Disease-free Survival Percentages Research Articles

Single-arm phase II trial of carboplatin and mirvetuximab soravtansine as neoadjuvant chemotherapy (NACT) for advanced- stage ovarian, fallopian tube or primary peritoneal cancer (EOC) who are folate receptor α positive (NCT04606914) (578)

Objectives: The primary objective is to assess the feasibility and safety of obtaining tissue, assessing alpha-folate receptor status, and initiating treatment based on this data using a 21-day schedule in the advanced-stage ovarian, fallopian tube, or peritoneal cancer patients, without an unacceptable interval debulking surgery (IDS) delay. Secondary objectives include assessing progression-free survival, percentage of disease-free survival at two years, ORR prior to IDS per iRECIST 1.1 and GCIG CA-125 criteria, and percentage of optimal cytoreduction and pathological complete response (pCR) at IDS. Methods: This is a phase II study design with carboplatin and mirvetuximab (FRa receptor monoclonal antibody.) Patients with biopsy-confirmed, newly diagnosed, advanced-stage serous epithelial ovarian cancer appropriate for NACT will have centralized tumor evaluation via immunohistochemistry for FRa receptor overexpression. IHC staining is 2+ in 75% of cells will define eligibility. Patients will receive NACT with one lead-in cycle of single-agent carboplatin AUC 5/6, physician’s choice), followed by AUC 5 carboplatin and Mirvetuximab 6mg/kg adjusted to ideal body weight every 21days for three cycles prior to interval cytoreductive surgery (iCRS.) Patients eligible for surgery will undergo an iCRS no sooner than three weeks but no later than six weeks following the completion of cycle 3. Postoperatively, patients will complete three additional cycles of carboplatin-mirvetuximab for a total of 6 intended cycles. A total of 70 patients will be included. Patients with BRCA mutations are not excluded from this trial and may receive standard of care maintenance therapy, including bevacizumab and/or PARP inhibitors per physician’s choice in the adjuvant setting. After completion of adjuvant treatment, participants will be assessed approximately every 12 weeks by radiologic imaging to monitor disease status using RECIST 1.1 criteria. Objectives: The primary objective is to assess the feasibility and safety of obtaining tissue, assessing alpha-folate receptor status, and initiating treatment based on this data using a 21-day schedule in the advanced-stage ovarian, fallopian tube, or peritoneal cancer patients, without an unacceptable interval debulking surgery (IDS) delay. Secondary objectives include assessing progression-free survival, percentage of disease-free survival at two years, ORR prior to IDS per iRECIST 1.1 and GCIG CA-125 criteria, and percentage of optimal cytoreduction and pathological complete response (pCR) at IDS. Methods: This is a phase II study design with carboplatin and mirvetuximab (FRa receptor monoclonal antibody.) Patients with biopsy-confirmed, newly diagnosed, advanced-stage serous epithelial ovarian cancer appropriate for NACT will have centralized tumor evaluation via immunohistochemistry for FRa receptor overexpression. IHC staining is 2+ in 75% of cells will define eligibility. Patients will receive NACT with one lead-in cycle of single-agent carboplatin AUC 5/6, physician’s choice), followed by AUC 5 carboplatin and Mirvetuximab 6mg/kg adjusted to ideal body weight every 21days for three cycles prior to interval cytoreductive surgery (iCRS.) Patients eligible for surgery will undergo an iCRS no sooner than three weeks but no later than six weeks following the completion of cycle 3. Postoperatively, patients will complete three additional cycles of carboplatin-mirvetuximab for a total of 6 intended cycles. A total of 70 patients will be included. Patients with BRCA mutations are not excluded from this trial and may receive standard of care maintenance therapy, including bevacizumab and/or PARP inhibitors per physician’s choice in the adjuvant setting. After completion of adjuvant treatment, participants will be assessed approximately every 12 weeks by radiologic imaging to monitor disease status using RECIST 1.1 criteria.

KLF11 promotes the progression of glioma via regulating Holliday junction recognition protein.

Understanding the molecular mechanism of glioma is very important for the diagnosis and treatment of glioma. Recently, a new study illustrated that KLF11 could be a potential prognostic and diagnostic biomarker in glioma, but the critical role is not illustrated. In this study, we found that KLF11 was highly expressed in glioma cancer tissues and cells, and KLF11 high expression of glioblastoma (GBM) and lower-grade glioma (LGG) were correlated with poorer overall survival and disease-free survival percentages. KLF11 knockdown inhibited glioma cell proliferation and migration, while KLF11 overexpression enhanced cell proliferation and migration. In vivo, knockdown of KLF11 reduced the tumor size of glioma. With regard to the molecular regulatory mechanism, we clarified that the Holliday junction recognition protein (HJURP) was positively regulated by KLF11. Meanwhile, we demonstrated that HJURP knockdown also inhibited glioma carcinoma progression. Overexpression of HJURP rescued the suppressed proliferation and migration function of glioma cells with depletion of KLF11. Therefore, our study demonstrated the function of KLF11 in glioma and showed KLF11 and HJURP could be prognostic and diagnostic markers in glioma, which provides a new insight of glioma therapy.

Efficacy of Pre-operative 18F-FDG PET/CT in Prognostic Prediction in Patients With Renal Cell Carcinoma

Background/Aim: This study analyzed the parameters provided by preoperative 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for prognostic prediction of renal cell carcinoma (RCC). Patients and Methods: FDG-PET/CT data from 66 clear cell RCC and 19 non-clear cell RCC cases between January 2015 and October 2018 were reviewed retrospectively. We compared the two groups according to recurrence/metastasis to determine prognosis-influencing factors. Multivariate Cox hazard regression models were constructed to evaluate factors potentially predicting disease-free survival (DFS) after adjustment for confounders. DFS was then compared between groups. Results: Standardized uptake values (SUV) of the PET/CT scan were independent predictors of prognosis after adjusting for confounders. RCC cases were divided into two groups by optimal cut-off values. Differences between DFS percentages in high and low SUV groups were significant. Similar results were obtained in clear cell RCC groups. Conclusion: Increased SUV of the PET/CT scan are significant predictors of worse prognoses in patients with surgically resected RCC.

Stratification of Prognosis in Patients With Ampullary Carcinoma After Surgery by Preoperative Platelet-to-lymphocyte Ratio and Conventional Tumor Markers.

The platelet-to-lymphocyte ratio (PLR) has recently been suggested as a new predictor of the prognosis in several carcinoma types. However, the clinical impact remains controversial in patients with ampullary carcinoma. Thus, the aim of this study was to investigate other useful biomarkers for identifying poor prognosis in patients with ampullary carcinoma. Forty-one patients with ampullary carcinoma underwent pancreaticoduodenectomy (PD) with curative resection between April 2000 and April 2017. Various clinicopathological findings of the patients and their tumors were evaluated as potential prognostic factors which might enable better stratification of prognosis. Platelet-to-lymphocyte ratio, as well as other markers, was found to be a prognostic factor in patients with ampullary carcinoma. The 2-year disease-free survival percentage was significantly higher in the group with low PLR than in the high PLR group (70.2% vs. 28.6%; p=0.005). Combinational analysis of the PLR and conventional TMs enabled us to stratify prognosis of the patients more clearly than by each marker alone. PLR was a useful prognostic factor for patients with ampullary cancer. The combination of preoperative PLR and conventional TMs markers may be powerful predictive factors for postoperative prognosis in patients with ampullary carcinoma following PD.

Scheduling the adjuvant endocrine therapy for early stage breast cancer

Based on the data available through published trial results, we build a mixed integer nonlinear programming (MINLP) model in order to find an optimal treatment plan for a given HR+ early stage breast cancer patient who is postmenopausal. The objective is to maximize the disease-free survival percentage at the end of the treatment period subject to the constraints on the risk of contralateral breast cancer and the risks of several side effects, including endometrial cancer, thromboembolic events, cardiovascular diseases, bone fractures, hot flushes, and vaginal bleeding. The results of numerical experiments suggest the effectiveness of some of the schedules currently used in practice, as well as suggest some attractive alternative treatment plans.

Ekspresja niektórych molekularnych markerów immunohistochemicznych i ocena ich znaczenia prognostycznego w rakach płaskonabłonkowych jamy ustnej i wargi

Head and neck cancer treatment optimization and individualization has become possible due to the implementation of the prognostic and predictive molecular markers in diagnostics. The aim of this study was an attempt to determine which of the investigated molecular markers may have prognostic and predictive value in head and neck cancers. The paraffin blocks from 47 patients with oral and lip squamous cell carcinoma (SCC) after surgical treatment in the Institute of Oncology in Gliwice in the period of 1998-2002 were investigated. For immunohistochemical studies the DAKO monoclonal antibodies were used: p53, Ki67, Cyclin D1, Cathepsin B and Cox2-Cayman Chemical antibody. Staining reactions were evaluated at 400x magnification. The average percent of staining cells was estimated in every case in the groups of patients with (N+) and without (No) node metastases. The results were subsequently juxtaposed with selected clinical and histological parameters. Statistical analysis was performed with Mann-Whitney and Kruskal-Wallis tests and the log rank test with a significance level of 0.05 (p = 0,05). Significantly higher expression of Ki67 in N+ patients (p = 0,010) were recorded, although average staining in the group of treated and the group of unhealed patients was statistically insignificant. Cathepsin B expression (<20% and > 20%) was correlated with 3 year-long survival and a slight higher average staining (33,5%) in unhealed in comparison with treated patients (29,0%) was notified. Everage expression of p53 in unhealed patients (33,1%) was slightly higher than in treated ones (28,4%). Weaker Cyclin D1 expression (<10%) correlated with higher disease free survival. Average Cycline D1 staining in the groups of unhealed patients (19,6%) was higher than in the treated ones (12,0%). There were no significant differences in COX-2 staining in correlation with clinical and histological parameters. Lower expression of Cyclin D1 and Cathepsin B in neoplastic cells correlated with higher percentage of disease free survival what suggests the prognostic value of these markers. Higher proliferation activity of primary tumor neoplastic cells correlated with node metastases what may has the predictive value in the course of the disease.The different markers expressions observed in the different oral cavity localizations confirm the necessity to select patients for further investigations with respect to uniform disease changes topography.

Prognostic factors and clinicopathologic characteristics of invasive adenocarcinoma of the uterine cervix

The purpose of this study was to evaluate the outcome of patients with cervical adenocarcinoma and to determine the characteristics and the prognostic factors of this entity. This retrospective study was done in the Department of Surgical Oncology of the Salah Azaiz Institute of Tunis with 79 cases of invasive adenocarcinoma of the uterine cervix that were collected from 1990 to 1999. Survival was analyzed according to the Kaplan-Meier method. Univariate analysis of prognostic factors was performed with the test of log rank. Cox regression model was used in multivariate analysis of prognostic factors. Mean age was 50 years, and metrorrhagia was mostly revealing in 73% of the cases. Early stages (I, IIa, IIb with 1/3 proximal parametrial invasion) and "pure" type adenocarcinoma were found in 78% and 87% of the cases, respectively. Treatment consisted of a radiosurgical combination in 52 cases; exclusive radiotherapy was practiced with 17 patients. The 5 year-overall and disease-free survival percentages were, respectively, 68% and 72.4%. Poor prognostic factors were age >50 years, tumor size >4 cm, advanced stage, tumor grade, and lymph nodes and lymph-vascular space involvement. With the use of multivariate analysis, only stage and lymph node metastases remained significant prognostic factors. This report shows survival and prognostic factors that are similar to those found in previous studies, but unlike the Western countries, our results demonstrate a high rate of early stages and no increase in frequency of cervical adenocarcinoma.

Transplant strategies for myelodysplastic syndrome

Myelodysplastic syndrome (MDS) is an acquired bone marrow disorder characterized by ineffective hematopoiesis and cellular dysfunction and has an increased risk of transforming into acute myeloid leukemia. Most patients are of advanced age with attendant comorbidities, making treatment difficult. Current treatment options have included supportive care and, in difficult cases, chemotherapy regimens designed for acute leukemia patients. A major effort has been made to determine the role of stem cell transplantation in adult MDS patients, currently the only curative option available for them. Based on relapse rates, studies indicate that allogeneic and autologous transplants provide better antileukemic activity than intensive chemotherapy schedules. Use of DNA methyltransferase inhibitors may assist in managing MDS patients while awaiting a transplant match, but the procedural mortality for transplant remains high. Reduced conditioning or nonmyeloablative conditioning, particularly in the elderly, has been attempted with some success. Reduced conditioning also increases the graft-versus-leukemia effect, allowing for a higher percentage of disease-free survival. Current use of peripheral blood as a source of stem cells for autotransplant is associated with an extremely low procedural mortality. Improvement in such transplant procedures as myeloablation, preparation of the autograft, and posttransplant prophylaxis are improving recovery rates for these patients. In addition, as the biology of this disease is being revealed, newer options will become available in the near future.

Longterm prognosis after hepatic resection for small hepatocellular carcinoma1

Treatment of small hepatocellular carcinoma (HCC) remains a critical issue. In addition, the longterm prognosis and prognostic factors of small hepatocellular carcinoma after hepatic resection are not well documented. The surgical outcomes of 135 consecutive patients with one to three HCCs of diameter <or= 3 cm who underwent curative hepatic resection between 1987 and 2001 were reviewed retrospectively. Postresection prognostic factors were evaluated by univariate and multivariate analysis using Cox's proportional hazards model. The overall incidence of postoperative complications was 25%, and three patients had hospital deaths (2%), including one (0.7%) operative death. The mean and median overall survival times, including hospital death after surgery, were 53 months and 43 months, respectively. The 3-, 5-, and 10-year disease-free survival percentages after hepatic resection were 49%, 30%, and 8%, respectively. The 3-, 5-, and 10-year overall survival percentages after hepatic resection were 73%, 55%, and 18%, respectively. Multivariate analysis revealed that age more than 60 years was an independent unfavorable prognostic factor affecting disease-free survival (hazard ratio 1.286, 95% confidence interval 1.107 to 1.863, p = 0.046), and the presence of liver cirrhosis was an independently significant factor of poor overall survival (hazard ratio 2.012, 95% confidence interval 1.049 to 3.861, p = 0.035). The cumulative incidence of postoperative recurrence was 82%. The 5-year overall survival in patients with tumor recurrence undergoing repeat hepatectomy (85%) was significantly greater than in patients without second resection (41%). Six patients (4%) survived longer than 10 years after hepatic resection (four with recurrence and two without recurrence). All four of these patients with postoperative recurrence underwent repeat hepatectomy. The postresection survival of patients with small hepatocellular carcinoma will differ depending on the presence of liver cirrhosis. Repeat hepatectomy may contribute to the prolongation of survival in such patients with postoperative recurrence.

RADICAL PERINEAL PROSTATECTOMY: ONCOLOGICAL OUTCOME DURING A 20-YEAR PERIOD

Purpose We examined 4 postulates: 1) radical perineal prostatectomy provides a substantial disease control benefit in men with clinically confined prostate cancer, 2) postoperative prostate specific antigen (PSA) levels are an excellent surrogate end point for defining disease control, 3) the biology of primary malignancy defines the interval to death after recurrence and 4) the interval from intervention to death from recurrence is so long that current series of alternative curative therapies have insufficient duration of observation to permit a comparison with the results of surgery. Materials and Methods A total of 1,242 men with a median age of 65.2 years who had stage cT1 to 2 N0M0 disease underwent radical perineal prostatectomy. The final pathology specimen was characterized in regard to disease extent, and Gleason grade and score. Patients were followed at 2 weeks, at 2 months and then at 6-month intervals for biochemical, physical and radiographic evidence of disease recurrence. Outcome was evaluated by determining time to biochemical failure (PSA 0.5 ng./ml. or greater) and cancer associated death. Results Median time to noncancer death was 19.3 years. Median cancer associated death end point was not reached by patients with organ and specimen confined disease, while it was 12.7 years for margin positive disease. At 5 years 8, 35 and 65% of the patients with organ confined, specimen confined and margin positive disease, respectively, had PSA failure. This served as an excellent surrogate end point, preceding cancer associated death by 5 to 12 years depending on the biological aggressiveness predicted by Gleason grade or score. Biologically aggressive organ confined disease that had been surgically removed was associated with a high percentage of disease-free survival. Conclusions Our study confirms our postulates. It also provides guidelines for comparing therapies among institutions and emphasizes that enthusiasm for new treatments may be based on insufficient followup. Patient selection may severely bias outcome independent of treatment when death is used as the end point. Our study establishes the value of PSA as a surrogate end point.

Menstrual cycle and timing of breast surgery in premenopausal node-positive breast cancer: Results of the International Breast Cancer Study Group (IBCSG) Trial VI

It has been postulated that breast cancer surgery performed during the follicular phase of the menstrual cycle is associated with poorer outcome. We tested this hypothesis by evaluating disease-free survival (DFS) for 1033 premenopausal patients who received definitive surgery either during the follicular phase (n = 358) or the luteal phase (n = 675). All patients were enrolled in a randomized trial conducted between July 1986 and April 1993. All had node positive breast cancer and randomization was stratified by estrogen receptor (ER) status. All patients received at least three cycles of adjuvant cyclophosphamide, methotrexate, and 5-fluorouracil (CMF). The median follow-up was 60 months. Patients who underwent definitive surgery for breast cancer in the follicular phase had a slightly worse disease-free survival than those operated on during the luteal phase (five-year DFS percentage: 53% versus 58%; hazard ratio, 1.13; 95% confidence interval (CI), 0.94-1.38; P = 0.20). The effect was significantly greater for the subpopulation of 300 patients with ER-negative primaries (P = 0.02 interaction effect; five-year DFS percentages 42% vs. 59%; hazard ratio 1.60; 95% CI, 1.12-2.25; P = 0.008). The effect of timing of surgery diminished for analyses based on lesser surgical procedures, e.g., excisional biopsies. In particular, no effect of timing was observed for fine needle aspiration procedures. Surgical procedures which are more extensive than a fine needle aspiration biopsy might be associated with worse prognosis if conducted during the follicular phase of the menstrual cycle. This phenomenon was seen predominantly for high risk breast cancer with low levels or no estrogen receptors in the primary tumor.

107 P - Results of a randomized adjuvant breast cancer trial comparing a conventional with a perioperative start of chemotherapy

Purpose The rationale of the present study was to validate the hypothesis of a favorable influence of a perioperative start of adjuvant chemotherapy in patients with operable breast cancer of various prognostic groups, as suggested by results of experimental data. Patients and methods Patients with operable breast cancer were entered into a prospective tria1 and randomized to receive epidoxorubicin (20 mg/sqm) and cyclophosphamide (200 mg/sqm; EC) either on days 1, 8 and 15 (= perioperatively) or on days 22, 29 and 36 (= postoperatively), day one being the day of surgery. Patients with lymph node involvement (N+, pre- and postmenopausal) and premenopausal patients without lymph node involvement (N-) and estrogen receptor (ER) negativity received 3 additional cycles of adjuvant chemotherapy with cyclophosphamide, methotrexate, fluouracil (CMF). All ER + patients received 20 mg tamoxifen per day for two years. Results No increased toxicity or problems with wound healing were found in patients from the perioperative group. With a present median follow-up of 70 months, 76 out of 221 (34%) eligible patients have relapsed. The estimated percentage of disease-free survival (DFS) at 5 years was 66 (±3.2) in all patients, 59 (±5.4) in patients from the perioperative and 72 (±4.2) in those from the postoperative groups (p = 0.09). Conclusion An advantage in DFS resulting from an earlier start of adjuvant chemotherapy than on postoperative day 22 can be excluded at this point of the study.

Primary (neoadjuvant) chemotherapy and radiotherapy compared with primary radiotherapy alone in stage IIb-IIIa breast cancer

A phase III randomized trial was activated to evaluate the efficacy of preoperative combined chemotherapy and radiotherapy as compared to preoperative radiation therapy alone, in patients with breast cancer presenting with a clinical stage of IIb-IIIa (TNM classification). From 1985 to 1990, 271 patients, aged 27-55 years, with stage IIb-IIIa breast cancer were randomized to receive either one or two courses of thiotepa 20 mg (i.m. injection) on the days 1, 3, 5, 7, 9, 11 (total dose per course 120 mg), methotrexate 40 mg/m2, i.v. on days 1 and 8, and 5-fluorouracil 500 mg/m2, i.v. on days 1 and 8 (TMF regimen) plus radiotherapy (Group I, 137 patients), or preoperative radiation therapy only (Group II, 134 patients). After the preoperative treatment all patients underwent mastectomy and complete axillary clearance, and then received 4-6 courses of TMF. The trial was conducted in a single institution (N.N. Petrov Research Institute of Oncology, St. Petersburg). Histopathological assessment of the mastectomy specimens showed complete regression of the tumour in 29.1% of the patients in group I and in 19.4% of the patients e.c. in group II. The estimated 5-year overall survival percentages were 86.1% for group I, and 78.3% for group II (P > 0.05). 5-year disease-free survival percentages were 81.0% and 71.6%, respectively (p < 0.05). Despite the low number of the patients included in the trial, we were able to detect a significant improvement in treatment results with a combination of chemotherapy and radiation therapy given prior to mastectomy over those of local therapy alone with radiation therapy followed by mastectomy, for average- and high-risk patients with operable breast cancer.

A randomized pilot study of high-dose epirubicin as neoadjuvant chemotherapy in the treatment of cancer of the bilharzial bladder

Seventy-one patients with T2 and T3 bladder cancer were randomized to receive either two courses of epirubicin 120 mg/m2 i.v. push every 21 days pre-operatively, and four additional courses post-operatively (group I = 34 patients), or radical surgery (group II = 37 patients). At a median follow-up of 24 months (range 22 months to 38 months) 25 patients from group I and 14 patients from group II are still alive and disease-free. The estimated two-year disease-free survival percentages were 73.5 and 37.9%, respectively (P = 0.05). After initial chemotherapy, resected specimens were subjected to histopathological study of chemotherapeutic effects. Necrosis was detected in 95% of cases with squamous cell carcinoma and in 57.3% of cases with transitional cell carcinoma. We conclude that the benefit which was obtained by pre-operative and post-operative chemotherapy with epirubicin is promising and may represent a significant improvement in the treatment of patients with carcinoma of the bilharzial bladder.