bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mortality trends in colorectal cancer (CRC) and influencing factors
Authors: Arrazubi V. , Majem M. , Navarro M. , Pareja L. , Biondo S. , Ribes J. , Cambray M. , Martínez-Villacampa M. , Soler G. , Germà J. 
Published: March 2020

13527 Background: A decline in overall cancer death rate was observed in the early 1990s after more than six decades of increase in cancer mortality. Effective prevention, screening and early detection as well as improved treatment strategies may be influencing factors. The aim of this study is to compare the overall survival of patients (pts) with CRC in two different years using our prospective regularly updated register database. Methods: Patients diagnosed of CRC during 1996 and 2000 were included in the study. To analyse the relation between variables the exact Fisher test was used. Survival curves were constructed according to the Kaplan-Meier method and compared by log rank analysis. Analyses were performed using the SPSS package. Results: 289 pts in 1996 and 380 in 2000 were included. Demographic data and tumour characteristics were similar in both groups. 42% of pts in 1996 and 56% in 2000 had received chemotherapy (ChT) (p<0.05). In adjuvant setting, 41.8% of patients with stage II-III colon cancer received ChT in 1996 and 57.5% in 2000 (p=0.019). ChT schedules for advanced CRC included Oxaliplatin and Irinotecan in 23% of ChT in 1996 and in 68% in 2000 (p<0.005). The number of palliative ChT lines was significantly higher in 2000 (p<0.05). Radiotherapy was administered as part of rectal cancer therapy to 48% of pts 1996 and to 60% in 2000 (p=0.05). From those, preoperative radiotherapy was administered to 21% of pts in 1996 and to 66% in 2000 (p<0.05). 4.1% of all pts were lost of follow up. With a median follow up of 104.5 months (m) for 1996 and 56.3 m for 2000, the 5-year overall survival (OS) was 45% and 61.6% respectively (p<0.001). The 5-year disease free survival (DFS) of pts with radical surgery was 73% and 81% respectively (p=0.09). The median survival of pts with radical surgery that relapse during follow up was 13.4 m in 1996 and 17.6 m in 2000 (p<0.04). There were statistical significant differences in OS between 1996 and 2000 in tumour site, stage II-III cancer and males, not in females. DFS for stages II-III was better in 2000, but no significant differences were observed. Conclusions: A positive CRC mortality trend was observed. The influencing factors were related with the use of ChT as an adjuvant treatment and the addition of new drugs in colon cancer therapies as well as preoperative radiotherapy for rectal cancer. No significant financial relationships to disclose.
Trends in rectal cancer survival in relation to the local control strategy
Authors: Latosinsky S. , Demers A. A. , Sun X. , Turner D. 
Published: March 2020

13536 Background: The Swedish Rectal Cancer Trial showed improved survival with improved local control due to adjuvant radiotherapy. Improved survival in several population-based studies, credited to improved local control due to quality assurance programs involving surgery, ± radiotherapy, has also been reported. In Manitoba (Canada) local control in rectal cancer was suboptimal in the mid 1990’s (local recurrence >18% in stage I-III) despite adopting the 1991 NIH chemo-radiotherapy guidelines. There continues to be no quality assurance program. We were interested in exploring trends in survival in Manitoba, particularly in the subset of patients where local control is an issue. Methods: All patients diagnosed with rectum and rectosigmoid adenocarcinoma from 1985 to 1999 were identified from the Manitoba Cancer Registry. Demographic, peri-operative and operative treatment information, and death dates were abstracted from the Registry. Manitoba population and death counts used in the calculation of age-specific relative survival probabilities were obtained from Statistics Canada. Survival was examined for all patients for the time periods of 1985–89, 1990–94 and 1995–99 and subsequently limited to those that underwent major rectal cancer surgery (Hartmann’s, anterior, and abdominal perineal resection). The Ederer II method was used in the estimation of survival probabilities. Results: A total of 3021 rectal cancer patients were identified with 1723 (57.0%) having major surgery. Five-year relative survival for all patients was 48.7%, 49.6% and 56.2% for the three periods respectively. The major surgery group results were 56.9%, 58.1% and 59.7%. Peri-operative radiotherapy was used in 38% of the 1995–99 major surgery group, twice the rate of 1985–89; peri-operative chemotherapy 41%, a ten-fold increase. Conclusions: Consistent with other studies, overall rectal cancer five-year survival in Manitoba has improved since 1985. Smaller survival improvements in the major surgery subgroup, despite increased radiotherapy use (as well as chemotherapy), suggests that better local control was not the major factor in the overall survival improvement, as has been suggested in other studies. Future work should include review of the local control strategy and factors to explain the improved survival. No significant financial relationships to disclose.
FOLFOX-4 vs. FOLFIRI vs. IROX as first line chemotherapy for metastatic colon cancer: efficacy and toxicity
Authors: Stanculeanu D. L. , Matache R. , Minea L. , Cringeanu A. , Anghel R. 
Published: March 2020

13541 Background: The combination of OXA or IRI with 5FU-LV are accepted as standard treatment for metastatic colorectal cancer. However, the right sequence in first or second line is still under debate. We developed a non-randomised prospective study in first line metastatic colorectal cancer comparing the efficacy and the toxicity of three different chemotherapy regimens - FOLFOX-4 vs. FOLFIRI vs. IROX. Methods: From January 2004 to January 2005 we included in the study 57 patients with metastatic non-resectable colon cancer - 22 in FOLFOX arm, 18 in FOLFIRI arm and 17 in IROX arm. In the FOLFOX arm patients received OXA 85 mg/m2 d1, LV 200 mg/m2 d1,2, 5FU 400 mg/m2 bolus d1,2, 5FU 600 mg/m2 as 22 hours CI d1,2 q15d; in the FOLFIRI arm - IRI 180 mg/m2, LV 400 mg/m2, 5FU 400 mg/m2 bolus and 5FU 2400 mg/m2 as 46 hours CI, q15d; in the IROX arm - IRI 300 mg/m2 d1, OXA 85 mg/m2 d2, q3w. The main patients characteristics were: median age 60 vs 62 vs 59; number of metastatic sites ≥ 2: 41% vs 33.33% vs 35.3%; performance status ECOG 0–1: 86.3% vs 83.3% vs 88.2%. The primary end-point was the objective response rate (CR + PR) and the secondary end-points was the toxicity. The objective response was evaluated every 3 months; at disease progression patients were offered to switch to a comparator regimen. Results: The objective response was 63.6% in FOLFOX arm (with a CR of 9%), 44% in FOLFIRI arm (CR - 5.5%) and 53% in IROX arm (CR - 11,7%); the stable disease rate - 27.3% in FOLFOX arm, 44.4% in FOLFIRI arm, 35.3% in IROX arm and the disease control rate - 91% in FOLFOX arm, 88.8% in FOLFIRI arm and 88.2% in IROX arm. The main grade 3–4 toxicities were: neutropenia - 22.7% vs 16.66% vs 29.4%; febrile neutropenia - 4.5% vs 5.5% vs 11.76%; diarrhea - 9% vs 22.2% vs 23.5%; nausea/vomiting - 4.5% vs 5.5% vs. 11.76%; neuropathy - 18.18% vs 0% vs 17.6%. No patients stoped the treatment because of side effects. Conclusions: All three regimens were well tolerated, with comparable results - with a slightly better disease control rate in the FOLFOX arm and a tendance of a better complete response rate in the IROX arm. The FOLFOX regimen had lower rates of nausea, vomiting, diarrhea; sensitive neuropathy and neutropenia were more common with regimens containing oxaliplatine. The IROX regimen had a higer incidence of adverse effects. No significant financial relationships to disclose.
Analysis of response pattern for patients with recurrent or metastatic colorectal cancer treated with Irinotecan, 5-FU, and low dose leucovorin (modified FOLFIRI) as 1st line chemotherapy
Authors: Lee M. A. , Kang J. H. , Hong Y. S. , Lee K. S. , Park S. M. , Kang W. K. , Park S. M. 
Published: March 2020

13546 Background: Irinotecan in combination with 5-fluorouracil (5-FU) and high dose leucovorin (LV), known as FOLFIRI regimen, has shown activity in recurrent or metastatic colorectal cancer. We analyzed the response pattern of irinotecan, 5-FU and low dose LV (modified FOLFIRI) as a first line therapy for patients with relapsed or metastatic colorectal cancer. Methods: Between September 2002 and November 2005, 46 patients with histologically confirmed recurrent or metastatic colorectal cancer were enrolled. The chemotherapy schedule consisted of irinotecan 180 mg/m2 intravenous (i.v) on day 1, 5-FU 400 mg/m2 as i.v bolus with 600 mg/m2 as a 22hr continuous infusion on day 1 and 2, leucovorin 20 mg/m2 on day 1 and 2, repeated every two weeks.We investigated the pattern of response to chemotherapy according to clinical parameters. Results: The overall response rate was 47.8%. There was no difference according to disease status and location of primary cancer, but Each metastatic lesions showed different response to chemotherapy. The response rate for metastatic lesions in liver was 54.2%, but only 7.7% for lung lesion. Most peritoneal lesions and lymphadenopathies showed stable disease (60.0% and 55.6%, respectively). 27 patients received 2nd line chemotherapy with oxaliplatin, 5-FU and leucovorin (FOLFOX regimen) after progressive disease. The overall response rate with FOLFOX was 15.2%. With 2nd line chemotherapy, response rate for lesions in liver was 23.5%, but 11.1% for lung lesions. For peritoneal seeding, no response was observed (72.7% stable disease). If the lesion did not achieve response to 1st line chemotherapy, it did not showed response to 2nd line treatment. Conclusions: The response to chemotherapy may be different according to metastatic site within same cancer. The lesions in liver may respond better than those in lung. If the lesion is classified ‘refractory‘ with 1st line treatment, or stage IV cancer with lung or peritoneal seeding only, we may consider more aggressive treatment to achieve better response. No significant financial relationships to disclose.
Does body mass index affect lymph node retrieval in colon resection for cancer?
Authors: Pimiento J. M. , Cristancho M. A. , Aboulhosn K. , Fancher T. , Palesty J. A. , Dudrick S. J. 
Published: March 2020

13571 Background: The management of colon cancer is a multidisciplinary effort that begins with adequate staging centered around the assessment of lymphatic spread. Multiple research groups have studied the number of lymph nodes retrieved and its relation with the outcome of patients with colon cancer, reporting better outcome in patients with a higher number of nodes retrieved. It has been well established that fatty tissue makes lymph node recovery difficult.Our objective was to evaluate if Body Mass Index (BMI) is associated with the number of lymph nodes retrieved, age, stage or location of the tumor. Methods: Retrospective chart review of patient who underwent colon resection for cancer between January 2001 to January 2005. Demographics, BMI and pathologic findings were recorded. Results: 395 patients had diagnosis of colon cancer, 140 underwent surgical procedures for these malignancies. Only 127 patients had complete records. The average age was 72 years. The average lymph node retrieval was 11.4. There was a significant relation between nodes harvested and specimen length (p 0.0028), age (p 0.0011), and stage IV cancer (p 0.002). There was no significant relationship between lymph node retrieval and BMI (p 0.1), location of the tumor (p 0.6) or stage I, II or III. Conclusion: We did not find any statistically significant correlation between BMI and lymph node retrieval, confirming reports that indicate the necessity of adequate lymph node harvest in patients with colon cancer for adequate staging and treatment. This may be because this study was done at a non-specialized center and because the operations were done by a number of different surgeons and the histopathology by numerous pathologists. The relation of improved lymph node harvest with greater specimen length supports other studies that point toward surgical and pathologic techniques as the most important factors in the appropriate staging of colon cancers. Hence, standardized surgical and histopathologic techniques need to be employed for harvesting adequate numbers of lymph nodes in resection specimens because number of nodes is critical to therapy, and an insufficient numbers of nodes may have a detrimental impact on colon cancer patient outcome. A prospective study should be performed in order to confirm the results of this study. No significant financial relationships to disclose.
Postoperative chemoradiotherapy in patients with rectal cancer, prognostic factors for disease control and survival
Authors: Hetnal M. , Malecki K. , Korzeniowski S. , Zemelka T. 
Published: March 2020

13575 Background: The aim of this paper is an assessment of results of adjuvant chemoradiotherapy in patients with rectal cancer with respect to prognostic factors, causes of treatment failures and treatment tolerance. Methods: 178 pts with Dukes’ stage B or C rectal cancer received postoperative chemoradiotherapy between 1993 and 2002. Median age was 62; 110 patients were males, 68 were females. Median follow-up time was 45 months. Main endpoints of the analysis were locoregional recurrence-free survival (LRRFS), distant relapse free survival (DRFS), disease free survival (DFS) and overall survival (OS). Kaplan-Meier method was used to calculate survival rates. Univariate and multivariate analyses of prognostic factors were performed using log rank and Cox’s proportional hazard method. Results: The 5-year LRRFS was 73%, DRFS was 80%, DFS was 61% and OS was 65%. Lymph node involvement and method of resection (AR favoured) were the only independent prognostic factors for LRRFS. Lymph node involvement, in particular when four or more are involved, was independent prognostic factors for DFS. For DRFS are histological grade, lymph node involvement and extracapsular extension of the lymph node metastases. For OS, the independent prognostic factors were infiltration of the pararectal fatty tissue, lymph node involvement in particular when four or more are involved, total number of chemotherapy cycles (at least six favoured). The 5-year LRRFS was 73%, DRFS was 80%, DFS was 61% and OS was 65%. Radiation therapy was well tolerated in 45% of patients. Most common early reactions were diarrhoea, nausea/vomiting and leucopoenia. Conclusions: Involvement of lymph nodes and method of resection were the only independent prognostic factors for LRRFS. Prognostic factors for OS were infiltration of the pararectal fatty tissue, lymph node metastases, four or more involved lymph nodes, total number of chemotherapy cycles. No significant financial relationships to disclose.
5-fluorouracil (5FU) pharmacokinetic and hormonal status in female colorectal cancer patients
Authors: Bononi A. , Gusella M. , Crepaldi G. , Padrini R. , Ferrazzi E. 
Published: March 2020

13576 Background: It is well known that females present a significantly reduced clearance of 5FU compared to males treated with the same doses.We tested the hypothesis that it may depend on the hormonal status, so that pre-menopausal women would have different 5FU pharmacokinetics compared with both postmenopausal women and elderly women. Methods: 48 colorectal cancer patients were prospectively studied: all of them were on adjuvant treatment based on 5FU repeated boluses. On the second day of the first cycle peripheral blood was drawn after drug administration. Plasma level were detected by HPLC analysis and pharmacokinetic parameters were calculated trough a one phase exponential decay model. Results: All patients had 100–90 Karnosky Performance status score. 12 were in pre-menopausal phase (age range : 40–55 years); among the others we distinguished a younger 19 people group (age lower than 70 years old) and an elderly 17 patient group (age equal or higher than 70 years old). They received a 5FU mean dose of 406 ± 15 mg/mq, not significantly different among the three groups. After intravenous bolus injection a high interindividual variability of 5-FU pharmacokinetics was detected: AUC0-∞ (area under the curve of drug plasma levels versus time) ranged between 368 and 1236 mg × min/L and the highest values (>1000) were found in two elderly patients, considered fit; anyway there was no significant difference among AUC of the three groups. 5FU total clearance ranged between 0.53 and 1.9 L/min and means were 1.07 ± 0.3, 1.02 ± 0.3 and 0.98 ± 0.3 L/min in pre-menopausal, postmenopausal and elderly women respectively; again 5FU clearance/ BSA (body surface area), half live elimination times and peak concentration plasma levels were not significantly different among the three groups. Conclusions: It seems that sexual hormonal status do not influence 5FU total body elimination capability, and that pharmacokinetic differences between genders should be related to other factors,as for example Body Composition. Funded by AIRC-Veneto No significant financial relationships to disclose.
Phase I study of pemetrexed plus cisplatin in unresectable, advanced gastric carcinoma in Taiwan
Authors: Chen J. , Chao Y. , Chen L. , Li C. , Reece W. , Khan R. , Pope E. , Otero J. C. 
Published: March 2020

14009 Background: Phase I of this Phase I/II study (H3E-AA-S038) was conducted to determine the recommended dose of pemetrexed (PT) when given with cisplatin (Cis) to patients with unresectable, advanced gastric carcinoma. Methods: Patients 18 to 70 years of age, with stage IV disease or post-surgery recurrence, no prior palliative chemotherapy, and an ECOG performance status of 0 or 1 were included. Patients received PT and Cis on Day 1 every 21 days. Cis was dosed at 75 mg/m2. PT dosage was planned at 600, 700, 800, and 900 mg/m2. Vitamin B12 and folic acid supplementation, and dexamethasone (or equivalent corticosteroid) prophylaxis were required. The initial number of patients to be enrolled per dose level (DL) was 3. If 0/3 patients had dose-limiting toxicity (DLT), PT dose was escalated. If 1/3 patients had DLT, 3 more patients were enrolled at that DL. If ≥2 patients had DLT, the dose was not escalated further. The recommended dose of PT for Phase II was the highest dose at which <2/6 patients experienced DLT. The following toxicities were defined as DLT: death due to toxicity; neutropenia [<0/5 × 109/L for ≥5 days, or <1.0 × 109/L with fever (≥38.5 ºC)]; thrombocytopenia (<10.0 × 109/L, or <50.0 × 109/L with bleeding); AST or ALT >20 × ULN; and non-hematological toxicities of CTC grade 3 or 4 (except nausea and vomiting). Intra-patient dose escalation was not permitted. Results: Sixteen patients were enrolled. The mean (±SD) age of enrolled patients was 52.8 (±10.0) years, and the majority were male (62.5%). At DL1, 0/3 patients experienced DLT. At DL2, 1/6 patients had DLT. At DL3, 3/7 patients had DLT, and so PT dose was not escalated. All DLTs occurred in cycle 1; 2 involved neutropenia, 1 tumor hemorrhage, and 1 hypokalemia. Grade 3/4 toxicities were experienced by 12/16 (75%) patients, including 9 (56%) hematological and 10 (63%) non-hematological events. Five out of thirteen (38%) patients with measurable disease had a RECIST response (2 had a complete response, 1 each at DL1 and DL2; 3 had a partial response, 2 at DL2 and 1 at DL3). At this interim analysis, 2 patients were still on therapy. Conclusions: The recommended dose of PT is 700 mg/m2. Phase II will examine response and safety of PT plus Cis in advanced gastric carcinoma. [Table: see text]
Targeted tumor therapy with the TGF-beta2 antisense compound AP 12009 for the treatment of advanced solid tumors
Authors: Oettle H. , Seufferlein T. , Schmid R. , Luger T. , Ludwig S. , Schmaus S. , Beyer M. , Fischer D. , Hafner M. , Schlingensiepen K. 
Published: March 2020

14012 Background: TGF-β overexpression in advanced tumors is correlated with tumor-induced immunosuppression, proliferation and angiogenesis. Furthermore, it is a key factor for induction of epithelial to mesenchymal transition (EMT), thus promoting invasion and metastasis. Targeted tumor therapy by an antisense oligonucleotide has already been proven to be successful in tumor therapy: AP 12009, a TGF-β2-mRNA-specific antisense oligodeoxynucleotide, has shown strong clinical indication of efficacy including complete and lasting remissions in malignant glioma. Methods: Spurred by the highly encouraging clinical data in malignant glioma and strong anti-tumor activity in a wide variety of preclinical assays, clinical studies in further indications were initiated. A multi-center dose-escalation phase I/II trial with AP 12009 in patients suffering from advanced solid tumors was started in 2005. Primary endpoint is to assess the maximum tolerated dose (MTD) as well as the dose-limiting toxicity (DLT). AP 12009 is administered i.v. in 14-day cycles. Results: Preclinically, in human pancreatic cancer and melanoma cell cultures AP 12009 significantly reduced the TGF-β2 secretion of cancer cells, inhibited tumor cell proliferation, and blocked migration of cancer cells. Additionally, AP 12009 reversed TGF-β2 mediated immunosuppression induced by pancreatic carcinoma cells. In the ongoing clinical phase I/II dose-escalation study, two cohorts of tumor patients have already been treated intravenously with AP 12009 as of Dec 2005. Further dose escalations are ongoing. So far, no DLT, no possibly related SAEs and only seven possibly related AEs were observed. MTD is not yet reached. The majority of patients received more than the minimum number of two cycles, one of them received ten full cycles. First signs of efficacy could also be observed. Conclusions: In conclusion, the preclinical results with pancreatic cancer and malignant melanoma cell cultures as well as the successful clinical application of AP 12009 in the lead indication malignant glioma form a rational basis for the use of the antisense compound AP 12009 as targeted therapy of advanced, TGF-β2 overexpressing tumors. [Table: see text]