Cervix Cancer Patients Research Articles

Patterns of Failure and Prognostic Factor Analyses in Locally Advanced Cervical Cancer Patients Staged by Positron Emission Tomography and Treated With Curative Intent

The aim of this retrospective analysis was to assess whether parameters derived from magnetic resonance imaging (MRI) and positron emission tomography (PET) provide incremental prognostic value compared with International Federation of Gynecology and Obstetrics (FIGO) stage in cervix cancer patients treated with curative intent using concurrent chemoradiotherapy. This was a retrospective study of patients with locoregionally advanced cervical cancer staged by examination under anesthesia and pretreatment MRI and PET. Potential prognostic factors examined were derived from either clinical evaluation (age, FIGO stage, clinical diameter, histology), MRI (corpus invasion, tumor volume), or PET (lymph node metastasis). Outcome measures examined were overall survival, relapse-free survival, time to failure, local failure, nodal failure, and distant failure. There were 206 eligible patients. The mean potential follow-up was 4.4 years. At 5 years, for all patients, overall survival rate was 59%. For all outcome measures apart from local failure, for which adenocarcinoma histology was the most powerful adverse prognostic factor (HR, 4.29; P < 0.0001), lymph node status on PET was the dominant unifactor and multifactor prognostic factor. Corpus involvement on MRI was significantly associated with nodal involvement on PET but of MRI-derived parameters only tumor volume has prognostic value, limited to time to failure and nodal failure. Nodal status on PET was the major predictor of outcome in locally advanced cervix cancer treated with chemoradiation and was superior to FIGO staging. Tumor volume measured from MRI appears to be an important predictor of loco-regional relapse.

Comparative Study of LDR (Manchester System) and HDR Image-guided Conformal Brachytherapy of Cervical Cancer: Patterns of Failure, Late Complications, and Survival

To compare patterns of failure, late toxicities, and survival in locally advanced cervical cancer patients treated by either low-dose-rate (LDR) or conformal high-dose-rate (HDRc) brachytherapy as a part of curative radiotherapy. A retrospective comparative study of 217 advanced cervix cancer patients was conducted; 90 of these patients received LDR and 127 received HDRc brachytherapy. All patients were staged using International Federation of Gynecology and Obstetrics (FIGO) rules, had pretreatment magnetic resonance imaging (MRI), and were treated with concurrent cisplatin chemoradiotherapy. Both groups matched for FIGO stage, MRI tumor volume, and uterine invasion status. Local and pelvic failures were similar 12-13% and 14% both in both groups. Abdominal and systemic failures in LDR group were 21% and 24%, whereas corresponding failures in HDRc group were 20% and 24%. Sixty-eight percent (87/127) of patients treated by HDRc remained asymptomatic, whereas 42% (38/90) of patients were asymptomatic from the bowel and bladder symptoms after treatment with LDR. The 5-year OS rate was 60% (SE = 4%). The 5-year failure-free survival rate was 55% (SE = 3%). There was no significant difference between the groups. Image-guided HDRc planning led to a large decrease in late radiation effects in patients treated by HDRc. Patterns of failure and survival were similar in patients treated either by LDR or HDRc.

Correlation of the social support and the respond model with the life quality of uterine cervix cancer patients

Objective To investigate the correlation of the social support and the respond model with the life quality of uterine cervix cancer patients. Methods The WHOQOL - BREF were adopted to study 286 uterine cervix cancer patients. Results The social support had a positive correlation with psychological and environmental factors in respond type, patients usually adopted facial type , and had positive correlation with psychological and physiological factors. Conclusions The social support should be comprehensively given when making nursing plan and health consultation for uterine cervix cancer patients, in order to value the effect of life quality, to improve the recovery and the life quality. Key words: Social support; Respond model; Uterine cervix cancer

Comparitive study of efficacy, tolerability of four field box technique vs. two field anterior posterior technique in locally advanced carcinoma cervix:A prospective analysis

Purpose: The pelvic failure rate decreases with increase in the radiation dose but the complications increase. The four field pelvic technique has a theoretical advantage of providing a higher tumor dose with less dose to the surrounding normal tissue thus reducing the complications.Result: Eighty-three patients completed treatment, 42 in Arm A and 41 in Arm B. The complete response achieved in the two groups was 85.75% and 87.8% (p = 0.67). Skin reactions were more in Arm B (p < 0.05). Grade II GIT symptoms were more common in both the groups (p = 0.75). Grade I GUT toxicity was the most common toxicity in both the arms (p = 0.38). The most common hematological toxicity in the two arms was of grade II (p = 0.78).Material and method: After satisfying the eligibility criteria histo-pathologically proven locally advanced carcinoma cancer cervix patients were randomized to four (Arm A) or two (Arm B) field techniques.Conclusions: Both two and four field box techniques are equally effective and feasible as stastically insignificant difference in the response rate and acute toxicities was observed in the two arms.

Correlation of dose–volume parameters, endoscopic and clinical rectal side effects in cervix cancer patients treated with definitive radiotherapy including MRI-based brachytherapy

Purpose Correlation of dosimetric parameters for MRI-based 3D treatment planning with rectoscopic findings and clinical rectal side effects. Methods and materials Rectosigmoidoscopy and rectal morbidity assessment were performed on 35 cervical cancer patients treated with external beam radiotherapy (EBRT) and HDR-intracavitary brachytherapy (ICB). The total doses, normalised to 2 Gy fractions (EQD2, α/ β = 3 Gy), in 0.1, 1.0 and 2.0 cm 3 ( D 0.1cc, D 1cc, D 2cc) of rectum were determined by summation of EBRT and ICB plans. Correlation analysis between clinical symptoms (LENT/SOMA) and rectoscopic changes (Vienna Rectoscopy Score, VRS) was performed. For dose–response analyses, the logit model was applied. Results Mean follow-up was 18 months. LENT/SOMA score was 1 in 4 patients, 2 in 8 patients, 4 in 1 patient. Telangiectasia was found in 26 patients (74%), five of them had ulceration corresponding to the 0.1 cm 3 volume (anterior wall). Mean values D 0.1cc, D 1cc, and D 2cc were 81 ± 13, 70 ± 9 and 66 ± 8 Gy, respectively. The ED50 values for VRS ⩾ 3 and for LENT/SOMA ⩾ 2 significantly increased with decreasing volumes. D 2cc was higher in patients with VRS ⩾ 3 compared to VRS < 3 (72 ± 6 vs 62 ± 7 Gy; p < 0.001) and in symptomatic vs asymptomatic patients (72 ± 6 vs 63±8 Gy; p < 0.001). VRS correlated with the LENT/SOMA score. Conclusions Rectosigmoidoscopy is sensitive in detecting mucosal changes, independent of clinical symptoms. The localization of these changes corresponds to the high dose volumes as defined by imaging. The development of mucosal and clinical changes in the rectum follows a clear dose–effect and volume–effect. DVH parameters could be established.

Time for global efforts with clinical trials for advanced cervical cancer patients

Time for global efforts with clinical trials for advanced cervical cancer patients

Region of Interest Analysis as a Tool for Exploring Adaptive IMRT Strategy for Cervix Cancer Patients

Region of Interest Analysis as a Tool for Exploring Adaptive IMRT Strategy for Cervix Cancer Patients

Dose Constraint Recommendations and a Predictive Nomogram of Incidence of Hematological Toxicity for Cervix Cancer Patients Treated with Concurrent Cisplatin and Intensity Modulated Radiation Therapy (IMRT)

Dose Constraint Recommendations and a Predictive Nomogram of Incidence of Hematological Toxicity for Cervix Cancer Patients Treated with Concurrent Cisplatin and Intensity Modulated Radiation Therapy (IMRT)

Germline Mutation in RNASEL Predicts Increased Risk of Head and Neck, Uterine Cervix and Breast Cancer

The BackgroundRibonuclease L (RNASEL), encoding the 2′-5′-oligoadenylate (2-5A)-dependent RNase L, is a key enzyme in the interferon induced antiviral and anti-proliferate pathway. Mutations in RNASEL segregate with the disease in prostate cancer families and specific genotypes are associated with an increased risk of prostate cancer.Infection by human papillomavirus (HPV) is the major risk factor for uterine cervix cancer and for a subset of head and neck squamous cell carcinomas (HNSCC). HPV, Epstein Barr virus (EBV) and sequences from mouse mammary tumor virus (MMTV) have been detected in breast tumors, and the presence of integrated SV40 T/t antigen in breast carcinomas correlates with an aggressive phenotype and poor prognosis.A genetic predisposition could explain why some viral infections persist and induce cancer, while others disappear spontaneously. This points at RNASEL as a strong susceptibility gene.Methodology/Principal FindingsTo evaluate the implication of an abnormal activity of RNase L in the onset and development of viral induced cancers, the study was initiated by searching for germline mutations in patients diagnosed with uterine cervix cancer. The rationale behind is that close to 100% of the cervix cancer patients have a persistent HPV infection, and if a defective RNase L were responsible for the lack of ability to clear the HPV infection, we would expect to find a wide spectrum of mutations in these patients, leading to a decreased RNase L activity. The HPV genotype was established in tumor DNA from 42 patients diagnosed with carcinoma of the uterine cervix and somatic tissue from these patients was analyzed for mutations by direct sequencing of all coding and regulatory regions of RNASEL. Fifteen mutations, including still uncharacterized, were identified. The genotype frequencies of selected single nucleotide polymorphisms (SNPs) established in the cervix cancer patients were compared between 382 patients with head and neck squamous cell carcinomas (HNSCC), 199 patients with primary unilateral breast cancer and 502 healthy Danish control individuals. We found that the genotype frequencies of only one of the 15 mutations, the yet uncharacterized 5′UTR mutation rs3738579 differed significantly between cancer patients and control individuals (P-value: 4.43×10−5).Conclusion/SignificanceIn conclusion, we have discovered an increased risk, a heterozygous advantage and thereby a protective effect linked to the RNASEL SNP rs3738579. This effect is found for patients diagnosed with carcinoma of the uterine cervix, HNSCC, and breast cancer thus pointing at RNASEL as a general marker for cancer risk and not restricted to familial prostate cancer.

SU-GG-T-56: Planning Target Volume Adaptation Using Convex Hull of CTVs for Cervix Cancer Patients

Purpose: Adaptive IMRT planning studies have shown that intra‐ and inter‐fractional organ motion can significantly decrease the coverage of the clinical target volume (CTV) for cervix cancer patients. Adaptive mid‐treatment re‐planning was effective in minimizing CTV underdosage, but this strategy only worked for patients with consistent bladder filling. This study investigated planning target volume (PTV) adaptation using a convex hull (CH) technique for patients whose bladder filling is variable over the course of radiation treatment.Method and Materials: Nine cervix cancer patients with variable bladder filling during the treatment were selected from 35 patients enrolled in an adaptive IMRT planning study. All patients were MR‐scanned once for planning and weekly during treatment. CTV and organs at risk (OAR) were contoured on each MR scan fused to planning CT with bony alignment. Contours were converted to 3D surface meshes for deformation analysis considering tissuebiomechanics. Two MR scans with full/empty bladder were identified and an adaptive PTV was found using a convex hull algorithm in the research planning software. IMRT plans were generated on the CH PTV and accumulated dose on deformed organs were simulated. Results: The average volume of CH PTV was 16% larger than that of small margin (3mm) PTV (477vs411cc). Most of the volume increase was found in the area of rectum where the concavity of the CTV was largest. The CH PTV had a non‐uniform margin around CTV representing patient‐specific CTV motion and deformation. The CH plan maintained target coverage but increased dose at OARs compared to adaptive mid‐treatment re‐planning. Discussion: Adaptive planning strategy using convex hull of CTVs demonstrates good target coverage for cervix cancer patients with variable bladder filling. Refindment of the CH to spare OARs might allow a reduction in critical organdose while still maintaining target coverage.

Is the change of serum nitric oxide level indicator of the survival during cervix cancer treatment?

16600 Background: Nitric oxide (NO) by having inhibitory and activating roles in the carcinogenesis can influence the outcome of cancer treatment. In this study we aimed to investigate the existence of a correlation between the serum NO levels and survival in the cervix cancer patients treated with chemoradiotherapy. Methods: 20 patients with FIGO stage 2B-3B invasive cancer of cervix treated with chemoradiotherapy in 2005 were included into the study. 50.4 external-beam pelvic radiotherapy and 14–20 Gy intracavitary boost dose were delivered. Patients received cisplatin (50 mg/m2) weekly with concurrent pelvic radiotherapy. On the first day (for basal level determination) and the 6th, 11th, 16th, 21st, 26th days of the treatment, 15 minutes before the irradiation blood samples were collected. Cisplatin administrated within two hours after the completion of radiotherapy. Serum NO levels were determined indirectly with the measurement of serum nitrite/nitrate levels. Results: Serum levels of NO which were obtained in the 26th day of the treatment were significantly higher than the basal levels (p < 0.01, one way ANOVA) It was showed that the patients whose serum NO levels were lower than the basal level in the 26th of the treatment had longer survival than the patients whose NO levels increased in that measurement (30 versus 27 months). The decreased NO serum levels were significantly associated with a longer survival (Pearson correlation r=0.04). Conclusions: The changes in the level of serum NO during chemoradiotherapy may be an indicator of survival. No significant financial relationships to disclose.

Relationship between the proportion of natural killer cells in peripheral blood lymphocytes and risk factors in cervical cancer

16546 Background: Natural Killer (NK) cells lyse target cells and provide source of immunoregulatory cytokines. The aim of this study was to investigate relationship between preoperative proportion of NK cells in peripheral blood lymphocytes and risk factors in cervical cancer patients who underwent radical hysterectomy. Methods: The pathologic reports of 57 cervical cancer patients who underwent radical hysterectomy from September 2004 to December 2007 were reviewed. Preoperative proportion of NK cells in peripheral blood were measured by flowcytometry method. We reviewed medical records for comparison of the risk factors which were supposed to be related to cervix cancer including age, clinical stage, squamous cell carcinoma antigen (SCC), cell type, tumor size, invasion depth, lymphovascular invasion and nodal metastasis. Group A (n=40) was defined as those with NK cells proportion < 15% and group B (n=17) with NK cells proportion ≥ 15%. Relationship between proportion of NK cell and prognostic factors of cervical cancer were analyzed. Results: NK cell proportion of Stage II cervix cancer patients was higher than that of stage I (p = 0.038). When comparing group A with group B, risk factors including clinical stage (p = 0.010), invasion depth (p = 0.034) and SCC level (p = 0.047) were significant decrease in group A. Other factors, such as nodal metastasis, tumor size, cell type and lymphovascular invasion, were not significant related between group A and group B. Conclusion: Risk factors of cervix cancer, such as clinical stage, invasion depth and SCC Ag level, were positively related to NK cells proportion. Increase of Natural Killer cell proportion in peripheral blood lymphocytes may be related to poor prognosis of cervix cancer. No significant financial relationships to disclose.

Protective effect on the urinary bladder mucosa of intravesical hyaluronic acid in cervix cancer patients treated with pelvic radiotherapy, weekly chemotherapy and high-dose-rate brachytherapy

Protective effect on the urinary bladder mucosa of intravesical hyaluronic acid in cervix cancer patients treated with pelvic radiotherapy, weekly chemotherapy and high-dose-rate brachytherapy

Interstitial fluid pressure, vascularity and metastasis in ectopic, orthotopic and spontaneous tumours

BackgroundHigh tumour interstitial fluid pressure (IFP) has been adversely linked to poor drug uptake in patients, and to treatment response following radiotherapy in cervix cancer patients. In this study we measured IFP values in a selection of murine and xenograft models, spontaneously arising or transplanted either intramuscularly (i/m) or orthotopically and analysed their relationship to tumour vascularity and metastatic spread.MethodsKHT-C murine fibrosarcoma, ME180 and SiHa human cervix carcinoma were grown either intramuscularly (i/m), sub-cutaneously (s/c) or orthotopically. Polyoma middle-T (MMTV-PyMT) transgenic spontaneous mammary tumours were studied either as spontaneous tumours or following orthotopic or i/m transplantation. IFP was measured in all tumours using the wick-in-needle method. Spontaneous metastasis formation in the lungs or lymph nodes was assessed in all models. An immunohistochemical analysis of tumour hypoxia, vascular density, lymphatic vascular density and proliferation was carried out in ME180 tumours grown both i/m and orthotopically. Blood flow was also assessed in the ME180 model using high-frequency micro-ultrasound functional imaging.ResultsTumour IFP was heterogeneous in all the models irrespective of growth site: KHT-C i/m: 2–42 mmHg, s/c: 1–14 mmHg, ME180: i/m 5–68 mmHg, cervix 4–21 mmHg, SiHa: i/m 20–56 mmHg, cervix 2–26 mmHg, MMTV-PyMT: i/m: 13–45 mmHg, spontaneous 2–20 mmHg and transplanted 2–22 mmHg. Additionally, there was significant variation between individual tumours growing in the same mouse, and there was no correlation between donor and recipient tumour IFP values. Metastatic dissemination to the lungs or lymph nodes demonstrated no correlation with tumour IFP. Tumour hypoxia, proliferation, and lymphatic or blood vessel density also showed no relationship with tumour IFP. Speckle variance analysis of ultrasound images showed no differences in vascular perfusion between ME180 tumours grown i/m versus orthotopically despite differences in IFP.ConclusionOur studies across a range of different tumour models showed substantial heterogeneity in tumour IFP, suggesting differences in the vascular development and interstitial fluid dynamics in the individual tumours. The results demonstrate a strong stochastic aspect to tumour IFP development, notably the variation apparent between different tumours within the same animal and the lack of correlation between donor and recipient tumours.

Chromosomal Radiosensitivity, DNA repair, SNP and Apoptosis in Lymphocytes of Cervix Cancer Patients

There is considerable evidence that even after similar radiotherapy treatment, patients differ widely in normal tissue reaction. It is believed that the observed differences are related to intrinsic biological factors. Despite the great number of investigations of the relationship between the cellular radiosensitivity and reactions of patients to radiotherapy, there is presently no convincing proof that any of such biological factors alone can be used to predict side effects caused by radiotherapy. Considering the complexity of the mechanisms involved in the maintenance of the cell, tissue and organ function, it seems necessary to analyze the relationship between many different biological factors related to cellular sensitivity to ionizing radiation. The aim of the present study was to examine, in peripheral blood lymphocytes of cervix cancer patients collected before radiotherapy (1) chromosomal radiosensitivity, (2) kinetics of DNA repair, (3) SNP polymorphisms of genes involved in DNA repair and (4) apoptosis. The preliminary study included 30 patients. From each donor, peripheral blood was collected, irradiated in vitro with 2 Gy of gamma rays and the following endpoints were analyzed: Analysis of micronuclei (MN): The frequency of micronuclei, as a measure of chromosomal radiosensitivity, was determined with the micronucleus (MN) assay according to a standard protocol. Analysis of DNA repair: The kinetics of DNA repair was assessed by analyzing the formation and loss of gamma-H2AX foci. After 1 and 24 hours after irradiation, the cells were fixed, incubated with anti-phospho-histone H2AX antibody and analyzed by flow cytometry. Analysis of SNP polymorphism: DNA was isolated from the lymphocytes and RFLP-PCR followed by enzymatic digestion was performed according to the manufacturer’s protocol. The XRCC1-Arg399Gln, XRCC3-IVS5-14.893 and OGG1-Ser326Cys polymorphisms were determined using the restriction enzymes HpaII, PvuII and Fnu4HI, respectively. Analysis of apoptosis: The frequency of spontaneous and radiation-induced apoptotic cells was determined after 1, 6 and 24 hours after irradiation by the annexin method and flow cytometry. The results of the present study have shown a substantial inter-patient variability of lymphocyte chromosomal radiosensitivity, kinetics of DNA repair, SNP polymorphisms and apoptosis. However, no significant relationship was found for any combination of these endpoints. Additional correlation analyses will be performed with the reaction of the healthy tissue of patients to radiotherapy, classified according to the EORTC/RTOG scale.

Possible role of the micronucleus assay in diagnostics and secondary prevention of cervix cancer: A minireview

Recent literature data are presented concerning micronuclei (MN) frequency in exfoliated cells of cervix cancer patients. These data strongly support a positive correlation between the MN level and malignization (changes from premalignant stage to cancer). It is suggested that the evaluation of frequency of MN in exfoliated cervical cells may be an additional criterion for establishing cervical cancer risk and the study of MN in cervix smears will increase the sensitivity and specificity of cytology which could impact in diagnostics and secondary prevention of cervical cancer.

International Phase III Trial of Chemoradiotherapy ± Hyperthermia for Locally Advanced Cervix Cancer: Interim Update on Toxicities

International Phase III Trial of Chemoradiotherapy ± Hyperthermia for Locally Advanced Cervix Cancer: Interim Update on Toxicities

Cytokine profile in Indian women with cervical intraepithelial neoplasia and cancer cervix

Cervical cancer develops from the preneoplastic cervical intraepithelial neoplasia (CIN). Host factors are critical in regulating tumor growth and cytokines, which modulate immunologic control may be of particular importance. The objective of this study was to assess the production of cytokines by peripheral blood mononuclear cells (PBMCs) in Indian women with cancer cervix and CIN. Sixty patients with cancer cervix (including all FIGO stage I–IV), 35 patients with CIN, and 30 healthy controls were enrolled in this study. The human papillomavirus (HPV) 16 and 18 status was determined in all the study groups. The PBMC culture supernatant was collected for cytokine estimations by enzyme-linked immunosorbent assay (interleukin-2 [IL-2], interferon-gamma [IFN-γ], interleukin-4 [IL-4], and interleukin-10 [IL-10]). IL-2 levels showed a significant decline in high-grade CIN and cancer patients, whereas IFN-γ levels were decreased only in patients with advanced cancer cervix. An increase in the levels of IL-4 and IL-10 was found in all cancer cervix and CIN grade III patients, as compared to those with early CIN grades and healthy controls. The cytokine ratios decreased significantly (P&lt; 0.001 for all the ratios), when cervical cancer patients were compared with controls and CIN cases. The type 2 and type 1 cytokine levels were significantly correlated (P&lt; 0.000) with HPV status. We conclude that a pronounced shift from type 1 to type 2 cytokine production is associated with more severe disease. These data reinforce the need for detailed analysis of immune dysregulation in CIN and cancer cervix patients.

Reducing by half the percentage of late-stage presentation for breast and cervix cancer over 4 years: a pilot study of clinical downstaging in Sarawak, Malaysia

Background: The registry of the Oncology Departmental in Sarawak General Hospital showed that 79% of nasopharyngeal, 77% of breast and 70% of cervix cancer patients were diagnosed at an advanced stage (stages III and IV) for year 1993. Hence, a low cost Early Cancer Surveillance Program was started in 1994, with the intent of downstaging these three most common cancers in Sarawak.Materials and methods: The program consisted of (i) training health staff in hospital and rural clinics to improve their skills in early cancer detection, (ii) raising public awareness through pamphlets, posters and sensitization by health staff.Results: Data analysis revealed that the program achieved downstaging in two of the cancers. Breast cancer in stage III and IV was reduced from 60% (1994) to 35% (1998) (P < 0.0001) and cervical cancer in stage III and IV from 60% (1994) to 26% (1998) (P < 0.0001). No reduction was observed for nasopharyngeal cancer at 88% (1994) to 91% (1998).Conclusions: The overall cost of this program was <US$34 000. It is cost-effective and easy to implement and would be a valuable alternative in countries where majority of the tumors are found in late stage (III and IV) where screening programs meet important difficulties. Our data analyses revealed important shortcomings in the PAP smear screening program where inadequate groups of women were screened. It resulted in a pick up rate of only 5% of the cases. This finding confirmed the need for the simple and complementary downstaging approach.

Predictive value of D-dimer and LDH levels in response to chemotherapy in metastatic colorectal cancer patients

14568 Background: Hemostatic activation is known to occur in malignant diseases and this may be associated with tumor progression and angiogenesis. D-dimer levels are elevated in lung, uterine cervix, prostate and colorectal cancer patients. We aimed to evaluate the association and predictive value of LDH and D-Dimer levels with chemotherapy response in metastatic colorectal cancer (MCRC) patients. Patients and Methods: Twenty-five chemotherapy-naive MCRC patients were enrolled into this study. Plasma CEA, CA19–9, D-Dimer and LDH levels were measured before and after 3 cycles of capecitabine + oxaliplatin combination chemotherapy. The comparison between groups were done by Wilcoxon W and Mann-Whitney U tests. Results: Median age was 58 years in 15 female, 10 male patients. All patients received Capecitabine 2,000 mg/m2/day orally on days 1- 14 + Oxaliplatin 130 mg/m2 intravenously on day 1 every 21 days. The chemotherapy response after 3 cycles of treatment were 2 complete response, 7 partial response, 8 stable disease and progressive disease in 8 patients. Plasma CEA, CA19–9, LDH and D-Dimer levels were not significantly different between two groups before chemotherapy (table). Plasma LDH and D-Dimer levels were significantly higher in progressive disease patients than patients with complete, partial or stable response after 3 cycles of chemotherapy, but plasma CEA and CA19–9 were not significantly different between these groups (table). Conclusion: We found that D-dimer and LDH levels dropped in responders while they increased in patients with disease progression. D- Dimer and LDH plasma levels decrease or increase after response and progressive disease, respectively, and can act as a predictive factor of the clinical outcome of the disease. [Table: see text] No significant financial relationships to disclose.