Post-chemotherapy Values Research Articles

Non-Invasive Study of Intracranial Pressure in Pre- and Post-Chemotherapy Patients for the Treatment of Breast Neoplasia

Introduction: Breast cancer is the most common type among women and brings to them significant organic changes. A new intracranial pressure monitorization method consists of an external system of sensors that detects micrometric deformations on the cranial bones and transmits, in real-time, electrical signals that are visualized on a monitor. Objective: To identify changes in intracranial pressure due to chemotherapy connections through non-invasive methodology. Methods: The present study was conducted at Hospital Santa Casa de Misericordia in the city of Ponta Grossa, PR, Brazil in 2017. The variables P2/P1 ratio (ICP morphological evaluation), laboratory parameters, comorbidities, and clinical aspects of the volunteers were evaluated. The vascular toxicity of chemotherapy often causes endothelial dysfunction, resulting in a loss of vasodilation effects and suppresses anti-inflammatory and vascular repair functions. Results: The values of the P2/P1 ratio before and after chemotherapy were also compared between groups. A statistically significant difference was observed in the pre-chemotherapy P2/P1 values compared to the post-chemotherapy values. Conclusion: Variations in ICP may occur in cancer patients. Further studies are necessary to evaluate if this change may contribute to the chemotherapy side effects occurrence.

MUC1 (CA27.29) before and after Chemotherapy and Prognosis in High-Risk Early Breast Cancer Patients.

Simple SummaryCA27.29 (MUC1) is a well described biomarker for prediction of prognosis and treatment efficacy. CA27.29 is mainly evaluated in the preoperative setting. However, testing of postoperative levels and additional assessment after chemotherapy might be more informative for analyzing the usefulness of CA27.29 in relation to the efficacy of chemotherapy. Thus, both pre- and post-chemotherapy values were assessed from patients enrolled in the breast cancer SUCCESS-A trial. Pre-chemotherapy assessment was associated with disease-free survival. It had no prognostic value in node-negative patients, but there was a clear association in node-positive patients. Furthermore, it was shown that post-chemotherapy CA27.29 assessment did not add any prognostic value, either on its own or in addition to pre-chemotherapy assessment. In conclusion, this indicates that pre- and post-chemotherapy values do not provide additional information. However, pre-chemotherapy CA27.29 could be a suitable tool to identify a group with unfavorable prognosis among node-positive patients.Soluble MUC1 has been discussed as a biomarker for predicting prognosis, treatment efficacy, and monitoring disease activity in breast cancer (BC) patients. Most studies in adjuvant settings have used preoperative assessment. This study, part of the SUCCESS-A trial (NCT02181101), assessed the prognostic value of soluble MUC1 before and after standard adjuvant chemotherapy. Patients with high-risk BC were treated within the SUCCESS-A trial with either three cycles of 5-fluorouracil, epirubicin, and cyclophosphamide followed by three cycles of docetaxel or three cycles of FEC followed by three cycles of docetaxel and gemcitabine. Cox regression analyses were performed to investigate the prognostic value of CA27.29 before and after chemotherapy relative to disease-free survival (DFS), along with established BC prognostic factors such as age, body mass index, tumor size, nodal status, estrogen receptor, progesterone receptor, HER2 status, and grading. Pre-chemotherapy and post-chemotherapy CA27.29 assessments were available for 2687 patients of 3754 randomized patients. Pre-chemotherapy CA27.29 assessment was associated with DFS in addition to established prognostic factors. It had no prognostic value in node-negative patients, but there was a clear association in node-positive patients. Post-chemotherapy CA27.29 assessment did not add any prognostic value, either on its own or in addition to pre-chemotherapy CA27.29 assessment.

Potential of combination of DCE-MRI and DWI with serum CA125 and CA199 in evaluating effectiveness of neoadjuvant chemotherapy in breast cancer

BackgroundTo determine the potential of the combination of DCE-MRI imaging method with DWI and serum CA125 and CA199 levels in the evaluation of the efficacy of neoadjuvant chemotherapy in breast cancer patients.MethodsSixty-five breast cancer patients who received neoadjuvant chemotherapy in our hospital from April 2016 to April 2017 were selected as research subjects. The patients received 4 courses of neoadjuvant chemotherapy. Lesions were monitored using DCE-MRI and DWI, while ELISA was used to measure the serum expression levels of the tumour markers CA125 and CA199. The patients were divided into the remission group and ineffective group based on pathological diagnosis.ResultsThere were significant differences in Kep, Ktrans, ADCmin, ADCmean, tumour volume, and serum levels of CA125 and CA199 in patients in the remission group, before and after neoadjuvant chemotherapy, and there were significant differences in post-chemotherapy values of these indexes between the remission group and the ineffective group (p < 0.01).ConclusionCombination of DCE-MRI diagnostic imaging with DWI can directly reflect the lesions in breast cancer patients after neoadjuvant chemotherapy. Serum levels of CA125 and CA199 levels are useful for evaluation of the impact of neoadjuvant chemotherapy on breast cancer patients, including risk of cancer cell metastasis and changes in some small lesions.

Prognostic value of neutrophil-lymphocyte ratio during palliative chemotherapy in patients with unresectable gallbladder adenocarcinoma.

253 Background: Neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) is a valuable prognostic marker in several kinds of solid tumors. This study aimed to evaluate the NLR, PLR and change of NLR and PLR over time as a prognostic marker in unresectable gallbladder cancer (GBC) which is treated with palliative chemotherapy. Methods: A total of 163 patients with pathologically confirmed unresectable GBC were enrolled. Baseline and post 1-cycle chemotherapy NLR and PLR were used in analysis. The changes in NLR and PLR were defined as the ratio of post chemotherapy value to baseline value. The relation between survival time and NLR and PLR changes were analyzed. Results: NLR and PLR had AUC value of 0.679, 0.660 in predicting 1-year overall survival (OS) and NLR 1.96 and PLR 111 were the optimal cutoff value with the highest sum of sensitivity and specificity. NLR change and PLR change had AUC value of 0.517, 0.519 in predicting 1-year OS and NLR change 0.4, PLR change 0.6 were the optimal cutoff value. Patients with NLR lower than 1.96 had better OS (16.1 months vs. 9.5 months, p &lt; 0.001) and similarly patients with PLR lower than 111 had better OS (17.3 months vs. 9.5 months, p &lt; 0.001). However, NLR change lower than 0.4 didn’t show better OS (9.2 months vs. 11.6 months, p = 0.178), and the same with PLR change lower than 0.6 (8.5 months vs. 11.3 months, p = 0.138). Conclusions: Baseline NLR and PLR is a valuable predictor of overall survival in unresectable GBC undergoing palliative chemotherapy, whereas NLR and PLR change over time is not.

SERUM VALUES OF ALKALINE PHOSPHATASE AND LACTATE DEHYDROGENASE IN EWING'S SARCOMA.

ABSTRACTObjective: To study the relationship between the serum levels of alkaline phosphatase (AP) and lactate dehydrogenase (LDH), and the percentage of tumor necrosis (TN) in patients with Ewing´s Sarcoma (ES). Methods: This is a case series with retrospective evaluation of patients with diagnosis of ES divided into 2 groups: Group 1, patients whose serum levels of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were obtained in the staging phase before preoperative chemotherapy (CT), and Group 2, patients whose values were measured after completion of the preoperative CT. The percentage of tumor necrosis (TN) of surgical specimens extracted in surgery was also evaluated. Results:Eighty four medical records from 1995 to 2015 were included. Both AP as LDH decreased in the patients studied, the pre CT value being higher than the post CT value. The average decrease of LHD was 272.95 U/L and AP was 10.17 U/L. The average tumor necrosis was 65.12 %. There was no statistical correlation between serums levels and the tumor necrosis percentage. Conclusion: The serum levels values of AP and LDH are not predictors for chemotherapy-induced necrosis in patients with ES. Level of Evidence IV, Case Series.

Absence of effect ofSLC22A2genotype on cisplatin-induced nephrotoxicity in oesophageal cancer patients receiving cisplatin and 5-fluorouracil: report of results discordant with those of earlier studies

Cancer patients treated with cisplatin chemotherapy frequently experience drug-induced nephrotoxicity. Clinical studies using a single chemotherapeutic regimen or large sample sizes for patients with the SLC22A2 808T allele have not been reported. Here, we examined 95 patients with oesophageal cancer who received 5-fluorouracil and cisplatin (FP) to determine whether nephrotoxicity was affected by SLC22A2 808G>T polymorphism. The change rate of the estimated glomerular filtration rate (eGFR) was used for the evaluation of cisplatin-induced nephrotoxicity and calculated for each patient according to the following formula: change rate = (prechemotherapy value - post-chemotherapy value)/prechemotherapy value. Genotyping of SLC22A2 808G>T was carried out using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The eGFR after FP chemotherapy was significantly lower than that before chemotherapy, and the mean difference in eGFR was 25·7 mL/min (P < 0·01). There was no significant difference in the mean change rate of the eGFR following FP chemotherapy between the SLC22A2 808GG genotype (n = 70) and the 808GT+TT genotypes (n = 25) (27·9% and 27·8%, respectively). In multiple regression analyses, the change rate of eGFR following FP chemotherapy was associated with the eGFR value prior to chemotherapy (P = 0·04). In FP chemotherapy for oesophageal cancers, cisplatin-induced nephrotoxicity seems to be unaffected by the SLC22A2 808G>T polymorphism. The eGFR prior to chemotherapy might be an important risk factor for cisplatin-induced nephrotoxicity. Our present study was estimated with a single chemotherapeutic regimen, eGFR, and was calculated using serum creatinine, age and the sex of the patient and sample sizes of 25 patients with SLC22A2 808T allele. However, further examinations with a larger sample size to corroborate the study results might be necessary.

The prognostic significance of the increase in the serum M30 and M65 values after chemotherapy and relationship between these values and clinicopathological factors in patients with advanced gastric cancer

In some studies, the prognostic and predictive significance of M30 and M65 has been reported to detect response to chemotherapy. In the present study, we aimed at determining the changes of serum M30 and M65 values after chemotherapy and the impact of these values on treatment response and progression-free survival (PFS) and overall survival (OS) of patients with advanced gastric cancer. A total of 31 patients with advanced gastric cancer was included. M30 and M65 values were measured by a quantitative enzyme-linked immunosorbent assay (ELISA) method in serum samples before and 48 h after the first chemotherapy cycle. Pre- and postchemotherapy values of M30 and M65 were compared. The difference between the mean values of serum M30 and M65 before and after chemotherapy was calculated and the prognostic significance of changes for survival was evaluated by univariate and multivariate analysis. Logistic regression analysis was performed to predict response to chemotherapy. Serum M30 and M65 levels were found to be increased significantly after chemotherapy (M30, 582.7 ± 111.5 U/l [pre mean] vs. 983.3 ± 214.1 U/l [post mean], p = 0.01; M65, 2,061.7 ± 431.2 U/l [pre mean] vs. 2,646.3 ± 433.1 U/l [post mean], p = 0.003). Means of the differences of M30 and M65 levels before and 48 h after chemotherapy were 400.5 ± 190 U/l ([M30-difference] M30-D) and 584.6 ± 335.4 U/l (M65-D), respectively. Patients with serum M30-D of <400.5 U/l had better median PFS and OS times than patients with M30-D >400.5 U/l (PFS, 9.9 vs. 4.3 months, p = 0.018 and OS, 13.6 vs. 8.1 months, p = 0.029). In addition, median PFS and OS intervals in patients with serum M65-D > 584.6 U/l were significantly worse than those of patients whose M65-D was lower than or equal to 584.6 U/l (4.1 vs. 11.4 months for PFS, p = 0.002 and 5.7 vs. 13.6 months for OS, p = 0.005). Patients with values above M30-D and M65-D had a better tumor response compared with patients with values below M30-D and M65-D (p = 0.02 and p = 0.006, respectively). In the logistic regression analysis, only M65-D was significantly found to be an independent factor in predicting response to chemotherapy (p = 0.018, OR:1.4). However, only M30 levels after chemotherapy were found to be an independent prognostic factor for PFS in the multivariate analysis. These results showed for the first time that both M30 and M65 in serum samples of patients with advanced gastric cancer were elevated 48 h after chemotherapy and these were poor prognostic factors for both PFS and OS of patients. Moreover, increased serum M65 levels after chemotherapy can be predict tumor response.

Abstract 5366: Extended phase II study of maintenance immunotherapy in advanced cancer

Abstract Purpose: Chemotherapy can induce prolonged remissions in patients with stage IV cancer (AC), yet nearly the majority of them, will ultimately relapse. In vitro studies suggest that natural killer cells (NK) mediate lytic activity against cancer cell lines and that high expression of vascular endothelial growth factor (VEGF) promotes tumor progression through neoangiogenesis. We have shown that a combination of low-dose interleukin-2 (IL-2) and 13-cis retinoic acid (RA) increased NK cells and decreased VEGF, in patients with AC with a clinical benefit from chemotherapy (Clin Cancer Res 7: 1251, 2001). Therefore, IL-2 and RA may improve long-term disease-free survival (DFS) and overall survival (OS) when administered in a post-chemotherapy minimal residual disease setting. Primary endpoint of the study was to evaluate if IL-2 and RA increased NK cells and decreased VEGF of patients with AC that had a clinical benefit from chemotherapy. Secondary endpoint was the evaluation of DFS, OS and toxicity of this regimen in various tumor types. Patients and methods: 500 patients with a wide range of AC that had a clinical benefit from chemotherapy were treated with self-administered subcutaneous IL-2, 1.8 X 106 IU and oral RA, 0.5 mg/Kg for 5 days/week for 2 consecutive cycles of 3 weeks, with a 1-week rest, for 1 year. Therapy was continued, with intermittent schedules for five years or until progression. NK cells, serum VEGF, tumor response and toxicity were assessed every 4 months. Results: Median age was 61 years (range 21-80), all patients had a good performance status and there were 248 females. After a median follow-up of 60 months (range 24-180), 4400 courses of chemotherapy and 2634 courses of immunotherapy were administered. A statistically significant improvement of NK cells [from a mean of 309 ± 76/mm3 to a mean of 579 ± 74 (p&amp;lt;0.001)] and a decrease of VEGF [from a mean of 520 ± 75 pg/mm3 to a mean of 150 ± 12 pg/mm3, (p&amp;lt;0.001)], with respect to baseline, post-chemotherapy values, were observed. 15 years DFS and OS were 32.6 and 36.8, respectively. Even with all the limitations of different patient populations, a significant improvement, with respect to NCI SEER data (*), could be observed in the 5-year OS rate for the most common treated metastatic cancers: Breast cancer 42.7% vs. 23.3% *, lung cancer 26.4% vs. 3.6% *, colorectal cancer 43.6% vs. 11.7%*, renal cancer 23% vs. 11% *. No WHO grade 3 or 4 toxicity was observed, while grade 2 cutaneous toxicity and fever occurred in 20% and 13% of patients, respectively. Mild hypothyroidism and grade 2 triglyceride elevation was observed in 5% and 15% of patients, respectively. 1 patient had to stop treatment for grade 2 urticaria. Conclusions: These data show that the administration of IL-2/RA, determines, with a modest toxicity profile, a sustained improvement of NK cells, a decrease of VEGF, and unexpected 5-year survival rates. Phase III randomized studies have been started, in Europe, for several tumor types. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5366. doi:1538-7445.AM2012-5366

Quantification of Serum Free RNA as a Predictive Biomarker for the Response to Chemotherapy in Patients with Lung Cancer: A Pilot Study

Background: It is well-known that cell-free nucleic acids rise in patients with many types of malignancies. Several recent experimental studies using cancer cell lines have shown that changes in cell-free RNA are predictive of the response to chemotherapy. The objective of this study was to determine whether quantification of free RNA can be used as a biomarker for clinical responses to chemotherapy in patients with lung cancer. Methods: Thirty-two patients with lung cancer (non-small cell lung cancer, n=24; small cell lung cancer, n=8) were divided into 2 groups according to their responses to chemotherapy (response group, n=19; non-response group, n=13). Blood samples were collected before and after two cycles of chemotherapy. Real-time quantitative RT-PCR was used for transcript quantification of the glyceraldehyde-3-phosphate dehydrogenase gene. Results: The pre chemotherapy values (Response group 41.36±1.72 vs. Non-response group 41.33±1.54, p=0.78) and post chemotherapy values (Response group 39.92±1.81 vs. Non-response group 40.41±1.47, p=0.40) for cell free RNA concentrations, expressed as Ct GAPDH (threshold cycle glyceraldehyde-3-phosphate dehydrogenase gene) levels, was not different between the two groups. There was no significant relationship between changes in the cell free RNA level clinical responses after chemotherapy (p=0.43). Conclusion: We did not find a correlation between quantification of serum cell free RNA levels and clinical responses to chemotherapy in patients with lung cancer. Further investigations are needed to determine whether the cell free RNA level is a useful predictor of responses to chemotherapy in patients with lung cancer.

The value of diffusion-weighted imaging for monitoring the chemotherapeutic response of osteosarcoma: a comparison between average apparent diffusion coefficient and minimum apparent diffusion coefficient

The objective of this study was to evaluate whether the average apparent diffusion coefficient (ADC) or the minimum ADC is more useful for evaluating the chemotherapeutic response of osteosarcoma. Twenty-two patients with osteosarcoma were examined in this study. Diffusion-weighted (DW) and magnetic resonance (MR) images were performed for all patients before and after chemotherapy. The pre- and post-chemotherapy values were obtained both in the average and minimum ADC. The pre-chemotherapy values of the average ADC and minimum ADC respectively were compared with the post-chemotherapy values. In addition, the ADC ratios ([ADC(post) - ADC(pre)] / ADC(pre)) were calculated using the average ADC and the minimum ADC. Twenty-two patients with osteosarcomas were divided into two groups, those with a good response to chemotherapy (> or = 90% tumor necrosis, n = 7) and those with a poor response (< 90% tumor necrosis, n = 15). The average ADC ratio and the minimum ADC ratio of the two groups were compared. With both the average ADC and the minimum ADC, post-chemotherapy values were significantly higher than pre-chemotherapy values (P < 0.05). The patients with a good response had a significantly higher minimum ADC ratio than those with a poor response (1.01 + or - 0.22 and 0.55 + or - 0.29 respectively, P < 0.05). However, with regard to the average ADC ratio, no significant difference was observed between the two groups (0.66 + or - 0.18 and 0.46 + or - 0.31 respectively, P = 0.19). The minimum ADC is useful for evaluating the chemotherapeutic response of osteosarcoma.

Prediction of final tumor response to preoperative chemotherapy by Tc‐99m MIBI imaging at the middle of chemotherapy in malignant bone and soft tissue tumors: Comparison with Tl‐201 imaging

The aim of this study was to assess the predictive power of 99mTc-MIBI scintigraphy performed in the middle of chemotherapy, for the final tumor response to chemotherapy, and compare it to that of (201)Tl in malignant bone and soft tissue tumors (MBST). Sixty-eight patients with MBST underwent 99mTc-MIBI and 201Tl scintigraphies at 15 min after tracer injection before the first, and after the third, chemotherapy cycles. After five cycles of chemotherapy and tumor resection, therapeutic effect was assessed by histopathology. Less than 90% and > or =90% necrosis were judged as poor and good response to chemotherapy, respectively. Tracers uptake ratios were calculated by dividing the lesion count density by that of the background. 99mTc-MIBI perfusion index was also calculated. The % reduction of the perfusion index (DeltaPI) and uptake ratios (DeltaUR) calculated by 100 x [(prechemotherapy value--postchemotherapy value)/prechemotherapy value] were compared with histologic response. The sensitivity, specificity, and accuracy for the prediction of effective chemotherapy in 99mTc-MIBI imaging were 80%, 95%, 88% in DeltaUR, and 74%, 74%, 74% in DeltaPI, respectively. The area under the receiver operator characteristic curve (A(z)) of the 99mTc-MIBI-DeltaUR (0.923) was significantly higher than that of DeltaPI (0.809, p = 0.025) but only marginally higher than that of the 201Tl-DeltaUR (0.865, p = 0.079). A(z) in 201Tl (0.865) was not significantly different from that of DeltaPI (0.809, p = 0.35). 99mTc-MIBI imaging performed in the middle of chemotherapy well predicts the final tumor response to chemotherapy in patients with malignant bone and soft tissue tumors.

Assessment of the Intestinal Permeability following Postoperative Chemotherapy for Human Malignant Disease

Purpose: Administration of anticancer drugs may damage gastrointestinal epithelium, thereby increasing the permeability of the gastrointestinal mucosa. We estimated the usefulness of oral lactulose and mannitol (L/M) test for assessment the extent of mucosal damage following postoperative chemotherapy for human malignant disease. Methods: The permeability index (PI): the urinary recovery ratio of excreted L to M was measured before and after chemotherapy in 31 patients with gastrointestinal cancers who underwent surgical resection. These findings were compared with data on 12 patients with breast cancer. The effect of chemotherapy was evaluated by the ratio of increase in PI, which was designed as post-chemotherapy value on day 7 divided by pre-chemotherapy value. Results: The mean PIs before chemotherapy in patients who underwent gastrectomy or colectomy were significantly higher than the value in those treated with mastectomy (p < 0.05). In the gastrointestinal cancer patients, the mean PIs significantly increased after chemotherapy compared with the pre-chemotherapeutic value (p < 0.01), however no significant difference was seen in breast cancer patients. When the ratios of increase in PI were calculated among gastric cancer patients, the total gastrectomy group showed a significantly higher increase in PI compared with the partial gastrectomy group (p < 0.05). Conclusions: Since the oral L/M absorption test is useful for assessing the degree of mucosal damage and measurement of intestinal permeability, this analysis should be recommended to determine the optimum timing and the adequate dosage of the anticancer drug administration.

Acute effect of carmustine on glucose metabolism in brain and glioblastoma.

Adjuvant chemotherapy benefits a minority of patients with recurrent glioblastoma; a critical question therefore is how to select such responders. Metabolic reaction of the tumor, studied by positron emission tomography (PET) with [18F]-fluoro-2-deoxy-D-glucose (FDG), may be a suitable test of tumor responsiveness. In an effort to evaluate their prognostic value, the early effects of carmustine on brain and recurrent glioblastoma glucose metabolism were studied. Positron emission tomography with [18F]fluoro-2-deoxy-D-glucose was used to study 10 patients with recurrent glioblastoma before and 24 hours after a first dose of carmustine (120 mg/m2). Absolute quantification of glucose metabolism was obtained, and metabolic changes were analyzed and confronted with survival duration. The mean ratios of pre- to postchemotherapy values were 0.98 +/- 0.06 (range, 0.90-1.06) for the cortex and 0.97 +/- 0.06 (range, 0.89-1.09) for the white matter. There was no statistical difference between pre- and post-chemotherapy metabolism. In the glioblastoma, individual ratios of pre- to postchemotherapy values were considerably more scattered than in the nonneoplastic tissues, ranging from 0.76 to 1.51. A significant positive correlation (P < 0.002) was found between post- to pre-chemotherapy ratios of glucose metabolism and survival length. In patients with recurrent glioblastoma, the first administration of carmustine produces no acute change of glucose metabolism in the noninvolved cerebral tissues. Acute changes of glucose metabolism in tumor tissue in response to this treatment varied, and a hypermetabolic reaction possibly predicts longer survival.