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4006 Background: Lymph node (LN) metastasis is associated with decreased survival in rectal cancer. It has been suggested that at least 14 LN be evaluated for adequate staging. However, a large percentage of patients have fewer than the recommended number of LN examined. We hypothesized that LN ratio would be predictive of overall survival in rectal cancer. Methods: Data was analyzed from Intergroup 0114, a mature trial of postoperative adjuvant chemotherapy and radiation in T3/4 and/or LN positive rectal cancer. Survival was the same for all arms allowing the entire group to be considered as one. The primary endpoint evaluated was overall survival. A proportional hazards model was used to determine the relative prognostic impact of LN ratio compared to number of LN examined, number of positive LN, number of negative LN and AJCC nodal stage. LN ratio was defined as the number of positive LN divided by the total number of LN examined. Four groups were analyzed based on proportion of positive LN: =0.25, >0.25–0.50, >0.50–0.75 and >0.75. Results: 1,648 patients were evaluable. There were 251 T1/2, 1,251 T3 and 146 T4 tumors. 513 patients were N0, 743 N1 and 392 N2. Median number of LN was 9. LN ratio was predictive of 5-year overall survival with rates of 0.71, 0.56, 0.50 and 0.43 respectively when analyzed by quartile (p15 nodes evaluated (p1 (p=0.04) and N2 (p=0.0002) disease. When comparing LN ratio (χ2=79.5, p2=4.7, p=0.03), number of positive LN (χ2=38, p2=32, p2=55.5, p No significant financial relationships to disclose.

3526 Background: In the US pts with stage II/III rectal cancer routinely receive pre or postoperative RT/FU. To date, in addition to chemoradiation, standard adjuvant chemotherapy has been limited to single agent FU. Improved survival with irinotecan and oxaliplatin in pts with metastatic colorectal cancer led to exploration of combination chemotherapy in the adjuvant setting in pts with rectal cancer. Methods: Pts on E3201 (T3–4 Nany M0, T1- 2 N + M0) had the option to receive FU with either pre- or postoperative RT (50.4 Gy). Pts were randomized to postoperative chemotherapy: FU (500mg/m2) + LV (500mg/m2) weekly x 6/8 wks x 3 cycles or irinotecan (FOLFIRI) (180mg/m2) vs oxaliplatin (FOLFOX) (85mg/m2) both administered with LV (400 mg/m2) FU (400mg/m2 bolus) + continuous FU (2.4 gm/m2/46 hours) q 2 wks x 8 cycles. Results: 225 pts of 3150 planned were recruited. 178 pts were randomized and 126 pts submitted treatment completion forms (accrual period 10/03–4/05). The Data Monitoring Committee closed E3201 when the GI Intergroup developed an alternative trial with bevacizumab (E5204). Toxicity information is reported for 93% of pts (165/178) ( Table ). There were no significant differences in toxicity between those pts treated with pre- vs postoperative RT/FU, although, for the subset of pts who received adjuvant FOLFIRI after postoperative RT/FU, there was a trend towards more diarrhea. Conclusion: FOLFOX as rectal adjuvant therapy is a common platform for new clinical trials, although there have been limited toxicity data reported. E3201 provides important comparative toxicity information demonstrating that FOLFOX can be safely administered to rectal cancer pts following chemoradiation. [Table: see text] [Table: see text]

10003 Background: Colon cancers exhibiting a high level of microsatellite instability (MSI-H) show distinct clinicopathological features, including both better prognosis and reduced response to 5-fluorouracil (5-FU)-based chemotherapy. We investigated the impact of adjuvant chemotherapy containing irinotecan in patients with MSI-H colon cancers. Methods: CALGB protocol 89803 randomized 1264 patients with resected stage III colon cancer to receive post-operative 5-FU and leucovorin (LV) with or without irinotecan. Paraffin blocks containing primary tumor and normal tissue were collected. Microsatellite instablility was assessed using a panel of mono- and di-nucleotide markers. Disease free survival (DFS) was measured from trial entry until documented disease progression or death from any cause. A statistical significance level of 0.2 was used in screening to generate hypotheses regarding MSI status and outcome. Median follow-up at analysis was 3.8 years. Overall C89803 showed no advantage for addition of irinotecan to 5-FU/LV. Results: Patients with and without tumor samples analyzed did not differ by treatment, age, gender, primary site, T-stage, differentiation, # positive nodes, or mucinous type. Of 482 tumors analyzed, 75 (16%) demonstrated MSI-H. MSI-H cancers were more likely to be located in the proximal colon (p [Table: see text]

3509 Background: FOLFIRI or FOLFOX are 1st-line treatments (Rx) for MCRC. Cetuximab is an IgG1 Mab that targets the epidermal growth factor receptor (EGFR) and is approved as monotherapy or in combination with irinotecan in irinotecan-refractory, EGFR + pts with MCRC. CALGB 80203 randomized untreated MCRC pts to FOLFOX or FOLFIRI ± cetuximab (independent of EGFR status.) Methods: Pts with performance status 0–1 with tumor blocks available for EGFR analysis received either irinotecan 180 mg/m2 over 1.5 hours (h) or oxaliplatin 85 mg/m2 over 2h combined with LV 400 mg/m2 over 2h and 5FU 400 mg/m2 bolus, then 46–48h CI 5FU 2400 mg/m2 q o w. Cetuximab dose: 400 mg/m2 loading dose, then 250 mg/m2 qw. Rx continued until progression or toxicity; subsequent Rx was not mandated although information was collected on such rx. Accrual goal was 2200 pts with intended 1° endpt of overall survival (OS). 80203 closed administratively in 1/05 (due to slow accrual) with 238 pts accrued. 2° endpts of response rate (RR), progression free survival (PFS), duration of R and toxicity are now able to be analyzed. Results: Accrual: FOLFIRI (A) - 61; FOLFIRI + cetuximab (B) - 59: FOLFOX (C) - 60; FOLFOX + cetuximab (D) - 58; approx median follow-up (f/u) is 12 months. RR (CR + PR, not all yet confirmed): A - 34%; B - 42%; C - 32%; D - 55%. RR was similar in the FOLFIRI or FOLFOX arms (A+B v. C+D; 38% v. 43%, p=0.44; chi-square) while C225 containing arms (B+D) v. non-C225 arms (A+C) had a superior RR (49% v. 33%; p=0.014, chi-square) It is too early to tell if there are differences in PFS, duration of response or OS. No significant differences in gr III diarrhea or any gr IV toxicities were seen. Conclusions: These results suggest that FOLFIRI and FOLFOX are similar in efficacy for pts with untreated MCRC and that adding cetuximab to either in1st-line Rx appears to increase response rates. PFS and duration of response do not appear different at this analysis. Further f/u and an analysis of prospective companion correlative studies may help to further clarify these results. [Table: see text]

4012 Background: CALGB 9781 was a prospective randomized Intergroup trial of trimodality therapy versus surgery alone for the treatment of stages 1–3 esophageal cancer. Methods: Five-hundred patients were targeted for enrollment with three years of follow-up planned. The primary endpoint was overall survival. All patents had EGD with biopsy, barium esophagogram and CT. Additional staging by EUS and/or thoracoscopy/laparoscopy was recommended. Patients were randomized to treatment with either surgery alone or cisplatin (100mg/m2) and 5FU (1000 mg/m2/d × 4d) weeks 1 and 5 concurrent with radiation therapy (50.4 Gy- 1.8 Gy/fx over 5.6 weeks) followed by esophagectomy with lymph node dissection. Results: A total of 56 patients were entered on study between October 1997 and March 2000 when the trial was closed due to poor accrual. Thirty patients were randomized to trimodality therapy and 26 to surgery alone. Patient characteristics were similar between groups. Surgical staging was conducted in just over 50% of patients in both groups. The primary toxicities of Gr 3 or greater with preoperative therapy were hematopoietic (54%), and esophagitis/dysphagia (40%). There were 14 and 17 patients with surgical complications on the trimodality and surgery alone arms, respectively, with 2 post-surgical deaths (within 30 days), both on the surgery alone arm. Postoperative hospital stays were 11.5 and 10 days, respectively. Median follow-up is 6 years. An intent- to- treat analysis showed a median survival of 4.5 yrs vs 1.8 yrs in favor of trimodality therapy (log-rank p=0.02). A log rank test with stratifications by N stage, staging approach and histology demonstrated a p-value of 0.005. 5-year survival was 39% (95% CI [21%, 57%]) vs 16% (95% CI [5%, 33%]) in favor of trimodality therapy. Analysis of progression-free survival is underway. Conclusions: This randomized study demonstrates a long-term survival advantage with the use of chemoradiation therapy followed by surgery in the treatment of esophageal cancer. Although accrual was well below that planned, the observed survival difference is statistically significant and suggests that trimodality therapy is an appropriate standard of care for patients with this disease. No significant financial relationships to disclose.

Colorectal cancer is the third most frequently diagnosed cancer in men and women in the United States. An estimated 104,950 new cases of colon cancer and 40,340 new cases of rectal cancer will occur in the United States in 2005. During the same year, an estimated 56,290 people will die from colon and rectal cancer. Because patients with localized colon cancer have a 90% 5-year survival rate, screening is a critical and particularly effective procedure for colorectal cancer prevention. Screening options include colonoscopy; combined fecal occult blood test (FOBT) and sigmoidoscopy; sigmoidoscopy alone; or double-contrast barium enema. For the most recent version of the guidelines, please visit NCCN.org

6514 Background: Mutations in RAS genes occur in 15–25% of AML pts. In vitro data suggest RAS mutations enhance sensitivity to cytarabine (Ara-C). We examined whether RAS mutation status impacts re...

3534 Background: Regular physical activity (PA) is strongly associated with a reduced risk of developing colon cancer. The influence of PA on the outcome of patients with established colon cancer i...

3530 Background: Regular aspirin use reduces the risk of colorectal neoplasia. In animals, aspirin and COX-2 inhibitors appear to inhibit tumor growth. The effect of aspirin use on outcome in patie...

3536 Background: Erbitux (Cetuximab), an IgG1 monoclonal antibody, is active in patients with metastatic colorectal cancer (CRC). A phase II study explored the activity of cetuximab in patients wit...

6007 Background: Previous studies have identified low patient accrual in large-scale cancer clinical trials, particularly for under-represented groups such as ethnic minorities, females, and patien...

Since t(8;21) and inv(16) disrupt core binding factor in AML and confer a favorable prognosis, these cytogenetic groups are often treated similarly, but hitherto have not been compared in a large study. We compared 144 adult AML patients (pts) with t(8;21) with 168 with inv(16) enrolled on the cytogenetic study CALGB 8461. t(8;21) pts were less frequently white (P=.01), had lower hemoglobin levels (P=.03), WBC (P Multivariable analysis (MVA) for CIR in pts Variable t(8;21) HR (95% CI); P inv(16) HR (95% CI); P HR=Hazard Ratio, CI=confidence intervals —, not included in final model Consolidation:Single vs multi-course HDAC 4.5 (2.1-9.4); In summary, once pretreatment factors and therapy are considered, the outcome of t(8;21) AML appears inferior to that of inv(16). Although these data should be confirmed prospectively, our analysis suggests that future studies should report the outcomes of pts with t(8;21) and inv(16) separately, and seek to identify and target therapeutically leukemogenic mechanisms accountable for these clinical differences.

Previous studies have identified broad cytogenetic risk groups in AML, by comparing outcome of pts with different recurring abnormalities, using cytogenetically normal pts as the reference group. Pts with better survival were considered as “favorable”, and those with worse outcome as “unfavorable” risk. To identify prognostic cytogenetic groups for complete remission (CR) and overall survival (OS), without the selection of a reference group, we used classification trees and tree-structured survival analysis (TSSA). We analyzed the outcome of 600 AML pts ≥60 years (yrs), enrolled in the prospective CALGB cytogenetic study 8461 and treated on CALGB front-line AML protocols. Analysis was restricted to cytogenetic aberrations occuring in ≥5 pts. Once prognostic cytogenetic abnormalities for CR and OS were identified, multivariable models were constructed. Median age was 68 (range, 60–86) yrs, and 98% had de novo AML. The most common karyotypes were normal (46%), complex with ≥3 abnormalities (complex ≥3, 19%), and ≥5 abnormalities (complex ≥5, 14%). Core binding factor ( CBF ) abnormalities, ie, inv(16) and t(8;21), occurred in 5%. Overall, 49.5% of pts achieved CR with only 7% (95%CI: 5%–9%) alive at 5 yrs. Table 1 shows prognostic cytogenetic risk groups identified by classification trees and TSSA for CR and OS, respectively. Table 1: Prognostic Cytogenetic Groups by Tree Analysis | CR | OS | |:------------------------------------------------:| ------- | ---------------------------------- | | Risk group | CR rate | Risk group | 5-yr OS (95% CI) | | *P

6542 Background: The optimal post-remission treatment (Rx) of AML patients with normal cytogenetics has not been extensively studied. Methods: We compared the outcome of 4 intensive post-remission treatment in 280 AML patients with normal cytogenetics, median age 44 (range, 18–59) years, who achieved complete remission (CR) on 5 successive front-line CALGB protocols. Patients were in CR after induction treatmen with AC + daunorubicin (D), ACD + etoposide (E) or ACDE + PSC-833. Post-remission intensification included 1 cycle HDAC (3 g/m2) followed by 1 cycle E+cyclophosphamide and 1 cycle mitoxantrone +diaziquone (Rx-I); HDAC for 3 cycles (Rx-II); IDAC (400 mg/m2) for 4 cycles or HDAC for 4 cycles (Rx-III), or HDAC+E followed by HD busulfan/E and ASCT (Rx-IV). IDAC and HDAC x 4 gave similar DFS (P=0.99) and OS (0.81) and were combined (I/HDAC) in further analysis. Median follow-up is 7.4 (range, 2.2–16.6) years. Results: The outcome of an intent-to-treat analysis of post-remission treatment is shown in the...

3500 Background: Irinotecan prolongs survival in second line 5FU-refractory metastatic colorectal cancer (MCRC). First line irinotecan, weekly bolus 5FU, and leucovorin (IFL) was superior to daily ...

3510 Background: Cetuximab (Erbitux) has demonstrated activity in patients with epidermal growth factor receptor (EGFR) expressing colorectal cancer (CRC) refractory to irinotecan (CPT-11) both as a single agent and in combination with irinotecan. This phase II study was designed to explore the activity of cetuximab in patients with EGFR+ CRC refractory to both CPT-11 and oxaliplatin (ox). Cetuximab is a chimeric monoclonal antibody that binds specifically to the EGFR preventing homo and heterodimerization and signal transduction. Methods: Patients were treated with cetuximab at standard doses 400 mg/m2 loading dose over 2 hours, then 250 mg/m2 over 1 hour weekly. Results: 350 patients with EGFR + CRC who had failed both CPT-11 and ox were enrolled. Median age 59; M:F::55:45; ECOG performance status 0:1::42:57. The most commonly encountered adverse events were an acne-like skin rash (84% any grade, 5% grade 3) and fatigue/malaise (40% any grade, 9% grade 3/4). Three patients experienced a grade 3/4 allerg...

4011 Background: In the treatment of advanced pancreatic cancer, chemotherapy regimens utilizing prolonged infusions of gemcitabine or combinations of gemcitabine and other agents have been associated with higher objective tumor response rates and, in some cases, improvements in progression-free survival when compared with gemcitabine administered as a standard 30-minute infusion. Comparisons between these novel regimens have been limited. We therefore performed a randomized phase II study of four investigational chemotherapy regimens in pts with documented metastatic pancreatic cancer. Methods: Pts were randomized to receive one of the following four treatments: gem 1000 mg/m2 d 1, 8, 15 with cisplatin 50 mg/m2 d1, 15 q 28d (Arm A); gem 1500 mg/m2 at a fixed dose rate of 10 mg/m2/minute d1, 8, 15 q 28d (Arm B); gem 1000 mg/m2 d1, 8 with docetaxel 40 mg/m2 d1, 8 q 21d (Arm C); or gem 1000 mg/m2 d1, 8 with irinotecan 100 mg/m2 d1, 8 q 21d (Arm D). Planned follow up per pt is 6 months. Results: Two hundred ...

3560 Background: 5FU and XRT administered preoperatively is a standard regimen for patients with T3/T4 rectal cancer. Preclinical data demonstrate radiation sensitization for O and 5FU. The aims we...

3506 The most important outcome predictor for resectable colon cancer (RCC) is the status of locoregional lymph nodes. This information is critical, as patients with positive nodes may benefit from...

3522 Background: MoAb 17–1A targets a cell surface antigen expressed on many adenocarcinomas and improved survival in early trials of adjuvant therapy in Stage III colon cancer. The primary clinica...

Between cell divisions the chromatin fiber of each chromosome is restricted to a subvolume of the interphase cell nucleus called chromosome territory. The internal organization of these chromosome territories is still largely unknown. We compared the large-scale chromatin structure of chromosome territories between several hematopoietic chicken cell types at various differentiation stages. Chromosome territories were labeled by fluorescence in situ hybridization in structurally preserved nuclei, recorded by confocal microscopy and evaluated visually and by quantitative image analysis. Chromosome territories in multipotent myeloid precursor cells appeared homogeneously stained and compact. The inactive lysozyme gene as well as the centromere of the lysozyme gene harboring chromosome located to the interior of the chromosome territory. In further differentiated cell types such as myeloblasts, macrophages and erythroblasts chromosome territories appeared increasingly diffuse, disaggregating to separable substructures. The lysozyme gene, which is gradually activated during the differentiation to activated macrophages, as well as the centromere were relocated increasingly to more external positions. Our results reveal a cell type specific constitution of chromosome territories. The data suggest that a repositioning of chromosomal loci during differentiation may be a consequence of general changes in chromosome territory morphology, not necessarily related to transcriptional changes.

Studies that use registry data have demonstrated superior long-term overall survival after curative surgical resection of colon cancer at hospitals where the volume of such surgeries is high. However, because such administrative data lack information on cancer recurrence, the true nature of this relation remains uncertain.To determine whether hospital procedure volume predicts long-term outcomes of colon cancer surgery.Nested cohort study within a randomized clinical trial.Intergroup 0089 national adjuvant colon cancer study conducted between 1988 and 1992.3161 patients with high-risk stage II and stage III colon cancer.Overall survival and recurrence-free survival, by hospital procedure volume as defined by Medicare claims data.With a median follow-up of 9.4 years, 5-year overall survival significantly differed across tertiles of hospital procedure volume (63.8% for patients who had resection at low-volume hospitals compared with 67.3% at high-volume hospitals; P = 0.04). After adjustment for other predictors of colon cancer outcome, the hazard ratio for overall mortality in patients treated at low-volume centers was 1.16 (95% CI, 1.03 to 1.32). However, the risk for cancer recurrence was not associated with hospital procedure volume. Five-year recurrence-free survival was 63.9% for patients who had resection at low-volume hospitals compared with 63.0% at high-volume hospitals (adjusted hazard ratio, 1.03 [CI, 0.89 to 1.18]). These findings did not materially change after stratification by other potential demographic and clinical predictors of outcome.According to prospectively recorded data from a large clinical trial, patients whose colon cancer was resected at low-volume hospitals experienced a higher risk for long-term mortality; however, this increased mortality was not attributable to differences in colon cancer recurrences.

Squamous cell carcinomas of the esophagus, while still frequent in many locations throughout the world, now comprise a smaller percentage of esophageal cancers in the United States than was previously believed. Such tumors occur most often in black men and in association with tobacco and alcohol abuse. Adenocarcinomas of the distal esophagus represent an increasing proportion of esophageal tumors. These neoplasms arise in columnar epithelium (ie, Barrett's esophagus) or extend into the esophagus from their site of origin in the proximal stomach. Esophageal adenocarcinomas appear more often in white than black subjects and in men more than women. The clinical features and diagnostic approaches to squamous cell tumors and adenocarcinomas of the esophagus are similar.

Purose. Determine the safety and efficacy of twice weekly gemcitabine and concurrent radiation to the upper abdomen followed by weekly gemcitabine in patients with surgically staged, locally advanced pancreatic cancer. Methods. Patients with surgically staged, locally advanced, nonmetastatic adenocarcinoma of the pancreas were treated with intravenous gemcitabine administered twice weekly (40 mg/m2/d) for 5 wk concurrent with upper abdominal radiation (50.4 Gy in 180 cGy daily fractions over 5.5 wk). At the completion of the chemoradiation, patients without disease progression were given gemcitabine (1000 mg/m2) weekly for five cycles. Each cycle consisted of 3 wk of treatment followed by 1 wk without treatment. Disease progression and response were assessed at 6- to 8-wk intervals. Results. From February through December 1999, 43 patients were entered into this phase II trial, 39 of whom were evaluable for treatment response. The median age was 59 yr (range: 39–84 yr); there were 18 males (47%) in the study. Grade III and IV hematologic toxicity occurred in 48 and 21% of patients, respectively, and was primarily leukocytopenia and neutropenia. Grade III and IV gastrointestinal toxicities occurred in 31 and 10% of patients, respectively. There was one death attributed to sepsis. The concurrent gemcitabine and radiation portion of the study was completed without treatment interruptions in 56% of patients. The overall median survival was 8.2 mo and the median survival in the 44% of patients demonstrating a sustained CA-19-9 response was 13.5 mo. Only six patients experienced local regional progression as their first site of failure. Two patients (5%) were still alive at 35 and 41 mo posttreatment. Conclusions. These results confirm the feasibility of twice weekly gemcitabine and radiation for the treatment of pancreatic cancer. Although this treatment strategy produced good local regional control, this did not result in a survival advantage. Stratifying patients by performance status and CA-19-9 response in future trials may be of value.

Background The practices of euthanasia and physician-assisted suicide remain controversial. Objective To achieve better understanding of attitudes and practices regarding euthanasia and physician-assisted suicide in the context of end-of-life care. Design Cohort study. Setting United States. Participants 3299 oncologists who are members of the American Society of Clinical Oncology. Measurements Responses to survey questions on attitudes toward euthanasia and physician-assisted suicide for a terminally ill patient with prostate cancer who has unremitting pain, requests for and performance of euthanasia and physician-assisted suicide, and sociodemographic characteristics. Results Of U.S. oncologists surveyed, 22.5% supported the use of physician-assisted suicide for a terminally ill patient with unremitting pain and 6.5% supported euthanasia. Oncologists who were reluctant to increase the dose of intravenous morphine for terminally ill patients in excruciating pain (odds ratio [OR], 0.61 [95% CI, 0.48 to 0.77]) and had sufficient time to talk to dying patients about end-of-life care issues (OR, 0.79 [CI, 0.71 to 0.87]) were less likely to support euthanasia or physician-assisted suicide. During their career, 3.7% of surveyed oncologists had performed euthanasia and 10.8% had performed physician-assisted suicide. Oncologists who were reluctant to increase the morphine dose for patients in excruciating pain (OR, 0.58 [CI, 0.43 to 0.79]) and those who believed that they had received adequate training in end-of-life care (OR, 0.86 [CI, 0.79 to 0.95]) were less likely to have performed euthanasia or physician-assisted suicide. Oncologists who reported not being able to obtain all the care that a dying patient needed were more likely to have performed euthanasia (P = 0.001). Conclusions Requests for euthanasia and physician-assisted suicide are likely to decrease as training in end-of-life care improves and the ability of physicians to provide this care to their patients is enhanced.

Many reform-minded observers of the U.S. health care system have asked recently whether we are training too many subspecialists in internal medicine. Of course, the answer to this question may not be the same for all subspecialties or all manners of professional career, but any proposed answer has extended consequences for the entire health care system and the patients it serves. Some have even begun to advocate a firm ceiling on the numbers of subspecialty training positions in the future. Who, in fact, should be deciding such matters? These decisions are complex and not easily made by government, consumers, or insurance companies on their own, nor should they. These decisions are best made by a profession willing to examine and regulate itself where necessary

To compare the pathogenesis, clinical presentation, therapy, and prognosis of primary central nervous system lymphoma in immunocompetent persons with these characteristics of the disease in patients with AIDS.All English-language papers published between 1980 and 1992 dealing with either lymphoma and the central nervous system or AIDS were reviewed. Patient characteristics, clinical presentation, histologic findings, and treatment and survival data were extracted from each case report and review.Data were available on 792 patients (from 40 reported series) with non-AIDS-associated primary central nervous system lymphoma and 315 patients (from 32 series) with AIDS-associated primary central nervous system lymphoma. Patients with AIDS initially consulted a physician more often when they had global neurologic symptoms compared with patients without AIDS, with more than 50% of the lesions on computed tomographic (CT) scans in patients with AIDS being ring-enhancing and multifocal, a pattern rarely described in immunocompetent patients. The overall survival of the patients without AIDS was 18.9 months compared with 2.6 months for patients with AIDS, with substantial differences remaining even for subgroups of patients similarly treated with radiation and chemotherapy.Primary central nervous system lymphoma is probably a substantially different disease in persons with and without AIDS with regard to patient characteristics, clinical and radiographic presentation, and prognosis. Recent advances in the treatment of this disease in patients without AIDS have not largely affected patients with AIDS. Substantial improvements in survival in these patients await advances in controlling their human immunodeficiency virus-associated disease.

• The purposes of this study were to determine whether continuous infusion of fluorouracil combined with externalbeam radiation therapy improved the resectability and survival of patients with pancreatic carcinoma. Sixteen patients with unresectable disease confined to the pancreas and celiac nodes were treated, and their outcome was compared with that of 24 patients with potentially resectable disease who were treated concurrently. The neoadjuvant therapy was completed with acceptably few toxic effects but with only a minor decrease in tumor size. Two patients underwent resection and remained free of disease 20 and 22.5 months later. However, the median survival of the entire neoadjuvant group was 8 months. All 24 patients with potentially resectable carcinoma underwent surgical exploration. Fifteen of the 24 patients underwent resection and survived a median of 12.5 months. Neoadjuvant chemoradiation may have improved outcome and resectability for two (12.5%) of 16 patients with unresectable pancreatic carcinoma, but more effective therapy options must be developed to improve outcome. ( Arch Surg . 1993;128:559-564)

After analysis of 26 prospectively accrued patients with distal rectal adenocarcinomas who underwent sphincter preservation treatment, we have concluded that tumors that invade only the submucosa can safely be treated with surgery alone and that tumors that invade the muscularis or further can be safely treated with surgery combined with chemoradiotherapy. None of the patients had either local or distant recurrence, with a median follow-up of 21 months. All patients have been fully continent. The results, although preliminary, imply that resection of distal rectal adenocarcinoma with sphincter preservation, and adjuvant therapy when appropriate, have achieved local and distant control equal to the conventional Miles' abdominoperineal resection, but without the need for a permanent colostomy.

The authorship of the report "The Modulation of Fluorouracil With Leucovorin in Metastatic Colorectal Carcinoma: A Randomized Phase III Trial," published in the October 1989 issue (J Clin Oncol 7:1419–1426, 1989) should have read: "by the Gastrointestinal Tumor Study Group." The following appendix should also have appeared at the end of the report

A rising CEA level is accepted as a sensitive indicator of recurrent colorectal carcinoma. In order to assess its efficacy in monitoring responses to chemotherapy in disseminated disease, 47 patients with documented metastatic colorectal cancer were studied. All had pretreatment CEA determinations and 40/47 (85%) patients had CEA levels greater than 4.0 ng/ml. Patients with hepatic metastases had the highest CEA values and none were found to have levels less than 4.0 ng/ml. Thirty patients received chemotherapy and had serial CEA determinations. 4/30 (13.3%) demonstrated probable tumor regression, 7/30 (23.3%) had stable disease, while 19/30 (63.3%) showed disease progression. CEA titers declined in all four responders, but in only one instance did the level fall to below 4.0 ng/ml and provide evidence of a tumor response not appreciated clinically. The only cytotoxic drugs effecting tumor regressions were 5-FU and 5-FUDR. CEA levels usually rose as disease progressed, but once elevated, absolute values did not correlate directly with tumor burden. The further usefulness of CEA assays in monitoring disseminated colorectal cancer awaits the development of improved chemotherapeutic agents.

The role of heparin in the treatment of the disseminated intravascular coagulation (DIC) associated with acute promyelocytic leukemia (APL) remains unclear. Between 1974 and 1985, we treated 27 patients with APL using four different chemotherapeutic regimens; 23/27 (85%) had evidence of DIC either at presentation or following the initiation of induction chemotherapy. The coagulopathy was treated primarily with fresh frozen plasma and platelet transfusions; only 2/27 (7%) patients received heparin. Twenty of 27 patients (74%) entered complete remission. Major bleeding or thrombotic complications occurred in 5/27 patients (19%), but 2 of these 5 patients presented after hemorrhage had already occurred. None of the 5 patients with bleeding or thrombosis entered complete remission. All of the hemorrhagic complications due to DIC in our study occurred before 1979, which may reflect changes in the management of leukemic patients. This observation emphasizes the risks inherent in the use of historical controls in this population. In conclusion the DIC associated with APL can be successfully treated with intensive blood product support without the use of heparin.

Fifty-two patients with advanced colorectal cancer were treated with a combination of 5-Fluorouracil (FU) plus methyl-1,3-cis (2-chlorethyl)-1-nitrosourea (MeCCNU). The treatment schedule program consisted of 5-FU, 300 mg/m2 i.v. bolus, daily for 5 days, repeated at 5-week cycles. MeCCNU was administered at a dose of 150 mg/m2 orally on day 1 of the initial 5-day course of FU and repeated at 10-week intervals. Eighty-four percent (44/52) of the patients with advanced measurable disease developed progressive disease by 4 months or one and a half cycles of therapy. Only two patients had definite partial regression of tumor over the period of observation. The median survival of all patients measured from the onset of treatment was 9 months and is comparable to literature reports of untreated advanced colorectal cancer. This therapeutic trial of combined FU and MeCCNU, employing a dose-schedule distinct from but comparable to previous studies has failed to confirm the substantial response rate reported by other investigators and reinforces the need for exploring new drugs and combinations of drugs in advanced colorectal cancer. The use of sequential plasma CEA determinations as a primary monitor of therapy is discussed in relationship to clinical trials and guidelines for determining significant quantitative changes in plasma CEA levels are recommended.

A randomized trial of Adriamycin (A) in combination with melphalan (M), (MA therapy), and in combination with M plus cyclophosphamide (C) (MAC therapy), was initiated in 40 evaluable patients with metastatic breast cancer. Twenty-two patients demonstrated an objective response to therapy: 9/20 to the MA regimen, and 13/20 to the MAC regimen. For the 22 responders, median duration of response is not yet achieved for either complete or partial responders, at 10 and 9 months, respectively. The addition of the two alkylating agents to Adriamycin was superior to the single alkylating agent addition, both in total response rate and in completeness of response. Maintenance therapy, after achieving the maximum cumulative dose of Adriamycin, was provided by cyclophosphamide plus methotrexate and 5-fluorouracil (CMF). In 19 patients completing induction and entering maintenance therapy, only one relapse has developed with maximun follow-up at 15 months.

Six patients with epithelial ovarian cancer had clinical diagnoses of central nervous system (CNS) metastases during a four-year period. A thorough review of the literature shows that involvement of the CNS by ovarian cancer is a rare phenomenon. Four of the six patients developed parenchymal brain metastases whereas carcinomatous meningitis was detected in the other two. These patients were younger and survived longer from initial diagnosis than the majority of women with ovarian cancer. Five of the six patients had previously received chemotherapy and had developed metastatic spread to extraperitoneal sites. Following extensive surgical resection, chemotherapy may provide intraperitoneal and systemic control, thereby extending survival and permitting occult CNS metastases to become apparent.

Colonic polyposis and carcinoma developed in a woman with Turcot's syndrome at the age of 31 years; astrocytoma developed when she was 37. Her brother and sister had died of astrocytoma at the ages of 18 and 33 years, respectively. Progressive neutropenia developed in the patient three months after radiotherapy for her brain tumor and acute myelomonocytic leukemia 19 months after treatment. Three laboratories independently evaluated cultures of her skin fibroblasts for in vitro sensitivity to cell killing (loss of colony-forming ability) by x-rays. Survival assays consistently revealed slight but significant radiosensitivity in an early-passage (six to 10 doublings) fibroblast subculture. A later subculture (21 to 29 doublings) showed no abnormality, a possible effect of selective in vitro loss of radiosensitive cells.