Among 373 patients diagnosed with nonmetastatic colorectal cancer between 1991 and 2004, we performed a prospective observational study nested within two large US cohorts to evaluate the association between mortality and prediagnosis circulating C-peptide (a marker of insulin secretion), IGFBP-1, insulin-like growth factor-I (IGF-I), and IGFBP-3.

Compared with patients in the bottom quartile, patients in the top quartile of plasma C-peptide had an age-adjusted hazard ratio (HR) for death of 1.87 (95% CI, 1.04 to 3.36; P = .03 for trend), whereas those in the top quartile of circulating IGFBP-1 had a significant reduction in mortality (HR = 0.48; 95% CI, 0.28 to 0.84; P = .02 for trend). Little change in these estimates was noted after adjusting for other covariates known or suspected to influence survival. No associations were noted between mortality and IGF-I or IGFBP-3, which are two components of the IGF axis not closely correlated with lifestyle factors.

Among patients with surgically resected colorectal cancer, higher levels of prediagnosis plasma C-peptide and lower levels of prediagnosis plasma IGFBP-1 were associated with increased mortality. Circulating insulin and IGFBP-1 are potential mediators of the association between lifestyle factors and mortality after colorectal cancer resection.

Tissue microarrays and immunohistochemistry were used to assess the densities of CD8⁺, CD45RO⁺, and FOXP3⁺ lymphocytes in tumor tissue and normal colonic mucosa from 967 stage II and stage III colorectal cancers. These were evaluated for associations with histopathologic features and patient survival.

FOXP3⁺ Treg density was higher in tumor tissue compared with normal colonic mucosa, whereas CD8⁺ and CD45RO⁺ cell densities were lower. FOXP3⁺ Tregs were not associated with any histopathologic features, with the exception of tumor stage. Multivariate analysis showed that stage, vascular invasion, and FOXP3⁺ Treg density in normal and tumor tissue were independent prognostic indicators, but not CD8⁺ and CD45RO⁺. High FOXP3⁺ Treg density in normal mucosa was associated with worse prognosis (hazard ratio [HR] = 1.51; 95% CI, 1.07 to 2.13; P = .019). In contrast, a high density of FOXP3⁺ Tregs in tumor tissue was associated with improved survival (HR = 0.54; 95% CI, 0.38 to 0.77; P = .001).

FOXP3⁺ Treg density in normal and tumor tissue had stronger prognostic significance in colorectal cancer compared with CD8⁺ and CD45RO⁺ lymphocytes. The finding of improved survival associated with a high density of tumor-infiltrating FOXP3⁺ Tregs in colorectal cancer contrasts with several other solid cancer types. The inclusion of FOXP3⁺ Treg density may help to improve the prognostication of early-stage colorectal cancer.

Thirty-three patients with gemcitabine-refractory, metastatic pancreatic cancer were treated continuously with RAD001 at 10 mg daily. Prior treatment with fluorouracil in the perioperative setting was allowed. Patients were observed for toxicity, treatment response, and survival.

Treatment with single-agent RAD001 was well-tolerated; the most common adverse events were mild hyperglycemia and thrombocytopenia. No patients were removed from the study because of drug-related adverse events. No complete or partial treatment responses were noted, and only seven patients (21%) had stable disease at the first restaging scans performed at 2 months. Median progression-free survival and overall survival were 1.8 months and 4.5 months, respectively. One patient (3%) had a biochemical response, defined as ≥ 50% reduction in serum CA19-9.

Although well-tolerated, RAD001 administered as a single-agent had minimal clinical activity in patients with gemcitabine-refractory, metastatic pancreatic cancer. Future studies in metastatic pancreatic cancer should assess the combination of mTOR inhibitors with other agents and/or examine inhibitors of other components of the PI3K/Akt/mTOR pathway.

Pooled efficacy data for 439 patients ≥ 65 years old randomized to BV plus chemotherapy (n = 218) or placebo plus chemotherapy (n = 221) in study 1 and study 2 were retrospectively analyzed on an intent-to-treat basis for overall survival (OS), progression-free survival (PFS), and objective response. Safety analysis was based on reports of targeted adverse events in treated patients.

Median OS with BV plus chemotherapy was 19.3 v 14.3 months with placebo plus chemotherapy (hazard ratio [HR] = 0.70; 95% CI, 0.55 to 0.90; P = .006). Patients treated with BV plus chemotherapy had a median PFS of 9.2 v 6.2 months for placebo plus chemotherapy patients (HR = 0.52; 95% CI, 0.40 to 0.67; P < .0001). The objective response rate was 34.4% with BV plus chemotherapy versus 29.0% with placebo plus chemotherapy (difference not statistically significant). Rates of BV-associated adverse events in the pooled BV plus chemotherapy group were consistent with those reported in the overall populations for the two studies.

Analysis of pooled patient cohorts age ≥ 65 years from two similar trials in mCRC indicates that adding bevacizumab to fluorouracil-based chemotherapy improved OS and PFS, similar to the benefits in younger patients. Also, the risks of treatment do not seem to exceed those in younger patients with mCRC.

Eligible patients were new referrals to an OPCC, had metastatic cancer, were at least 18 years old, and were well enough and able to speak and read English sufficiently to provide informed consent and complete questionnaires. Patients received a consultation by a palliative care team. The primary end points of symptom control and patient satisfaction were assessed using the Edmonton Symptom Assessment Scale (ESAS) and patient-adapted Family Satisfaction with Advanced Cancer Care (FAMCARE) scale at baseline, 1 week, and 1 month. Initial and follow-up scores were compared using paired t tests.

Of 150 patients enrolled, 123 completed 1-week assessments, and 88 completed 4-week assessments. At baseline, the mean ESAS Distress Score (EDS) was 39.5. The mean improvement in EDS was 8.8 points (P < .0001) at 1 week and 7.0 points (P < .0001) at 1 month. Statistically significant improvements were observed for pain, fatigue, nausea, depression, anxiety, drowsiness, appetite, dyspnea, insomnia, and constipation at 1 week (all P ≤ .005) and 1 month (all P ≤ .05). The mean improvement in FAMCARE score was 6.1 points (P < .0001) at 1 week and 5.0 points (P < .0001) at 1 month.

This phase II study demonstrates efficacy of an OPCC for improvement of symptom control and patient satisfaction with care. Randomized controlled trials are indicated to further evaluate the effectiveness of specialized outpatient palliative care.

Investigators used single-variable deterministic sensitivity analysis to evaluate the effect of varying each input of the model independently for three representative case examples based on National Comprehensive Cancer Network guidelines (NCCN). The main outcome of interest was 10-year mortality prediction.

The analyses show that Adjuvant!'s 10-year mortality predictions are most sensitive to patients’ comorbidity levels and the extent of nodal involvement for the cases, particularly among older women. Comorbidity was the most influential input except in younger women, aged 40 years.

The Adjuvant! model is sensitive to patient comorbidity, and impact on the model outputs are significant enough that they are likely to affect physician recommendations and patients’ treatment choices. For example, incorrect assessments of comorbidities could lead physicians to overtreat or undertreat a patient who is in a gray zone relative to the NCCN guidelines. These results point to the importance of accurately assessing comorbidities in patients with breast cancer when using Adjuvant! and highlight the need for a standardized process of comorbidity ascertainment.

Four hundred seventy-one patients with TN breast cancer diagnosed between 1996 and 2005 and treated with primary systemic chemotherapy were included. pCR was defined as no residual invasive cancer in the breast and axillary lymph nodes. Overall survival (OS) and recurrence-free survival (RFS) were estimated using the Kaplan-Meier product-limit method and compared between groups using the log-rank test. Cox proportional hazards models were fitted for each survival outcome to determine the relationship of patient and tumor variables with outcome.

Median follow-up time was 24.5 months. One hundred patients (21.2%) were black, and 371 patients (78.8%) were white/other race. Seventeen percent of black patients (n = 17) and 25.1% of white/other patients (n = 93) achieved a pCR (P = .091). Three-year RFS rates were 68% (95% CI, 56% to 76%) and 62% (95% CI, 57% to 67%) for black and white/other patients, respectively, with no significant difference observed between the two groups (P = .302). Three-year OS was similar for the two racial groups. After controlling for patient and tumor characteristics, race was not significantly associated with RFS (hazard ratio [HR] = 1.08; 95% CI, 0.69 to 1.68; P = .747) or OS (HR = 1.08; 95% CI, 0.69 to 1.68; P = .735) when white/other patients were compared with black patients.

Race does not significantly affect pCR rates or survival outcomes in women with TN breast cancer treated in a single institution under the same treatment conditions.

One hundred fourteen women with T2-4 N0-1, estrogen receptor (ER) –positive tumors were randomly assigned to neoadjuvant letrozole or letrozole plus metronomic cyclophosphamide. Twenty-four tumor proteins involved in apoptosis, cell survival, hypoxia, angiogenesis, growth factor, and hormone signaling were assessed by immunohistochemistry in pretreatment samples (eg, caspase 3, phospho- mammalian target of rapamycin, hypoxia-inducible factor 1 [HIF-1], vascular endothelial growth factor, mitogen-activated protein kinase [MAPK], phosphorylated epidermal growth factor receptor, phosphorylated ER [pER]). A multivariate generalized linear regression approach was applied using a penalized least-square minimization to perform variable selection and regularization. Ten-fold cross-validation and iterative leave-one-out were employed to validate and test the model, respectively. Tumor size, nodal status, age, tumor grade, histological type, and treatment were included in the analysis.

Ninety-one patients (81%) attained a disease response, 48 achieved a complete clinical response (43%) whereas 22 did not respond (19%). Increased pER and decreased p44/42 MAPK were significant factors for complete response to treatment in all leave-one-out iterations. Increased p44/42 MAPK and HIF-1 were significant factors for treatment resistance in all leave-one-out iterations. There was no significant interaction between these variables and treatment.

Activated ER form was an independent factor for sensitivity to chemoendocrine treatment, whereas HIF-1 and p44/42 MAPK were independent factors for resistance. Although further confirmatory analyses are needed, these findings have clear potential implications for future strategies in the management of clinical trials with aromatase inhibitors in the breast cancer.

Patients who had mRCC with sarcomatoid features in the primary tumor and who were treated with VEGF-targeted therapy were retrospectively identified. Pathology slides were reviewed to determine the percentage of sarcomatoid differentiation. Objective response rate, percentage of tumor burden shrinkage, progression-free survival (PFS), and overall survival (OS) were determined.

Forty-three patients who had sarcomatoid mRCC were identified. The median percentage of sarcomatoid features was 14% (range, 3% to 90%). Patients were treated with either sunitinib (49%), sorafenib (28%), bevacizumab (19%), or sunitinib plus bevacizumab (5%). Partial responses were observed in eight patients (19%); 21 patients (49%) had stable disease; and 14 patients (33%) had progressive disease as their best response. Partial responses were limited to patients who had underlying clear-cell histology and less than 20% sarcomatoid elements. Median tumor shrinkage was –2% (range, –85% to 127%), and 53% achieved some degree of tumor shrinkage on therapy. Median PFS and OS were estimated to be 5.3 months and 11.8 months, respectively.

Patients who have mRCC and sarcomatoid differentiation can demonstrate objective responses and tumor shrinkage to VEGF-targeted therapy. Patients who have clear-cell histology and a lower percentage of sarcomatoid differentiation may have better outcomes with VEGF-targeted therapy.

Previously untreated stage III to IVB NPC were randomly assigned to (1) neoadjuvant docetaxel 75 mg/m² and cisplatin 75 mg/m² every 3 weeks for two cycles, followed by cisplatin 40 mg/m²/wk concurrent with radiotherapy, or (2) CRT alone. Planned accrual was 30 patients per arm to detect 20% difference of toxicities based on 95% CIs.

From November 2002 to November 2004, 65 eligible patients were randomly assigned to neoadjuvant chemotherapy followed by CRT (n = 34) or CRT alone (n = 31). There was a high rate of grade 3/4 neutropenia (97%) but not neutropenic fever (12%) during neoadjuvant chemotherapy. No significant differences in rates of acute toxicities were observed between the two arms during CRT. Dose intensities of concurrent cisplatin, late RT toxicities and quality of life scores were comparable in both arms. The 3-year progression-free survival for neoadjuvant versus control arm was 88.2% and 59.5% (hazard ratio = 0.49; 95% CI, 0.20 to 1.19; P = .12). The 3-year overall survival for neoadjuvant versus control arm was 94.1% and 67.7% (hazard ratio = 0.24; 95% CI, 0.078 to 0.73; P = .012).

Neoadjuvant docetaxel-cisplatin followed by CRT was well tolerated with a manageable toxicity profile that allowed subsequent delivery of full-dose CRT. Preliminary results suggested a positive impact on survival. A phase III study to definitively test this neoadjuvant-concurrent strategy is warranted.

We examined the incidence of these events in 439 patients with WM, 193 and 136 of whom were previously treated with and without an NA, respectively, and 110 of whom had similar long-term follow-up without treatment. The median follow-up for all patients was 5 years.

Overall, 12 patients (6.2%) either developed transformation (n = 9; 4.7%) or developed t-MDS/AML (n = 3; 1.6%) among NA-treated patients, compared with one patient (0.4%) who developed transformation in the non-NA treated group (P < .001); no such events occurred among untreated patients. Transformation and t-MDS/AML occurred at a median of 5 years from onset of NA therapy. The median survival of NA-treated patients who developed transformation did not differ from other NA-treated patients as a result of effective salvage treatment used for transformed disease. However, all NA-treated patients who developed t-MDS/AML died at a median of 5 months.

These data demonstrate an increased incidence of disease transformation to high-grade NHL and the development of t-MDS/AML among patients with WM treated with NAs.

We evaluated 104 adult patients (median age, 41 years) who underwent unrelated donor UCBT for lymphoid malignancies. UCB grafts were two-antigen human leukocyte antigen–mismatched in 68%, and were composed of one (n = 78) or two (n = 26) units. Diagnoses were non-Hodgkin's lymphoma (NHL, n = 61), Hodgkin's lymphoma (HL, n = 29), and chronic lymphocytic leukemia (CLL, n = 14), with 87% having advanced disease and 60% having experienced failure with a prior autologous transplant. Sixty-four percent of patients received a reduced-intensity conditioning regimen and 46% low-dose total-body irradiation (TBI). Median follow-up was 18 months.

Cumulative incidence of neutrophil engraftment was 84% by day 60, with greater engraftment in recipients of higher CD34⁺ kg/cell dose (P = .0004). CI of non–relapse-related mortality (NRM) was 28% at 1 year, with a lower risk in patients treated with low-dose total-body irradiation (TBI; P = .03). Cumulative incidence of relapse or progression was 31% at 1 year, with a lower risk in recipients of double-unit UCBT (P = .03). The probability of progression-free survival (PFS) was 40% at 1 year, with improved survival in those with chemosensitive disease (49% v 34%; P = .03), who received conditioning regimens containing low-dose TBI (60% v 23%; P = .001), and higher nucleated cell dose (49% v 21%; P = .009).

UCBT is a viable treatment for adults with advanced lymphoid malignancies. Chemosensitive disease, use of low-dose TBI, and higher cell dose were factors associated with significantly better outcome.

Eligible patients were former or current smokers with chemotherapy-naive stage IIIB or IV NSCLC. All patients received up to six cycles of carboplatin (area under the curve = 6) and paclitaxel (200 mg/m²), with random assignment to one of the following three erlotinib treatments: erlotinib 150 mg on days 1 and 2 with chemotherapy on day 3 (150 PRE); erlotinib 1,500 mg on days 1 and 2 with chemotherapy on day 3 (1,500 PRE); or chemotherapy on day 1 with erlotinib 1,500 mg on days 2 and 3 (1,500 POST). The primary end point was response rate.

Eighty-six patients received treatment. The response rates for the 150 PRE, 1,500 PRE, and 1,500 POST arms were 18% (five of 28 patients), 34% (10 of 29 patients), and 28% (eight of 29 patients), respectively. The median overall survival times were 10, 15, and 10 months for the 150 PRE, 1,500 PRE, and 1,500 POST arms, respectively. The most common grade 3 and 4 toxicities were neutropenia (39%), fatigue (15%), and anemia (12%). Grade 3 and 4 rash and diarrhea were uncommon.

Patients treated on the 1,500 PRE arm had the highest response rate and longest survival, with ranges similar to those reported for carboplatin, paclitaxel, and bevacizumab in a more restricted population. Further evaluation of this strategy in a phase III trial is proposed.

Automated quantitative analysis, a fluorescent-based method for analysis of in situ protein expression, was used to assess a series of cell lines to find the threshold of detection of TTF1 expression. Then two independent cohorts (176 and 237 cases, respectively) were measured by the same technique, and TTF1 expression was correlated with survival.

Tumors expressed TTF1 in 45% and 58% of the cases in each cohort. TTF1 was consistently expressed in adenocarcinomas (n = 61 and 73; Spearman = 0.313 and 0.4 for the first and second set, respectively; P < .0001) independent of their differentiation and stage. Survival analysis showed that patients with stage I adenocarcinoma with TTF1 expression had a longer median overall survival than those without expression (n = 43, 44.3 v 26.2 months, P = .05 for the first cohort; n = 87; 49.7 v 38.5 months, P = .03 for the second cohort) Multivariate analysis revealed an independent lower risk of death for patients with stage I adenocarcinoma with TTF1-expressing tumors (hazard ratio = 0.479, 95% CI, 0.235 to 0.977; P = .043).

TTF1 expression defines a subgroup of patients with a favorable outcome and may be useful for prognostic stratification of patients with stage I lung adenocarcinoma.

This article is based on work done by and consultations obtained from leading experts in the field over a 6-month period that culminated in a full-day symposium designed to systematically review the most pertinent MEDLINE published reports and develop a roadmap to elucidate the molecular steps of carcinogenesis, reduce the extent or prevent the need for therapies, eliminate recurrences, and reduce morbidity.

Expression profiling of pure DCIS will help elucidate the molecular characteristics that distinguish high-risk lesions from clinically irrelevant lesions. The development of new methods of extracting RNA from processed tissues may provide opportunities for research. Mammography often underestimates the pathologic extent of DCIS; other imaging methods need to be investigated for detection and monitoring of disease stability or progression. Novel biologic agents are being delivered in neoadjuvant clinical trials, and alternative methods for breast irradiation are being studied. Future trials of treatment versus no treatment for biologically selected cases of DCIS should be developed.

There is a critical need for a concerted international effort among patients with DCIS, clinicians, and basic scientists to conduct the research necessary to improve fundamental understanding of the biology and clinical behavior of DCIS and prevent development of invasive breast cancer.

The statistical and clinical significance of 13 potential prognostic factors were analyzed in a cohort of 8,800 children diagnosed with NB between 1990 and 2002 from North America and Australia (Children's Oncology Group), Europe (International Society of Pediatric Oncology Europe Neuroblastoma Group and German Pediatric Oncology and Hematology Group), and Japan. Survival tree regression analyses using event-free survival (EFS) as the primary end point were performed to test the prognostic significance of the 13 factors.

Stage, age, histologic category, grade of tumor differentiation, the status of the MYCN oncogene, chromosome 11q status, and DNA ploidy were the most highly statistically significant and clinically relevant factors. A new staging system (INRG Staging System) based on clinical criteria and tumor imaging was developed for the INRG Classification System. The optimal age cutoff was determined to be between 15 and 19 months, and 18 months was selected for the classification system. Sixteen pretreatment groups were defined on the basis of clinical criteria and statistically significantly different EFS of the cohort stratified by the INRG criteria. Patients with 5-year EFS more than 85%, more than 75% to ≤ 85%, ≥ 50% to ≤ 75%, or less than 50% were classified as very low risk, low risk, intermediate risk, or high risk, respectively.

By defining homogenous pretreatment patient cohorts, the INRG classification system will greatly facilitate the comparison of risk-based clinical trials conducted in different regions of the world and the development of international collaborative studies.

To stage patients before any treatment, the INRG Task Force, consisting of neuroblastoma experts from Australia/New Zealand, China, Europe, Japan, and North America, developed a new INRG staging system (INRGSS) based on clinical criteria and image-defined risk factors (IDRFs). To investigate the impact of IDRFs on outcome, survival analyses were performed on 661 European patients with INSS stages 1, 2, or 3 disease for whom IDRFs were known.

In the INGRSS, locoregional tumors are staged L1 or L2 based on the absence or presence of one or more of 20 IDRFs, respectively. Metastatic tumors are defined as stage M, except for stage MS, in which metastases are confined to the skin, liver, and/or bone marrow in children younger than 18 months of age. Within the 661-patient cohort, IDRFs were present (ie, stage L2) in 21% of patients with stage 1, 45% of patients with stage 2, and 94% of patients with stage 3 disease. Patients with INRGSS stage L2 disease had significantly lower 5-year event-free survival than those with INRGSS stage L1 disease (78% ± 4% v 90% ± 3%; P = .0010).

Use of the new staging (INRGSS) and risk classification (INRG) of neuroblastoma will greatly facilitate the comparison of risk-based clinical trials conducted in different regions of the world.

Patients were eligible if they had measurable disease and had previously received an anthracycline and/or a taxane in the neoadjuvant, adjuvant, or metastatic setting. The primary end point of the study was tumor response per Response Evaluation Criteria in Solid Tumors (RECIST). The study was designed in two stages. Sorafenib was administered as 400 mg twice daily on days 1 through 28 of each 4-week cycle.

Twenty-three patients were enrolled with a median age of 54 years (range, 37 to 70 years). Twenty-two (96%) had prior anthracycline treatment and 16 (70%) had prior taxane treatment. Patients received sorafenib for a median of two cycles (range, one to 15 cycles) with a median follow-up of 2.4 years (range, 2.2 to 2.6 years). There were no grade 4 toxicities and few grade 3 toxicities. Among the 20 patients eligible for efficacy analysis, no patients experienced a partial response or complete response per RECIST criteria. Thus, the trial stopped at the end of the first stage per study design. Two patients (10%; 90% CI, 1.8% to 28.3%) achieved stable disease lasting longer than 6 months.

Sorafenib as a single agent, although well tolerated, did not exhibit activity when measured by tumor shrinkage in patients with MBC who had received prior treatment. Further research should focus on combinations with standard therapy and end points more sensitive to effects of targeted agents, such as disease stabilization.

The 10-year Kaplan-Meier (KM) local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), and breast cancer–specific survival (BCSS) were computed for 6,428 women who had T1 to 2, N0 to 1, M0 breast cancer that was diagnosed in British Columbia between 1989 and 2003, and who were treated with BCS and RT without chemotherapy. Intervals from BCS to RT were grouped by weeks as follows: ≤ 4 (n = 83), greater than 4 to 8 (n = 2,288; reference group); greater than 8 to 12 (n = 2,606); greater than 12 to 16 (n = 961); greater than 16 to 20 (n = 358); and greater than 20 weeks (n = 132). Cox proportional hazards models and matching were used to control for confounding variables.

The median follow-up time was 7.5 years. The 10-year KM outcomes were as follows: LRFS, 95.4%; DRFS, 90.5%; and BCSS, 92.5%. Compared with the greater than 4 to 8 weeks group, hazard ratios (HR) were not significantly different for any outcome among patients who were treated up to 20 weeks after BCS. However, LRFS (hazard ratio [HR], 2.00; P = .15), DRFS (HR, 1.86; P = .02) and BCSS (HR, 2.15; P = .009) were inferior for women with BCS-to-RT intervals greater than 20 weeks compared with those greater than 4 to 8 weeks. The matched analysis yielded similar results.

Outcomes were statistically similar for BCS-to-RT intervals up to 20 weeks, but they were inferior for intervals beyond 20 weeks. Time can be reasonably allowed for the breast to heal and for patients to consider treatment options, but RT should start within 20 weeks of BCS.

Two hundred eighty-eight consecutive patients who were surgically treated at a single referral center were analyzed. Because a shift toward a systematic, more aggressive surgical approach (ie, liberal en bloc resection of adjacent organs) was in place from 2002 onward, patients were divided in two groups accordingly. Overall survival, crude cumulative incidence (CCI) of local recurrence, and distant metastases were estimated. Univariable and multivariable analyses were carried out.

Patients who underwent operation in the early period had a 5-year local recurrence rate of 48% compared with 28% for patients who were treated in the recent period. The number of distant metastases was greater in the recent group (22% v 13%), and overall survival was similar. In addition to the period of treatment, important independent determinants for local recurrence-free survival were histologic grade, histologic subtype, and radiation therapy. Overall, liposarcomas and grades 1 to 2 tumors had the greatest local benefit at 5 years.

In a single institution, the adoption of a policy of more liberal visceral en bloc resections was paralleled by greater local control. This benefit might translate into a prognostic improvement only on a longer follow-up for patients with a more indolent disease, whereas systemic failures seem to be the main problem in high-grade tumors. Radiation therapy could add some additional benefit to local outcome and possibly to survival.

A total of 382 patients with primary RPS were analyzed. Sixty-five patients had a simple resection of the tumor, 120 patients had a complete compartmental resection (systematic resection of noninvolved contiguous organs), 130 patients had a contiguously involved organ resection, 21 patients had a systematic re-excision, 38 patients had an incomplete gross resection, and eight patients had a biopsy alone. Radiotherapy and chemotherapy were administered to 121 and 145 patients, respectively.

One, 3-, and 5-year overall survival (OS) rates were 86% (95% CI, 0.82 to 0.89), 66% (95% CI, 0.61 to 0.71), and 57% (95% CI, 0.51 to 0.62), respectively. Median overall survival was 6 years. In the multivariate analysis, high grade, tumor rupture, gross residual disease, and positive margins were associated with decreased OS. Low grade, no tumor rupture, negative histologic margins, a high number of patients undergoing operation per center, and compartmental resection compared with standard procedures were associated with decreased abdominal recurrences. Compartmental resection is a significant variable, predicting a 3.29-fold lower rate of abdominal recurrence compared with simple complete resection.

Complete compartmental surgery without tumor rupture should be performed when possible to achieve clear margins. This surgery should be performed in a high-volume center. The role of adjuvant treatments should be evaluated in a randomized trial in association with this optimal surgery.

Sera from 670 E1694 patients banked at baseline and three additional time points were tested for S100B protein using chemiluminescence.

S100B testing results showed that the higher the S100B level is, the higher the risk of relapse and death, regardless of the cutoff value. Univariate analysis showed that baseline S100B ≥ 0.15 µg/L is significantly correlated with overall survival (OS; P = .01). Multivariate analysis was performed adjusting for significant prognostic factors (ulceration and lymph node status) and treatment. Baseline S100B was a significant prognostic factor for survival (hazard ratio = 1.39; 95% CI, 1.01 to 1.92; P = .043). S100B values measured at later time points over 1 year were also demonstrated to be significant prognostic factors for relapse-free survival (RFS) and OS. Lower S100B values at baseline and during follow-up were associated with longer survival. A changing S100B from low at baseline to high on follow-up seemed to be associated with the worst RFS and OS.

For patients with high-risk surgically resected melanoma, a high baseline or increasing serum S100B is an independent prognostic marker of risk for mortality that may allow us to refine the application of adjuvant therapy in the future.

In this population-based cohort study using data from the Cancer Registry and the Medical Birth Registry of Norway, 42,511 women, age 16 to 49 years and diagnosed with cancer from 1967 to 2002, were eligible. They were grouped as not pregnant (reference), pregnant, or lactating at diagnosis. Cause-specific survival for all sites combined, and for the most frequent malignancies, was investigated using a Cox proportional hazards model. An additional analysis with time-dependent covariates was performed for comparison of women with and without a postcancer pregnancy. The multivariate analyses were adjusted for age at diagnosis, extent of disease, and diagnostic periods.

For all sites combined, no intergroup differences in cause-specific death were seen, with hazard ratio (HR) of 1.03 (95% CI, 0.86 to 1.22) and HR 1.02 (95% CI, 0.86 to 1.22) for the pregnant and lactating groups, respectively. Patients with breast (HR, 1.95; 95% CI, 1.36 to 2.78) and ovarian cancer (HR, 2.23; 95% CI, 1.05 to 4.73) diagnosed during lactation had an increased risk of cause-specific death. Diagnosis of malignant melanoma during pregnancy slightly increased this risk. For all sites combined, the risk of cause-specific death was significantly decreased for women who had postcancer pregnancies.

In general, the diagnosis of most cancer types during pregnancy or lactation does not increase the risk of cause-specific death. Breast and ovarian cancer diagnosed during lactation represents an exception. We confirmed the "healthy mother effect" for women with a postcancer pregnancy.

PFH was a randomized control trial with two conditions, peer phone counseling (PC) and self-help (SH), that involved smokers (n = 796) enrolled in the CCSS cohort.

Long-term quit rates were higher in PC versus SH participants. Long-term smoking cessation outcomes were lower among those who were nicotine dependent, of lower educational levels, and among men, and were higher among those who used nicotine replacement therapy and who had higher levels of situational self-efficacy. There were no significant differences in relapse rates between conditions or in quit attempts among continued smokers.

Cessation rates continue to be significantly higher among participants in the PC condition versus SH, although the differences were not large. This article highlights differences in long-term engagement with smoking cessation among those who received the intervention.

Patients 16 to 85 years of age with primary AML, known karyotype, and uniform postremission chemotherapy enrolled onto two consecutive trials were eligible and were randomly assigned to induction either with a standard-dose (cytarabine, daunorubicin, and 6-thioguanine) and a high-dose (cytarabine and mitoxantrone) combination, or with two courses of the high-dose combination. Subgroups were defined by karyotype, nucleophosmin and FLT3 mutation, WBC count, serum lactate dehydrogenase, and residual blasts.

In 1,284 patients, the overall survival at 4 years in those younger and older than 60 years was 37% versus 16% (P < .001) and the ongoing remission duration was 46% versus 22% (P < .001). Similar age-related differences in outcome were found for all defined subgroups. No difference in outcome according to randomly assigned treatment regimen was observed in any age group or prognostic subset. Regarding prognostic subgroups, molecular factors were also considered.

Under harmonized conditions, older and younger patients with AML show modest differences in their risk profiles and equally no dose response to intensified chemotherapy. Their observed fundamental difference in outcome across all subgroups remains unexplained. Further molecular investigation may elucidate the age effect in AML and identify new targets.

In a pragmatic randomized controlled trial, 115 patients with inoperable lung cancer were randomly assigned to receive either standard care or a structured QOL diary (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and the related lung cancer module LC13) that they completed at home each week for 16 weeks. Patients were encouraged to share the QOL information with health professionals involved in their care. Changes in QOL over time (measured by the Functional Assessment of Cancer Therapy–Lung questionnaire and the Palliative Care Quality of Life Index), discussion of patient problems, and satisfaction with communication and general care were assessed at baseline and at 2 and 4 months after baseline.

Analysis of QOL indicated a small but consistent difference between patients in the diary group and the standard care group. The diary group had a poorer QOL in many domains. Two different QOL summary scores (total and overall QOL) indicated a statistically significant between-group difference. No effects were found in relation to satisfaction with care, communication, or the discussion of patient problems.

The regular completion of a QOL questionnaire without appropriate feedback to health care professionals and without the provision of appropriate support may have a negative impact on inoperable lung cancer patients. Further research should focus on identifying features such as feedback loops that are required for the successful and meaningful use of QOL questionnaires in routine patient care.

Patients (age, 18 to 75 years; WHO ≤ 2) with ED-SCLC, and any response to chemotherapy, were randomly assigned to either observation or PCI. Health-related quality of life (HRQOL) and patient-reported symptoms were secondary end points. The European Organisation for the Research and Treatment of Cancer core HRQOL tool (Quality of Life Questionnaire C30) and brain module (Quality of Life Questionnaire Brain Cancer Module) were used to collect self-reported patient data. Six HRQOL scales were selected as primary HRQOL end points: global health status; hair loss; fatigue; and role, cognitive and emotional functioning. Assessments were performed at random assignment, 6 weeks, 3 months, and then 3-monthly up to 1 year and 6-monthly thereafter.

Compliance with the HRQOL assessment was 93.7% at baseline and dropped to 60% at 6 weeks. Short-term results up to 3 months showed that there was a negative impact of PCI on selected HRQOL scales. The largest mean difference between the two arms was observed for fatigue and hair loss. The impact of PCI on global health status as well as on functioning scores was more limited. For global health status, the observed mean difference was eight points on a scale 0 to 100 at 6 weeks (P = .018) and 3 months (P = .055).

PCI should be offered to all responding ED SCLC patients. Patients should be informed of the potential adverse effects from PCI. Clinicians should be alert to these; monitor their patients; and offer appropriate support, clinical, and psychosocial care.

Patients were given ch14.18 for 4 days at 28-day intervals. Patients received IL-2 during the second and fourth courses of ch14.18 and granulocyte-macrophage colony-stimulating factor (GM-CSF) during the first, third, and fifth courses. The MTD was determined based on toxicities occurring with the second course. After the determination of the MTD, additional patients were treated to confirm the MTD and to clarify appropriate supportive care.

Twenty-five patients were enrolled. The MTD of ch14.18 was determined to be 25 mg/m²/d for 4 days given concurrently with 4.5 x 10⁶ U/m²/d of IL-2 for 4 days. IL-2 was also given at a dose of 3 x 10⁶ U/m²/d for 4 days starting 1 week before ch14.18. Two patients experienced dose-limiting toxicity due to ch14.18 and IL-2. Common toxicities included pain, fever, nausea, emesis, diarrhea, urticaria, mild elevation of hepatic transaminases, capillary leak syndrome, and hypotension. No death attributable to toxicity of therapy occurred. No additional toxicity was seen when cis-retinoic acid (cis-RA) was given between courses of ch14.18. No patient treated at the MTD developed HACA.

ch14.18 in combination with IL-2 was tolerable in the early post-HDC/SCR period. cis-RA can be administered safely between courses of ch14.18 and cytokines.

Between 1987 and 1992, 945 men with locally advanced prostate cancer were randomly assigned to RT and adjuvant goserelin or RT alone. Fine and Gray's regression was used to evaluate treatment effect on cardiovascular mortality. Covariates included age, prevalent cardiovascular disease (CVD), hypertension, diabetes mellitus (DM), body mass index, race, Gleason score, stage, acid phosphatase level, prostatectomy history, and nodal involvement.

After a median follow-up of 8.1 years, there were 117 cardiovascular-related deaths but no treatment-related increase in cardiovascular mortality. At 9 years, cardiovascular mortality for men receiving adjuvant goserelin was 8.4% v 11.4% for men treated without adjuvant goserelin (Gray's P = .17). In multiple regression analyses, treatment arm was not significantly associated with increased risk of cardiovascular mortality (adjusted hazard ratio [HR] = 0.73; 95% CI, 0.47 to 1.15; P = .16; when censoring at time of salvage goserelin therapy, HR = 0.99; 95% CI, 0.58 to 1.69; P = .97). Traditional cardiac risk factors, including prevalent CVD and DM, were significantly associated with greater cardiovascular mortality.

GnRH agonists do not seem to increase cardiovascular mortality in men with locally advanced prostate cancer. Further studies are warranted to evaluate adverse effects of GnRH agonists in men with lower cancer-specific mortality.

We used linked Surveillance, Epidemiology and End Results-Medicare data to construct a cohort of men who underwent radical prostatectomy (RP) between 1991 and 1999 and who had positive regional lymph nodes. We classified men as receiving adjuvant ADT if they received ADT within 120 days of RP, and we compared them to the men who had not received adjuvant ADT. We used propensity scores to balance potential confounders of receiving adjuvant ADT (ie, tumor characteristics, extent of nodal disease, demographics, receipt of radiation therapy) and Cox proportional hazard methods to measure the impact of adjuvant ADT on overall survival (OS), stratified by propensity score quintile. We conducted a sensitivity analysis that used 90, 150, 180, and 365 days as the definition for adjuvant ADT.

A total of 731 men were identified, 209 of whom received ADT within 120 days of RP. There was no statistically significant difference in OS between the adjuvant ADT and non-ADT group (HR, 0.97; 95% CI, 0.71 to 1.27). There was no statistically significant survival difference with 90, 150, 180, and 365 days as the adjuvant ADT definition.

Deferring immediate ADT in men with positive lymph nodes after RP may not significantly compromise survival. Because observational studies should be considered hypothesis-generating studies, these results should be validated in a prospective fashion in a similar patient population.

The treatment regimen consisted of four to six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone followed by mobilizing therapy with either the dexamethasone, carmustine, melphalan, etoposide, and cytarabine protocol or the etoposide, methylprednisolone, cytarabine, and cisplatin protocol and stem-cell collection. Patients in complete remission (CR) or partial remission (PR) underwent myeloablative chemoradiotherapy (fractionated total-body irradiation and high-dose cyclophosphamide) and autoSCT.

From June 2000 to April 2006, 83 patients were enrolled onto the study. Main subgroups were PTCL not specified (n = 32) and angioimmunoblastic T-cell lymphoma (n = 27). Fifty-five (66%) of the 83 patients received transplantation. The main reason for not receiving autoSCT was progressive disease. In an intent-to-treat analysis, the overall response rate after myeloablative therapy was 66% (56% CR and 8% PR). With a median follow-up time of 33 months, 43 patients are alive; the estimated 3-year overall and disease-free survival rates for patients in CR (calculated from CR to the date of relapse) and 3-year progression-free survival rate were 48%, 53%, and 36%, respectively.

The results of this prospective study suggest a substantial impact on outcome for upfront autoSCT in PTCL and should be further evaluated in randomized trials. Pretransplantation treatment needs to be improved to increase the transplantation rate.

We conducted an analysis of CNS events from 20-year follow-up data on 899 eligible patients with aggressive lymphoma treated on Southwest Oncology Group protocol 8516, a randomized trial of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin), ProMACE (prednisone, methotrexate, doxorubicin, cyclophosphamide, etoposide)-CytaBOM (cytarabine, bleomycin, vincristine, methotrexate), and m-BACOD (methotrexate, bleomycin, cyclophosphamide, etoposide). Patients with BM involvement randomly assigned to receive ProMACE-CytaBOM (63 patients) or m-BACOD (58 patients) were to receive CNS prophylaxis, whereas those randomly assigned to receive CHOP or MACOP-B did not.

CNS relapse is uncommon (25 of 899 patients), with a cumulative incidence of 2.8%. CNS relapse occurs early (median time to relapse, 5.4 months from diagnosis). Indeed, 20 of 25 patients with CNS relapse relapsed during chemotherapy, or within 6 months of completion. The number of extranodal sites and the International Prognostic Index were predictive of CNS relapse. There was no significant benefit of CNS prophylaxis in patients with BM involvement at diagnosis; however, given the small number of events, the power of this analysis is limited.

The early occurrence of CNS events suggests that these patients had subclinical disease at initial diagnosis. As such, strategies to better detect and treat patients with subclinical CNS disease at diagnosis would be anticipated to result in a decrease in the incidence of CNS relapse, without subjecting those patients not destined for CNS relapse to unnecessary and potentially toxic prophylaxis strategies.