-Ning Wong, Rosalia Viterbo, Richard Evan Greenberg, Robert G. Uzzo, Alexander Kutikov, Marc C. Smaldone, David Y. T. Chen
Journal: Journal of Clinical Oncology (2015)

383 Background: Per the NCCN guidelines, inguinal lymph node dissection (ILND) is recommended for patients with intermediate (T1b) or high (Any T2 or Grade 3) risk disease even in the absence of palpable inguinal nodes. Our objective was to assess temporal trends in utilization of ILND and to determine factors associated with the receipt of ILND using National Cancer Database (NCDB). Methods: The NCDB was queried for all patients diagnosed with T2 penile cancer from 1998-2011. Temporal trends for receipt of ILND were assessed. Adjusting for patient, demographic, and clinicopathologic characteristics, multivariable logistic regression models were used to examine the association between available covariates and receipt of ILND. Results: Of 2019 patients identified over the study period, 693 (34.3%) underwent ILND. Rates of ILND did not significantly improve from 1998 to 2011 (34.2 to 40.0%; p = 0.09). Significant differences were observed in patients undergoing ILND with respect to age (p&lt;0.001), Hispanic ethnicity (p=0.04), insurance status (p&lt;0.001), and facility type (p&lt;0.001), while no changes were seen with respect to race, income, education, urban/rural location, tumor grade, or Charlson co-morbidity score. Following adjustment, patients with high grade disease (OR 1.35 [CI 1.1-1.7]) and those treated at academic centers (OR 3.2 [CI 2.2-4.7]) were more likely to receive ILND, while patients &gt;70 years of age (OR 0.41 [CI 0.28-0.60]) were less likely to receive ILND. Conclusions: In the NCDB, less then 35% of patients with T2 penile cancer receive ILND and the rates have not significantly changed over the last decade. Referral of patients with this uncommon, highly morbid lethal disease to experienced centers may increase adherence to guideline recommended care.
Patient controlled methyphenidate [PCM] for cancer-related fatigue [CRF]: A randomized controlled trial
Authors: E. Bruera, L. Driver, V. Valero, L. Shen, J. Willey, J. L. Palmer, T. Zhang
Journal: Journal of Clinical Oncology (2005)

8045 Background Fatigue is the most common symptom associated with cancer and cancer treatment. PCM is well tolerated and has been found to be effective for fatigue in preliminary reports [Bruera E et al. J Clin Oncol, 2003; 21(23): 4439–4443]. The purpose of this double-blind study was to evaluate the effectiveness of methylphenidate as compared to placebo. Methods Advanced cancer patients with fatigue intensity ≥ 4 on a 0 to 10 numerical scale (0=no fatigue, 10=worst fatigue). and hemoglobin ≥10g/dl were included. Patients were randomized to receive PCM 5 mg every 2 hours as needed for 7 days [maximum 20 mg/day] or placebo. On day 8, all patients were offered to receive PCM for 4 weeks. Assessments included research nurse daily phone symptom and toxicity evaluation; weekly Edmonton Symptom Assessment System (ESAS), FACIT-F, Sleeping Pattern Assessment and overall effectiveness of the treatment. Results A total of 112 patients were randomized, 52 patients in PCM and 53 in placebo were evaluable. FACIT-F fatigue subscale and ESAS results at baseline and day 8 are shown in table below. FACIT-F (p=0.45) and ESAS-F (p=0.25) were not significantly improved by PCM in patients with severe fatigue ≥8. Patients reported PCM as ≥ moderately effective in 24/52 cases (46%) Vs 14/53 for placebo (26%, p=0.035). The mean difference in FACIT-F fatigue subscale, and ESAS-Fatigue between baseline, Day 15 and 36 were 15 ±11 (p<0.001), -3.5 ±2.8 (p<0.001); and 16±13 (p<0.001), -3.3 ±3 (P<0.001), respectively. No significant toxicities were observed. Conclusions: 1) Both PCM and placebo resulted in major clinical improvement; 2) PCM was not significantly superior to placebo after one week; 3) longer follow up studies are justified due to the increased response to PCM at days 15 and 36; 4) The role of daily research nurse phone call should be explored as a palliative intervention; 5) Double blind randomized controlled trials against placebo remain essential in symptom control research. No significant financial relationships to disclose.
A Randomized Phase II/III Study of R-THP-Cop Vs R-CHOP for Patients Younger Than 70 Years with DLBCL
Authors: Naoe Goto, Takuro Matsumoto, Yuhei Shibata, Junichi Kitagawa, Nobuhiro Kanemura, Yoshikawa Takeshi, Senji Kasahara, Hideko Goto, Kenji Fukuno, Takeshi Hara, Toshiki Yamada, Michio Sawada, Takeshi Takahashi, Koshiro Saito, Hisataka Moriwaki, Hisashi Tsurumi
Journal: Blood (2014)
Is contralateral prophylactic mastectomy (CPM) overused? Results from a population-based study.
Authors: Sarah T. Hawley, Reshma Jagsi, Steven J. Katz
Journal: Journal of Clinical Oncology (2012)

26 Background: The growing rate of CPM among women diagnosed with breast cancer has raised concerns about potential for over-treatment yet, little is known about factors that affect the decisions for this surgical treatment option. Methods: We surveyed 2,245 women newly diagnosed with breast cancer and reported to the Detroit and Los Angeles SEER registries from 6/05-2/07. We merged these data to SEER and re-surveyed them again approximately 4 years later (n=1,525). The primary outcome was receipt of CPM. We modeled surgical treatment decision making in two stages: any mastectomy (including CPM) vs. lumpectomy, and CPM vs. unilateral mastectomy (UM) among mastectomy-treated patients. The primary independent variable was clinically significant risk of developing contralateral disease (family history of at least 2 family members with breast cancer and/or a positive genetic test). We also evaluated the degree to which worry about recurrence drove initial treatment decisions (very vs. somewhat/not at all) and controlled for race/ethnicity, age, stage and SEER site. Results: Of the 1,446 women who had not had a recurrence of breast cancer by the time 2 survey, 35% considered CPM and 7.4% received it. Among those who received a mastectomy for the affected breast the figures were 53% and 19%, respectively. About 70% of patients who received CPM were clinically at very low risk for contralateral disease. 90% of those who got CPM reported being very worried about recurrence when making their treatment decision, compared to 80% of those who received UM (p&lt;0.05). Multivariate regression showed that receipt of CPM vs. UM was associated with having a family history (OR 5.1; 95% CI: 2.49-10.1) and a positive genetic test (OR: 10.93; 95% CI: 3.37-35.71), but was also associated with greater worry about recurrence (OR: 2.07; 95% CI: 1.01-4.51). Conclusions: Many women considered CPM despite the fact that very few of them had clinically significant risk of contralateral breast cancer. Most women who had CPM did not have a clinical indication for considering it and thus not expected to benefit in terms of disease free survival. More research is needed about the underlying factors driving decision-making for CPM.
Evaluation of 3 T pelvic MRI imaging in prostate cancer patients receiving postprostatectomy IMRT.
Authors: Vivek Verma, Hiram Alberto Gay, Ling Chen, Jeff M. Michalski, Robert L. Grubb
Journal: Journal of Clinical Oncology (2015)

242 Background: The purpose of the study was to evaluate the utility of a 3 T pelvic magnetic resonance imaging (MRI) in detecting a local recurrence in post-prostatectomy prostate cancer patients prior to receiving adjuvant or salvage intensity-modulated radiation therapy (IMRT). Methods: Ninety prostate cancer patients status post-prostatectomy with rising prostate-specific antigen (PSA) had a 3 T pelvic MRI prior to IMRT. The following variables were analyzed for predicting positive findings on MRI: initial presenting and initial post-op PSA, PSA at the time of imaging, PSA velocity, surgical margins, Gleason score, pathological stage, pre-RT digital rectal examination, and type of surgical prostatectomy. Results: The only significant variable predictive of a positive MRI was positive margins. Specifically, 15 of 46 (33 %) patients with positive margins had a positive MRI, while 5 of 44 (11 %) patients with negative margins had a positive MRI. In the MRI positive group, the location of the positive findings on MRI corresponded with the pathology report in 9 of 12 (75 %) cases. Conclusions: Post-prostatectomy patients with pathologic positive margins are three times more likely to have positive findings on a 3 T MRI. [Table: see text]
Capecitabine chemoradiation (X-RT) as neoadjuvant therapy for patients (pts) with locally advanced breast cancer (LABC) refractory to anthracyclines
Authors: M. F. Gaui, G. Amorim, R. Arcuri, G. Pereira, D. Moreira, C. Djahjah
Journal: Journal of Clinical Oncology (2005)

698 Background: In Brazil, LABC remains a serious health problem and represents approximately 30% of all newly diagnosed breast cancers. Anthracycline-based neoadjuvant therapy is a standard treatment, but approximately 30% of pts do not respond. For these refractory pts, there is no standard approach. In our institution, these pts receive RT, but almost half (46%) of pts are not rendered operable by RT alone. Because X is the reference treatment for patients with anthracycline- and/or taxane-pretreated MBC and X and RT are supra-additive in in vivo models, there is a clear rationale for evaluating X-RT in this pt group. Methods: Eligible pts had inoperable LABC refractory to FAC, ECOG PS 0, 1 and 2 and adequate bone marrow, renal and hepatic functions. Pts received RT 200cGy/d x5w (total dose 50Gy) plus X 850mg/m2 bid orally d1–14, q3w for 2 cycles. Pts underwent surgery, if appropriate, after completion of neoadjuvant therapy. Pts with hormone receptor-positive tumors received tamoxifen after surgery. Results: Baseline characteristics of the 24 pts enrolled between Jan 2003 and May 2004: median age 47 years (range, 26–70); median tumor size (after anthracyclines) 80cm2 (range, 36–357cm2); inflammatory carcinoma (21%); hormone receptor-positive tumor (54%). Two pts were excluded from this analysis as they received the incorrect X dosing regimen. 18 (75%) pts were operable after X-RT; 4 pts (25%) did not undergo surgery because of disease progression. Median tumor size after X-RT was 49 cm2 (range, 6–196 cm2). The median relative reduction in tumor size was 33%. After surgery, median residual tumor size was 11 cm2 (range, 0−72) and the median number of positive nodes was 2 (range, 0−27). Pathological complete response was observed in 4 (17%) pts. The most common treatment-related adverse events (all grade 1/2) were mucositis, diarrhea, nausea and emesis. There were no grade 3/4 or hematological/laboratory adverse events. Conclusions: Our data indicate that neoadjuvant X-RT is feasible, well tolerated and effective in pts with LABC refractory to FAC, rendering a high proportion (75%) of pts eligible for surgery. No significant financial relationships to disclose.
High Frequency of Monoclonal Immunoglobulins Exhibiting Natural Autoantibody-Like Activity in Patients with Multiple Myeloma and Waldenström Macroglobulinemia
Authors: Peggy Lymberi, Evangelos Terpos, Aikaterini Hatzioannou, Evangelos Eleutherakis-Papaiakovou, Apostolos Balafas, Efstathios Kastritis, Meletios Athanasios Dimopoulos
Journal: Blood (2011)
A phase II trial of high-dose cetuximab (cmab) plus irinotecan in patients (pts) with KRAS wild-type (WT) metastatic colorectal cancer (MCRC) who progressed on standard-dose cmab plus irinotecan.
Authors: A. M. Patta, J. A. McMahon, C. Samborski, M. Fakih
Journal: Journal of Clinical Oncology (2011)

598 Background: Prior clinical data suggest a dose-related response to cmab when combined with irinotecan in pts with KRAS WT tumors who do not develop grade 2 and above rash with standard cmab dosing. However, the investigation of higher doses of cmab in the setting of acquired or innate resistance to standard dose cmab has not been previously investigated. We conducted a phase II clinical trial of high-dose cmab plus irinotecan in KRAS WT pts with standard-dose cmab plus irinotecan – refractory disease to address this question. Methods: Pts with KRAS WT MCRC progressing on standard dose of cmab with irinotecan were eligible for study. Pts should have received a minimum of 6 weeks of prior standard dose cmab plus irinotecan and progressed within 4 weeks from the last dose. Cmab was administered at 500 mg/m 2 /week and irinotecan was administered at the same dose/schedule on which the patient previously progressed. 12-week PFS rate was the primary endpoint. Results: 8 pts were treated on study: median age 68 yrs (45-85), 5 pts were males, ECOG performance status was 1 in all 8 pts. Grade ≥ 3 toxicities consisted of hypomagnesaemia (4 pts), anemia (1 pt), leucopenia (1 pt), fatigue (1 pt), and diarrhea (1 pt). 6 pts achieved stable disease (with regression in target lesions noted in 3 pts). 12 week PFS rate is 5/8 and 18 week PFS is 4/8. 3 pts remain on study at 4.5, 5, and 8 months from enrollment. Conclusions: High-dose cmab/irinotecan is well tolerated except for hypomagnesemia. Encouraging prolonged disease stabilizations warrant further investigation of this approach in pts in KRAS WT population. Accrual is ongoing. [Table: see text]