tbuckley/cabot-search huggingface dataset:
Fertility after chemotherapy for testicular cancer.
Authors: R E Drasga, L H Einhorn, S D Williams, D N Patel, E E Stevens
Journal: Journal of Clinical Oncology (1983)

Sixty-nine patients with disseminated testicular cancer and no prior retroperitoneal lymphadenectomy treated with cisplatin, vinblastine, and bleomycin with or without doxorubicin were evaluated for semen analysis, serum gonadotropins, and testosterone. Since 1979, 41 men have been prospectively studied. Before treatment 77% were oligospermic, 17% were azoospermic, and only 6.6% could meet requirements for sperm banking. After 2 mo of therapy, 96% were azoospermic. A group of 28 patients treated between 1975 and 1979 were retrospectively evaluated. Normal sperm counts were found in 46% of those studied. Only 17% were azoospermic. Thirty-two percent have impregnated their wives, resulting in 5 healthy babies, 1 spontaneous abortion, and 3 ongoing pregnancies. These results show that (1) significant impairment of spermatogenesis exists before therapy, precluding the possibility of sperm banking in most patients, (2) combination chemotherapy in testicular cancer has substantial effects on gonadal function, rendering almost all patients azoospermic, and (3) a high degree of recovery of spermatogenesis occurs sometime after 2-3 yr from the initiation of treatment.
Ambulatory 2 hours infusion of 5-FU modulated by low-dose leucovorin in the palliative treatment of advanced epithelial cancer patients with low performance status
Authors: D. L. da Silva, A. F. Ferreira Filho, A. P. Wunder, M. P. dos Santos, C. Hummes, R. Muller
Journal: Journal of Clinical Oncology (2008)

20600 Background: In the context of palliative care, when clinically indicated for symptomatic control, chemotherapy regimens should ideally offer a fair chance of anticancer activity and clinical benefit, be feasible with a simple method of administration and have a favorable toxicity profile. We evaluated, in a cohort of advanced epithelial cancer patients, most of them already treated with multiple previous lines of chemotherapy, an adaptation of the active and well tolerated ‘de Gramont‘ regimen. Methods: Patients (pts) with histologically proven advanced epithelial neoplasms, adequate bone marrow, hepatic and renal function, ECOG status ≤ 3, were treated with EV bolus leucovorin 20 mg\/m2 D1 and D2 + 5-FU 400 mg\/m2 EV bolus D1 and D2 + a two-hours infusion of 5-FU 600 mg\/m2 D1 and D2, every two weeks. Results: Twenty pts (17 females, 3 males; mean age 54,5 years, range 44–76), with a mean of 2,3 previous lines of chemotherapy (range 0–6), received a total of 155 cycles (mean of 7 cycles/patient, range 3–19), of the adapted de Gramont regimen. The primary tumors were: breast (10 PTS), gastro-intestinal (6 PTS), ovary (2 PTS), head and neck (1 patient), unknown primary carcinoma (1 patient). The ECOG status of the pts was as follows: ECOG 1 (3 pts), ECOG 2 (12 pts), and ECOG 3 (5 pts), mean of 2,1. The partial response rate was 28% (95% CI: 8–48); 8 patients (38%) demonstrated stable disease and 1 patient had a complete response. Clinical benefit with improved performance status and/or decrease in pain was noted in 16 pts. The median time to progression was 24 weeks (95% CI: 16 - 32), and the mean overall survival was 36 weeks. No grade 4 toxicities were detected and grade 3 toxicities were as follows: leucopenia (3 pts) and anemia (1 patient). Common grade 1/2 toxicities were: hand-foot syndrome (4 pts), anemia (6 pts), mucositis (6 pts), diarrhea (6 pts), conjunctivitis (1 patient). The toxicities were managed with 20% dose reductions and/or chemotherapy delays. Overall, dose reductions occurred in 9 patients and chemotherapy delays in 13 patients. Conclusions: The adapted de Gramont Regimen, as described, is well tolerated and active in the palliative setting of patients with advanced epithelial cancer and low ECOG performance status. No significant financial relationships to disclose.
Intrinsic drug resistance in human kidney cancer is associated with expression of a human multidrug-resistance gene.
Authors: A T Fojo, D W Shen, L A Mickley, I Pastan, M M Gottesman
Journal: Journal of Clinical Oncology (1987)

The cloning of the cDNA for the mdr1 gene, whose expression is associated with the development of multidrug-resistance in cultured cells, has made it possible to explore the mechanism of multidrug resistance in human tumors. We have found that normal human kidney, six of eight adenocarcinomas of the kidney, and four cell lines derived from kidney adenocarcinomas express high levels of mdr1 mRNA. Two criteria suggest that primary multidrug resistance in human adenocarcinomas of the kidney results, at least in part, from expression of the mdr1 gene: (1) mdr1 mRNA levels are elevated in four unselected kidney adenocarcinoma cell lines that show a multidrug-resistant phenotype; and (2) multidrug resistance in these kidney cancer cell lines is reversed by verapamil and quinidine, agents known to reverse mdr1-associated drug resistance in cell lines selected for multidrug resistance in vitro. These results suggest that appropriate pharmacological intervention to reverse multidrug resistance might make adenocarcinomas of the kidney more sensitive to chemotherapy with agents such as Adriamycin (Adria Laboratories, Columbus, OH) and the vinca alkaloids.
Prognostic value of low platelets in MDS patients with del(5q)
Authors: N. Galili, A. Ahmed, F. Quddus, S. Jandani, Z. Gul, A. Siddiki, M. Mumtaz, M. Mehdi, D. Devuni, A. Raza
Journal: Journal of Clinical Oncology (2007)

7078 The most common (10–15%) chromosomal abnormality found in myelodysplastic syndromes (MDS) is an interstitial deletion of the long arm of chromosome 5 (del(5q)). The recent finding that lenalidomide is efficacious for MDS patients with del(5q) as either the sole abnormality or as part of a complex karyotype has focused renewed interest in the prognostic characteristics of these patients. We analyzed 189 patients with del(5q), 70 having isolated and 119 having additional chromosomal abnormalities. The median survival for the isolated del(5q) patient was 2.45 years and for those with complex abnormalities was 0.63 years (p=0.001). Each of these groups was then divided by IPSS category; median survival for Low/Int1 (n=56) was 2.46 years and 0.49 years for Int2/High (n=10, p=0.019).Thus our median survival times match previously published results and we have a representative dataset. Since 5q- syndrome patients with normal to high platelets have the best survival, platelet count may be of prognostic significance. We determined the median platelet count for our dataset to be 115,000 and analyzed median survival for patients with greater (n=89) or less (n=88) than the median value. Survival for those with higher platelet counts was 2.6 years, but dropped to 0.54 years with lower counts (p=0.0001). We then analyzed each of these two groups independently for survival based on IPSS, blast % and karyotype. Median survival for patients with &gt;115,000 platelets and either Low/Int1-risk (n=62), &lt;5% blasts (n=46) or an isolated del(5q) (n=46) was 2.95–3.0 years. The survival of these patients dramatically decreased (0.63 years) if they had Int2/High IPSS (n=19) or &gt;10% blasts (=11). The presence of additional chromosomal abnormalities decreased survival to 1.85 years (n=28). A different range of survival times occurred with patients that had &lt;115,000 platelets. Their median survival based on Low/Int1 IPSS (n=20), &lt;5% blasts (n=18) or isolated del(5q)(n=20) was only 0.68–0.84 years. Int2/High IPSS (n=64), &gt;5% blasts (n=50) or additional chromosomal abnormalities (n=68) lowered survival to 0.44–0.49 years. Thus lower platelet counts in del(5q) MDS patients with favorable IPSS (median survival 0.84 years), &lt;5% blasts (median survival 0.68 years) or isolated del(5q) (median survival 0.74 years) appear to have poor prognosis. No significant financial relationships to disclose.
The risk of less extensive surgical staging in endometrial cancer
Authors: K. Fuh, J. Y. Shin, D. S. Kapp, K. Osann, C. B. Powell, L. Chen, J. K. Chan
Journal: Journal of Clinical Oncology (2008)

16587 Background: To evaluate the risk of nodal metastases in endometrial cancer. Methods: Demographic, clinico- pathologic, treatment and surgery information were obtained from the Surveillance, Epidemiology and End Results Program of the National Cancer Institute between 1988 and 2001 on all patients with endometrial cancer who underwent a lymphadenectomy. Kaplan-Meier and Cox regression analyses were used for analyses. Results: Of 15,283 women diagnosed with endometrial cancer, the median age at diagnosis was 64 years (range 22–99). The majority (79.8%) of patients were Caucasian; 6.3% were Hispanic, 5.9% African-American, and 5.7% were Asian. 12,067 had stage I-II disease and 3,216 had stage III-IV disease. 13,419 patients had endometrioid, 1,483 papillary serous, and 381 had clear cell carcinoma. Grade 1, 2, and 3 disease was found in 26.3%, 37.0%, and 30.8%, respectively. 37.6% of women received adjuvant radiation. 13.1% of women with stage I-IV disease had lymph node metastasis. The survival of patients with nodal metastasis was 53.2% vs. 91.4% with negative lymph nodes (p<0.001). In a subset of patients with similar eligibility criteria based on the Post Operative Radiation Therapy in Endometrial Carcinoma (PORTEC) clinical trial (stage IC grade 1 and all grade 2 disease), 10% of these patients had nodal metastasis. After excluding patients with stage IV disease, the risk of nodal metastasis was 6.0%. Of those with grade 2 cancers, the risk of nodal metastasis was 10.8%. In multivariate analysis, age, race, stage, grade, primary surgery, histology, and nodal metastasis all remained as significant independent prognostic factors for survival. Conclusions: In the overall study group, patients with endometrial cancer have a 10% risk of nodal metastases. The information obtained from lymphadenectomy can potentially circumvent or guide adjuvant therapy. No significant financial relationships to disclose.
Combined inhibition of MAPK and mTOR signaling inhibits growth, induces cell death and abrogates invasive growth of melanoma cells
Authors: F. Meier, C. Zielinski, K. Lasithiotakis, T. Sinnberg, K. T. Flaherty, B. Schittek, D. Kulms, C. Garbe
Journal: Journal of Clinical Oncology (2008)

20033 Background: The RAS-RAF-MEK-ERK (MAPK) and the PI3K-AKT-mTOR (AKT) signaling pathways are constitutively activated and subserve key functions in melanoma progression. However, a phase II clinical study revealed that sorafenib, a potent RAF inhibitor, is not effective in patients with metastatic melanoma. Similarly, the selective mTOR inhibitor CCI-779 has been proved ineffective. Recent experimental data suggest that in melanoma an effective treatment strategy must take into account more than one deregulated signaling pathway. Methods: We investigated whether combined targeting of MAPK and AKT signaling pathways has therapeutic effects in melanoma. A panel of pharmacological inhibitors was utilized in order to block the MAPK and AKT signaling pathways at different levels in 6 human metastatic melanoma cell lines. The effects on melanoma cell growth, survival and invasion in monolayer and organotypic culture were investigated. Results: Combination of the RAF inhibitor sorafenib with the mTOR inhibitor rapamycin potentiated growth inhibition in all melanoma cell lines tested (p<0.05, combination treatment vs. monotreatment). Similar results were obtained with combinations of the MEK inhibitors U0126 or PD98059 with rapamycin. Combined treatment of melanoma cells with sorafenib and rapamycin led to an approximately 2-fold increase of cell death compared with sorafenib monotreatment (p<0.05). Moreover, sorafenib in combination with rapamycin completely suppressed invasive melanoma growth in organotypic culture. These effects were associated with complete downregulation of the antiapoptotic proteins Bcl-2 and Mcl-1. Conclusions: Sorafenib combined with rapamycin appears to be a promising strategy for the effective treatment of melanoma and merits clinical investigation. No significant financial relationships to disclose.
Monoclonal Gammopathy of Undetermined Significance and Risk of Infections: A Population-Based Study
Authors: Sigurdur Y. Kristinsson, Tang Min, Ruth Pfeiffer, Magnus Björkholm, Lynn Goldin, Cecilie Blimark, Ulf-Henrik Mellqvist, Anders Wahlin, Ingemar Turesson, Ola Landgren
Journal: Blood (2010)
Weekly carboplatin and <i>nab</i>-paclitaxel plus trastuzumab, or plus or minus bevacizumab: Clinical response in patients with breast cancer
Authors: J. A. Bernstein, T. Schubbert, K. Kong, R. S. Mehta
Journal: Journal of Clinical Oncology (2006)

10699 Background: We previously reported a high, complete pathological remission rate in the neoadjuvant setting using carboplatin and metronomic paclitaxel plus or minus trastuzumab (TC ± H) following anthracycline therapy in patients with HER2+ and triple negative (ER-, PR- and HER2-) breast cancer, respectively. [SABCS 2004 abstract #1110 &amp; SABCS 2005 # 5056] . We now report the clinical outcome of patients with breast cancer who were treated with carboplatin and a 130-nm, albumin-bound form of paclitaxel (nab-paclitaxel) plus trastuzumab (nab-TCH) in HER2+ patients, or plus or minus bevacizumab (nab-TC ± B) in HER2- patients or trastuzumab-exposed HER2+ patients. Methods: Twelve consecutive patients with performance status of 0–2 were treated in the neoadjuvant or metastatic setting from April 2005 to December 2005. Of the 12 patients, 10 received prior anthracycline therapy, 10 received prior taxane therapy, 4 received prior carboplatin therapy, and 4 received prior trastuzumab therapy. Patients received carboplatin calculated at an area under the concentration-time curve (AUC) of 2 and nab-paclitaxel at 80–100 mg/m 2 weekly for 3 weeks followed by 1 week of rest. Either concurrent trastuzumab therapy was administered at 4 mg/kg loading dose, followed by maintenance dose of 2 mg/kg/wk (3 patients) or concurrent bevacizumab therapy was administered at 10mg/kg every 2 weeks (8 patients). One patient received carboplatin and nab-paclitaxel alone. Results: At this point, 9 pts are evaluable. Eight of the first 9 patients achieved a major clinical response (89%, 95% CI: 52%−100%), with 2 of the 8 responders obtaining a documented complete clinical response. Of the 3 remaining patients, 1 had clinical resolution of malignant ascites, 1 had normalization of tumor marker, and 1 had resolution of pain at early follow up. None of the patients had neutropenic fever or grade 3/4 neuropathy or arthralgia. Conclusions: The above combinations (nab-TCH or nab-TC ± B demonstrated promising antitumor activity in patients with breast cancer in the neoadjuvant and metastatic breast cancer. We have initiated a phase II study exploring nab-TCH and nab-TCB (sequenced after doxorubicin and cyclophosphamide) in the neoadjuvant setting. [Table: see text]
The clinical significance of oophorectomy in gastric patients
Authors: H. Song, J. Kim, Y. Do, W. Lee, S. Ryu, I. Kim, S. Sohn
Journal: Journal of Clinical Oncology (2009)

e15646 Background: The oophorectomy in isolated metastasis of ovary can lead to long term survival in patients with gastric cancer, but the clinical significance of oophorectomy in stage IV gastric cancer patients is not known well in this time. Methods: We reviewed the medical record of the 55 gastric cancer patients who were metastasis or recurrent in ovary at Dongsan Medical Center, Kimyung University School of Medicine, Daegu, Korea from 1985 to 2008. Results: Twenty-one patients were metastasis to ovary at the time of diagnosis of gastric cancer, and 34 patients were recurrent in ovary after the gastric resection. The mean age was 45.3 ± 11.6 years in metastatic cancer and 46.8 ±12.6 years in recurrent cancer patients. The stage at the time of gastric resection in 34 recurrent patients were I in 3, II in 1, III in 18, and IV in 10. Adjuvant chemotherapy were performed in 26 (76.5%) patients. Oophorectomy were performed in 33 (97.1%) of recurrent cancer, and 17 (81.0%) of metastatic cancer. The 1-year and 2-year survival rate of metastatic cancer were 14.7%, and 0%, and 1-year, 2-year, and 3-year survival rate of recurrent cancer were 47.2%, 18.1%, and 0%, respectively. The median survival duration of metastatic cancer were 8.9 ±1.0 months, and recurrent cancer were 11.4 ±2.3 months. Recurrent cancer were better survival than metastatic cancer patients (p=0.014). The long-term survival (over 2 years) was noted in 5 patients of recurrent cancer patients. The stage of gastric cancer was correlated to overall survival time in total patients (p=0.028). But, the relapse-free survival time after gastrectomy is the only factor to predict survival duration after oophorectomy in recurrent cancer patients (p=0.029). Age, stage of gastric cancer, extent of involvement of ovary, and systemic chemotherapy were not related to survival time of recurrent cancer patients. Conclusions: The survival time in patients with oophorectomy in recurrent gastric cancer was correlated to relapse-free survival time after gastric resection. No significant financial relationships to disclose.
Multicenter randomized phase III trial comparing tamoxifen alone or with transarterial lipiodol chemoembolization (TLC) for unresectable hepatocellular carcinoma (HCC) in cirrhotic patients
Authors: M. Doffoel, D. Vetter, O. Bouche, F. Bonnetain, A. Abergel, S. Fratte, J. P. Grange, N. Stremdoerfer, A. Blanchi, L. Bedenne
Journal: Journal of Clinical Oncology (2005)

4006 Background: Chemoembolization in the palliative treatment of HCC remains controversial. The FFCD 9402 multicenter phase III trial was designed to compare the effects of the association chemoembolization-tamoxifen (CT group) with tamoxifen alone (T group) on the overall survival (OS) and the quality of life (QoL). Methods: From 1995 to 2002, 138 patients were randomized between Tamoxifen (20 mg per day) with or without TLC with Epirubicin and stratified according to center and Okuda stage (I vs II). Among them 123 cirrhotic patients of Child-Pugh (CP) class A or B with unresectable HCC were eligible: 61 in the T group and 62 in the CT group. Analyses were performed in intent to treat with 5% type I and 20% type II error. Survival curves were estimated with Kaplan-Meir Method: OS was compared with Log-Rank test and multivariate Cox’s proportional hazards model. The Spitzer QoL index was longitudinally compared with a mixed model analysis of variance. Results: Baseline characteristics were similar: Child-Pugh class (71% A), etiology of cirrhosis (76% alcoholic), tumor stage (70% multinodular), Okuda stage (72% I) and unilobar portal vein obstruction (10%). In the CT group the mean courses per patient was 2.8 ± 2.3. At 2 years, the OS was respectively 22% and 25% in the T and CT groups (p=0.68). Multivariate analysis identified 4 significant prognostic factors: AFP > 400 ng/ml (p=0.007), hepatalgia (p=0.006), hepatomegaly (p=0.023) and < 6 included patients per center (p=0.032). The longitudinal QoL level did not differ (p=0.70). Among Okuda I, the 2 year-survival was respectively 28% in the T group and 32% in the CT group (p=0.58). The prognostic factors were similar to the whole population with moreover: Spitzer index (p<0.0001), male sex (p=0.008), and CP class (p=0.026). Conclusions: This study suggests that the TLC in the palliative treatment of HCC with cirrhosis did not improve the survival and the quality of life. No significant financial relationships to disclose.
Economic impact of hyponatremia in hospitalized patients with cancer
Authors: M. A. Callahan, H. T. Do, D. W. Caplan, K. Yoon-Flannery, R. Seifeldin
Journal: Journal of Clinical Oncology (2007)

17053 Background: Hyponatremia, defined as a serum sodium concentration ([Na + ]) =134 mEq/L, is a common electrolyte abnormality in hospitalized cancer patients that may be caused by the primary tumor or metastasis, diagnostic or therapeutic interventions, or a secondary complication. Hospital-acquired hyponatremia is associated with higher costs of care, but many patients present with hyponatremia at admission. Methods: This retrospective case-controlled study assessed the outcomes and cost of care among patients hospitalized for neoplasm who presented with hyponatremia at admission. Laboratory and cost-accounting data from 841 adult patients admitted to an 811-bed university hospital between January 2004 and May 2005 with a principal diagnosis of neoplasm and either mild-to- moderate or moderate-to-severe hyponatremia (serum [Na + ] 130–134 mEq/L or &lt;130 mEq/L, respectively) were compared with data from control subjects with matching ICD-9 codes and normal serum [Na + ] (135–145 mEq/L) at admission during the same period. Endpoints included hospital length of stay (LOS), ICU admissions, in-hospital mortality, and total costs per admission. Results: Hyponatremia was evident in 18.9% of patients admitted for neoplasm. Patients with moderate-to-severe hyponatremia (n=192) and mild-to- moderate hyponatremia (n=649) demonstrated a significantly longer hospital LOS, higher ICU admission rate, higher in-hospital mortality, and higher median costs than control subjects (n=3610) (Table). These differences among groups remained significant after adjustments were made for age, race, sex, and comorbidity score. Conclusions: Cancer patients presenting with hyponatremia at admission have a longer hospital LOS and higher risk of death and cost of care than do cancer patients presenting without hyponatremia. [Table: see text] No significant financial relationships to disclose.
Phase angle, determined by bioelectrical impedance, as a prognostic indicator in advanced colorectal cancer
Authors: D. Gupta, C. A. Lammersfeld, S. Dahlk, J. Burrows, P. G. Vashi, J. Grutsch, C. G. Lis
Journal: Journal of Clinical Oncology (2004)

3689 Background: Bioelectrical impedance analysis (BIA) is widely used in the clinical setting to assess changes in body composition. Phase angle, determined by BIA, detects changes in tissue electrical properties, which is an indicator of cellular health and integrity. Phase angle has been found to be a prognostic indicator in several chronic conditions, such as human immunodeficiency virus, liver cirrhosis, COPD, lung cancer, and patients receiving dialysis. This study was conducted to investigate the prognostic role of baseline phase angle measurements in advanced colorectal cancer. Methods: We evaluated a case series of 81 histologically confirmed stages III-IV colorectal cancer patients treated at Cancer Treatment Centers of America at Midwestern Regional Medical Center between January 2000 and March 2003. A dietitian conducted bioelectrical impedance analysis on all patients during their first admission for treatment. Resistance and reactance were measured, and phase angle was then calculated. Phase angle measurements were divided into three mutually exclusive tertiles with cut-offs of 5.17 and 6.19. Kaplan Meier method was used to calculate survival across the three categories of phase angle. Survival analyses for phase angle were also conducted after adjusting for tumor stage. Log-Rank test was used to study the equality of survival distributions across the strata. Results: Patients with phase angle below 5.17 had a median survival of 10.1 months (95% CI, 6.2 to 13.9; n = 25), those between 5.17 and 6.19 had 22.6 months (95% CI, 16.4 to 28.7; n = 29), and those above 6.19 had 25.6 months (95% CI, 21.4 to 29.8; n = 27); the difference being statistically significant (p = 0.003). Phase angle continued to be statistically significantly associated with survival even after adjusting for tumor stage (p = 0.012). Conclusions: This study demonstrates that a phase angle < 5.17, independent of tumor stage, is an adverse prognostic indicator in patients with advanced colorectal cancer. Similar studies in other cancer types with larger sample sizes are needed to further validate the prognostic significance of phase angle in the cancer treatment setting. No significant financial relationships to disclose.