The presence of benign prostatic glandular tissue at surgical margins does not predict PSA recurrence

Background: Serum prostate specific antigen (PSA) increases after radical prostatectomy are thought to indicate recurrent disease, although some suggest they result from benign prostatic epithelial tissue left at surgical margins. Aims: To investigate whether presence, location, and extent of benign prostatic tissue at radical prostatectomy surgical margins influence patient outcome. Methods: One hundred and ninety nine patients with prostate cancer and negative surgical margins were studied. The prostectomy specimens were totally embedded using the whole mount technique. The apex and bladder neck, dissected as a cone from the specimen, were serially sectioned. The total length of benign prostatic tissue at the margins, measured for each location using an ocular micrometer, was obtained by summing the length of all positive sites. The presence, anatomical location, and extent of benign prostatic tissue at the margin were correlated with clinicopathological characteristics and postoperative PSA increases. Results: Fifty five cases had benign prostatic glandular tissue at the surgical margin. The mean length was 2.19 mm (0.1–14.7). The most frequent location of benign prostatic tissue was the apex (40 patients). Presence, anatomical location, and length of benign prostatic tissue at the margin were not significantly associated with age, preoperative PSA, prostate weight, pathological stage, tumour volume, largest tumour dimension, Gleason score, extraprostatic extension, seminal vesical invasion, tumour multifocality, perineural invasion, or PSA recurrence. Conclusions: Benign prostatic tissue was frequently found in margins of apex and bladder base, but uncommon in the anterior or posterior prostate. The presence of benign prostatic tissue at surgical margins had no prognostic relevance

Gefitinib plus celecoxib in chemotherapy-naïve patients with stage IIIB/IV non-small cell lung cancer (NSCLC): A phase II study from the Hoosier Oncology Group

7066 Background: Gefitinib, an inhibitor of the epidermal growth factor receptor (EGFR) pathway, has single agent activity in NSCLC. Preclinical studies demonstrate significant interactions between the EGFR and cyclo-oxygenase 2 (COX-2) pathways and that simultaneous inhibition against NSCLC may have benefits over gefitinib alone. Methods: Eligibility required that pts were chemotherapy-naïve, had stage IIIb (with pleural effusion) or IV NSCLC and an ECOG PS 0–1. Pts received gefitinib 250mg orally daily plus celecoxib 400mg orally every 12 hours. Cycles consisted of 21 day treatment and continued until unacceptable toxicity or progression of disease. The primary objective of this single arm, two-stage, phase II study was to evaluate the overall response rate. If ≤ 10 out of 30 pts achieved a complete (CR) or partial response (PR), the study would be stopped early. If &gt;10 out of 30 pts had a CR or PR, enrollment would continue to 50 pts. Results: From 1/04 to 11/04, 31 pts were enrolled: male/female 13/18; median age 70.8 years (range, 19–93); 67.7% had adenocarcinoma; ECOG PS 0/1 13/18; stage IIIb/IV 2/29; 5 were current smokers, 9 were remote (&gt;30 years) or never smokers, 16 quit smoking &gt; 3 months ago. Median number of cycles was 4 (range, 0–16). 6 pts (19.4%) discontinued therapy due to toxicity, including 3 who died due to treatment. Select grade 3/4 toxicities included: pulmonary (6.5%), hepatic (6.5%), diarrhea (6.5%), skin (3.2%). Responses included PR 5 (16.1%), stable disease 8 (25.8%), and progressive disease 18 (58.1%). Median duration of response, progression free survival, and overall survival was 5.7, 2.8, and 7.2 months, respectively. All responders were females with adenocarcinoma, 2 were remote or never smokers and 3 were former smokers. Conclusion: Gefitinib plus celecoxib in an unselected population of chemotherapy naïve patients with advanced NSCLC and a PS of 0–1 has a lower response rate and overall efficacy compared with historical controls of chemotherapy. [Table: see text] </jats:p

Pemetrexed in patients (pts) with relapsed small cell lung cancer (SCLC): A phase II study from the Hoosier Oncology Group

7063 Background: Patients with relapsed SCLC have a dismal prognosis. Pemetrexed is a well tolerated agent, which is active against non-small cell lung cancer. We postulated that Pemetrexed may also be active and well tolerated in pts with relapsed SCLC, for whom few effective options exist. Methods: Eligible pts had small cell or a poorly differentiated neuroendocrine cancer, received 1 or 2 prior chemotherapy regimens and had an ECOG PS 0–2. Pts received Pemetrexed 500 mg/m2 iv once every 3 weeks along with vitamin B12, folic acid, and dexamethasone for up to 6 cycles or progressive disease or intolerable side effects. Chemosensitive (S) pts (relapse &gt; 90 days following 1st line chemo) and chemoresistant (R) pts (PD ≤ 90 days following 1st line chemo) were analyzed separately. The primary objective of this phase II study was to estimate the clinical benefit rate [partial response (PR) or stable disease (SD)] in the 2 populations. Pts were to be accrued in 2 stages. If 8 of 18 and 3 of 21 pts achieved a PR or SD in the S and R populations, respectively, accrual would have continued to a total of 46 (S arm) and 50 (R arm) pts in each arm. Results: From 1/05 to 9/05, 43 pts were enrolled. Criteria to proceed to stage II were not met for either arm. S arm (n = 20): M/F 12/8; median age 63 (range, 45–79), PS 0/1/2 7/8/5. R arm (n = 23): M/F 17/6; median age 65 (range, 42–79), PS 0/1/2 7/10/6. Select grade 3/4 toxicities (combined group): 4 pts with neutropenia; 2 pts each with anemia, AST/ALT, bilirubin elevation; 1 pt each with thrombocytopenia, febrile neutropenia, infection with neutropenia, and rash. S arm: 1 PR and 1 SD were confirmed. R arm: 1 PR and 1 SD were confirmed. Conclusions: Pemetrexed 500 mg/m2 has minimal single agent activity in pts with relapsed SCLC. [Table: see text] </jats:p

Phase III study of cisplatin (P) plus etoposide (E) with concurrent chest radiation (XRT) followed by docetaxel (D) vs. observation in patients (pts) with stage III non-small cell lung cancer (NSCLC): An interim toxicity analysis of consolidation therapy

7043 Background: Concurrent chemo radiotherapy is the standard treatment for pts with unresectable stage III NSCLC. A previously reported phase II study (Gandara et al J Clin Oncol 2003) suggests that consolidation D after concurrent PE/XRT may further improve survival. HOG LUN01–24, is an ongoing phase III clinical trial comparing chemo radiation. A preliminary analysis of the differences in toxicities between PE/XRT with or without consolidation D was performed. Methods: Eligible pts had previously untreated, unresectable stage III NSCLC, ECOG PS 0–1 at time of study entry (and PS 0–2 at the time of randomization), ≤ 5% weight loss in preceding 3 months, FEV-1 &gt; 1 L. Treatment consisted of P 50 mg/m2 days 1, 8, 29, 36 with E 50 mg/m2 days 1–5 and 29–33, given concurrently with chest XRT to 5,940 cGy (180 cGy/day) beginning on day 1. Non-progressive pts were randomized (4–8 weeks after completing PE/XRT) to receive D 75 mg/m2 iv every 21 days for 3 cycles vs. observation. We report an interim toxicity analysis associated to consolidation D. Results: From 3/02 to 12/05 220 have been registered and 149 pts have been randomized to consolidation D (n=73) or observation (n=76). Median age was 63.6 years (range 33–86); male/female 34.1%/65.9%; PS 0/1 at study entry 59.1%/40.9%; stage III A/B 40.6%/59.4%; 50.2% had FEV-1 &gt; 2 (range 1–4.2); 44.3% were current smokers. Randomized pts have PS 0/1/2 44.3%/53%/2.7. Selected grade 3/4 toxicities associated to D include: neutropenia 23.3%, febrile neutropenia 8.2%, and pulmonary toxicity 9.6%. In addition, 26.7% of pts had dose modifications or delays on D arm, 45.2% had at least one grade 3/4 toxicity and 20.5% were hospitalized due to D-related toxicity, including 4 pts (5.5%) whose death was considered therapy related. Conclusions: Concurrent PE/XRT followed by consolidation D is associated with a high rate of grade 3/4 toxicities and hospitalizations, including treatment-related deaths. Updated toxicity data will be presented at the ASCO meeting. Whether consolidation D confers a survival advantage is not yet known. [Table: see text] </jats:p

Increased fat in pancreas not associated with risk of pancreatitis post-endoscopic retrograde cholangiopancreatography

Bhupesh Pokhrel,1 Eun Kwang Choi,1 Omer Khalid,2 Kumar Sandrasegaran,3 Evan L Fogel,1 Lee McHenry,1 Stuart Sherman,1 James Watkins,1 Gregory A Cote,1 Henry A Pitt,4 Nicholas J Zyromski,4 Beth Juliar,1 Glen A Lehman11Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, 2Department of Gastroenterology, St Louis University School of Medicine, St Louis, MO, 3Department of Radiology, 4Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USABackground: A preliminary study has shown increased pancreatic fat in patients with idiopathic pancreatitis and sphincter of Oddi dysfunction. In this study, we aimed to determine if an increased quantity of pancreatic fat is an independent risk factor for pancreatitis post-endoscopic retrograde cholangiopancreatography (ERCP).Methods: In this case control study, we retrospectively reviewed a local radiological and ERCP database to identify patients who had had abdominal magnetic resonance imaging (MRI) followed by ERCP no more than 60 days later between September 2003 and January 2011. Percentage of fat was determined by recording signal intensity in the in-phase (Sin) and out-of-phase (Sout) T1-weighted gradient sequences, and calculation of the fat fraction as (Sin - Sout)/(Sin) &times; 2 by an abdominal radiologist blinded to clinical history. Controls matched for age, gender, and other pancreatobiliary disease were selected from a group with no post-ERCP pancreatitis (before fat content of the pancreas was analyzed).Results: Forty-seven patients were enrolled. Compared with controls, subjects with post-ERCP pancreatitis were similar in terms of age (41.4 years versus 41.1 years), gender (21.2% versus 20.2% males), pancreatobiliary disease characteristics, and most ERCP techniques. Measurements of pancreatic head, body, and tail fat and body mass index were similar in patients and controls.Conclusion: Increased pancreatic fat on MRI criteria is not an independent predictor of post-ERCP pancreatitis.Keywords: magnetic resonance imaging, obesity, pancreatic fat, post-ERCP pancreatitis, sphincter of Oddi dysfunctio