bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined chemotherapy and surgery for metastatic gallbladder cancer improve median survival
Authors: Gallardo J. O. , Rubio B. , Díaz J. C. , Maluenda F. 
Published: March 2020

14136 Background: Metastatic gallbladder cancer (MGBC) is a rapidly progressive disease, orphan of treatment; its median survival is only 3 to 4 months. Since 1999 we had demonstrated that gemcitabine (Gem) and gemcitabine-cisplatin (Gem-plat) are active regimens against this disease, but median survival increases to only 8 months. We had seen some complete responses and cases with impressive partial responses, but all of them are transients, recurrence appears in all pts. The benefit of combining CHTx and surgery had not been tested in MGBC, but has demonstrated promising results in others GI cancers. Methods: A retrospective analysis was performed in data from 9 patients (pts) who had liver resection for MGBC. Gem o gem-plat was given to all patients. Between September 1999 and July 2005 we had included more than 70 pts in two trials and others 25 pts had been treated outside of clinical trials. Among then, 9 patients with metastases from MGBC who were treated with Gem ± plat, were sent for resection of residual tumors. All pts received radio-chemotherapy after resection The primary endpoint was overall survival. Safety was a secondary end point. Results: We report the results of the first 9 patients with at least 9 months follow-up post surgery. Median overall survival is 17 months (9+ - 24). Only one pt is free of recurrence, (at 9 months), all others died due to relapse. Liver was the most frequent site of recurrence (8/8), but also peritoneal cavity and duodenum. All pts presented recurrence distant to initial tumor site. Most possible explanation for recurrence in 3 cases was R1 resection. In the CHTx phase no one pts required a dose reduction. Grade ≥3 was rare, vomiting in 2.0%, febrile neutropenia in 1.3%. There was no toxic death. Surgical complications (within 30 days of surgery) were low, with no one requiring reoperation, and no deaths were observed. Conclusions: Chemotherapy with Gem ± cisplatin was safely administered. Surgical mortality and morbidity rates were low. Even though a high proportion of patients died due to relapse, and thus suggest that this approach in inconvenient, this combined therapy offer a double life expectancy compare to chemotherapy alone. No significant financial relationships to disclose.
Efficacy of gemcitabine/irinotecan in female patients ≤ 56 yrs with metastatic pancreatic cancer
Authors: Posey J. A. 
Published: March 2020

14139 Background: Pancreatic cancer remains extremely lethal due to marginally effective systemic therapies. Erlotinib, a tyrosine kinase inhibitor combined with gemzar has recently been approved for use in advanced disease for a modest improvement in survival. Other combinations with gemzar have demonstrated higher response rates in randomized trials, but without survival benefit. Gemzar and irinotecan was an early combination with promise from phase I/II findings; however, results from a randomized trial did not support wide use of the regimen. Methods: Five successive female patients, not on-study, with unresectable pancreatic cancer were treated with gemcitabine(Gem) and irinotecan (CPT-11) from 10/00 to 12/05 following a highly successful outcome in one patient who remains alive and without active disease. Two patients received Gem at 1 gm/m2/CPT-11 at 100 mg/m2 on days 1+8 every 21 days and three patients received fixed-dose rate (FDR) Gem 900 mg/m2 and CPT-11 at 100 mg/m2 on days 1 + 15 every 28 days. Ages at presentation were 47, 49, 50, 53, and 56. All patients had metastatic disease with primary tumors involving the head 2, body 2, and neck 1. One patient had recurrent metastatic disease following adjuvant xeloda/ XRT. One pt had a hx of diabetes. Number of courses ranged 4–12. One pt received in addition CI 5-FU/ XRT and 1 pt received 5 doses of FDR Gem prior to progressing and receiving combination treatment. Results: 39 courses of Gem/CPT-11 were administered on D1 + 8 or 15. Treatment delays occurred twice with both schedules due to grade 3 neutropenia. Grade ½ toxicities include nausea, fatigue, and diarrhea. 3 CR, {2 > 4 yrs}, 1SD, 1MR Conclusions: The quality and durability of the observed responses in this subset of pancreatic cancer patients’ has prompted an archival comparative tissue analysis of patients enrolled on PANCAN institutional trials during this period. No significant financial relationships to disclose.
Phase II study of concurrent S-1/cisplatin and radiation therapy in locally advanced or metastatic esophageal cancer
Authors: Cho S. , Shim H. , Ahn J. , Yang D. , Kim Y. , Park C. , Lee J. , Chung I. , Kim H. 
Published: March 2020

14154 Background: Although 5-FU and cisplatin had been widely used as radiosensitizer, the toxicities such as mucositis or bone marrow suppression were problematic. In this study, 5-FU was replaced with S-1. The primary end point of this study was to define the safety and the secondary end point was to evaluate the pathologic response and clinical efficacy as the first line therapy in locally advanced or metastatic esophageal cancer. Methods: Patients with locally advanced or metastatic esophageal cancer without history of previous chemotherapy or radiotherapy were eligible. Cisplatin was given intravenously with 75 mg/m2 on day 1 every 3 weeks. S-1 was administered at the dose of 80 mg/m2/day orally divided two times for 2 weeks followed by 1 week rest. Radiotherapy was started concomittently at day 1, total dose of 5040 cGY for 6 weeks. During radiotherapy, patients received 2 cycles of chemotherapy. Results: From May 2004 to Aug 2005, 33 patients were enrolled into this study. 6 patients were dropped out due to poor compliance (3), economic problem (2) and TEF (1) during treatment. 27 patients were evaluable for response and toxicity. The median age was 66 years (range, 54–82). Clinical response was 77.8% (21 pts) and pathologic response was shown in 29.6% (8 pts). The improvement of dysphagia was shown in 22 patients (81.5%). There were 7 (25.9%) pts with grade 3 neuropenia. Grade 3–4 odynophagia during concurrent chemoradiotherapy was observed only one patient. Conclusions: The concurrent chemoradiotherapy combined with S-1 and cisplatin was well tolerated and effective in advanced esophageal cancer to relieve obstructive symptoms and tumor regression. No significant financial relationships to disclose.
A phase I/II study of S-1 and CPT-11 therapy for patients (pts) with metastatic gastric carcinoma (GC)
Authors: Uetake H. , Inokuchi M. , Sugihara K. , Danenberg K. D. , Danenberg P. V. , Danenberg P. V. 
Published: March 2020

14156 Background: S-1 was recently developed as a first line chemotherapy for the treatment of metastatic GC. We performed a phase I study of S-1 plus CPT-11 therapy for metastatic GC and reported that the maximum tolerated dose and the recommended dose (RD) of CPT-11 were 90 and 80 mg/m2, respectively. Objectives of the present trial were to estimate the response rate (RR) of this regimen. Methods: Eligibility criteria were as follows; histologically proven CRC with measurable metastatic lesions, PS 0–2, age < 80, adequate organ functions, and written informed consent. No prior chemotherapy except adjuvant setting was allowed. S-1 was administered orally, 80 mg/m2/day on 14 consecutive days with 14 days’ rest for 4 weeks, and CPT-11 was infused at the RD in phase I trial on days 1 and 8. This schedule was repeated every 4 weeks. Results: Objective responses according to RECIST criteria were observed in 26 of the 42 pts (RR = 62%). Nineteen pts were with Grade 3 and 4 neutropenia and 10 with diarrhea Median survival time was 444 days. Intratumoral gene expression was analyzed using laser capture microdissection and RT-PCR method (Response Genetic Inc). Lower gene expression was observed in tumor cell of responder (P = 0.01). Conclusions: High RR and mild toxicity profile of S-1 plus biweekly CPT-11 therapy may be favorable for metastatic GC. No significant financial relationships to disclose.
Prognostic risk factors for survival following adjuvant chemotherapy for locally advanced urothelial bladder cancer
Authors: Cordia I. , Ohlmann C. H. , Engelmann U. , Heidenreich A. 
Published: March 2020

14510 Background: A recent meta-analysis has demonstrated a 25% relative risk reduction of death and an absolute survival benefit of 9% at 3 years for adjuvant chemotherapy following radical cystectomy (RCx) for lymph node positive bladder cancer. It was the aim of our analysis to identify predictors of survival following standard chemotherapy in lymph node positive bladder cancer. Methods: A retrospective analysis of 156 consecutive patients with lymph node positive urothelial bladder cancer was performed. All patients underwent systemic chemotherapy with 4 cycles gemictabine/cisplatin 4 to 6 weeks after RCx. The prognostic significance of the number of positive lymph nodes, lymph node diameter, extranodal extension, bilateral lymph node involvement, pT stage, grade, tumor diameter, presence of lymphatic (LI) or vascular invasion (VI) was analysed. Statistical analysis was performed by uni- and multivariate analysis. Results: Median follow-up is 6.5 (12 â€“ 3.5) years, minimum follow-up is 36 months. Median survival time is 56 months, 56% of the patients died due to tumor progression. pT stage (p = 0.002), tumor diameter (p = 0.005), LI (p = 0.0015) or VI (p = 0.0028), lymph node diameter (p = 0.026) and extranodal extension (p = 0.0002) were significant risk factors associated with survival by univariate analysis. Neither the number or bilaterality of positive lymph nodes nor tumor grade were associated with survival time. On multivariate analysis only extranodal extension (p = 0.001) and tumor diameter (p = 0.05) remained significant and independent prognostic predictors. Median survival was 64 and 21 months in patients with or w/o extranodal extension (p = 0.0001), resp.; median survival was 81 and 28 months in patients w/o and with LI/VI (p = 0.001). In patients with extranodal extension or LI/VI adjuvant chemotherapy had no impact on survival. Conclusions: Analysis of multiple pathohistological and clinical parameters reveal that extranodal extension, primary tumor diameter and presence of LI/VI represent risk factors predicting survival following adjuvant chemotherapy in lymph node positive bladder cancer. Patients exhibiting these adverse factors might be considered for a more aggressive systemic approach. No significant financial relationships to disclose.
Perioperative immunomodulation with interferon-alpha in patients with renal cell carcinoma: Early results of a controlled phase II trial
Authors: Klatte T. , Ittenson A. , Röhl F. , Ecke M. , Allhoff E. P. , Böhm M. 
Published: March 2020

14525 Background: Complex perioperative immunodysfunction occurs in patients with renal cell carcinoma undergoing surgery. Earlier, we presented evidence of a survival benefit in patients, who received perioperative immunomodulation with interleukin-2 (JCO 23 (16S):4601, 2005). Here, we report on the effect of interferon-alpha (IFN-α). Methods: Fifty-four consecutive patients, who underwent tumor nephrectomy, were enrolled into this prospective one stage phase II trial from June 2003 to May 2005. Patients were alternately assigned to the two study groups: 27 received immunomodulation with IFN-α (4 doses 9 million IU s.c a week before operation, followed by a daily dose of 3 million IU until a day before the operation), 27 did not. Parameters of immunity (differential blood count, CD3, CD4, CD8, CD16, CD19, CD28, CD56, HLA-DR, VEGF, IL-10) were measured in venous blood before and during IFN-α, one day before and immediately after the operation, and on the 1., 3., 5., and 10. postoperative day. The primary endpoint was tumor-specific survival. T-test, χ2-test and the log-rank test were used for statistical analysis. Results: The study groups did not differ with respect to age, sex, tumor stage and grade, histological type, operation time and technique. IFN-α related toxicity was WHO grade 0 (11%), 1 (59%), 2 (26%), and 3 (4%). During IFN-α administration leukocytes, CD19, HLA-DR and VEGF dropped significantly, while no difference was observed in T-cell and NK-cell markers, and IL-10. All patients showed postoperatively elevated leukocyte counts. T-cell and activation markers decreased, but CD3, CD4 and CD28 alterations were significantly less accentuated in patients who had been treated with IFN-α. Median follow-up was 14 months. The 1- and 2-year rates (±SE) of tumor-specific survival were 96% (±4%) and 83% (±12%) in the IFN-α group and 85% (±7%) and 85% (±7%) in the control group, respectively (p = 0.52). Also, no difference was seen in progression-free survival (p = 0.32). Conclusions: In this study with limited follow-up, perioperative IFN-α medication was not associated with a survival benefit, but was well tolerated. Interestingly, the decline in VEGF during administration suggests a role of IFN-α in the inhibition of angiogenesis. No significant financial relationships to disclose.
Pre-treatment PSA doubling time (PSADT) predicts biochemical response to chemotherapy in patients with androgen sensitive PSA progression after local therapy
Authors: Mehta A. , Stein M. , Goodin S. , Yao S. , Shih J. , Todd M. , Dipaola R. S. 
Published: March 2020

14528 Background: As phase III studies are developed in patients with androgen sensitive (AS) PSA progression after local therapy, efforts to stratify patients based on likelihood of benefit is critical. In an effort to define a pretreatment PSADT cutoff that predicts chemotherapy response in AS patients for use in hypothesis testing in phase III studies, we assessed patients with pretreatment PSA data in two of our prior published phase II studies of docetaxel (D) or mitoxantrone (M) chemotherapy in patients with AS PSA progression without metastasis. Methods: A retrospective analysis of PSADT was performed on 36 pts with AS PSA progression following local therapy without metastasis with available pretreatment PSA values (23 pts with D and 13 pts with M). PSADT was calculated as [LN(2)]/b, where b is the slope of the regression of LN(PSA) vs time. A t-test was used to compare the PSADT of responders vs non-responders; ANOVA was used for the combined data. A logistic regression analysis with ROC curves was used to evaluate the value of PSADT in discriminating response. Results: Mean PSADT of patients with ≥50% decrease in PSA with therapy was 204 vs. 99 days (P = 0.02). For D only, mean PSADT of pts with any PSA decrease (mean 52%) vs. increase was 211 vs. 115 days (P = 0.04). The mean PSADT of pts with ≥50% PSA decrease only on D was 203 vs. 174 days (P = 0.31). Overall, logistic regression analysis showed that PSADT is a good test to discriminate which pts will have some decrease in PSA while on treatment (P = 0.03). ROC curves (AUC = 0.807) for pts with a decline in PSA on treatment showed that the best balance of sensitivity and specificity was for a PSA DT cutoff of 70 days (sens = 70.0%, spec = 71.4%). Sensitivity was highest at a DT of 50 days (85%), and specificity at 180 days (93%). Conclusions: This study suggests that pretreatment PSADT may be a useful predictor of response to therapy in patients with AS PSA progression after local therapy, but will require larger confirmatory studies. A PSADT cutoff of 70 days can be considered to stratify patients in future trials in this patient population. No significant financial relationships to disclose.
A phase II trial of docetaxel plus carboplatin in hormone refractory prostate cancer (HRPC) patients who have progressed after prior docetaxel chemotherapy: Preliminary results
Authors: Oh W. K. , Manola J. , Ross R. W. , Berkowitz A. , Ryan C. W. , Eilers K. M. , Beer T. M. 
Published: March 2020

14533 Background: Treatment options for HRPC patients who progress after docetaxel chemotherapy are limited. Carboplatin may enhance the efficacy of docetaxel chemotherapy. Methods: We prospectively treated HRPC patients with documented PSA or radiographic progression during a minimum of 2 cycles of docetaxel-based chemotherapy or within 45 days of completing therapy. No prior platinum was allowed, though patients may have received other prior chemotherapy. Patients received docetaxel 60 mg/m2 and carboplatin AUC (4) every 21 days until progression or unacceptable toxicity. Measurable response was assessed by RECIST criteria. PSA declines were assessed per PSA Working Group; 2 patients were not evaluable as they received only 1 cycle of therapy but are included in the denominator. Results: Interim data is available on the 1st stage of patients (n = 16) enrolled in this ongoing phase II trial. Median age was 69 years (range 46–81), 94% white. Baseline performance status was 0 or 1 in 88%. Prior therapies included antiandrogens (80%) and ketoconazole (47%); docetaxel was used alone (33%), with estramustine (33%) or another agent (33%). Median PSA at baseline was 44 ng/ml (range 4.9–4801). Patients received a median of 3 cycles of docetaxel/carboplatin (range 1–12+). PSA declines of ≥50% were noted in 3 of 16 patients (19%, 90% C.I. 5–42%). In addition, 5 patients had SD, suggesting clinical benefit in 50% (90% C.I. 28–72%). Of 10 patients with measurable disease at baseline, 2 (20%; 90% C.I. 4–51%) had confirmed PR. Therapy was well-tolerated, with no treatment-related deaths and five grade 3 toxicities, including anemia (1), leukopenia (3) and hyperglycemia (1). Median time to progression was 2.7 months (range 0–13.4); median survival was 11.7 months (95% C.I. 6.7–14.0). Conclusions: In preliminary analyses, docetaxel plus carboplatin demonstrated encouraging activity in patients who progressed after docetaxel-based therapy. PSA declines ≥50% were seen in 19%; measurable responses in 20%. Accrual is ongoing. Final analyses will include correlation of response to serum markers of neuroendocrine differentiation. (Supported by BMS). No significant financial relationships to disclose.
Variation in local treatment of prostate cancer by hospital within New Jersey
Authors: Blom T. R. , Somer R. A. , Shih W. , Sarno M. , McNally D. , Todd M. , Yao S. , Lu-Yao G. , Dipaola R. , Stein M. N. 
Published: March 2020

14551 Background: Although prostate cancer diagnosis and treatment vary through the US, few studies have assessed variations in local therapy between multiple hospitals located within a very narrow geographic region. Methods: To determine the variation of diagnosis and treatment of prostate cancer between hospitals in a local region, data was derived and analyzed from 1,301 patients from fifteen Cancer Institute of New Jersey Oncology Group network hospitals. Tumor registry data from patients with a histological confirmed diagnosis of prostate cancer accessioned over a one-year period between January 1, 2003 and December 31, 2003 was analyzed by a multivariate logistic regression model. Results: Median age of the cohort was 66 and mean number of cases diagnosed at these hospitals for this period was 87 (26–161). When the cohort was assessed overall, 192 cases assessed were African American, 1049 Caucasian, 51 Hispanic, and 32 Asian. Median Gleason score was 6. A total of 463 patients underwent Prostatectomy, and 538 had radiation therapy. Multivariate analysis demonstrated that age and hospital were associated with use of surgery versus no surgery. Race and Gleason score were not associated with use of surgery in this group of hospitals. Multivariate analysis also demonstrated that age and hospital were associated with utilizing radiation therapy versus not utilizing radiation therapy. Again, race and Gleason score were not associated with utilization of radiation therapy in these NJ hospitals. Conclusions: Overall, the most important factors predicting for surgery, and radiation therapy, were age and hospital, which were independent of race and Gleason score. These data support our ongoing assessment of hospital and geographic characteristics that may be responsible for these associations. No significant financial relationships to disclose.
DHAIS (Diagnosis-Helping-Accuracy-Imaging-Study) study: Combined endorectal MR and MR spectroscopic imaging in the diagnosis of prostate cancer
Authors: Pomara G. , Simone M. , Fontana L. , Giusti S. , Bartolozzi C. , Francesca F. 
Published: March 2020

14562 Background: The DHAIS study is a prospective, three-step investigation, consisting in an initial two-step phase (Diagnosis-Accuracy) followed by an extension phase (Helping). The purpose was to compare endorectal MRI and MR spectroscopic imaging (MRSI) results with biopsy results (Diagnosis) and definitive histology after radical retropubic prostatectomy (RRP) (Accuracy). The helping extension will investigate the ability of combined MRI and MRSI to detect prostate cancer foci in men with prior negative prostate biopsy. Methods: MRI and MRSI were performed in 37 consecutive pts for increased PSA and/or abnormal rectal examination. A dedicated radiologist identified areas of interest as normal, equivocal or suspicious on MRI and MRSI separately. All pts underwent prostate biopsy (TRUS 10-core biopsy) by the urologist who was blind to imaging results. Patients with positive biopsies underwent RRP. MRI and MRSI results were compared to biopsy and step-section histology. Those pts with negative biopsies will underdo a second set of 10-core prostate biopsy with up to 4 additional biopsies targeted at the equivocal or suspected sites (Helping-phase). Results: Prostate cancer was detected in 8 of 37 subjects (21.6%). Six pts underwent RRP. The sensitivity, specificity, positive and negative predictive values (PPV, NPV) and the accuracy of MRI, MRSI and combined MRI/MRSI are shown in the Table. Conclusions: MRI and MRSI have the potential to identify cancer foci and potentially direct TRUS in patients undergoing TRUS biopsy. The third phase of this study could demonstrate the utility during repeated biopsies. Further larger studies are required to quantify the amount of benefit. [Table: see text] No significant financial relationships to disclose.