tbuckley/cabot-search huggingface dataset:
Chemotherapy (CT) alone for epidural spinal cord compression (ESCC) from germ cell tumors (GCT).
Authors: C. Grommes, G. J. Bosl, L. M. DeAngelis
Journal: Journal of Clinical Oncology (2010)

2031 Background: Testicular GCT rarely causes ESCC. Most GCT metastases respond to CT but ESCC is usually treated with radiation therapy (RT). We investigated the use of CT alone to treat ESCC in these patients. Methods: This retrospective study included all patients with a histological diagnosis of a testicular GCT seen at MSKCC between 1998-2009. Patients with epidural metastasis were identified. Age, race/ethnicity, clinical features, histology, treatment, and outcome were analyzed. Results: There were 1079 patients with a GCT and 21 had ESCC (1.9%). Mean age was 33 years (range 14-59). Six patients had a seminoma and 15 a non-seminomatous GCT. Five patients had ESCC located in the C-spine, 10 in the T-spine, and 5 in the L-spine. The ESCC in 10 patients was treated with CT only. These patients developed ESCC a median of 51 months after initial diagnosis compared to a 73 months interval in those treated with RT and CT. The patient group receiving CT only was similar in their clinical presentation (back pain, motor and sensory deficits, incontinence, reflex abnormalities, and ambulation) and degree of ESCC on MRI to the group receiving RT and CT. Back pain improved in all patients after treatment. Clinical improvement was more likely in the CT alone group (90% versus 55%). Patients who received RT and CT had a higher percentage of non-seminomatous GCT (82% versus 60%), T-spine involvement (64% versus 40%), multifocal ESCC (36% versus 0%), and a higher proportion of failed CT regimens (45% versus 30%). Median survival after ESCC was 62 months for those treated with CT alone versus 68 months for those receiving CT and RT. Conclusions: This is the largest series of patients with ESCC caused by testicular GCT. The study demonstrates that CT alone is sufficient to treat ESCC effectively, particularly in those expected to have chemosensitive disease. No significant financial relationships to disclose.
Hypothyroidism secondary to radiation and chemotherapy in pediatric Hodgkin's Disease
Authors: M. L. Metzger, M. M. Hudson, J. Wilimas, M. Krasin, K. Larry, S. C. Howard
Journal: Journal of Clinical Oncology (2004)

8532 Background: Hypothyroidism in pediatric Hodgkin's disease (HD) survivors is reported due to neck irradiation (RT). An effect of chemotherapy remains controversial. Methods: Records of 467 newly diagnosed HD patients treated on different regimens between 1979 and 2002 were reviewed. Radiation dose to the neck and clinical features were recorded. Hypothyroidism was defined as a TSH > 4.7 or need for thyroxine therapy. The cumulative incidence of hypothyroidism was calculated using SAS version 8.2 and treating relapse, death, or second cancer as competing risks. Results: Of 457 evaluable patients, 261 (57%) were male, 378 (83%) white; median age was 15.2 years (range 3 –21.7) and median time of thyroid follow up was 4.5 years (range 0.1 to 22.3). Treatment regimens used during this period were COPP, COPP/ABVD, VAMP, VEPA, VAMP/COP or Stanford V combined with RT or RT alone in selected patients with localized disease. The Table shows the cumulative incidence of hypothyroidism at 5 and 10 years according to the RT dose given. Patients in Group1 had no RT, a 7% incidence of hypothyroidism, and served as the reference group. Comparison of Group3 and Group4 shows a significant difference in cumulative incidence of hypothyroidism (p=0.004). Age at treatment was not a risk factor for developing hypothyroidism. The relative risk for females compared to males of developing hypothyroidism was 1.6 (p=0.0002) while the relative risk for blacks of developing hypothyroidism was 0.36 (p=0.0015) compared to non-blacks.Conclusions: Chemotherapy added to moderate (21–26.9Gy) dose RT, resulted in a higher incidence of hypothyroidism than high dose RT (>27Gy) alone. Table: Hypothyroidism Cumulative Incidence according to Radiation Dose / Chemotherapy No significant financial relationships to disclose.
Fewer live births occur with letrozole than standard therapy for unexplained infertility, study shows
Authors: Susan Mayor
Journal: BMJ (2015)

Ovarian stimulation with letrozole results in fewer multiple pregnancies but a lower rate of live births than standard therapy with gonadotrophin or clomiphene, a study reported in the New England Journal of Medicine has shown.1

Researchers enrolled 900 couples with unexplained infertility from 12 US centres to the study, which was funded by the National Institutes of Health and other research institutions. The women, who were aged 18 to 40 and had at …
Serum pepsinogens and gastrin-17 and gastric and esophageal cancers: A long-term prospective study
Authors: F. Kamangar, J. Ren, C. C. Abnet, P. R. Taylor, S. M. Dawsey, Y. Qiao
Journal: Journal of Clinical Oncology (2008)

4561 Background: Recent studies have suggested that gastric atrophy, as indicated by low serum pepsinogen I/ pepsinogen II ratio (PGI/II ratio), is associated with increased risks of esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma. The association between serum gastrin and upper gastrointestinal tract cancers has been minimally studied. We tested the association between serum PGI/II ratio and serum gastrin-17 (G17) and risk of upper gastrointestinal tract cancers in a long-term prospective study. Methods: Cases and controls for this study were selected from a cohort of 29,584 residents of Linxian, China, who were followed from 1985 to 2001. For this study, we selected a random sample of esophageal squamous cell carcinomas (N = 300), gastric cardia adenocarcinomas (N = 600), all diagnosed gastric non-cardia adenocarcinomas (N = 363), and a random sample of the entire cohort (N = 1,050). Baseline serum PGI, PGII, and G17 were measured using enzyme-linked immunosorbent assays (ELISA). Cox regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (95% CI). Results: The HR (95% CI) for low serum PGI/II ratio were 1.56 (0.99 - 2.47), 2.12 (1.42 - 3.16), and 2.72 (1.77 - 4.20) for ESCC, cardia cancer, and noncardia cancer, respectively. The corresponding HR (95% CI) for G17 were 0.92 (0.69 - 1.21), 1.04 (0.81 - 1.34), and 1.50 (1.12 - 2.00), respectively. Serum anti-H. pylori positivity did not modify the results. Conclusion: Our results confirm recent findings that suggest that gastric atrophy is associated with higher risk of ESCC and gastric cardia adenocarcinomas. The mechanisms responsible for these associations should be investigated. No significant financial relationships to disclose.
Response to the combination of cetuximab, bevacizumab and irinotecan (cetux/bev/iri) in patients (pts) previously treated with 3rd-line panitumumab, following disease progression on oxaliplatin, irinotecan and a fluoropyrimidine
Authors: E. E. Tubb, M. Jacobs, E. P. Mitchell
Journal: Journal of Clinical Oncology (2007)

14586 Background: There are 2 monoclonal antibodies (mAbs) targeting the epidermal growth factor receptor (EGFR) available for the treatment of advanced metastatic colorectal cancer- panitumumab, a fully human IgG2 kappa mAb and cetuximab, a chimeric IgG1 mAb. The ability to administer one agent after prior treatment with the other is unknown and further, not trivial given the possibility for cross-reactivity. In our institution, we evaluated an exploratory treatment schedule. Methods: We report the status of 8 colon cancer pts treated with panitumumab monotherapy as 3 rd -line and subsequently treated with cetux/bev/iri as salvage chemotherapy. All were initially treated on 1 of 2 multicenter phase 2 studies enrolling pts on panitumumab; all pts had documented progressive disease (PD) during or after fluoropyrimidine and adequate doses of irinotecan and oxaliplatin, and low (1–9%) or high (=10%) EGFR tumor membrane staining by IHC. Pts received panitumumab 6 mg/kg q2weeks (wks) until PD or intolerability. Following PD they received bev 5 mg/kg and iri 250 mg/m 2 q2wks and cetux 400 mg/m 2 , then 250 mg/m 2 qwk. The endpoint was time to tumor progression (TTP). Results: The 8 pts (2 men, 6 women) were among those enrolled in 1 center. Median age was 67 years (range 51–81); 6 pts had low and 2 pts had high EGFR tumor expression. The median number of cycles of panitumumab was 8 (range 3–14); 1 had a partial remission (PR) for 24 wks, 4 had stable disease (SD) for a median of 14 wks (range 12–16) and 3 pts had PD. Following PD on panitumumab pts received cetux/bev/iri. The median number of cycles was 13 (range 2–17+); 1 had a PR of 20 wks, 6 had SD for a median of 20 wks (range 8–32+) and 1 pt had PD after 4 cycles. Median TTP was 24 wks (range 7–36+). Conclusion: In these 8 pts, prolonged TTP to the combination of cetux/bev/iri was observed following PD on panitumumab and standard chemotherapy. This combination may provide a potential treatment strategy for these heavily pretreated pts with advanced colon cancer. However, further investigation is needed. No significant financial relationships to disclose.
Use of serum VEGF (SVEGF) levels to predict outcome of esophageal cancer (EC) patients undergoing preoperative chemoradiation (CRT).
Authors: F. De Vita
Journal: Journal of Clinical Oncology (2010)

4140 Background: Increased sVEGF concentrations have been correlated with outcome in many solid tumors, including EC. 72 pts with untreated locally advanced EC undergoing CRT were evaluated to elucidate the association of sVEGF levels with clinico-pathologic parameters andoutcome. Methods: Blood samples were obtained from pts before and after CRT. Fifty age- and sex-matched healthy blood donors were used for determination of normal sVEGF levels. sVEGF levels were determined using an ELISA kit. Results: Pretreatment sVEGF levels were significantly higher in pts than in the control group (455.2 ± 108 vs. 85.1 ± 21 pg/mL; p < 0.001). sVEGF levels were significantly higher in EUS stage III than EUS stage II disease (655.7 ± 87.3 vs. 381.2 ± 48.7 pg/mL; p = 0.0025). Preoperative sVEGF levels were not correlated with age, gender, PS, histology, grading, tumor location and platelets. All pts were evaluable for CRT response: basal sVEGF levels in responding group (pCR + pPR: 49 pts) were significantly lower than those of non-responding group (SD + PD:23 pts): 315.3 ± 95.3 vs. 689.58 ± 132.1 pg/mL; p = 0.0010). The mean follow up time was 31.2 ± 15.3 months. The 3-years OS for all pts was 37%: pts with VEGF levels higher than 455.2 pg/mL had a lower 3-year OS rate than pts with lower VEGF levels (61% vs. 17%; p < 0.001). The 3-years DFS rate for all pts was 32%: pts with VEGF levels higher than 455.2 pg/mL had a lower 3-year DFS rate than pts with lower VEGF levels (70% vs. 19%; p < 0.0014). Conclusions: Our results suggest that sVEGF levels correlate with tumor burden and are useful in predicting the outcome of EC patients undergoing preoperative CRT. No significant financial relationships to disclose.
Preliminary Studies of the Effectiveness of Local Irradiation in the Induction of Lymphoid Tumors in Mice&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;
Authors: Henry S. Kaplan, M. D.
Journal: JNCI Journal of the National Cancer Institute (1949)

Preliminary Studies of the Effectiveness of Local Irradiation in the Induction of Lymphoid Tumors in Mice Get access Henry S. Kaplan, M. D. Henry S. Kaplan, M. D. Department of Radiology, Stanford University School of Medicine, San Francisco Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 10, Issue 2, October 1949, Pages 267–270, https://doi.org/10.1093/jnci/10.2.267 Published: 01 October 1949 Article history Received: 25 July 1949 Published: 01 October 1949
Abstract P217: Metabolic Effects of a Nutrient-Dense High Fiber Supplement
Authors: Michele Mietus-Snyder, Mark K Shigenaga, Jung H Suh, Swapna V Shenvi, Ashutosh Lal, Tara McHugh, Donald Olson, Joyce C McCann, Ronald M Krauss, Bruce N Ames
Journal: Circulation (2012)

Achieving recommended dietary intakes of vitamins and minerals, fiber, and other health-promoting small molecules, such as fruit polyphenolics and essential fatty acids, is difficult, even for healthy adults consuming generally good diets. We assessed the hypothesis that short term consumption of a comprehensive nutrition bar can favorably impact metabolic biomarkers linked to future disease risk. Methods: An approximately 100 kcal nutrition bar containing a vitamin, mineral, and docosahexaenoic acid (DHA)-fortified polyphenolic-rich whole food matrix composed of fruit, walnuts, and dark chocolate blended with insoluble and soluble fiber was developed. Pooled results are presented from 3 pilot trials in which 25 generally healthy adults (15 F, 10 M) were enrolled in 2-wk interventions to study the effect of twice-daily consumption of the bar on plasma lipoprotein subfractions (ion mobility analysis), and redox status (thiol amino acids) in addition to conventional biomarkers associated with dyslipidemia, insulin resistance, and inflammation. All variables were continuous, and paired t-tests were used to test for significant change between baseline and follow-up measures. Results: Mean HDL cholesterol increased by 6.6 + 9.7% ( p = 0.001), predominantly due to a rise in the large buoyant HDL2b subclass which rose from 1665.9 ± 1017.7 to 2089.4 ± 1197.6 nmol/L ( p &lt; 0.0001; 28% increase). Plasma triglyceride and LDL cholesterol levels did not change significantly but there was a trend towards increased LDL peak particle diameter (p = 0.086). Mean plasma homocysteine decreased from 12.6 ± 6.4 to 10.2 ± 3.7 µM (p=0.006, 19.2% decline). Measures of insulin resistance and inflammation did not change. Weight remained stable despite intake of 200 additional daily calories. Participants reported a significant decrease in hunger on an analog scale and compensatory decreased intake of other foods. Summary: Twice daily consumption of a low-calorie complete nutritional supplement increases satiety and large HDL particle concentrations within 2 weeks without weight gain.
Characterization of carrier females and affected males with X-linked recessive nephrolithiasis.
Authors: S C Reinhart, A G Norden, M Lapsley, R V Thakker, J Pang, A M Moses, P A Frymoyer, M J Favus, J A Hoepner, S J Scheinman
Journal: Journal of the American Society of Nephrology (1995)

X-linked recessive nephrolithiasis (XRN) was described in a large kindred in which nephrolithiasis; proximal tubular dysfunction, proteinuria, nephrocalcinosis, and renal failure occur only in males. Carrier females are asymptomatic, but formal studies of them have not been done. The gene for XRN has been mapped to the pericentromeric region of the X chromosome, close to the loci for several eye disease genes. We studied six affected males, 13 carrier females, and 25 normal members of this family including 7 females whose genetic haplotype predicted them to be carriers. Studies were done in the Clinical Research Unit on a diet containing 400 mg of calcium and 2 g of sodium, and by an additional outpatient urine collection was obtained on a 1-g calcium intake. Hypercalciuria occurred in five of six affected males, 4 of 12 carrier females, and three of seven predicted carriers. Significant proteinuria was present in all affected males and in no other subjects. Low-molecular-weight proteinuria was present in all affected males: the excretion of alpha 1-microglobulin exceeded normal by 3- to 14-fold, of beta 2-microglobulin exceeded normal by 100- to 400-fold, and of retinol-binding protein exceeded normal by 1,000- to 3,000-fold. The excretion of these proteins was less strikingly elevated in carrier females, but the excretion of alpha 1-microglobulin was abnormal in 9 of 15 carriers, beta 2-microglobulin was abnormal in 12 of 15, and retinolbinding protein in was abnormal 12 of 13, and this pattern was similar in predicted carriers. The urinary concentrating ability was abnormal in four affected males with renal insufficiency but normal in all other subjects. Urinary wasting of potassium, phosphorous, and glucose occurred infrequently, and no subject was hypouricemic. Formal ophthalmologic studies were normal in five affected males. Thus, the most consistent urinary abnormalities in XRN are hypercalciuria and low-molecular-weight proteinuria, the latter of which appears to be a marker for the carrier state.
Updated results of phase I trial of sorafenib (S) and bevacizumab (B) in patients with metastatic renal cell cancer (mRCC)
Authors: J. A. Sosman, K. T. Flaherty, M. B. Atkins, D. F. McDermott, M. L. Rothenberg, W. L. Vermeulen, K. Harlacker, A. Hsu, J. J. Wright, I. Puzanov
Journal: Journal of Clinical Oncology (2008)

5011 Background: We conducted a Phase I trial of S and B to study inhibition of the vascular endothelial growth factor (VEGF) pathway at both the ligand (B) and receptor (S), and platelet derived growth factor receptor (S) in mRCC. Methods: Pts with measurable mRCC, adequate organ function, and PS 0–1 were eligible. Cohorts of at least 6 pts were enrolled to define the MTD and DLT of B given IV q 2wks and S po QD on 28-day cycles. Response and toxicity were assessed after 2 cycles. Initial doses were S at 200mg BID and B at 5 mg/kg with modification based on observed toxicities. High dose pyridoxine was administered in some cohorts attempting to ameliorate hand-foot syndrome (HFS) symptoms. Results: 47/48 pts completed their 1st response evaluation. Median age was 61 yrs (35–83 ); M/F: 40/8; PS: 0/1= 32/16; 41 clear cell, 7 non-clear cell; 41 had prior nephrectomy; 6 prior IFN and 9 prior IL-2. The table summarizes dose levels explored and toxicities. Toxicities included PUD, rash, weight loss, proteinuria, hypertension, and HFS with no evidence of microangiopathy. Three pts had late vascular events after >12 mos of treatment (TIA, AMI) Pryidoxine did not ameliorate HFS. Only 4/48 pts stopped therapy due to toxicities. MTD was S 200 mg PO QD and B 5 mg/kg IV Q 2 wks. 46/48 pts were evaluable for response. Twenty-one of 46 (46%) had PR by RECIST, including 2 pts with sarcomatoid RCC. Additionally, 23 pts had SD and 1 PD at 1st eval.with 1 dying from disease progression prior to 1st eval. Median time to progression (TTP) was 11.2 months with 10 pts (21%) progression-free at 18 mos. Conclusions: While toxicities led to a MTD with lower doses of each agent, B + S had impressive antitumor activity based on both OR and TTP. B appears to significantly increase S-related toxicity, especially HFS. We have opened a Phase II trial with correlative and PK studies for S and B to investigate the mechanism of enhanced S-related toxicity. The combination has been incorporated into E2804 (BeST) a multi-arm Phase II trial of combination regimens. The study was supported by U01 CA099177 and CTEP-NCI. # pts Bevacizumab (mg/kg) Sorafenib (mg) Pyridoxine Supplement # with DLT Description of DLT 12 5 200 bid None 4 Gr 3 HFS, rash 6 3 200 qd None 0 NA 6 5 200 bid 300 mg qd 1 Gr 3 HFS 6 5 400 bid 300 mg qd 2 Decreased PS, anorexia 6 10 200 bid 300 mg qd 2 Gr 3 HFS, Gr 3 skin rash 6 10 200 qd None 2 Gr 3–4 HTN 6 5 200 qd None 0 NA Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer, Genentech Bayer, Genentech Bayer
Prognostic and predictive value of HER2, PR, ER, and KI67 in the PACS01 trial comparing epirubicin-based chemotherapy to sequential epirubicin followed by docetaxel
Authors: H. H. Roche, F. M. Penault-Llorca, C. Sagan, M. Lacroix-Triki, Y. Denoux, V. Verriele, J. Jacquemier, M.-C. Baranzelli, F. Bibeau, A.-L. Martin
Journal: Journal of Clinical Oncology (2005)

605 Background: To define the value of biopathological parameters as prognostic and predictive markers in patients (pts) with node positive, operable breast cancer involved in the phase III trial PACS 01. Methods: We retrospectively analyzed the prognostic value of ER, PR, HER2, and Ki-67, in 1190 patients with primary operable node positive breast cancer patients treated with either Arm A: 6 cycles of FEC100 (595 pts) or arm B: docetaxel 100 mg/m replaced FEC100 for the last 3 cycles (595 pts), extracted from the data base of 1999 pts enrolled in PACS01 trial. This subgroup was similar to the whole population of the trial in terms of age, node involvement, and ER positivity. A panel of pathologists centrally and blindly reviewed the cases. All four markers were tested by immunohistochemistry centrally. Results were correlated to clinical out come at a median follow up of 59.7 months (SABCS 2004). Results: Using 5 years of follow-up data, we showed i) for arm B, a better DFS: unadjusted log rank (log) p =0,023 and OS: log p=0.015, ii) an association between HER2 overexpression and/or amplification (DFS: log p =.0002; OS log p<.0001), high Ki-67 (DFS: log p <0.0001; OS: log p <0.0001) and worse outcome. ER+ /PR + and ER-/PR+ pts had a better outcome than pts whose tumors were ER-/PR-or ER+/PR- (p<0.001 for both). Her2 positivity was not a poor prognosis factor for pts in arm B which is suggesting its role as a putative predictive factor of response to sequential treatment. Conclusion: This retrospective investigation demonstrated that HER2, PR, ER, and Ki-67 expressions had significant prognostic value for N+ patients. Furthermore, HER2 could be used to discern groups of individuals who could benefit from the use of sequential chemotherapy with anthracycline and docetaxel. More results will be presented at the meeting. No significant financial relationships to disclose.
Molecular markers that predict for recurrence in men with margin-positive localized prostate cancer.
Authors: P. Yip, J. Kench, K. Rasiah, R. Benito, C. Lee, S. Henshall, R. Sutherland, L. Horvath
Journal: Journal of Clinical Oncology (2010)

4650 Background: Men with positive margins after radical prostatectomy (RP) for localized prostate cancer (PC) have a 40-50% biochemical relapse rate. Adjuvant radiotherapy after RP improves biochemical progression-free survival in patients with positive surgical margins, extraprostatic extension (EPE) and/or seminal vesicle involvement (SVI) but is associated with a 5-fold increase in bladder and rectal toxicity. There is an urgent need to identify new prognostic markers to better define the group of patients who would benefit from multimodality therapy. Methods: Nuclear b-catenin, membranous secreted frizzled-related protein 4 (sFRP4), AZGP1 and macrophage inhibitory cytokine-1 (MIC-1) have previously been identified as molecular markers of outcome in localized PC by our group. From these previous studies, 186 localized PC cases had positive margins. Using Kaplan-Meier and Cox Proportional Hazards analyses, we assessed the association between these four molecular markers and biochemical relapse in men with margin-positive localized PC. Results: Among the published cohort of 330 men with localized prostate cancer, we identified 186 with positive margins post RP; 53% had preoperative PSA >10 ng/ml, 72% EPE, 24% SVI and 57% RP Gleason score ≥ 7. There were 67/186 (36%) men who received adjuvant therapy (46 hormonal treatment and 21 radiotherapy). Three of the four molecular markers predicted for biochemical relapse on univariate analysis: AZGP1 (p=0.009), membranous sFRP4 (p=0.03) and MIC-1 (p=0.04). Only absent or low AZGP1 expression (HR 2.2, 95% CI 1.2-4.0, p=0.01) was an independent predictor of recurrence in margin positive localized PC when modeled with preoperative PSA (HR 1.6, 95%CI 0.8-3.1, p=0.2), EPE (HR 1.5, 95%CI 0.7-3.3, p=0.2), SVI (HR 1.4, 95%CI 0.7-3.0, p=0.4), Gleason score ≥ 7 (HR 1.3, 95%CI 0.6-2.9, p=0.5) and adjuvant treatment (HR 1.4, 95%CI 0.7-2.6, p=0.4) in a multivariate analysis. Conclusions: AZGP1 is a potential molecular marker for biochemical relapse in men with localized PC and positive margins after RP. Routine assessment of this biomarker may lead to better selection of patients who will benefit from post-RP radiotherapy and avoid morbidity in men at less risk. No significant financial relationships to disclose.