Overall Survival Estimates For Patients Research Articles

Conditional Risks of Biochemical Failure and Prostate Cancer–Specific Death in Patients Undergoing External Beam Radiotherapy

As patients achieve years of survival after treatment for prostate cancer, the risk of biochemical failure (BF) or prostate cancer-specific death (PCSD) may evolve over time, with clinical relevance to both patients and clinicians. To determine conditional BF-free survival, PSCD, and overall survival estimates for patients with low- or intermediate-risk prostate cancer enrolled in the Radiation Therapy Oncology Group (RTOG) 0126 and RTOG 0415 clinical trials. A secondary objective was to determine whether prognostic factors at diagnosis remain relevant at later points in follow-up. A pooled secondary analysis of patients treated with external-beam radiotherapy alone and enrolled in the prospective randomized clinical trials RTOG 0126 and RTOG 0415 was performed. Patients included for analysis were enrolled between March 2002 and December 2009 with a median follow-up of 6.9 years. Overall survival was calculated using the Kaplan-Meier method at various survivorship time points. Cumulative incidence was used to calculate BF rates using the Phoenix definition, as well as PCSD. Risk factors such as Gleason score, tumor (T) stage, prostate-specific antigen level, and the equivalent dose in 2 Gy fractions of prescribed dose were analyzed at different time points using multivariable Cox proportional hazards modeling. Data were analyzed from November 2021 to February 2023. Conditional risks of BF and PCSD after completion of external-beam radiotherapy. A total of 2591 patients (median [IQR] age, 69 [63-73] years) were included in the study with a mean (range) PSA level of 7.1 (4.7-8.9) ng/mL, 1334 patients (51.5%) with a Gleason score 6 disease, and 1706 patients (65.8%) with T1 disease. Rates of BF from time of treatment were 1.63% (95% CI, 1.20%-2.18%) at 1 year, 7.04% (95% CI, 6.09%-8.08%) at 3 years, 12.54% (95% CI, 11.28%-13.88%) at 5 years, and 22.32% (95% CI, 20.46%-24.24%) at 8 years. For patients surviving 1, 3, and 5 years without BF, the rates of BF in the next 5 years were 14.20% (95% CI, 12.80%-15.66%), 17.19% (95% CI, 15.34%-19.14%), and 18.85% (95% CI, 16.21%-21.64%), respectively. At the initial time point, the rate of PCSD in the next 5 years was 0.66% (95% CI, 0.39%-1.04%). For patients who achieved 1, 3, 5, and 8 years of survivorship, the rates of PCSD in the next 5 years were 1.16% (95% CI, 0.77-1.67) at 1 year, 2.42% (95% CI, 1.74%-3.27%) at 3 years, 2.88% (95% CI, 2.01%-3.99%) at 5 years, and 3.49% (95% CI, 0.98%-8.73%) at 8 years. In this secondary analysis of 2 randomized clinical trials of patients undergoing external beam radiotherapy for prostate cancer, the conditional risks of BF and death from prostate cancer increased with time for patients with low- and intermediate-risk prostate cancer treated with radiotherapy alone. These results could inform optimal trial design and may be helpful information for patients evaluated in follow-up. ClinicalTrials.gov Identifier: NCT00033631; NCT00331773.

Prognostic impact of lymphopenia and neutrophil-lymphocyte ratio for patients with anal squamous cell carcinoma.

Outcomes after definitive chemoradiation for squamous cell carcinoma are generally favorable. However, biomarkers to further yield prognostic information are desired. Treatment-related lymphopenia as well as an elevated baseline neutrophil-lymphocyte ratio have been associated with worse survival in several cancer types. We evaluated absolute lymphocyte count and neutrophil-lymphocyte ratio at baseline and at treatment-related nadir in patients with anal cancer for associations with oncologic endpoints. We conducted a retrospective analysis of 428 consecutive patients with non-metastatic anal cancer treated with definitive, intensity-modulated radiation therapy-based chemoradiation. We analyzed absolute neutrophil and lymphocyte counts at several timepoints: pretreatment, weekly during treatment, and in the six weeks following treatment completion. Neutrophil-lymphocyte ratio was calculated at baseline and treatment-related nadir. We estimated oncologic endpoints using life tables and compared them using the log-rank test. We conducted univariate and multivariable time-to-event analyses using Cox proportional hazards. Median absolute lymphocyte count at baseline and nadir were 1.80 [interquartile range (IQR), 1.45-2.32] k/µL and 0.26 (IQR, 0.18-0.36) k/µL, respectively, and 31% developed treatment-related grade 4 lymphopenia. Median neutrophil-lymphocyte ratio at baseline and nadir were 2.34 (IQR, 1.68-3.30) and 8.80 (IQR, 5.86-12.68), respectively. Estimates of overall survival, local failure-free survival, distant metastasis-free survival (DMFS), and freedom from colostomy at 5 years were 87%, 86%, 82%, and 88%, respectively. Baseline and nadir absolute lymphocyte count were not associated with selected outcomes on univariate analysis. On multivariable analysis, factors independently associated with death included T3-T4 disease, HIV-positive status, treatment break, and baseline neutrophil-lymphocyte ratio >3. Baseline neutrophil-lymphocyte ratio showed a trend toward association with distant progression or death (P=0.07). The 5-year overall survival estimates for patients with baseline neutrophil-lymphocyte ratios ≤3 and >3 were 92.3% and 80.6%, respectively. Lymphopenia during and after chemoradiation for anal cancer is common but does not appear to be associated with worse survival, recurrence, or metastases. However, elevated baseline neutrophil-lymphocyte ratio was independently associated with overall survival, local recurrence-free survival, and DMFS. Further studies are needed to determine the clinical utility of baseline neutrophil-lymphocyte ratio to guide treatment and follow-up.

Axillary nodal metastatic burden in patients with breast cancer with clinically positive axillary nodes.

The aim of this study was to determine preoperative factors and tumour characteristics related to a high nodal tumour burden in patients with clinically node-positive breast cancer. These findings were used to construct a predictive tool to evaluate the patient-specific risk of having more than two axillary lymph node metastases. Altogether, 507 consecutive patients with breast cancer and axillary lymph node metastasis diagnosed by preoperative ultrasound-guided needle biopsy were reviewed. These patients underwent breast surgery and axillary lymph node dissection at Helsinki University Hospital between 2010 and 2014. Patients were grouped into those with one or two, and those with more than two lymph node metastases. There were 153 patients (30·2 per cent) with one or two lymph node metastases and 354 (69·8 per cent) with more than two metastases. Five-year disease-free survival was poorer for the latter group (P =0·032). Five-year overall survival estimates for patients with one or two and those with more than two lymph node metastases were 87·0 and 81·4 per cent respectively (P =0·215). In multivariable analysis, factors significantly associated with more than two lymph node metastases were: age, tumour size, lymphovascular invasion in the primary tumour, extracapsular extension of metastasis in lymph nodes, and morphology of lymph nodes. These factors were included in a multivariable predictive model, which had an area under the curve of 0·828 (95 per cent c.i. 0·787 to 0·869). The present study provides a patient-specific prediction model for evaluating nodal tumour burden in patients with clinically node-positive breast cancer.

Abstract P2-14-04: Delayed initiation of adjuvant chemotherapy in older women with breast cancer

Abstract Background: Early stage breast cancer patients benefit from adjuvant chemotherapy, but delays in initiation of treatment can negatively impact outcomes. Delays may be more common in older women. In this study we evaluate the survival impact of delays in adjuvant chemotherapy initiation in patients over 65 years of age and identify factors associated with delays. Methods: Patients age 66 years and older diagnosed between 2001 and 2013 with localized or regional breast cancer were identified in the SEER-Medicare and Texas Cancer Registry-Medicare databases. All patients received adjuvant chemotherapy within 9 months of surgery. Patients were required to have continuous Medicare Parts A and B coverage and no HMO enrollment 12 months before and 12 months after diagnosis. We grouped patients according to time from surgery to chemotherapy in 4 groups: 0-30, 31-60, 61-90, and > 90 days. Delayed chemotherapy initiation was defined as > 90 days. We used multivariable logistic regression to identify predictors of delayed chemotherapy. We estimated overall survival (OS) and breast cancer-specific survival (BCSS) using Kaplan-Meier method. Inverse probability treatment weights were applied to survival analyses. Cox proportional hazard models were used to determine the association between delays in chemotherapy and outcome after adjustment for other variables. Results: 25,902 women were included in the analysis, and the median age was 71 years. The median time from surgery to chemotherapy was 43 days. From 2001-2013 this interval increased from 38 days to 47 days (p < 0.001). Chemotherapy delays were observed in 10.6% of the patients. In multivariable analysis, factors associated with an increased risk in chemotherapy delays included: older age, black or Hispanic race/ethnicity, being single, more comorbidities, hormone receptor positivity, mastectomy, Oncotype DX testing, and having a full state buy-in Medicare plan. Chemotherapy delay was associated with worse OS. The 5 year OS estimates for patients receiving chemotherapy 0-30, 31-60, 61-90 and > 90 days after surgery were 0.82, 0.81, 0.80 and 0.73 respectively (p < 0.001). A similar trend was seen with BCSS (p < 0.001). After multivariable adjustment chemotherapy delay was associated with worse OS (HR=1.32, 95%CI 1.24-1.40) and BCSS (HR=1.38, 95%CI 1.24 - 1.52) compared with patients in the 0-30 day category. In a stratified analysis among patients with known breast cancer subtype, we observed that a delay in adjuvant chemotherapy initiation was associated with worse OS among patients with hormone receptor-positive (HR=1.45, 95%CI 1.05-2.01), HER2-positive (HR=1.52, 95%CI 1.03-2.23), and triple negative (HR=1.90, 95%CI 1.32-2.73) breast cancer. Discussion: Delays in initiating adjuvant chemotherapy in older women with breast cancer are associated with worse OS and BCSS. Our data demonstrates that delays should be avoided and should encourage providers to initiate chemotherapy ≤ 90 days after surgery. In addition, the multidisciplinary medical team should be aware of the socioeconomic factors that may impact patients’ ability to receive timely treatment. Further studies should seek to elucidate the causes of these inequities in care. Citation Format: Demetria Smith-Graziani, Xiudong Lei, Sharon Giordano, Hui Zhao, Meghan Karuturi, Mariana Chavez-MacGregor. Delayed initiation of adjuvant chemotherapy in older women with breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-14-04.

Adjuvant Radiation Improves Recurrence-Free Survival and Overall Survival in Adrenocortical Carcinoma.

Adrenocortical carcinoma (ACC) is a rare malignancy with high rates of recurrence and poor prognosis. The role of radiotherapy (RT) in localized ACC has been controversial, and RT is not routinely offered. To evaluate the benefit of adjuvant RT on outcomes in ACC. This is a retrospective propensity-matched analysis. All patients were seen through the University of Michigan's Endocrine Oncology program, and all those who underwent RT were treated at the University of Michigan. Of 424 patients with ACC, 78 were selected; 39 patients underwent adjuvant radiation. Adjuvant RT to the tumor bed and adjacent lymph nodes. Time to local failure, distant failure, or death. Median follow-up time was 4.21 years (95% CI, 2.79 to 4.94). The median radiation dose was 55 Gy (range, 45 to 60). The 3-year overall survival estimate for patients improved from 48.6% for patients without RT (95% CI, 29.7 to 65.2) to 77.7% (95% CI, 56.3 to 89.5) with RT, with a hazard ratio (HR) of 3.59 (95% CI, 1.60 to 8.09; P = 0.002). RT improved local recurrence-free survival (RFS) from 34.2% (95% CI, 18.8 to 50.3) to 59.5% (95% CI, 39.0 to 75.0), with an HR of 2.67 (95% CI, 1.38 to 5.19; P = 0.0035). RT improved all RFS from 18.3% (95% CI, 6.7 to 34.3) to 46.7% (95% CI, 26.9 to 64.3), with an HR 2.59 (95% CI, 1.40 to 4.79; P = 0.0024). In the largest single institution study to date, adjuvant RT after gross resection of ACC improved local RFS, all RFS, and overall survival in this propensity-matched analysis. Adjuvant RT should be considered a part of multidisciplinary management for patients with ACC.

Clinical significance and prognostic value of receptor conversion in hormone receptor positive breast cancers after neoadjuvant chemotherapy

BackgroundNeoadjuvant chemotherapy (NAC) is widely used in advanced breast cancer patients. However, there is little known about conversion frequency of estrogen receptor (ER) and/or progesterone receptor (PR) status for hormone receptor positive-breast cancer patients after NAC and their correlation with prognosis.MethodsIn this study, 231 breast cancer patients with residual disease after NAC were enrolled and divided into receptor stable group (having no conversion in both ER and PR status pre- and post-NAC) and any receptor conversion group (having any conversion in either ER or PR status). Univariate and multivariate survival analyses were used to compare survival differences between the two groups.ResultsFifty-five patients (23.8%) had ER and/or PR conversion after NAC. Younger patients (≤ 50 years) were more likely to have receptor conversion (P = 0.014). For 213 patients (92.2%) who received adjuvant endocrinotherapy after surgery, the 5-year disease free survival (DFS) estimates for patients in the any receptor conversion group (55.2%) was worse than patients in the receptor stable group (73.7%, Log-rank test, P = 0.015). While the 5-year overall survival estimates for patients with or without receptor conversion were not statistically different (86.0 vs. 82.4%, Log-rank test, P = 0.587). In multivariate Cox proportional hazard analyses, patients with any receptor conversion had worse DFS (hazard ratio, 1.995; 95% confidence interval, 1.130–3.521, P = 0.031).ConclusionsIt is necessary to recommend patients to test biomarkers in residual disease and pay more attention to patients who have any receptor conversion. These patients may need more individual therapy after surgery.

Neurocognitive Outcomes and Dosimetric Correlates in Central Nervous System Germ Cell Tumors

To evaluate clinical outcomes of patients with central nervous system germ cell tumor (CNS GCT) who received radiation therapy (RT) as a component of definitive treatment, with a focus on longitudinal neurocognitive outcomes in relation to radiation dose-volume parameters and clinical and pathologic variables. Sixty consecutively treated pediatric and young adult patients with CNS GCT who received definitive RT at our institution from 1995 to 2015 were reviewed. Forty-three patients underwent age appropriate neuropsychologic assessment with at least three measures of interest after diagnosis. Variance of neuropsychometric evaluations from normative means was evaluated by t-test. Differential dose-volume histograms for 14 brain volumes were obtained in 35 patients. Dose-volume parameters were modelled with time and clinical variables using neurocognitive test scores as the response variable. Median age at diagnosis of the overall cohort was 12 years (range, 2 – 28 years). Pure germinoma was diagnosed in 65% patients and nongerminomatous germ cell tumor (NGGCT) in 35%. Eighty six percent of patients were treated with craniospinal irradiation (CSI), 12% with whole ventricle irradiation, and 2% with focal RT. With a median follow-up of all patients of 6.2 years (range, 0.36 – 18.4 years), 5 patients developed recurrent disease, with all but one failing outside the high dose region. The 5 year event-free survival (EFS) and overall survival (OS) estimates for patients with pure germinoma were 91% and 100%, respectively, while 5 year EFS and OS estimates for patients with NGGCT were and 79.6% and 90.0%, respectively. The median time from start of RT to neurocognitive assessment was 4.1 years (range, 0.41 – 11.1 years). Domains significantly worse than normative expectations included intelligence, attention, memory, executive function, adaptive, psychosocial, visuomotor, and academic measures. Using the Conners’ Continuous Performance Test-II (CPT-II), there was an association between time after irradiation and mean dose to the mammillary bodies and Response Style Indicator (β) Scores were lower (less concern about mistakes) at a rate of -0.00167 points/Gy/day (p=0.007). Statistically significant (p≤0.05) associations were found between time and mean dose to several supratentorial brain regions (hippocampi, bilateral subventricular zones, left temporal lobe) and CPT Detectability (d') Scores were higher (lower discriminating power) at a rate ranging from 0.000345 to 0.00433 points/Gy/day. This study confirms excellent disease control rates achieved with RT as a component of CNS GCT management. However, patients do experience cognitive late effects of disease and treatment with deficits in attentional regulation associated with extent and location of irradiation. Ultimately, we aim to use identified dosimetric factors to inform proton-based treatment planning to limit these long term complications.

Outcome of radical cystectomy series in the management of muscle invasive bladder cancer: Liverpool experience.

396 Background: Cystectomy has become one of the standard forms of therapy for patients with muscle invasive bladder cancer with long term follow-up data supporting radical surgical management. Methods: Data are collected retrospectively on patients who underwent cystectomy at the Royal Liverpool University Hospital. The aim was to document the overall survival of patients undergoing cystectomy at this centre. Results: Data were collected on 147 patients between September 2007 and June 2013. Median patient age was 66 (IQR: 61, 72) with 33 (23%) females. 107 (73%) patients had muscle invasive TCC, 13 (9%) had recurrent non-muscle invasice disease, 9 (6%) had salvage surgery following radical radiotherapy and 6 (4%) had persistent carcinoma in situ. 28 patients (20%) had hydronephrosis. 34 (23%) patients underwent neo-adjuvant chemotherapy. 2 (1%) patients had Combined synchronous urethrectomy and 5 (3%) had Combined synchronous nephroureterectomy. Post operatively positive lymph nodes were observed in 22 (19%) of surgical specimens and 83 (72%) had persistent muscle invasive disease. Survival rates at 12 and 60 months are 0.92 (0.88, 0.97) and 0.52 (0.39, 0.71) respectively. Multivariate analysis show that post operative T (HR: 3.99 (1.05, 15.18)) and N (HR: 5.40 (2.17, 13.44)) status are both independent predictors of over all survival. Conclusions: Real life data from our centre showed that the patient population and overall survival estimates for patients with muscle invasive bladder cancer treated with radical cystectomy and lymph node dissection are consistent with previous published literature. .

Management Trends and Outcomes for Stage I to II Mantle Cell Lymphoma Using the National Cancer Data Base: Ascertaining the Ideal Treatment Paradigm

Mantle cell lymphoma (MCL) is a rare, albeit aggressive subset of non-Hodgkin lymphoma, resulting in varied treatment approaches. Given the paucity of data defining the optimal management for early-stage MCL, we conducted an analysis using the National Cancer Data Base (NCDB) to identify practice patterns and outcomes. The NCDB was queried for patients with stage I to II MCL diagnosed from 1998 to 2012 receiving chemotherapy (CT) or radiation therapy (RT), or both (CT+RT). Univariate and multivariable analyses for factors associated with treatment selection were completed using logistic regression. Propensity scores with inverse probability treatment weighting (IPTW) were calculated based on the conditional probability of receiving CT+RT. The log-rank test and Cox proportional hazards modeling with IPTW adjustment were conducted for the survival analyses. In total, 2539 patients were identified. The key characteristics were as follows: 69% were male, 71% were aged ≥60 years, 28% had extranodal involvement, and 51% had stage I disease. Of the 2539 patients, 70% underwent CT, 11% underwent RT, and 19% underwent CT+RT. The use of CT+RT decreased from 23.1% to 14.1% in 1998 to 2002 and 2010 to 2012 (P<.001). CT+RT usage was lower for patients with the following characteristics: age ≥60 years, female sex, stage II disease, and the presence of B symptoms. With a median follow-up period of 42.8 months, the unadjusted 3-year overall survival estimates for patients receiving CT, RT, or CT+RT were 67.8%, 72.4%, and 79.8%, respectively (P<.001). After correcting for indication bias through IPTW-adjusted modeling, CT+RT reduced the risk of overall mortality compared with monotherapy (hazard ratio 0.65, P=.029). Although uncommon, patients with stage I-II MCL can have favorable outcomes. Despite a continued decline in the usage of consolidative RT, combined modality therapy improves survival in this cohort compared with monotherapy.

A retrospective analysis of primary gastric diffuse large B-cell lymphoma with or without concomitant mucosa-associated lymphoid tissue (MALT) lymphoma components

Primary gastric diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease entity that includes patients with (DLBCL/MALT) and without detectable mucosa-associated lymphoid tissue (MALT) lymphoma components (de novo DLBCL). We sought to evaluate the clinical characteristics and outcome of this disease in a large number of cases. Patients with primary gastric DLBCL (n=162) seen on 2001-2011 at the Tianjin Medical University Cancer Institute and Hospital and the First affiliated Hospital of Chinese PLA General Hospital were retrospectively reviewed. The distribution of sex, age, Lugano staging, and other main clinical characteristics was similar between the de novo DLBCL and DLBCL/MALT groups (p>0.05). However, the proportion of patients with a stage-modified international prognostic index (m-IPI) ≥ 2 was higher in the de novo DLBCL (34 %) than the DLBCL/MALT group (17 %) (p=0.026). In addition, the Helicobacter pylori infection rates were higher in the DLBCL/MALT (75 %) than the de novo DLBCL group (36 %) (p<0.001). Five-year progression-free survival (PFS) and overall survival (OS) estimates were similar for patients in the de novo DLBCL (p=0.705) and DLBCL/MALT groups (p=0.846). Surgical treatment did not offer survival benefits when compared with chemotherapy for 5-year PFS (p=0.607) and OS estimates (p=0.554). There were no significant differences in 5-year PFS and OS estimates for patients treated with rituximab-chemotherapy (p=0.261) or conventional chemotherapy (p=0.227). Non-GCB subtype and m-IPI ≥ 2 were independently associated with shorter OS, and advanced stages of lymphoma were independently associated with shorter PFS.

Long-term outcome with lenalidomide and dexamethasone therapy for newly diagnosed multiple myeloma.

8096 Background: The combination of lenalidomide and dexamethasone (Len-Dex) is a commonly used initial therapy for newly diagnosed multiple myeloma. While the short-term outcomes with respect to response and toxicity is well-known, long-term outcome with this combination as initial therapy is not well described. Methods: We studied 286 consecutive patients with newly diagnosed MM seen at our institution, who received initial therapy with Len-Dex, and who had complete follow up records. Data regarding the clinical course was obtained from medical records. Results: The median (range) age at diagnosis was 63 (28-92) yrs; 166 (58% were ≤ 65 yrs and175 (61%) were male. The median estimated follow-up was 3.9 yrs (95% CI, 3.4, 4.2) and 203 (71%) pts were alive at the time of last follow up. The median estimated duration on Len-Dex was 5.3 mos (95% CI, 4.6, 6.4). The best overall response (≥PR) was 72%, including 26% with VGPR or better and 14 (5%) not being evaluable for a response. At last follow up, 41 (14%) patients were continuing on therapy. There were 93 pts (32%) who stayed on therapy for 12 months or more. Among these patients, the ORR was 86%, including 45% with VGPR or better. The median overall survival (OS) for the entire cohort from diagnosis was 7.4 yrs (95% CI; 5.8, NR) and the estimated 5-yr survival was 67%. There were 16 (5.5%) pts who died within a year of diagnosis. The median time to first disease progression, irrespective of transplant status, was 30.2 mos (95% CI, 25, 42). Overall, 143 (50%) of the patients have gone to stem cell transplant. Censoring those patients who proceeded to SCT prior to relapse at the time of BMT, the median TTP was 25.5 mos (95% CI, 22, 29). The median OS was 7.4 yrs for those ≤65 yrs, compared with 6.2 yrs for the older patients (P=0.01). The 5-yr OS estimate for patients in ISS stage 1, 2 and 3 were 82, 65, and 44 months respectively. Conclusions: The current study provides long-term estimates of responses and survival in a series of patients treated initially with lenalidomide and dexamethasone. The median survival of nearly 8 years reflects the efficacy of the novel agents both at diagnosis and at relapse and confirms the survival improvements seen in MM in the last decade.

Prognostic Factors in Renal Cell Carcinoma: Association of Preoperative Sodium Concentration with Survival

Conventional renal cell carcinoma (RCC) has a variable natural history, and determining individual prognosis is important to guide management. We have examined the prognostic significance of a large number of hematologic and biochemical variables, as well as traditional tumor-related factors in patients with RCC. Patients undergoing nephrectomy for newly diagnosed RCC between September 1998 and March 2005 were invited to participate. Clinical, pathologic, and laboratory data were recorded in each case, and immunophenotyping was carried out on a subset of patients. A planned subset analysis of patients presenting with N0M0 disease was done. Two hundred twelve patients with RCC formed the study population. In addition to tumor-related factors, multivariate analyses revealed preoperative serum sodium concentration to be independently and significantly associated with overall survival and disease-free survival when considered as both a continuous variable and when dichotomized to above and below the median value [139 mmol/L; reference range 135-145 mmol/L, hazard ratio 0.44, 95% confidence interval (95% CI) 0.22-0.88, P = 0.014]. Five-year overall survival estimates for patients above and below the median serum sodium were 67.6% (95% CI 54.2-80.9) and 44.3% (95% CI 32.8-55.8), respectively. These findings persisted in the N0M0 subgroup analysis. We have confirmed the prognostic value of traditional tumor-related factors but, to our knowledge, these are the first data to show that low preoperative sodium concentration may be an important factor associated with reduced survival in patients with RCC, suggesting that serum sodium should be considered with established prognostic variables in modeling survival in RCC.

Survival and Late Mortality in Long-Term Survivors of Pediatric CNS Tumors

To describe the pattern of survival and late mortality among contemporary long-term survivors of pediatric CNS tumor. The study population comprised 643 pediatric patients with primary CNS tumor treated at St Jude Children's Research Hospital (Memphis, TN) from 1985 to 2000 who survived > or = 5 years from diagnosis. Patients were classified according to primary tumor type, location of tumor, and survival. Cause of death was obtained from the medical record and categorized as progression, malignant transformation, second malignancy, medical complication, or external cause. Overall survival estimates for patients who survived at least 5 years postdiagnosis was 91.3% +/- 2% and 86% +/- 3% at 10 and 15 years postdiagnosis, respectively. A significant difference in the survival rates according to original tumor type (P = .001) was seen. Sixty-six (10%) of 643 patients experienced late mortality: 38 patients (58%) died of progressive disease while 14 patients (21%) died of second malignant tumor. Twelve patients (18%), predominantly with diencephalic tumor location, died of a specific medical cause: cardiovascular disease (n = 2), cerebrovascular accident (n = 1), metabolic collapse and/or sepsis (n = 7), respiratory failure (n = 1), or shunt malfunction (n = 1). Late mortality occurs in a substantial number of long-term survivors of pediatric CNS tumors and is most influenced by the initial tumor histopathology. Progressive disease remains the most common cause of death within the first decade of diagnosis. Teenage patients requiring treatment for panhypopituitarism may be especially vulnerable and deserve significant medical surveillance.

2302: Greater Than 6 Months of Androgen Deprivation Therapy Does Not Improve Overall Survival for High-Risk Prostate Cancer Patients Treated With Radiotherapy or Prostatectomy

To analyze the effect of the duration of androgen deprivation (AD) in the definitive treatment of high-risk prostate cancer. A total of 579 patients with high-risk prostate cancer were treated definitively at the Cleveland Clinic from 1998 to 2003 with either external beam radiation (RT, n=390), radical prostatectomy (RP, n=165), or permanent prostate implant (PI, n=24). High-risk disease was defined as: initial PSA (iPSA)> 20, Gleason score (GS) 8–10, clinical stage T3, or iPSA 10–20 and GS 7. The study endpoints were: biochemical failure [(bF), using the ASTRO consensus definition for RT and PI patients and two consecutive PSA’s ≥0.2ng/ml for RP patients], clinical failure [(cF), defined as the detection of biopsy proven local recurrence, or evidence of definite metastases to bone, lymph nodes, or elsewhere] and overall survival (OS). Cox proportional hazards regression was used to determine what factors, including iPSA, GS, stage, AD, age, race, income, BMI, and smoking history correlated with bF, cF, and OS. Median follow up was 60 months (range: 24–114). Median age for all patients was 67 years (range: 41–85). AD was given to 426 (73.6%) patients, with 82.6% of those patients receiving 1–6 months (median 6 months) and 17.4% receiving >6 months (median 15 months) of AD. Univariate analysis revealed that > 6 months of AD had no statistically significant impact on bF or cF, but did result in a statistically significant worse OS, (p=0.0003). Other factors found to result in worse OS on univariate analysis included GS ≥ 8 (p=0.0424), active tobacco use (p=0.0467), and increasing number of pack-years smoked (p=0.0139). Kaplan-Meier estimates of OS for patients receiving no AD vs. 1–6 months of AD vs. > 6 months of AD were 92%, 92%, and 76% at 5-years and 78%, 84%, and 67% at 7-years, respectively (p=0.0007). The use of >6 months of AD remained an independent predictor of death on multivariate analysis (RR 2.158, p=0.0329), as did Gleason score and increasing number of pack-years smoked. While smoking and use of >6 months of AD both had a detrimental effect on OS, no synergistic effect between the two factors was detected. In high-risk patients treated with radiotherapy or prostatectomy, longer duration of androgen deprivation (> 6 months) does not improve biochemical or clinical failure rates, and appears to result in worse overall survival. The cause of this lower overall survival is unknown and warrants further investigation.

Treatment of Anaplastic Histology Wilms' Tumor: Results From the Fifth National Wilms' Tumor Study

An objective of the fifth National Wilms' Tumor Study (NWTS-5) was to evaluate the efficacy of treatment regimens for anaplastic histology Wilms' tumor (AH). Prospective single-arm studies were conducted. Patients with stage I AH were treated with vincristine and dactinomycin for 18 weeks. Patients with stages II to IV diffuse AH were treated with vincristine, doxorubicin, cyclophosphamide, and etoposide for 24 weeks plus flank/abdominal radiation. A total of 2,596 patients with Wilms' tumor were enrolled onto NWTS-5, of whom 281 (10.8%) had AH. Four-year event-free survival (EFS) and overall survival (OS) estimates for assessable patients with stage I AH (n = 29) were 69.5% (95% CI, 46.9 to 84.0) and 82.6% (95% CI, 63.1 to 92.4). In comparison, 4-year EFS and OS estimates for patients with stage I favorable histology (FH; n = 473) were 92.4% (95% CI, 89.5 to 94.5) and 98.3% (95% CI, 96.4 to 99.2). Four-year EFS estimates for patients who underwent immediate nephrectomy with stages II (n = 23), III (n = 43), and IV (n = 15) diffuse AH were 82.6% (95% CI, 60.1 to 93.1), 64.7% (95% CI, 48.3 to 77.7), and 33.3% (95% CI, 12.2 to 56.4), respectively. OS was similar to EFS for these groups. There were no local recurrences among patients with stage II AH. Four-year EFS and OS estimates for patients with bilateral AH (n = 29) were 43.8% (95% CI, 24.2 to 61.8) and 55.2% (95% CI, 34.8 to 71.7), respectively. The prognosis for patients with stage I AH is worse than that for patients with stage I FH. Novel treatment strategies are needed to improve outcomes for patients with AH, especially those with stage III to V disease.

Adjuvant continuous infusion 5-FU, whole-abdominal radiation, and tumor bed boost in high-risk stage III colon carcinoma: A southwest oncology group pilot study

Results of a combined modality adjuvant pilot program of low-dose continuous-infusion 5-fluorouracil, whole-abdominal radiation, and tumor bed boost in patients with colon cancer with involved nodes and serosal involvement are presented. Forty-one eligible patients with completely resected T3N1-2M0 colon cancer (modified Astler-Coller C2) were treated with 5-fluorouracil (5-FU) at a dose of 200 mg/m2/day by continuous infusion and 30 Gy of concomitant whole-abdominal radiation in 1 Gy fractions. An additional 16 Gy boost to the tumor bed was administered in 1.6 Gy fractions. After completion of combined modality treatment and a 21-day rest period, patients received 4 days of 5-FU at a dose of 1000 mg/m2 by continuous infusion every 28 days for nine cycles. Five-year disease-free and overall survival estimates were 58 and 67%, respectively, for all T3N1-2 patients. Five-year disease-free and overall survival estimates for the 19 patients with four or fewer nodes were both 61%. Five-year disease-free survival and overall survival estimates for the 20 patients with more than four involved nodes were 55% and 74%, respectively (the exact number of involved nodes were unknown for two patients). Disease-free and overall survival estimates for patients treated with 5-FU and radiation compare favorably to the 5-FU plus levamisole arm of the intergroup adjuvant colon study (Int 0035/SWOG 8591) in patients with more than four positive nodes where the 5-year disease-free and overall survival estimates were 35% and 39%, respectively. Disease-free and overall survival estimates for patients with four or fewer nodes in the 5-FU plus levamisole arm of the intergroup study were 64 and 68%, which is not markedly different from results obtained with radiation and 5-FU in the current study. There were no treatment-related fatalities. Seventeen percent of patients had severe and 7% had life-threatening toxicity of any kind. One patient had an acute partial bowel obstruction and two patients had chronic low grade enteritis. Continuous infusion 5-FU and whole-abdominal radiation with tumor bed boost should be further investigated in a larger trial of T3N1-2 colon cancer.