Cycles Of Adjuvant Chemotherapy Research Articles

Cytoreductive surgery for late recurrence after surgically treated stage IV ovarian cancer-a case report

Recurrence is a common finding after surgically treated ovarian cancer even in cases submitted to initially R0 resection. However, it is well known that an aggressive surgical approach is perfectly justified at the moment of relapse, being the only solution in order to increase the survival rates. We present the case of a 62 year old patient who was previously submitted to surgery for stage IV ovarian cancer followed by 6 cycles of adjuvant chemotherapy. At 4 years follow up she was diagnosed with disseminated abdominal recurrences and she was submitted to secondary cytoreduction. Postoperatively, adjuvant chemotherapy with platinum based regimens was instituted.

Randomized study of tailored neoadjuvant chemotherapy according to the expression of tau, topo II α, and ERCC1 versus standard chemotherapy in HER2-negative breast cancer.

1025 Background: We hypothesized that selecting chemotherapy (CT) agents according to the expressions of drug sensitivity predictive biomarkers from tumor sample may improve the treatment efficacy for breast cancer (BC). Methods: Patients (pts) with stage II/III HER2 negative BC were eligible. Tumor biopsy samples were tested with immunohistochemistry study for the expression of tau, topo II α, and ERCC1. Four cycles of neoadjuvant CT were given after randomization, followed by operation. For control arm, Docetaxel (T)/ epirubicin (E) was given. For tailored arm, 1 of the 7 different CT regimens that containing 2 drugs among T, E, cisplatin, vinorelbine, and weekly high dose 5FU/leucovorin were given according to the expression of tumor biomarkers. After operation, 2-4 cycles of adjuvant CT were given and the choice of regimens were at investigators discretion. The primary endpoint was the primary tumor (T) pathological complete response (pCR) rate, and 268 pts were planned to be recruited. In the pre-pla...

Palliative oxaliplatin-based chemotherapy after exposure to oxaliplatin in the adjuvant setting for colon cancer.

Little is known regarding the efficacy of oxaliplatin-based chemotherapy for metastatic colon cancer patients who have already received adjuvant oxaliplatin-based chemotherapy. We retrospectively reviewed 22 consecutive patients who developed recurrence after adjuvant oxaliplatin-based chemotherapy for stage III colon cancer and received another course of oxaliplatin-based chemotherapy for their metastatic disease. The main endpoint was progression-free survival (PFS). A total of 635 patients received oxaliplatin-based chemotherapy for stage III colon cancer at the British Columbia Cancer Agency from 2006 to 2011. A total of 176 patients recurred, 22 (12.5%) of whom were re-exposed to oxaliplatin in the metastatic scenario. Oxaliplatin in combination with fluoropyrimidine was given as first, second and third line in in 3 (13.6%), 14 (63.6%), and 5 (22.7%) patients respectively. Median time from the last cycle of adjuvant oxaliplatin-based chemotherapy to the first cycle of palliative oxaliplatin-based chemotherapy was 44.3 months. Median PFS and overall survival (OS) were 3.3 (95% CI, 1.4-5.1) and 10.0 months (95% CI, 5.3-14.6), respectively. There was no difference in PFS for patients re-exposed to oxaliplatin less than 36 months compared to longer (3.6 versus 3.1 months, P=0.793, HR =0.88). In this population-based study, only a small proportion of pts who recurred after oxaliplatin-based adjuvant therapy received oxaliplatin in the metastatic setting. Re-exposure of oxaliplatin in combination with fluoropyrimidine is associated with only modest PFS benefit. Larger studies evaluating the role of oxaliplatin re-exposure are needed.

Clinical evaluation of postoperative chemotherapy based on genetic testing in patients with stage IIIA non-small cell lung cancer.

We performed a retrospective analysis to evaluate whether a postoperative chemotherapy selection method based on four tumoral gene expression tests would improve prognosis in patients with stage IIIA non-small cell lung cancer (NSCLC) after surgery. Between January 2007 and July 2011, 148 patients with stage IIIA NSCLC underwent radical lobectomy with four cycles of adjuvant postoperative chemotherapy. Forty-five patients had tailored treatment plans based on the results of tumoral gene expression tests. The tests consisted of quantitative real-time polymerase chain reaction analyses to measure the messenger ribonucleic acid levels of the excision repair cross-complementing gene 1, ribonucleotide reductase Ml, type III β-tubulin, and thymidylate synthase genes in tumor tissues. One hundred and three patients received conventional chemotherapy. Disease responses were assessed after two cycles and every three months after the first four cycles of chemotherapy. The one and two-year survival rates and diesease-free survival (DFS) rates were recorded, and the adverse effects documented. The one and two-year DFS rates in the genetically tested group were better than those in the non-tested group, and the differences were statistically significant (P < 0.05). The two-year Kaplan-Meier DFS curve analysis results were significantly better in the genetically tested group (X(2) = 8.228, P = 0.004). The adverse effects during the treatments were not significantly different (P > 0.05) between the two groups. The chemotherapy selection method based on four tumoral gene expression tests demonstrated its feasibility to improve the efficacy of adjuvant postoperative chemotherapy and benefit stage IIIA NSCLC patients by yielding better DFS without increasing the adverse effects of chemotherapy.

The clinical value of surgeons' efforts of preventing intraoperative tumor rupture in stage I clear cell carcinoma of the ovary: A Korean multicenter study

ObjectiveTo demonstrate the survival impact of intraoperative tumor rupture in women with stage I clear cell carcinoma (CCC) of the ovary. MethodsA total of 193 patients with stage I CCC of the ovary who had undergone a complete staging operation followed by ≥three cycles of adjuvant platinum-based chemotherapy, were retrospectively reviewed. Survival analysis was performed and compared between three stage groups: IA/IB, IC1, and IC2/IC3. ResultsThere were 70, 51, and 72 women with ovarian CCC in stages IA/IB, IC1, and IC2/IC3, respectively. Intraoperative tumor rupture occurred in 69 (35.8%) patients. Gross endometriosis (p=0.020) and significant peritumoral adhesion (p<0.001) were associated with intraoperative tumor rupture. However, neither laparoscopic approach nor large tumor size >10cm were associated with intraoperative tumor rupture. Patients with stage IC2/IC3 compared to those with stage IC1, had poorer progression-free survival (PFS) (5-year PFS, 68.5% versus 91.7%; p=0.010) and overall survival (OS) (5-year OS, 81.1% versus 95.4%; p=0.027). However, there was no significant difference between patients with stages IA/IB and IC1 CCC in PFS (5-year PFS 88.8% versus 91.7%; p=0.291) and OS (5-year OS 94.6% versus 95.4%; p=0.444). Stage IC2/IC3 was the only independent poor prognostic factor for OS (hazard ratio, 3.50; 95% confidence interval, 1.31 to 9.36). ConclusionSurgical spillage of tumor cells does not appear to have a negative impact on survival outcomes of women with stage I ovarian CCC who received ≥three cycles of adjuvant platinum-based chemotherapy.

A non-randomized confirmatory study regarding selection of fertility-sparing surgery for patients with epithelial ovarian cancer: Japan Clinical Oncology Group Study (JCOG1203).

Fertility-sparing treatment has been accepted as a standard treatment for epithelial ovarian cancer in stage IA non-clear cell histology grade 1/grade 2. In order to expand an indication of fertility-sparing treatment, we have started a non-randomized confirmatory trial for stage IA clear cell histology and stage IC unilateral non-clear cell histology grade 1/grade 2. The protocol-defined fertility-sparing surgery is optimal staging laparotomy including unilateral salpingo-oophorectomy, omentectomy, peritoneal cytology and pelvic and para-aortic lymph node dissection or biopsy. After fertility-sparing surgery, four to six cycles of adjuvant chemotherapy with paclitaxel and carboplatin are administered. We plan to enroll 250 patients with an indication of fertility-sparing surgery, and then the primary analysis is to be conducted for 63 operated patients with pathologically confirmed stage IA clear cell histology and stage IC unilateral non-clear cell histology grade 1/grade 2. The primary endpoint is 5-year overall survival. Secondary endpoints are other survival endpoints and factors related to reproduction. This trial has been registered at the UMIN Clinical Trials Registry as UMIN000013380.

Treatment results and prognostic factors for intracranial nongerminomatous germ cell tumors: single institute experience.

This study aimed to evaluate the treatment of intracranial nongerminomatous germ cell tumors (NGGCT) and to identify the prognostic factors for survival. Thirty-nine patients with nondisseminated NGGCTs, excluding those with pure mature teratomas, were treated between January 1985 and December 2010. Twenty-four patients received gross total or partial removal, 11 had excision biopsies, and 4 had no surgery. Radiotherapy was given postoperatively or definitively with a median tumor bed dose of 54Gy (range 30-54) with or without craniospinal irradiation. All patients received ten cycles of adjuvant chemotherapy, vinblastine, bleomycin, etoposide, and cisplatin after radiotherapy, except for one with mixed anaplastic astrocytoma component who received oral temozolomide. Survival and prognostic factors were estimated by the Kaplan-Meier method and log-rank tests, respectively. After a median follow-up of 77.7months (range 14-336), the 6-year overall survival (OS) and progression-free survival (PFS) were 74.4 and 79.5%, respectively. Inferior PFS was associated with lesions in the suprasellar region (p = 0.017), poor pathological features (p = 0.048), and with poor image (p < 0.0001) and tumor marker (TM) response (p = 0.003) to irradiation. Decreased OS was associated with lesions in the suprasellar region (p = 0.026) and with poor image (p < 0.0001) and TM response (p = 0.027) to irradiation. Neither the extent of surgery nor the radiation field was found to significantly influence survival. By our multimodality approach, patients achieved comparable outcomes. Other than poor pathological features, patients with poor responses to radiotherapy are prone to early recurrence and inferior survival. These patients should be focused for more intensive adjuvant treatment.

The role of adjuvant chemotherapy for lymph node-positive upper tract urothelial carcinoma following radical nephroureterectomy: a retrospective study.

To evaluate the effect of adjuvant chemotherapy (AC) on mortality after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) with positive lymph nodes (LNs) and to identify patient subgroups that are most likely to benefit from AC. We retrospectively analysed data of 263 patients with LN-positive UTUC, who underwent full surgical resection. In all, 107 patients (41%) received three to six cycles of AC, while 156 (59.3%) were treated with RNU alone. UTUC-related mortality was evaluated using competing-risks regression models. In all patients (T(all) N+), administration of AC had no significant impact on UTUC-related mortality on univariable (P = 0.49) and multivariable (P = 0.11) analysis. Further stratified analyses showed that only N+ patients with pT3-4 disease benefited from AC. In this subgroup, AC reduced UTUC-related mortality by 34% (P = 0.019). The absolute difference in mortality was 10% after the first year and increased to 23% after 5 years. On multivariable analysis, administration of AC was associated with significantly reduced UTUC-related mortality (subhazard ratio 0.67, P = 0.022). Limitations of this study are the retrospective non-randomised design, selection bias, absence of a central pathological review and different AC protocols. AC seems to reduce mortality in patients with pT3-4 LN-positive UTUC after RNU. This subgroup of LN-positive patients could serve as target population for an AC prospective randomised trial.

ITOC2 – 017. Prolonged survival for patients with recurrent glioblastoma multiforme who are treated with tumour lysate-pulsed autologous dendritic cells

<h3>Background</h3> Recurrent glioblastoma multiforme (rGBM) is a life threatening condition, with a mortality rate of approximately 100%. Despite recent advances in therapy, the survival rate in rGBM patients has not meaningfully changed in the past several decades. We have treated two cohorts of rGBM patients, one consisting of patients with early progression, and one consisting of patients with progression following several cycles of adjuvant temozomolide chemotherapy, with autologous dendritic cells pulsed with autologous tumour cell lysate (DCVax®-L). Such treatment is intended to activate the immune system against the tumour cells, with the expectation that the ensuing immune attack may delay progression and time to death. <h3>Aim</h3> To determine survival characteristics of patients with rGBM who are treated with DCVax-L. <h3>Methods</h3> Disease progression in patients with GBM was determined through magnetic resonance imaging. Progression needed to be determined by independent review on two consecutive scans for early progressor classification to avoid enrolling patients with pseudoprogression. Assessment of progression was done using modified RANO criteria. <h3>Results</h3> Nineteen (19) patients diagnosed with GBM were determined to have rapid recurrence following radiation therapy with concomitant temozolomide chemotherapy. The life expectancy for such patients is typically poor, and they were provided the DCVax-L treatment as part of a compassionate use approach in parallel to ongoing late stage clinical trials. Median overall survival in this cohort from initial GBM diagnosis is 15.1months (95% confidence interval (CI): 10.5–17.2), and the range is 8.1–>31months. A literature search revealed six publications with comparable populations of patients (Brandes et al., 2008; Roldan et al., 2009; Sanghera et al., 2010; Kang et al., 2010; Gunjur et al., 2011; Linhares et al., 2013). The table below demonstrates that these patients typically have a life expectancy of 8–10months. Reference (<i>n</i>) Population Median Survival (95% CI) DCVax-L (19) post RT+chemo, confirmed 2months later 15.1months (10.5–17.2) Brandes et al. (2008) (18) PD at 4weeks pos RT+chemo, confirmed after two more tmz cycles 10.2 months (n.a.) Roldan et al. (2009) (10) PD at 4–6weeks post RT+chemo, confirmed after <mml:math><mml:mrow><mml:mo>⩾</mml:mo></mml:mrow></mml:math>1 more tmz cycle(s) 9.1months (4.9–19.1) Kang et al. (2010) (10) PD at two consecutive scans post RT+chemo 10.8 (n.a.) Sanghera et al. (2010) (29) PD at two consecutive scans within 8weeks post RT+chemo8.3months (n.a.) Gunjur et al. (2011 (27) PD at two consecutive scans within 3months post RT+chemo, or clinical deterioration 10.4months (n.a.) Linhares et al. (2013) (13) PD at two consecutive scans within 3months post RT+chemo 9.0 months (3.7–14.3) A second cohort of patients with rGBM consisted of eight patients with recurrence following several adjuvant temozolomide treatment cycles. Median overall survival (OS) for these patients is 14.7months from the time of surgery for first recurrence. The comparator for this cohort is derived from Friedman et al. (2009), who reported mOS of 8.7–9.3months from the time of first recurrence for rGBM patients treated with Bevacizumab with or without irinotecan. <h3>Results and conclusion</h3> The results obtained in two cohorts of patients with rGBM suggest that treatment with autologous DC pulsed with autologous tumour cell lysate can extend survival by 5months or more.

Biomarkers of fatigue related to adjuvant chemotherapy for breast cancer: evaluation of plasma and lymphocyte expression.

BackgroundFatigue is common in cancer patients receiving adjuvant chemotherapy. To further understand the mechanism of fatigue and search for potential biomarkers, we conducted this prospective study. MethodsWe enrolled breast cancer (BC) patients before their first adjuvant Adriamycin-based chemotherapy cycle. Patients responded to the brief fatigue inventory (BFI) and Chalder fatigue questionnaires and had their blood drawn for both plasma evaluation and evaluation of the peripheral mononuclear cell fraction (PMNCF) mRNA expression of various biomarkers. We evaluated FSH, LH, estradiol, DHEA, DHEAS, IL6, IL2, ILIRA, IL1β, CRP, Cortisol in the plasma and IL2, IL10, IL6, TGF-β, KLRC1, TNF, BTP, SNCA, SOD1, BLNK, PTGS2 and INF γ expression in the PMNCF.Results11 patients did not exhibit an increase in their BFI scores and served as controls, whereas 32 patients exhibited an increase in their BFI scores compared with the baseline scores. From the biomarkers we evaluated in the PMNCF, the only one significantly associated with fatigue was TGF-β (p = 0.0343), while there was a trend towards significance with KLRC1 (p = 0.0627). We observed no evidence of significant associations of any plasma biomarkers with the development of fatigue. However when we analyzed patients with more severe fatigue, plasma IL1-RA levels correlated directly with higher fatigue scores (p = 0.0136).ConclusionsWe conclude that fatigue induced by chemotherapy in BC patients is associated with changes in IL1-ra plasma levels and in TGF-β lymphocyte expression. Its mechanism may be different than that observed in long-term BC survivors or that induced by radiation therapy.Trial registrationNCT02041364 [ClinicalTrials.gov]

Effect of dendritic cell/cytokine-induced killer cell immunobiological cancer therapy combined with adjuvant chemotherapy in patients with triple-negative breast cancer ⁎

Abstract Objective The aim of the present study was to investigate the effect of dendritic cell (DC)/cytokine-induced killer cell (CIK) immunobiological cancer therapy in patients with triple-negative breast cancer (TNBC) who underwent adjuvant chemotherapy. Methods From January 2010 to October 2013, 120 patients with postoperative TNBC were recruited and included in the study. Patients were enrolled in one of two groups according to whether they accepted DC/CIK immunobiological cancer therapy during adjuvant chemotherapy; the patients in the DC/CIK group underwent adjuvant chemotherapy combined with DC/CIK immunobiological cancer therapy, and the control group underwent adjuvant chemotherapy alone. When six cycles of adjuvant chemotherapy and six cycles of DC/CIK immunobiological cancer therapy had been completed, differences between the two groups with regard to quality of life (QoL), immunological indicators (CD3, CD4, CD8, and NK cell levels), disease-free survival (DFS), and side effects of chemotherapy and DC/CIK treatment were evaluated. Results In the DC/CIK group, the proportion of NK cells and CD3+ and CD4+ T-cell subgroups significantly increased, and the proportion of CD8+ cells decreased when they were compared before and after DC/CIK therapy (P &lt; 0.05). However, there were no significant changes in the control group. By the final follow-up, DFS of the treatment group and the control group was 38.4 and 34.2 months, respectively. The QoL improved in the patients treated with chemotherapy plus DC/CIK therapy compared with the patients treated with chemotherapy alone, and the difference between groups was significant (P &lt; 0.05). The side effects of two groups were tolerable and not significantly different between the two groups. Conclusion The DC/CIK treatment had potential benefits for patients with TNBC compared with the control group, and was not associated with any obvious side effects. Therefore, DC/CIK therapy is a safe and effective method for the treatment of TNBC.

Long-term outcome of patients with clinical stage I high-risk nonseminomatous germ-cell tumors 15 years after one adjuvant cycle of bleomycin, etoposide, and cisplatin chemotherapy

To report the long-term results of adjuvant treatment with one cycle of modified bleomycin, etoposide, and cisplatin (BEP) in patients with clinical stage I (CS I) nonseminomatous germ-cell tumors (NSGCT) at high risk of relapse. In a single-arm, phase II clinical trial, 40 patients with CS I NSGCT with vascular invasion and/or >50% embryonal cell carcinoma in the orchiectomy specimen received one cycle of adjuvant BEP (20 mg/m(2) bleomycin as a continuous infusion over 24 h, 120 mg/m(2) etoposide and 40 mg/m(2) cisplatin each on days 1-3). Primary end point was the relapse rate. Median follow-up was 186 months. One patient (2.5%) had a pulmonary relapse 13 months after one BEP and died after three additional cycles of BEP chemotherapy. Three patients (7.5%) presented with a contralateral metachronous testicular tumor, and three (7.5%) developed a secondary malignancy. Three patients (7.5%) reported intermittent tinnitus and one had grade 2 peripheral polyneuropathy (2.5%). Adjuvant chemotherapy with one cycle of modified-BEP is a feasible and safe treatment of patients with CS I NSGCT at high risk of relapse. In these patients, it appears to be an alternative to two cycles of BEP and to have a lower relapse rate than retroperitoneal lymph node dissection. If confirmed by other centers, 1 cycle of adjuvant BEP chemotherapy should become a first-line treatment option for this group of patients.

Docetaxel plus FOLFOX4 compared with FOLFOX4 as adjuvant chemotherapy for gastric cancer.

181 Background: To compare the efficacy of docetaxel plus FOLFOX4 to FOLFOX4 as adjuvant chemotherapy for gastric cancer patients. Methods: 320 patients with stage IB-IV (M0) gastric cancer were enrolled into the retrospective study. All patients received a total or subtotal gastrectomy with at least D1 lymph nodes dissection. 193 patients received FOLFOX4 as adjuvant chemotherapy. 127 patients received biweekly docetaxel plus FOLFOX4 (DOF regimen) as adjuvant chemotherapy. Docetaxel was administered at 40 mg/m2 on day 1, followed by FOLFOX4 regimen. Both of the regimens were repeated every 2 weeks for a maximum of 12 cycles. Results: In comparison with patients in FOLFOX4 group, patients in DOF group were relatively younger (p=.001), with more advanced disease in pN stage (p=.035) and pTNM stage (p=.031), received more cycles of adjuvant chemotherapy (p=.004), and had a higher percentage of adjuvant radiation (p =.002). After adjustment of unbalanced variables as mentioned above, no statistical difference was observed between DOF group and FOLFOX4 group in terms of 3-year disease-free survival (54% vs 69%, p = 0.100, HR 1.362, 95% CI (0.943-1.967)) and 3-year overall survival(70% vs 72%, p = 0.810, HR 1.049, 95% CI (0.711-1.548)). Stratified analysis according to clinicopathologic characters showed that there were almost no statistical differences of 3-year overall survival rates between two groups, except the primary site (middle 1/3) (p =.025) and pTNM stage (IIb stage) (p =.035) in favor of FOLFOX4 group. The incidences of grade 3/4 adverse events were obviously higher in DOF group than in FOLFOX4 group,including decreased appetite (18.1% V 10.4%, P = 0.046), diarrhea (4.7% V 0%, p=0.004 ), hypersensitivity reactions to oxaliplatin (3.1% V 0%, p=0.024) and neutropenia (47.3% V 31.6%, p=0.004). Conclusions: Compared to FOLFOX4 regimen, adjuvant docetaxel plus FOLFOX4 did not show significant survival advantages in gastric cancer patients. However, a more serious toxicity profile was observed in docetaxel plus FOLFOX4 arm. Further studies are needed to decide whether triplet regimen is appropriate as adjuvant chemotherapy of gastric cancer.

Palliative oxaliplatin-based chemotherapy after exposure to oxaliplatin in the adjuvant setting for colon cancer.

753 Background: Little is known regarding the efficacy of oxaliplatin-based chemotherapy for metastatic colon cancer patients who have already received adjuvant oxaliplatin-based chemotherapy. Methods: We retrospectively reviewed 22 consecutive patients who developed recurrence after adjuvant oxaliplatin-based chemotherapy for stage III colon cancer and received another course of oxaliplatin-based chemotherapy for their metastatic disease. The main endpoint was progression-free survival (PFS). Results: 635 patients received oxaliplatin-based chemotherapy for stage III colon cancer at the British Columbia Cancer Agency from 2006 to 2011. 176 pts recurred, 22 (12.5%) of whom were re-exposed to oxaliplatin in the metastatic scenario. Oxaliplatin in combination with fluoropyrimidine was given as first line in 3 pts (13.6%), as second line in 14 (63.6%), and third line in 5 (22.7%). Median time from the last cycle of adjuvant oxaliplatin-based chemotherapy to the first cycle of palliative oxaliplatin-based chemotherapy was 44.3 months. Median PFS and OS were 3.3 (95% CI 1.4-5.1) and 10.0 months (95% CI 5.3-14.6), respectively. There was no difference in PFS for patients who were re-exposed to oxaliplatin in less than 36 months or later than that (3.6 versus 3.1 months, p=0.793, HR=0.88). Conclusions: In this population-based study, only a small proportion of pts who recurred after oxaliplatin-based adjuvant therapy received oxaliplatin in the metastatic setting. Re-exposure of oxaliplatin in combination with fluoropyrimidine is associated with only modest PFS benefit. Larger studies evaluating the role of oxaliplatin re-exposure are needed.

Refractory left pleural effusion in an older patient: Atypical presentation of colorectal carcinoma.

The current study reports the case of a 60-year-old male that presented with a four-month history of recurrent chest pain. Chest X-ray examination revealed a left-sided pleural effusion. A closed thoracic drainage procedure was performed, but the chest pain relapsed shortly afterwards. The pleural fluid was exudative, with no tumor cells detected. A computed tomography scan subsequently revealed a large mass located in the splenic curve of the colon, with involvement of the greater curvature of the stomach. Endoscopic biopsies confirmed the diagnosis of adenocarcinoma. A gastrointestinal stromal tumor was excluded by endoscopic ultrasonography and biopsy. A subtotal colectomy with partial excision of the stomach, diaphragm and left liver lobe was successfully performed, followed by the administration of six cycles of adjuvant chemotherapy. At present, the patient is asymptomatic and there is no evidence of tumor recurrence following a 12-month follow-up. The present study summarizes the characteristics of refractory left pleural effusion by colorectal malignancies.

Evaluation of Serum Antioxidants during Adjuvant Chemotherapy of Breast Cancer- A Prospective Observational Study

Background: The enzymatic and non-enzymatic antioxidant defense systems of the cell prevent oxidant mediated damage to different biomolecules by neutralizing free radicals generated during anticancer drug metabolism. Reduced glutathione (GSH) and glutathione dependent enzymes such as glutathione peroxidase (GPx) and glutathione-s-transferase (GST) are the key determinants of cellular response to oxidative stress. The objective of this study was to evaluate changes in serum levels of these antioxidants after first cycle of adjuvant chemotherapy in breast cancer patients. Material and Methods: Histopathologically proven 60 breast cancer patients were included in the present study. The blood samples were taken after surgery before chemotherapy and after 3 weeks of administration of first cycle of chemotherapy. 30 healthy female controls were selected for comparison. Serum GSH and GST were estimated by spectrophotometric methods and serum GPx was estimated by ELISA. Results: The serum levels of GSH, GST and GPx were significantly decreased (P<0.0001) after first cycle of adjuvant chemotherapy in breast cancer patients as compare to levels before chemotherapy. A significant positive correlation was found between serum levels of GSH and GST as well as GSH and GPx after first chemotherapy cycle. Conclusion: Our data suggests that administration of chemotherapeutic drugs causes depletion of reduced glutathione and glutathione-dependent enzymatic antioxidants such as GST and GPx, which may be due to higher oxidative stress after chemotherapy.

Early vs. Late Chemoradiation Therapy and the Postoperative Interval to Adjuvant Therapy Do Not Correspond to Local Recurrence in Resected Pancreatic Cancer.

ObjectiveStandard postoperative therapy for pancreatic cancer consists of both chemotherapy alone and chemoradiation. We sought to investigate whether the sequence of chemotherapy and chemoradiation and overall time to initiation of adjuvant therapy would impact local vs. distant recurrence.MethodsAfter Institutional Review Board approval, resected pancreas cancer patient charts were evaluated for medical background, surgical, pathological, chemoradiation (CRT), and follow-up. Local recurrence (LR) was defined as failures occurring in the postoperative bed and regional lymph nodes. Early vs. late CRT was defined by whether CRT was given early (within 1–2 cycles of adjuvant chemotherapy) or late in the course of adjuvant chemotherapy (after the 3rd cycle of chemotherapy). The postoperative interval variance was compared to LR factors such as progression-free survival (PFS) and overall survival (OS).ResultsOf the 34 eligible patients, 47% (n=16) underwent early CRT and 41% (n=14) underwent late CRT. 12% (n=14) did not undergo any induction chemotherapy. At median follow-up of 22 months, 53% (n=18) had metastases, 24% (n=8) had LR, and 24% (n=8) were disease free. Kaplan-Meier curves revealed that early vs. late CRT did not appear to significantly impact OS (p=0.63), PFS (p=0.085) or LR (p=0.19). Postoperative interval did not affect PFS (p=0.42) or OS (p=0.93).ConclusionsEarly vs. late CRT and the time to initiation of adjuvant therapy were not significantly associated with LR in patients with resected pancreatic cancer. Future prospective studies are required to determine if sequencing of chemotherapy, CRT, or the postoperative interval impact survival and patterns of recurrence.

Effects of Herceptin on circulating tumor cells in HER2 positive early breast cancer.

The objective of this study was to determine the changes in peripheral blood circulating tumor cells in HER2-positive early breast cancer before and after Herceptin therapy, and to explore the effects of the HER2 gene and Herceptin on circulating tumor cells. CK19 mRNA expression in peripheral blood was evaluated by qRT-PCR as an index of circulating tumor cells in 15 cases of HER-2-positive breast cancer and 18 cases of HER2-negative breast cancer before, and after chemotherapy as well. Ten cases of HER2-positive breast cancer continued on Herceptin therapy for 3 months after chemotherapy, and their peripheral blood was again drawn and assayed for CK-19 mRNA expression. Preoperatively, all cases of HER2-positive cancer were positive for CK19 mRNA in peripheral blood, but 6 cases of HER2-negative breast cancer were positive (33.3%), where there was a substantial difference between the two groups. After 6 cycles of adjuvant chemotherapy, CK19 positive rates in cases of HER2-positive and -negative breast cancer reduced by 93.3 and 11.1%, respectively, with a significant difference still existing. After 3 months of Herceptin therapy, expression of CK19 mRNA declined considerably in 10 cases of HER2 positive breast cancer (113.66 ± 88.65 vs 63.35 ± 49.27, P = 0.025). HER-2 gene expression closely correlated with circulating tumor cells in peripheral blood of early breast cancer patients. Moreover, Herceptin, a monoclonal antibody for HER2, can reduce the number of circulating tumor cells, which can be an early predictive factor for Herceptin therapy effectiveness against breast cancer.

Left hepatectomy in a 3-month-old infant with congenital hepatoblastoma

Hepatoblastoma, the most common malignant liver tumor of infancy is known to present at a median age of 18 months. However, we happened to manage a case of a 3-month-old male infant with hepatoblastoma involving the left lobe of the liver. He underwent complete primary surgical excision of the tumor (left hepatectomy) and received six cycles of adjuvant chemotherapy thereafter. At a follow-up of 2 years, he is tumor-free as diagnosed by radiological investigations and follow-up serum alpha-fetoprotein (AFP) levels. Even on a thorough literature search, we did not find a similar report of an infant who has undergone elective primary surgical excision, except for the instances requiring emergency hepatectomy for hemoperitoneum resulting from perinatal tumor rupture. This is probably one of the youngest children in world literature with congenital hepatoblastoma, undergoing successful hepatectomy at presentation.

Social functioning of elderly persons with malignant diseases.

Malignant disease, its treatment and consequences of treatment can often lead to social marginalization and reduced quality of life. The aim of this research was to determine how elderly patients with malignant diseases function in their social environment. Sociodemographic questionnaire and interview were used to investigate a group of 49 elderly persons undergoing adjuvant chemotherapy treatment against early carcinomas (P1), and a group of 51 elderly persons with advanced stages of cancer undergoing systemic chemotherapy (P2). There were two cycles of assessment: one just before the beginning of the first cycle of adjuvant or systemic chemotherapy, and the other three months later. The research paradigm was based on the relation between individual treatment and the impact of the malignant disease on functional and social incompetence. The obtained findings were compared with the group of 50 healthy elderly people (K) who share the same relevant features but do not suffer from malignant diseases. It was found that most healthy older people live in share house, whereas those who suffer from malignant diseases mostly live in separate households. In both groups of patients and healthy group older people are mostly taken care of by their children. Individuals in both groups of patients have been frequently visited by their relatives during initial stages of treatment, unlike the elderly people in the control group. However, the difference did not reach a statistical significance. Three months after the beginning of chemotherapy, there was a statistically relevant difference in favor of the group undergoing adjuvant treatment. Home visits eventually become less frequent, whereas communication by telephone becomes more frequent. It was also found that visits by friends and neighbors are statistically more frequent among subjects who undergo adjuvant treatment, both before the treatment began and three months later when compared to other groups. Our research shows that elderly people are subject to social exclusion, especially those with malignant diseases. Special care should be dedicated to monitoring of social functioning during treatment of patients with malignant disease considering the detected trend of deterioration and significance for further recover and cure.