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Cancer-related dyspnea is a common, distressing, and difficult-to-manage symptom in cancer patients, resulting in diminished quality of life and poor prognosis. Buspirone, a non-benzodiazepine anxiolytic which does not suppress respiration and has proven efficacy in the treatment of generalized anxiety disorder, has been suggested to relieve the sensation of dyspnea in patients with COPD. The main objective of our study was to evaluate whether buspirone alleviates dyspnea in cancer patients. We report on a randomized, placebo-controlled trial of 432 patients (mean age 64, female 51 %, lung cancer 62 %) from 16 participating Community Clinical Oncology Program (CCOP) sites with grade 2 or higher dyspnea, as assessed by the Modified Medical Research Council Dyspnea Scale. Dyspnea was assessed by the Oxygen Cost Diagram (OCD; higher scores are better) and anxiety by the state subscale of the State‐Trait Anxiety Inventory (STAI-S; lower scores are better) at baseline and after the 4-week intervention (post-intervention). Mean scores from baseline to post-intervention for buspirone were OCD 8.7 to 9.0 and STAI-S 40.5 to 40.1 and for placebo were OCD 8.4 to 9.3 and STAI-S 40.9 to 38.6 with raw improvements over time on both measures being greater in the placebo group. Analysis of covariance (ANCOVA) controlling for baseline scores showed no statistically significant difference between groups for OCD (P = 0.052) or STAI-S (P = 0.062). Buspirone did not result in significant improvement in dyspnea or anxiety in cancer patients. Thus, buspirone should not be recommended as a pharmacological option for dyspnea in cancer patients.

BACKGROUND: Race/ethnicity and culture influence illness perceptions, health beliefs and behaviors, and communication with health care providers. However, information about the impact of race/ethnicity on the understanding of cancer diagnosis and treatment plan is limited. METHODS: Nine hundred seventy-three cancer patients completed an information needs-assessment questionnaire prior to starting treatment at 20 geographically distinct clinical cancer sites within the University of Rochester Community Clinical Oncology Program network. Chi2 Test was used to examine the association between race/ethnicity and education, occupation, and perception and use of available information. T test and analysis of covariance were used to examine race/ethnicity-based differences in concerns over understanding cancer diagnosis/treatment plan and the effect of race/ethnicity controlling for demographics. RESULTS: There were 904 non-Hispanic white and 69 nonwhite (blacks, Latinos, and others) patients in the sample. Whites and nonwhites were comparable in educational attainment and occupation. However, there was a statistically significant race/ethnicity-based difference in concerns over understanding the diagnosis and treatment plan for cancer, even after controlling for sex (male, female), age, education, and occupation (p < .001). More nonwhite patients indicated that additional information would have been helpful in dealing with these concerns (p

A 57-year-old white woman with metastases to lungs and liver from virilizing adrenocortical carcinoma (ACC) was treated with radical nephroadrenalectomy followed by oral mitotane 3 to 6 g/day for 5 months. She developed complete response and remained free of disease for more than 25 years. Here we present the case and review the literature. ACC is a rare tumor and may occur at any age. About 60% are functional tumors with hormonal secretions and clinical manifestations due to specific hormone secretions: Cushing's syndrome due to cortisone, virilizing tumor due to androgens, feminizing tumor due to estrogens, or hypertension due to aldosterone. Stage I and II disease is curable with surgery. Stage III and IV disease may benefit from mitotane orally with gradual adjustment of the dosage to a tolerable level. Plasma mitotane level at 14 to 20 g/L results in optimal response both in hormonal secretion and symptom control, as well as tumor regression. Addition of chemotherapy (streptozotocin or a combination of etoposide, cisplatin and doxorubicin) to mitotane also produced responses along with increased survival among responders. An international study has been started by randomizing between two of the above combinations by the Collaborative Group for Adrenocortical Carcinoma Treatment.

Several studies have shown that patients’ expectancy for the development of nausea following chemotherapy are robust predictors of that treatment-related side effect and some studies have shown that interventions designed to influence expectancies can affect patients’ reports of symptoms. In this randomized multicenter Community Clinical Oncology Program (CCOP) trial, we investigated the effect of an expectancy manipulation designed to reduce nausea expectancy on chemotherapy-induced nausea in 358 patients scheduled to receive chemotherapy treatment. Patients in the intervention arm received general cancer-related educational material plus specific information about the efficacy of ondansetron specifically designed to diminish nausea expectancy. Patients in the control arm received only the general cancer-related educational material. Nausea expectancy was assessed both prior to and following the educational intervention. We observed a significant reduction in nausea expectancy in the intervention group (p = 0.024) as compared to the control group (p = 0.34). In the intervention group, patients’ expectations of nausea assessed prior to the intervention correlated significantly with average nausea (r = .27, p = .001); whereas nausea expectancy assessed following the intervention did not (r = 0.1, p = 0.22). In our study, the expectancy manipulation reduced patients’ reported expectations for the development of nausea but did not reduce occurrence of nausea. Furthermore, post-intervention nausea expectancy compared to pre-intervention expectancy was less predictive of subsequent nausea. Explanations for these findings include the possibility that the expectancy manipulation was not strong enough, and the possibility that changing nausea expectancies does not change occurrence of nausea.

A relatively young patient with chronic gastroesophageal reflux disease (GERD), obesity, smoking, and alcohol intake presented with widespread metastatic disease in lymph nodes, liver and lungs from a lower esophageal adenocarcinoma extending into the gastroesophageal junction associated with Barrett's mucosa and dysplasia.A complete response was achieved with six cycles of chemotherapy that sustained for more than 4 years without further recurrence. Unfortunately, there was presence of esophageal metaplasia after complete response which eventually converted to low to high grade dysplasia and ultimately to a second primary localized lower esophageal adenocarcinoma that was treated with thoracoabdominal esophagectomy and lymphadenectomy. No evidence of disease recurrence was seen 2 years later. The pathogenesis of a recent increase in the incidence of GERD, Barrett's esophagus and lower esophageal adenocarcinoma are discussed. Surgery, radiotherapy and combination chemotherapy are effective in the early stages leading to tumor shrinkage and prolongation of life and even cure in some cases. Lower esophageal adenocarcinoma is frequently associated with Barrett's high-grade dysplasia. Since there has been a dramatic increase in the incidence of Barrett's dysplasia, appropriate surveillance with upper gastrointestinal endoscopy and preventive strategies, such as the use of aspirin, cyclo-oxygenase II inhibitors and other nonsteroidal antiinflammatory drugs known to be chemopreventive agents against colon, esophagus, gastric and bladder cancers, need to be studied.

Analysis of a genome screen of 504 brothers with prostate cancer (CaP) who were from 230 multiplex sibships identified five regions with nominally positive linkage signals, on chromosomes 2q, 12p, 15q, 16p, and 16q. The strongest signal in these data is found on chromosome 16q, between markers D16S515 and D16S3040, a region suspected to contain a tumor-suppressor gene. On the basis of findings from previous genome screens of families with CaP, three preplanned subanalyses were carried out, in the hope of increasing the subgroup homogeneity. Subgroups were formed by dividing the sibships into a group with a positive family history (FH+) that met criteria for “hereditary” CaP (n=111) versus those which did not meet the criteria (n=119) and by dividing the families into those with a mean onset age below the median (n=115) versus those with a mean onset age above the median (n=115). A separate subanalysis was carried out for families with a history of breast cancer (CaB+ [n=53]). Analyses of these subgroups revealed a number of potentially important differences in regions that were nonsignificant when all the families were analyzed together. In particular, the subgroup without a positive family history (FH−) had a signal in a region that is proximal to the putative site of the HPC1 locus on chromosome 1, whereas the late-age-at-onset group had a signal on 4q. The CaB+ subgroup revealed a strong linkage signal at 1p35.1.

Background Since the publication of the first genome screen for prostate cancer (CaP) 5 years ago, over a dozen linkage studies have appeared. Most attention has been directed to chromosome 1, where two separate regions have been identified as harboring a prostate cancer susceptibility locus: HPC1 in the 1q24-25 interval and PCaP in the 1q42.2-43 interval. Linkage analysis of chromosome 16 has also provided evidence of harboring two loci predisposing to CaP. Methods We report on a replication linkage study of chromosomes 1 and 16 in 45 new and 4 expanded multiplex CaP families. Multipoint Z-scores were obtained for 30 highly polymorphic short-sequence tandem repeat markers spanning chromosome 1, and 22 markers spanning chromosome 16. Results The replication sample gave no evidence for a CaP susceptibility locus in the 1q24-25 interval and equivocal evidence for such a locus at 1q42.2-43. With respect to chromosome 16, positive Z-scores were obtained over a contiguous interval covering the entire p arm and the proximal half of the q arm. Conclusions The linkage analysis of our replication sample does not support the existence of HPC1, and the evidence for the existence of PCaP remains equivocal. Evidence of a susceptibility locus on 16p remains strong, but the evidence for a susceptibility locus on 16q is weakened.

Introduction Pemetrexed is synergistic with gemcitabine in preclinical models of non-small cell lung cancer (NSCLC). The optimal dose and utility of gemcitabine and pemetrexed was evaluated in a dose-escalating study. Methods The phase 1 study included patients with advanced tumors, whereas the phase 2 study included patients with locally advanced or metastatic NSCLC. Gemcitabine was infused over 30 minutes, followed by pemetrexed administered over 10 minutes on day 1 of a 14-day cycle. Treatment continued for 12 cycles or until disease progression. All patients received folic acid, Vitamin B 12 , and steroid prophylaxis. Results Maximum tolerated dose was gemcitabine 1500 mg/m 2 , followed by pemetrexed 500 mg/m 2 . Fifty-three patients (29 male, 24 female) were enrolled in the phase 2 study. Response rate was 20.8% (95% CI: 0.108–0.341), and the clinical benefit rate (CR + PR + SD) was 64.2%. Median time to disease progression was 4.6 months (95% CI: 2.79–6.18), median survival was 10.1 month (95% CI: 5.95–14.09, censorship=20.75%), and 1-year survival was 41.0%. Common grade 3 or 4 adverse events (% of patients) were neutropenia (28.3%), fatigue (22.6%), and febrile neutropenia (9.4%). Conclusions Twice-monthly gemcitabine and pemetrexed was well tolerated, with overall survival and clinical benefit indicating disease activity in NSCLC patients.

Renal cell carcinoma is a chemo- and radiation-resistant malignancy that is very rare in childhood. In advanced cases, survival is extremely poor, but cure can be achieved with complete tumorectomy. We report a 14-year-old female with left renal cell carcinoma, with regional lymphadenopathy extending up to the diaphragm. Complete tumor resection was impossible. The tumor progressed after 10 months of treatment with high-dose interleukin-2. After 7 months of outpatient vascular endothelial growth factor receptor antibody bevacizumab and no significant adverse effects, dramatic tumor shrinkage enabled complete resection. Pediatr Blood Cancer 2008;50:903–904. © 2007 Wiley-Liss, Inc.

Summary Background Most women receiving systemic therapy for breast cancer experience hot flashes. We undertook a randomised, double-blind, placebo-controlled, multi-institutional trial to assess the efficacy of gabapentin in controlling hot flashes in women with breast cancer. Methods 420 women with breast cancer who were having two or more hot flashes per day were randomly assigned placebo, gabapentin 300 mg/day, or gabapentin 900 mg/day by mouth in three divided doses for 8 weeks. Each patient kept a 1-week, self-report diary on the frequency, severity, and duration of hot flashes before the start of the study and during weeks 4 and 8 of treatment. Analyses were by intention to treat. Findings Evaluable data were available on 371 participants at 4 weeks (119 placebo, 123 gabapentin 300 mg, and 129 gabapentin 900 mg) and 347 at 8 weeks (113 placebo, 114 gabapentin 300 mg, and 120 gabapentin 900 mg). The percentage decreases in hot-flash severity score between baseline and weeks 4 and 8, respectively were: 21% (95% CI 12 to 30) and 15% (1 to 29) in the placebo group; 33% (23 to 43) and 31% (16 to 46) in the group assigned gabapentin 300 mg; and 49% (42 to 56) and 46% (34 to 58) in the group assigned gabapentin 900 mg. The differences between the groups were significant (p=0·0001 at 4 weeks and p=0·007 at 8 weeks by ANCOVA for overall treatment effect, adjusted for baseline values); only the higher dose of gabapentin was associated with significant decreases in hot-flash frequency and severity. Interpretation Gabapentin is effective in the control of hot flashes at a dose of 900 mg/day, but not at a dose of 300 mg/day. This drug should be considered for treatment of hot flashes in women with breast cancer.

BACKGROUND Patients may use their past experiences with nausea, as well as information about the incidence of nausea from chemotherapy that other patients have experienced, to form a prediction, or response expectancy, of nausea from their own upcoming chemotherapy. Mounting evidence suggests that these expectancies relating to nausea are significant predictors, and, likely, contributing factors to the development of treatment-related nausea. METHODS The patients in the current study were participants in the control arm of a multicenter clinical trial conducted between November 1999 and July 2001 by the University of Rochester Community Clinical Oncology Program. All patients in the current report were age ≥ 18 years and were about to begin a first cancer treatment regimen containing doxorubicin. RESULTS Expectancy of nausea assessed before patients received their first doxorubicin-based chemotherapy treatment was found to be a strong predictor of subsequent nausea and in fact was stronger than previously reported predictive factors, including age, nausea during pregnancy, and susceptibility to motion sickness. Women who believed it was “very likely” that they would have severe nausea from chemotherapy were five times more likely to experience severe nausea than fellow patients who thought its occurrence would be “very unlikely.” CONCLUSIONS Further studies confirming an expectancy of nausea as a risk factor are warranted as are studies examining the benefit to a patient's quality of life from modifying antiemetic treatment guidelines to take into account symptom expectancies. Finally, ethically acceptable interventions that are designed to reduce patients' nausea expectancies or increase their expectancies of nausea control should be developed and studied. Cancer 2004. © 2004 American Cancer Society.

Purpose: Fatigue and depression typically occur together in cancer patients, suggesting a common etiology, perhaps based on serotonin. This randomized clinical trial tested whether paroxetine, a selective serotonin reuptake inhibitor antidepressant known to modulate brain serotonin, would reduce fatigue in cancer patients and whether any reduction was related to depression. Patients and Methods: Cancer patients undergoing chemotherapy for the first time were assessed for fatigue. Of 704 patients who reported fatigue at their second chemotherapy cycle, 549 patients were randomly assigned to receive either 20 mg of oral paroxetine hydrochloride daily or placebo for 8 weeks. The assessments of fatigue and depression were performed at cycles 3 and 4 of chemotherapy. Results: A total of 244 patients treated with paroxetine and 235 patients treated with placebo provided assessable data. No difference was detected in fatigue between patient groups. At the end of the study, there was a difference between groups in the mean level of depression (Center for Epidemiologic Studies Depression scores, 12.0 v 14.8, respectively; P < .01). Conclusion: Paroxetine had no influence on fatigue in patients receiving chemotherapy. A possible explanation is that cancer-related fatigue does not involve a reduction in brain 5-HT levels.

BACKGROUND Substantial evidence suggests that genetic factors play an important role in both the risk of prostate cancer and its biologic aggressiveness. Here we investigate prostate cancer susceptibility and aggressiveness with genome-wide linkage analyses of affected brothers. METHODS We first undertook a new genome-wide linkage study of 259 brothers with prostate cancer. Our analyses tested whether the proportion of marker alleles shared by brothers was correlated with disease status or Gleason score. To further clarify 11 linkage regions observed here or previously, we genotyped and analyzed an additional 101 finely spaced markers in the 259 men, and in 594 previously studied brothers, allowing for a pooled genome-wide analysis of 853 affected brothers. RESULTS In the new study, we detected linkage to prostate cancer on chromosome 16q23 (P = 0.009), replicating previous results, and to chromosome 11q24 (P = 0.001). In the pooled analysis, the 16q23 linkage was strengthened (P = 0.0005), as was our previous linkage to chromosome 16p (P = 0.0001), and we detected linkage to chromosome 2q32 (P = 0.009). When evaluating Gleason score, our new study detected linkage to chromosome 7q32 (P = 0.0009), again replicating previous results, and to chromosomes 5p15 (P = 0.003), 9q34 (P = 0.009), 10q26 (P = 0.03), and 18p11 (P = 0.02). In the pooled analysis of Gleason score, we observed stronger linkage to chromosome 7q32 (P = 0.0002), but slightly weaker linkage to chromosomes 5q33 (P = 0.005) and 19q13 (P = 0.009) than previously reported. In addition, the new linkages to chromosomes 10q26 and 18p11 were strengthened (P = 0.0002 and P = 0.002, respectively). CONCLUSIONS Our results provide compelling evidence for loci harboring prostate cancer susceptibility and tumor aggressiveness genes, especially on chromosomes 16q23 and 7q32. Prostate 57: 298–308, 2003. © 2003 Wiley-Liss, Inc.

This study examined the concurrent and longitudinal relationships between traumatic stress symptoms and demographic, medical, and psychosocial variables among women recently diagnosed with primary breast cancer. Participants were 117 women drawn from a parent study for women recently diagnosed with primary breast cancer. At baseline, the Impact of Event Scale (IES) total score was related to intensity of postsurgical treatment and lower emotional self-efficacy. At the 6-month follow-up, the IES total score was significantly related to younger age, to the increased impact of the illness on life, and to the baseline IES total score assessment. These results suggest that it is important to intervene for traumatic stress symptoms soon after the diagnosis of breast cancer. Furthermore, these results suggest women at greatest risk are those who are younger, who receive postsurgical cancer treatment, who are low in emotional self-efficacy and whose lives are most affected by having cancer.

e20641 Background: Distress is hypothesized to increase morbidity and mortality among cancer patients-possibly through exacerbating toxicities and interfering with activities of daily living (ADL’s...

9631 Background: Unique challenges face elderly cancer survivors, including issues of quality of life. Impaired cognitive function is a common complaint among aging cancer patients. The purpose of this multicenter longitudinal study was to investigate the frequency and severity of self-reported problems with memory and concentration over time. Methods: Patients undergoing treatment for solid tumors self-rated problems with memory and concentration using an 11-point Likert Scale (0 = Not present to 10 = “As bad as you can imagine”) at baseline before treatment began (T1), at their worst during treatment (T2), and at 6 months following treatment (T3). Any symptom level ≥ 7 was classified as “severe.” Repeated measures analyses were used to examine differences in symptoms over time and between patients treated with and without chemotherapy. Results: Of 595 participants, 351 (59%) were aged ≤64 years and 244 (41%) were ≥65 years; 356 (60%) received chemotherapy, with or without radiation and 239 (40%) radiati...

9016 Background: Sleep disturbance is a prevalent and, potentially, chronic problem among cancer patients, persisting for many months and years after treatments. As part of a multi-center longitudinal survey of patients beginning cancer treatments, we prospectively investigated the prevalence and severity of self-reported sleep disturbance. Methods: 596 Cancer patients (mean age=61; 66.4%=female) receiving chemotherapy and/or radiation (37.1%=chemotherapy, 40.1%=radiation therapy, 22.8%=both) from 17 NCI CCOPs reported whether they experienced any sleep disturbance using an 11-point Likert Scale (0 = “Not present” to 10 = “As bad as you can imagine”) prior to treatments, during treatments, and 6 months after finishing treatments. A side effect level 7 was considered “severe.” Results: Sleep disruption was reported by 31.9% (median=2; 10.6% severe) at baseline, 77.2% (median=4; 28.5% severe) during treatment and 65.1% (median=2; 15% severe) at 6 months post-treatment. Repeated-measures ANOVAs revealed statistically significant treatment group (chemotherapy, radiation, or both), age (< 61 or ≥ 61 yrs), and gender by time interactions (all p No significant financial relationships to disclose.

8144 Background: Previously, we have reported that a patient’s specific expectation of nausea is a strong predictor of its subsequent occurrence; however, factors contributing to the development of...

8083 Background. Research literature assumes patients are more likely to leave decisions about treatment to doctors. This study looks at self-reporting on decision-making, information-seeking among cancer pts. Methods. The URCC CCOP Research Base surveyed 1015 cancer pts, following diagnoses and referral to a CCOP treatment facility. Pts. responded at pre-treatment and post-treatment. Respondents were asked their preference level in making final decisions about treatments on a scale from “1” (pts. wanted the final decision) to “5” (doctor makes the decision solely). How actively the respondents sought information from “1” (not at all) to “5” (very active) was also assessed. Results. At pre-treatment, 64.6% of 952 respondents preferred some responsibility for treatment decisions, 24.2% wanted their opinions seriously considered in doctors’ final decisions, 11.2% preferred doctors make all decisions. At post-treatment, 53.7% of 752 respondents preferred some responsibility in treatment decisions, 16.0% felt...

Fifty-six patients with T1-T3 and T2-T3 N0 medial lesions of breast carcinoma were randomized after modified radical mastectomy to receive either cytoxan, methotrexate, 5-fluorouracil (5-Fu) (CMF) chemotherapy for 1 year (group A) or CMF for 1 year and postoperative radiation therapy (group B). Thirty-two patients received chemotherapy alone and 25 patients received both chemotherapy and radiation therapy. Twenty-five of 32 group A patients (median age 52) and 20/24 group B patients (median age 50) were evaluable. Leukopenia was the major cause of drug dose reduction in both groups. In group A, 4/25 patients (16%) had leukopenia at less than the 2500 level, whereas 8/20 (40%) group B patients had leukopenia at the same level. If 70% of all three drug dosages are considered as adequate chemotherapy, 21/25 (84%) patients received adequate chemotherapy in group A, and 10/20 (50%) in group B (p approximately equal to 0.029 from contingency table). It appears that radiation therapy in postmastectomy patients hinders adequate drug dose delivery in an adjuvant setting.

Using autologous s e r u m as medium, localized leukocyte mobilization into a plastic chamber at the site of mechanical abrasion was quantified in 5 patients with florid CML, one patient with chronic eosinophilic leukemia in the florid state, 3 patients (5 studies) with CML and partial response (remission or relapse), 6 patients with CML in good remission, and in 7 patients with CML in the blastic phase. The cumulative total number of cells was expressed as totaI leukocyte mobilization (TLM) x lOS/cm~ at 24 hrs. Leukocyte dearance/cm2 in 24 hrs. was expressed in milliliters of blood and was obtained by dividing TLM (corrected for non-granulocytes) by the absolute granulocyte count in the peripheral blood. Although the median TLM was found to be elevated in CML with florid disease (130 x 106/cm2 at 24 hrs.) and in CML with partial remission and relapse (104 x lw), it fell to 74 x 106 in 6 patients in remission. This is to be compared with the median TLM for 46 normal subjects (76 x IW/cm2 at 24 hrs.). Median leukocyte clearances showed the lowest values in CML in the florid state (1.0 ml/cmz in 24 hrs), improving to 4.4 ml when a partial response was present, and to 9.3 ml in remission. This compares with 19.7 ml/cm2 in 24 hours for 46 normal subjects. The median T L M in 7 patients with CML in blastic phase was 14 x 1Oe/cm2 a t 24 h, and the leukocyte clearance was reduced to 1.4 ml. These data suggest a defeft in cell-migration in all stages of CML, which is inversely correlated with clinical state. The data reinforce the reported prolongation of circulation time of leukocytes in CML, and suggest a mechanism for this in the impaired ability of CML leukocytes to migrate across the vessel wall.

A 70-year-old man who had squamous cell carcinoma of the lip later presented with right mental neuropathy, ipsilateral progressive involvement of all three divisions of the 5th, the 7th and 8th cranial nerves, and complete ophthalmoplegia. Biopsy proven metastasis to the mandible was demonstrated. Although repeated studies of CT scan of the head and cerebral angiography were negative, CSF examination revealed positive cytology, elevated protein and low sugar content. Although vascular dissemination from the primary lip lesion to the mandible and brain stem cannot be ruled out, extension through perineurial space via the 5th cranial nerve have been speculated. This case demonstrates two unusual features of squamous cell carcinoma of the lip, namely metastasis to the mandible and meningeal spread with multiple cranial neuropathies.

The clinical and pathologic findings in two cases of pure chondrosarcoma of the breast are presented. As with other sarcomas, both tumors were large (5.5 and 25 cm in greatest diameter), did not invade the skin or axillary lymph nodes, and occurred in women more than 40 years old. Infiltrating margins, cellular atypism, and high mitotic rates adversely affected the prognosis.