tbuckley/cabot-search huggingface dataset:
The therapeutic effect of radiofrequency ablation(RFA) combining with/without chemotherapy in treating inoperable liver metastases of colorectal cancers
Authors: H. Pan, S. Wang, Y. Zheng, W. Jin
Journal: Journal of Clinical Oncology (2006)

13581 Background: Patients (pts) with colorectal cancer often develop metastases to the liver without extra hepatic spread. Surgery is the mainstay of treatment in these pts, but only 20% of pts are suitable for a surgical approach and some pts are reluctant to receive surgery. This study is to compare the therapeutic effect of RFA combining with chemotherapy and RFA alone in treating inoperable liver metastases of colorectal cancers. Methods: From May 2001 to July 2005, 26 patients have inoperable liver metastases derived from colorectal cancer whose primary tumors were resected. Among them, 14 pts received chemotherapy from 3 months before RFA to 3 months after RFA (13 pts received systemic chemotherapy with FOLFOX4, 1 pt received FOLFIRI), 12 pts didn’t receive any chemotherapy. The metastatic lesions in liver were evaluated by CT scan every 3 months. Results: Pts’ characteristics: m/f 18/8; median age 57 yrs (range, 31–68); primary tumor: colon 15, rectum 11; karnofsky’s score≥60. Median no. of LM: 2.2 (range, 1–7), mean size of LM: 24mm (range, 12–97 mm). The last time of follow-up visit is Nov 2005, 11 pts has been dead because of tumor progression, 14 pts is still living, and 1 patient is lost to follow-up. The main complication of RFA is fever, local pain and elevation of hepatic enzyme. Reactive pleural effusion occurred in 1 patient which disappeared after thoracentesis. No RFA related bleeding,pneumathorax,perforation of digestive tract,infection and needle track implantation occurred. The median survival,1-year survival rates and 2-year survival rates in all pts were 33 months, 83.8% and 64.1% respectively. The median time to local progression in all pts is 346 days. In the pts treated with RFA alone, the median survival,1-year survival rates and 2-year survival rates were 18 months, 71.3% and 38.2% respectively; in the pts treated with RFA and chemotherapy, they were 36.5 months, 92.9% and 85.1% respectively (P=0.0210). In the pts treated with RFA alone, the median time to local progression is 346 days; in the pts treated with RFA and chemotherapy, it is 317 days (P&gt;0.05). Conclusions: RFA Combining with chemotherapy is safe and may be more effective than RFA alone in treating inoperable liver metastases of colorectal cancer. No significant financial relationships to disclose.
Single institutional experience with rituximab in the treatment of B cell lymphoproliferative malignancies and autoimmune disorders
Authors: A. Jajeh, R. Catchatourian, J. Samuel, L. Hussein, B. Yim, J. Jacob-Sharma, P. Menini
Journal: Journal of Clinical Oncology (2007)

14150 Background: This is a retrospective analysis of usage of rituximab( Rituxan) a monoclonal antibodies against CD20 expressing B lymphocytes.The duration of period studied is from December first,2004 to July first,2006.This involved one single institution, John Stroger hospital of Cook County,chicago. Methods: A total of two hundred and thirty 230 treatment courses recorded.This involved a total of 208 patients.Some patients treated with more than one course in combination with different chemotheraputic agents. Results: . A total of 208 patients received Rituxan. Median number of doses is 8 (range 1–18). This include 92 patients with Diffuse large B-cell NHL, six patients with Burkitt’s lymphoma, thirty six patients with low grade NHL, three patients with mantle cell lymphoma, three patients with orbital lymphoma, three patient with AIDS related NHL, twenty seven patients with chronic lymphocytic leukemia CLL, ten patients with MALT/Gastric lymphoma, ten patients with ITP and 7 patient with warm autoimmune hemolysis, 7 patients given Rituxan as part of Rheumatoid Arthritis treatment. The complete response rate CR, near CR, partial response improved with adding Rituxan to 85% in Diffuse large grade Bcell lymphoma, one third high IPI score. Only 15% were refractory or relapsed after response. In low grade Bcell NHL 1/3 of patients received multiple prior treatments and the response rate were improved and disease progression was delayed. Most patients are of younger mean age 55 range (19–80).One third of patients recieved maintenace rituxan .Transfusion reaction occurred in less than 10%, severe leucopenia 3%, GI perforation in one patient, focal leukoencephalopathy PML in one with CNS involvement, tumor lysis syndrome occured in three patients, severe mucocutaneous reaction occured in one patient.One patient with RA and warm immune hemolysis died with sever pancytopenia after two months from recieving four doses. . Conclusions: This is a single institution experience where 60 percents are african american. This also show that Rituxan usage has became a standard therapy in Bcell lymphoproliferative malignancies.The improvement in response rate and progression free survival match other published phase III multicentered studies. No significant financial relationships to disclose.
Lung cancer survival with herbal medicine and vitamins: Ten-year follow-up.
Authors: M. F. McCulloch, M. Broffman, M. van der Laan, A. Hubbard, L. Kushi, A. M. Kramer, J. Gao, J. M. Colford
Journal: Journal of Clinical Oncology (2010)

e18130 Background: Improved outcomes are needed in non-small cell lung cancer. Up to 48% of patients use herbal medicine, but there has been little assessment of survival efficacy. Methods: We examined the effect of Chinese herbal/vitamin therapy (CHM+V) on survival in a consecutive case series of all non-small cell lung cancer patients (n = 239) seen in a 5-year period. Short-term CHM+V during conventional therapy was compared to long-term use. CHM+V combined with conventional therapy was compared to conventional alone using concurrent registry controls. Results: Long-term CHM+V compared to short-term reduced risk of death in stage IIIB by 83% (HR=0.17; 95% CI 0.08, 0.36) and stage IV by 72% (HR=0.28; 95% CI 0.12, 0.61). Combination therapy compared to conventional alone reduced risk of death in stage IIIA by 71% (HR=0.29; 95% CI 0.18, 0.46), stage IIIB by 66% (HR=0.34; 95% CI 0.19, 0.59), and stage IV by 78% (HR=0.22; 95% CI 0.12, 0.39). Median survival: Stage II, long term: 44.0 mos, short term: 53.0 mos; Stage IIIA, long term: 52.0 mos, short term: 21.9 mos; Stage IIIB, long term: 43.0 mos, short term: 7.0 mos; Stage IV, long term: 33.0 mos, short term: 8.0 mos. Conclusions: Long-term use showed better survival than short-term. Combination therapy improved survival compared to conventional alone. Prospective randomized trials are justified. Stage II Stage IIIA Stage IIIB Stage IV Herbs/vitamins: long vs. short term No. subjects (long term) 22 66 71 22 No. subjects (short term) 11 9 13 21 Propensity score Cox 0.82 [0.32, 2.11] 0.50 [0.22, 1.14] 0.17*** [0.08, 0.36] 0.28** [0.12, 0.61] MSM Cox regression 0.78 [0.39, 1.59] 0.82 [0.17, 3.94] 0.47 [0.10, 2.31] 0.26 [0.01, 4.25] Long-term herbs/vitamins + conventional therapy vs. conventional alone No. subjects (combination) 22 66 71 22 No. subjects (conventional alone) 1,202 2,598 1,974 6,079 Propensity score Cox, adjusted 0.91 [0.59, 1.42] 0.51*** [0.39, 0.67] 0.38***[0.28, 0.50] 0.31*** [0.20, 0.48] MSM Cox regression 0.91 [0.47, 1.35] 0.42*** [0.28, 0.55] 0.43*** [0.31, 0.56] 0.29*** [0.21, 0.38] Hazard ratio [95% CI]. * p < 0.05, ** p < 0.01, *** p < 0.001. No significant financial relationships to disclose.
Similar response to spironolactone in Whites and African-American patients with resistant hypertension
Authors: S. Husain, M. Nishizaka, E. Pimenta, K. K. Gaddam, S. Oparil, D. A. Calhoun
Journal: Circulation (2008)

Primary aldosteronism (PA) is a common cause of resistant hypertension with a prevalence of approximately 20%. Spironolactone is the drug of choice for the medical management of patients with PA. Blacks have been reported to have low-renin HTN and respond better to diuretics and calcium channel blockers. Racial differences in response to spironolactone in patients with resistant hypertension have not been previously described. Consecutive subjects referred to the University of Alabama at Birmingham hypertension clinic for resistant hypertension had been evaluated with a plasma aldosterone concentration (PAC), plasma renin activity (PRA), and a 24-hr urine collection for aldosterone, sodium, and potassium during the patient’s usual diet. The BP response to spironolactone was compared retrospectively in patients. For clinical reasons, subjects had been treated with a median dose of 25 mg of spironolactone and the BP response at 6 weeks, 3 and 6 months was compared retrospectively. A total of 117 patients with resistant hypertension were included in the analysis, including 59 white and 58 black subjects. Both groups had a similar number of antihypertensive medications at baseline. PAC, PRA, U-aldo and serum potassium levels were also similar. BP reduction at 6-weeks, 3- and 6-months after treatment with spironolactone was similar in black and white subjects. At 3 months, the mean reduction in systolic BP was –19.5±19.0 and –23.2±20.0 for blacks and whites, respectively (p= 0.321). These data indicate that African American and white subjects with resistant hypertension respond equally well to spironolactone.
Factors contributing to high symptom burden during chemotherapy for advanced lung cancer: The risk of being underserved.
Authors: C. S. Cleeland, T. R. Mendoza, G. R. Palos, C. Lu, L. A. Nazario, G. R. Lynch, G. M. Mobley, X. S. Wang
Journal: Journal of Clinical Oncology (2010)

9003 Background: Patients undergoing chemotherapy for late-stage non-small cell lung cancer (NSCLC) have multiplesymptoms related to disease and therapy. We determined factors associated longitudinally with high symptom levels during therapy. Methods: We enrolled 102 patients with stage III–IV NSCLC from a tertiary cancer center and 83 patients from 3 public hospitals. Using the M. D. Anderson Symptom Inventory, symptom severity and interference were measured weekly during the first 4-5 cycles of chemotherapy (15 weeks) or until discontinuation of therapy. Patients rated symptoms using an automated computer-telephone system. Group-based trajectory modeling was used to identify groups of patients with high vs. low symptom severity across the study period. Results: The low-symptom group (64%) began with low symptom severity that decreased during therapy (slope =−0.03, p<.005). The high-symptom group (36%) began with high symptom severity that increased during therapy (slope = 0.071, p<0.001). Over the treatment period, overall mean symptom severities for the high- and low-symptom groups were 4.6 and 2.0, respectively. The overall mean symptom interferences for the high- and low-symptom groups were 4.7 and 1.1, respectively. The low-symptom group did not show any significant change in interference scores (1.93 at baseline vs. 1.89 at end of treatment, p<0.85), whereas the high-symptom group demonstrated significantly higher interference scores at the end of treatment (3.93 vs. 5.55, p<0.001). As expected, the high-symptom group had poorer performance status than the low-symptom group (OR = 4.10, 95% CL: 2.1, 7.6). Other major predictors of membership in the high-symptom group included various factors associated with being underserved, including being treated at a public hospital (OR = 3.0, 95% CL: 1.6, 5.6) having less education (p<.009), being single (p<0.003), and being minority (p<0.003). Conclusions: Treatment site (public versus tertiary hospital) was a major predictor of persistent high symptom burden for patients with advanced NSCLC during chemotherapy. Disparities in resources and access to symptom management and supportive care may be partially responsible for these findings. No significant financial relationships to disclose.
Association of copy number variants in colorectal liver metastases with 5-fluorouracil resistance
Authors: R. G. Watson, F. Muhale, L. Thorne, J. Yu, B. O’Neil, J. M. Hoskins, M. O. Myers, H. L. McLeod, J. T. Auman
Journal: Journal of Clinical Oncology (2009)

e14502 Background: Resistance to 5-fluorouracil (5-FU) represents a major contributor to cancer-related mortality in advanced colorectal cancer patients. Previous work has shown that thymidylate synthase (TYMS) copy gains were associated with significantly shorter survival, while increased expression of thymidine phosphorylase (TP) led to greater sensitivity to 5-FU in vitro. We assessed TYMS and TP copy number in colorectal liver metastases from untreated patients and patients treated with 5-FU in an effort to elucidate the underlying molecular mechanisms for 5-FU resistance. Methods: Liver metastases were procured from 59 patients who had received 5-FU within 6 months preceding liver resection (treated samples) and from 46 patients who had received no 5-FU treatment in the 6 months prior to their liver resections (untreated samples). DNA copy number of TYMS and TP was evaluated in frozen colorectal liver metastases using quantitative real time PCR. Results: For TYMS, 8.9% of the treated samples showed copy number gain, as compared to 4.8% of the untreated samples. Loss of TYMS was rare, with only 1 and 2 occurrences seen in the treated and untreated samples, respectively. For TP, both groups exhibited similar copy number gains (25% for treated, 29% for untreated); however, a greater proportion of the treated samples exhibited loss of TP (20% vs. 10%). Collectively, the treated samples have a much higher incidence of genetic alterations potentially associated with resistance (TYMS gain or TP loss) than untreated samples (30% vs. 10%, p = 0.03 Fisher exact test). Conclusions: Colorectal liver metastases treated with 5-FU exhibit DNA copy variants that may reduce 5- FU's efficacy. Our data suggest that these genetic alterations may have important implications for the management of advanced colorectal cancer patients with recurrent disease. No significant financial relationships to disclose.
Rethinking the role of nodal status in TNM staging of node-positive breast cancer
Authors: S. J. Anderson, J. L. Bryant, J. Jeong, G. Tang, J. P. Costantino, E. Mamounas, C. E. Geyer, N. Wolmark
Journal: Journal of Clinical Oncology (2007)

10584 Background: Among TNM staging criteria, the number of positive lymph nodes [PNOD] is the strongest predictor of patient outcome. Based on SEER data, Vinh Hung (2004) asserted that the ratio of the number of positive nodes to the number of nodes removed [NODR] may better predict outcome. We evaluated this assertion in patients from 13 node-positive NSABP phase III trials. Methods: The impact of PNOD, its logarithm (LPNOD) and NODR on survival (S) and recurrence free survival (RFS) were assessed via Cox PH models in 19,768 patients with node-positive breast cancer in 13 NSABP clinical trials. The cohort was split into 2 groups: 9 older trials (Protocols B-05, B-07, B-08, B-09, B-10, B-11, B-12, B-15 and B-16) consisting of 9,915 patients and 4 newer trials (B-22, B-25, B-28 and B-31) consisting of 9,853 patients. Only randomized eligible patients with follow-up were considered. Models were fit to the outcomes for the older trials and validated in the newer trials. Results were adjusted for age, protocol and tumor size. We used Wald z-scores, Nagelkerke R 2 , and residual analyses to assess the strength of the relationship between nodal status and outcomes. Results: Median time on study was 19.8 years in the older trials and 10.6 years in the newer trials. Ten-year models across the protocols revealed that the relative hazard ratio for each of the outcomes studies was logarithmic according to the number of positive nodes for = 30 positive nodes. Using LPNOD and NODR compared to PNOD improved the strength of association but did not greatly improve goodness of fit ( Table 1 1). For all endpoints, the strength of association and goodness of fit associated with nodal status and other TNM factors attenuated in newer protocols. Conclusions: Nodal status and other TNM factors currently used for breast cancer staging continue to be strong indicators of patient prognosis. However, these factors should be augmented to account for new genetic and biological markers. [Table: see text] No significant financial relationships to disclose.
Improved safety profile of nolatrexed dihydrochoride in the ETHECC Trial when compared to the safety of the phase II program in unresectable hepatocellular carcinoma (uHCC)
Authors: R. G. Gish, S. Wadler
Journal: Journal of Clinical Oncology (2004)

4260 Background: We compare the patients' safety profile in the Phase III ETHECC (E) trial to the combined patient safety profile of patients treated with nolatrexed dihydrochloride (THYMITAQ) (T) in the 3 uHCC Phase II studies. T is a folate analogue inhibitor of Thymidylate Synthase (TS) that binds directly to the folate site of TS. Methods: The hematological (H) toxicities (anemia, neutropenia, and thrombocytopenia) and non-hematological (NH) toxicities (mucositis, nausea, vomiting, diarrhea, and rash) data are compared between 117 T patients from the E trial (following the second independent Data Safety Monitoring Board [DSMB] in May 2003) and 129 T patients from the Phase II studies in HCC (Studies 008 [Stuart et al]; 014 [Mok et al]; 015 [ASCO 2003]). Results: There is a reduction in the number of patients experiencing grade 3–4 H and NH toxicities in the E© trial compared to the Phase II data: mucositis by 50%; nausea by 67%; vomiting by 50%; diarrhea by < 50% (with no grade 4 in E); rash by 92%; and neutropenias by 36%. The percentages of febrile neutropenia (13.7%) and infection (5.1%) were also low in the E trial. The percentages of grade 3–4 thrombocytopenia (characteristic of HCC) were about the same without increased association of severe bleeding events (6.0%). Conclusions: The reduction in the number of patients experiencing NH toxicities is a direct result of the supportive care measures incorporated in the E trial. These include the prophylactic use of antiemetics for nausea and vomiting, the use of antihistamines for rash, as well as adequate hydration and oral measures for the treatment of mucositis. Overall, there is an improved outcome in the safety profile in the Phase III study as a result of intensification and active management of expected toxicities. With newer and more effective means of mitigating (or ameliorating) symptoms, these toxicities will become easily controlled. An update with safety data from the third Data Safety Monitoring Board (DSMB) in January 2004 will be communicated at the meeting. No significant financial relationships to disclose.
N0937(Alliance): Final clinical results and correlative data from the phase II trial of cisplatin (C) and the novel agent brostallicin (B) in patients with metastatic triple-negative breast cancer (mTNBC).
Authors: Alvaro Moreno-Aspitia, Heshan Liu, David W. Hillman, Kendrith M. Rowland, Xochiquetzal Geiger, Philip J. Stella, Peter Kourlas, Howard M. Gross, Nina J. Karlin, Martin J. Bury, Gamini S. Soori, Aziza Nassar, Edith A. Perez
Journal: Journal of Clinical Oncology (2013)

1059 Background: Relapsed TNBC is characterized by its poor prognosis. B is a synthetic DNA minor groove binding non-cross resistant agent that is fully active against DNA-mismatch repair deficient tumor cells. C increases GSH/GST in which enhances the efficacy of B. Methods: Phase II study in pts with mTNBC. C Day 1 followed by B Day 2, repeated every 21 days. Aim: Efficacy of C + B in mTNBC. Primary endpoint: PFS at 3 mo. Secondary endpoints include ORR, duration of response (DOR), 6-mo PFS, OS and AE profile. Tertiary endpoints include assessment of baseline GSH levels, prevalence of BCRA1 mutation and pERK, and correlations with outcome. Results: Closed 3/2012. 48 pts accrued (1 ineligible pt). Median f/u 11.4 mo (6.6-14.8); 2 pts still on treatment. 47 pts evaluable for the PFS endpoint and AEs. 49% received therapy as 3rd-5th line. Median number of cycles = 4 (range 1-15). There are currently 9 confirmed responses (8 PR and 1 CR); DOR = 2.6-14.5 mo. The 3-mo PFS = 51%; 6-mo PFS = 28%; the median TTP is 3.2 mo. AE data: 75% G3/4 hematologic AE: febrile neutropenia 19%. Non-hematologic AEs included G3 (47%) and G4 (15%): G3 fatigue 17%; and no G5 non-heme AE. No correlation of GSH/GST levels with outcome was found. Among 35 pts with evaluable data, no association between BRCA1 expression and outcomes was found. pERK expression was negatively associated with 3-mo PFS, but not 6-mo PFS. Cytoplasmic pERK expression was negatively associated with tumor response (p=0.03). No significant effect of BRCA-1 or pERK expression was found on OS. Conclusions: This trial showed B + C is an active regimen, especially in heavily pretreated mTNBC pts. Correlative data demonstrated a negative association between pERK expression and outcomes. A randomized phase II trial is in development. Clinical trial information: NCT01091454.
Interruption of imatinib (IM) in GIST patients with advanced disease after one year of treatment: Updated results of the prospective French Sarcoma Group randomized phase III trial on long term survival
Authors: M. Rios, A. Lecesne, B. Bui, A. Adenis, F. Bertucci, F. Duffaud, J. Emile, S. Chabaud, D. Perol, J. Blay
Journal: Journal of Clinical Oncology (2007)

10016 Background: IM the first-line treatment for advanced GIST, must be given continuously until disease progression (PD) or intolerance (Blay et al, ASCO 2004). The impact on long term overall survival (OS) of IM discontinuation in responding patients (pts) and its re-introduction at progression is unknown. Methods: This prospective multicenter BFR14 study was initiated in June 2002. After 1 year of IM 400mg/day, 58 pts free from progression were randomly offered to continue or interrupt IM until PD. Pts allocated to the interruption (I) arm could restart IM (same dose) in case of PD. Primary endpoint was progression-free survival (PFS); secondary endpoints were OS, secondary response after IM re-introduction, identification of molecular determinants of response. Survival data were compared using the log-rank test. Results: Pt characteristics were well balanced between the two arms. Current median follow- up after randomization is 37 months (range 0–42): 29/32 pts (91%) in arm I vs. 16/26 pts (62%) in continuous (C) arm experienced PD. IM interruption was significantly associated with reduced PFS (p&lt;10 -4 ) with a median of 6 months (95% CI, 3.5–9.5) for arm I. Among the 26 pts of I arm who restarted IM after first progression, 24 (92%) achieved tumor control (OR or SD), one progressed, one died from an unrelated cause. The 2-yr OS rates were 87% and 92% for arms I and C, respectively (P = 0.78). Conclusions: Despite a significant increase of PD in the experimental arm, IM re-introduction is safe and allows a tumor control in the majority of pts. No unfavourable impact of IM interruption on OS was reported. Treatment interruption could be a therapeutic option in advanced GIST pts exhibiting intolerance to IM. Updated results including mutational analysis will be presented at the meeting. No significant financial relationships to disclose.