Phase I Study of Fludarabine Plus Cyclophosphamide in Patients With Previously Untreated Low-Grade Lymphoma: Results and and Long-Term Follow-Up—A Report From the Eastern Cooperative Oncology Group

2000 ◽  
Vol 18 (5) ◽  
pp. 987-987 ◽  
Author(s):  
Howard S. Hochster ◽  
Martin M. Oken ◽  
Jane N. Winter ◽  
Leo I. Gordon ◽  
Bruce G. Raphael ◽  
...  
Keyword(s):  
Phase Ii ◽  
Bone Marrow Involvement ◽  
Survival Rates ◽  
Eastern Cooperative Oncology Group ◽  
Disease Free Survival ◽  
Low Grade ◽  
Survival Times ◽  
Free Survival ◽  
Disease Free

PURPOSE: To determine the toxicity and recommended phase II doses of the combination of fludarabine plus cyclophosphamide in chemotherapy-naive patients with low-grade lymphoma. PATIENTS AND METHODS: Previously untreated patients with low-grade lymphoma were entered onto dosing cohorts of four patients each. The cyclophosphamide dose, given on day 1, was increased from 600 to 1,000 mg/m2. Fludarabine 20 mg/m2 was administered on days 1 through 5. The first eight patients were treated every 21 days; later patients were treated every 28 days. Prophylactic antibiotics were required. RESULTS: Prolonged cytopenia and pulmonary toxicity each occurred in three of eight patients treated every 3 weeks. The 19 patients treated every 28 days, who were given granulocyte colony-stimulating factor as indicated, did not have undue nonhematologic toxicity. Dose-limiting toxicity was hematologic. At the recommended phase II/III dose (cyclophosphamide 1,000 mg/m2), grade 4 neutropenia was observed in 17% of all cycles and 31% of first cycles. Grade 3 or 4 thrombocytopenia was seen in only 1% of all cycles. The median number of cycles per patient was six (range, two to 11) for all patients enrolled. The response rate was 100% of 27 patients entered; 89% achieved a complete and 11% a partial response. Nineteen of 22 patients with bone marrow involvement had clearing of the marrow. Median duration of follow-up was more than 5 years; median overall and disease-free survival times have not been reached. Kaplan-Meier estimated 5-year overall survival and disease-free survival rates were 66% and 53%, respectively. CONCLUSION: The recommended dosing for this combination in patients with previously untreated low-grade lymphoma is cyclophosphamide 1,000 mg/m2 day 1 and fludarabine 20 mg/m2 days 1 through 5. The regimen has a high level of activity, with prolonged complete remissions providing 5-year overall and disease-free survival rates as high as those reported for other therapeutic approaches in untreated patients.

scholarly journals Validation of a clinicopathological score for the prediction of post-surgical evolution of pituitary adenoma: retrospective analysis on 566 patients from a tertiary care centre

2019 ◽  
Vol 180 (2) ◽  
pp. 127-134 ◽  
Author(s):  
S Asioli ◽  
A Righi ◽  
M Iommi ◽  
C Baldovini ◽  
F Ambrosi ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Proliferative Activity ◽  
Disease Free Survival ◽  
Low Grade ◽  
High Grade ◽  
Tumour Type ◽  
Disease Evolution ◽  
Free Survival ◽  
Disease Free

Objective and design A clinicopathological score has been proposed by Trouillas et al. to predict the evolution of pituitary adenomas. Aim of our study was to perform an independent external validation of this score and identify other potential predictor of post-surgical outcome. Methods The study sample included 566 patients with pituitary adenomas, specifically 253 FSH/LH-secreting, 147 GH-secreting, 85 PRL-secreting, 72 ACTH-secreting and 9 TSH-secreting tumours with at least 3-year post-surgical follow-up. Results In 437 cases, pituitary adenomas were non-invasive, with low (grade 1a: 378 cases) or high (grade 1b: 59 cases) proliferative activity. In 129 cases, tumours were invasive, with low (grade 2a: 87 cases) or high (grade 2b: 42 cases) proliferative activity. During the follow-up (mean: 5.8 years), 60 patients developed disease recurrence or progression, with a total of 130 patients with pituitary disease at last follow-up. Univariate analysis demonstrated a significantly higher risk of disease persistence and recurrence/progression in patients with PRL-, ACTH- and FSH/LH-secreting tumours as compared to those with somatotroph tumours, and in those with high proliferative activity (grade 1b and 2b) or >1 cm diameter. Multivariate analysis confirmed tumour type and grade to be independent predictors of disease-free-survival. Tumour invasion, Ki-67 and tumour type were the only independent prognostic factors of disease-free survival. Conclusions Our data confirmed the validity of Trouillas’ score, being tumour type and grade independent predictors of disease evolution. Therefore, we recommend to always consider both features, together with tumour histological subtype, in the clinical setting to early identify patients at higher risk of recurrence.

Age and Response after Autologous Stem Cell Transplantation (ASCT) Define a Group of Long-Term Event-Free Survivors among Patients (Pts) with Low-Grade Follicular Lymphoma (FL): A Single Institution Experience.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1883-1883
Author(s):  
Charalambos Andreadis ◽  
Elise A. Chong ◽  
Edward A. Stadtmauer ◽  
Selina M. Luger ◽  
David L. Porter ◽  
...  
Keyword(s):  
Multivariable Analysis ◽  
Disease Free Survival ◽  
Autologous Bone Marrow ◽  
Large Cell ◽  
High Dose ◽  
Low Grade ◽  
Free Survival ◽  
Disease Free

Abstract Introduction: FL is generally responsive to conventional-dose chemotherapy but long term disease-free survival (DFS) is uncommon. High-dose chemo-radiotherapy followed by ASCT has the potential to induce remission in this disease but the long-term benefit of this modality remains to be determined. Methods: Between 1990 and 2003, we transplanted 52 pts originally diagnosed with low-grade FL (31 grade 1, 21 grade 2). Twenty-five (48%) had biopsy-proven large cell transformation (FL grade 3 or diffuse large cell lymphoma) before ASCT. The median number of prior therapies was 2 (range: 1 to 7). Prior to ASCT, 45 pts (87%) were responsive to salvage therapy with 20 pts (38%) in CR. Five pts (10%) had chemo-resistant disease at the time of ASCT. High-dose regimens included BCNU-cyclophosphamide-etoposide (31%), melphalan/TBI (27%), and cyclophosphamide/TBI (25%). Thirty-eight pts (73%) received peripheral stem cells (PSCT) and 14 pts (27%) received autologous bone marrow (BM) with 4-hydroxyperoxycyclophosphamide (4-hc) purging in 9 cases (17%). The median age was 49 yrs (range: 29–65). Results: There was 1 treatment-related death during the first 100 days. After ASCT, 36 pts (69%) achieved a CR, 2 (4%) had a PR, and 7 (13%) had stable disease. Among those in CR, 20 (56%) had a CR pre-ASCT, 14 (41%) had a lesser response, and 1 (3%) was chemo-resistant. Median follow-up (f/u) of survivors was 5.3 yrs (range: 1.7 months to 12.4 yrs). The median overall survival (OS) has not yet been reached. The median event-free survival (EFS) is 3.4 yrs (range: 1.7 months to 12.4 yrs). Among complete responders, more than 50% are disease free at last follow-up (range 1.7 months to 12.1 yrs). Variables favorably affecting EFS and OS are age < 60 yrs (p = 0.007, 0.015 respectively), achievement of a CR after ASCT (p = 0.002, 0.001), absence of transformation (p = 0.038, 0.017), BM vs. PSCT (p = 0.042, 0.086), and 4-hc BM purging (p = 0.044, 0.059). Number of prior regimens, response prior to ASCT, type of preparative regimen, and addition of TBI, were not significantly associated with EFS, DFS, or OS. In multivariable analysis, achievement of CR after ASCT and age < 60 yrs are the only significant predictors of EFS and OS. Adjusted for age, 53% of pts with a CR after ASCT are alive and event-free at last f/u (range: 2.4 months to 12.4 yrs) (Figure 1). In contrast, the median EFS among pts without a CR is 0.5 yrs (range: 1.7 months to 5.3 yrs). Conclusion: ASCT is a reasonable therapeutic approach to FL, resulting in long term EFS for some pts, even with relapsed, refractory and/or transformed disease. In our experience, significant predictors of EFS and OS after ASCT are complete response and age <60. The appropriate application and timing of ASCT in the management of pts with FL needs to be further evaluated in randomized, controlled clinical trials. Figure Figure

Can High Dose Therapy Change the Course of Low Grade Lymphoma? A Study Considering Patients as Their Own Control.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1882-1882
Author(s):  
Stephane Vignot ◽  
Nicolas Mounier ◽  
Guillaume Sergent ◽  
Pauline Brice ◽  
Jean-Pierre Marolleau ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Tumor Burden ◽  
High Dose ◽  
Low Grade ◽  
High Dose Therapy ◽  
Free Survival ◽  
Dose Therapy ◽  
New Strategy ◽  
Disease Free

Abstract Low grade lymphoma patients (pts) have an indolent evolution with median survival ranging between 8–10 years. During disease’s course, high dose therapy (HDT) and autologous stem-cell transplantation (ASCT) can be considered as an alternative to sequential chemotherapies. However, efficacy of this strategy remains controversial. The purpose of our study is to evaluate ASCT efficacy by comparing retrospectively for each pts disease free survival (DFS) after ASCT with DFS observed with pts’ last chemotherapy regimen (LCR) just before intensification. Between apr 1988 and feb 2002, 109 low grade lymphoma pts were treated with HDT and ASCT in our department, 61 were male, the median age was 49 yrs [range 28–65]. Histological subtypes were mostly follicular small cell (86 %). At time of diagnosis, LDH were normal for 85 pts; 60 pts had high tumor burden. IPI was 0 for 16 %, 1 for 70 % and 2 for 14 %. Prior to ASCT, pts had experienced a median of 2 progressions (range 1 to 5). At time of graft, 102 pts present complete or partial response and 7 pts present stable disease. Two principal intensification chemo regimens were used before ASCT: VP16/cyclophosphamide in 84 pts and BEAM in 12. TBI was associated for 86 pts. At June 2002, the median follow up was 6.4 yrs from diagnosis and 4.5 yrs from ASCT. 3 years after ASCT, survival rate was 72 % and DFS rate was 50 %. Median DFS decreased with nb of progression (p=0.02): Median DFS according to nb of progression Nb of progression 1 2 3 > 3 Nb pts (%) 17 (16) 57 (52) 28 (26) 7 (6) Median DFS in yrs 6.4 5.1 1.8 1.0 Considering pt with more than 1 progression (n=92) as his own control, DFS was longer after ASCT than after LCR for 61 % of pts. Median DFS was 2.5 yrs after ASCT and 2.0 yrs after LCR. At 3 yrs, DFS rate was 48 % after ASCT and 37 % after LCR (p<0,001): Figure Figure This study demonstrates that HDT and ASCT significantly increase DFS in comparison with the LCR for low grade lymphoma patients. Such methodology could be useful to evaluate new strategy incorporating monoclonal antibody.

Retrospective long-term follow-up analysis in 21 patients with chordomas of various sites treated at a single institution

1991 ◽  
Vol 75 (3) ◽  
pp. 374-377 ◽  
Author(s):  
Martin E. Keisch ◽  
Delia M. Garcia ◽  
Robert B. Shibuya
Keyword(s):  
Survival Rates ◽  
Disease Free Survival ◽  
Subtotal Resection ◽  
Survival Times ◽  
Actuarial Survival ◽  
Free Survival ◽  
Content Type ◽  
Long Term Follow Up ◽  
Radiotherapy Alone ◽  
Disease Free

✓ Twenty-one patients with chordoma were treated at the Radiation Oncology Center, Mallinckrodt Institute of Radiology, between 1949 and 1986. Thirteen patients had sacrococcygeal tumors, five had clival tumors, two had nasopharyngeal tumors, and one had a lumbar spine tumor. Nine patients were treated with surgery alone, eight patients with subtotal resection and postoperative irradiation, and four patients with radiotherapy alone after biopsy. The 5- and 10-year actuarial survival rates were 74% and 46%, respectively. The 10-year actuarial survival rate was significantly better in patients treated with surgery alone or surgery and irradiation than in those treated with radiotherapy alone (52%, 32%, and 0%, respectively, p = 0.02). Although all patients ultimately suffered a recurrence, those with lumbosacral tumors treated with surgery and irradiation had a longer mean disease-free survival period (6.6 years) than those treated with surgery alone (4.1 years) (p = 0.08). Disease-free survival times of patients with base of the skull tumors was not significantly different between the treatment groups. Irradiation after resection of chordomas appears to increase the time to first relapse in lumbosacral tumors and should be considered after subtotal resection.

scholarly journals The Identification of Prognostic Factors and Survival Statistics of Conventional Central Chondrosarcoma

Sarcoma ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Sjoerd P. F. T. Nota ◽  
Yvonne Braun ◽  
Joseph H. Schwab ◽  
C. Niek van Dijk ◽  
Jos A. M. Bramer
Keyword(s):  
Prognostic Factors ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Selection Procedure ◽  
Tumor Location ◽  
Low Grade ◽  
High Grade ◽  
Dedifferentiated Chondrosarcoma ◽  
Free Survival ◽  
Disease Free

Introduction. Chondrosarcomas are malignant bone tumors that are characterized by the production of chondroid tissue. Since radiation therapy and chemotherapy have limited effect on chondrosarcoma, treatment of most patients depends on surgical resection. We conducted this study to identify independent predictive factors and survival characteristics for conventional central chondrosarcoma and dedifferentiated central chondrosarcoma.Methods. A systematic literature review was performed in September 2014 using the Pubmed, Embase, and Cochrane databases. Subsequent to a beforehand-composed selection procedure we included 13 studies, comprising a total of 1114 patients.Results. The prognosis of central chondrosarcoma is generally good for the histologically low-grade tumors. Prognosis for the high-grade chondrosarcoma and the dedifferentiated chondrosarcoma is poor with lower survival rates. Poor prognostic factors in conventional chondrosarcoma for overall survival are high-grade tumors and axial/pelvic tumor location. In dedifferentiated chondrosarcoma the percentage of dedifferentiated component has significant influence on disease-free survival.Conclusion. Despite the fact that there are multiple prognostic factors identified, as shown in this study, there is a need for prospective and comparative studies. The resulting knowledge about prognostic factors and survival can give direction in the development of better therapies. This could eventually lead to an evidence-based foundation for treating chondrosarcoma patients.

scholarly journals Adult Granulosa Cell Tumors of the Ovary: A Retrospective Study of 36 FIGO Stage I Cases with Emphasis on Prognostic Pathohistological Features

2018 ◽  
Vol 2018 ◽  
pp. 1-11
Author(s):  
Emina Babarović ◽  
Ivan Franin ◽  
Marko Klarić ◽  
Ani Mihaljević Ferrari ◽  
Ružica Karnjuš-Begonja ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Univariate Analysis ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Figo Stage ◽  
Free Survival ◽  
Granulosa Cell Tumors ◽  
Diffuse Growth ◽  
Disease Free

Objective. Adult granulosa cell tumors (AGCTs) represent 2%–5% of all ovarian malignancies. The aim of this study was to analyze clinical and pathohistological parameters and their impact on recurrence, overall, and disease-free survival in FIGO stage I AGCT patients. Methods. The tumor specimens analyzed in this retrospective study were obtained from a total of 36 patients with diagnosis of ovarian AGCT surgically treated at the Department of Gynecology, Rijeka University Hospital Centre, between 1994 and 2012. Clinical, pathological, and follow-up data were collected. Results. The mean age at diagnosis was 54.5 years with a range of 24–84. The majority of the patients, 30 (83%), were in FIGO stage IA, 3 (8%) in stage IC1, 1 (3%) in stage IC2, and 2 (6%) in stage IC3. During follow-up period (median 117.5 months, range 26–276), recurrence occurred in 4 patients (12%) with 2 deaths of the disease recorded. In univariate analysis, the 5-year survival rates were significantly shorter in patients with FIGO substage IC (p=0.019), with positive LVSI (p=0.022), with presence of necrosis (p=0.040), and with hemorrhage (p=0.017). In univariate analysis, the 5-year disease-free survival rates were significantly shorter in patients treated with fertility surgery (p=0.004), with diffuse growth pattern (p=0.012), with moderate and severe nuclear atypia (p=0.032), and with presence of hemorrhage (p=0.022). FIGO substage IC proved to be independent predictor for recurrence (OR = 16.87, p=0.015, and OR = 23.49, p=0.023, resp.) and disease-free survival (p=0.0002; HR 20.84, p=0.02) at the uni- and multivariate analyses. Conclusions. FIGO substage IC is predictive of recurrence and disease-free survival in patients with early-stage AGCTs. LVSI, presence of necrosis and hemorrhage, diffuse growth pattern, and nuclear atypia in AGCTs seem to be associated with overall and disease-free survival, so these pathological features should be taken into consideration when managing patients with AGCT.

scholarly journals 15-year Follow-up of Comparing Mastoscopic and Conventional Axillary Dissection in Breast Cancer: A Multicentres, Randomized Controlled Trial

2020 ◽  
Author(s):  
Chengyu Luo ◽  
Guang Cao ◽  
wenbin Guo ◽  
Jie Yang ◽  
Qiuru Sun ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Axillary Lymph ◽  
Term Survival ◽  
Free Survival ◽  
Significant Difference ◽  
Disease Free

Abstract Backgroud: Longer follow-up was necessary to testify the exact value of mastoscopic axillary lymph node dissection (MALND).Methods：From January 1, 2003 to December 31, 2005,1027 patients with operable breast cancer were randomly assigned to two groups: MALND and CALND. 996 eligible patients were enrolled. The end points are disease free survival and overall survival.Results：The final cohort of 996 patients was followed for an average of 184 months. The distribution of all events was fairly similar between two groups of patients. The incidence of local in-breast events did not differ in a significant manner between two cohorts. Similarly, the rate of distant metastases was not significantly different with 30.0% in MLND and 32.6% in CALND. And no significant difference was observed in other primary tumor between two groups (p=0.46). Patients who remain alive with no event comprise a total of 37.2% in MALND and 35.4% in CALND. Other primary cancers and deaths from other causes were distributed equally between two groups. The 15-year disease-free survival rates were41.1 percent for the MALND group and 39.6 percent for the CALND group (p=0.79). MALND was found to be not inferior for overall survival (P =0.54). The 15-year overall survival rates were 49.5 percentafter MALND and 51.2 percentafter CALND (p=0.86). Probability of overall survival was not significantly different between two groups.Conclusions：MALND does not increase unfavorable events, and also does not affect the long-term survival of patients. Therefore, MALND should be one of the preferred approaches for breast cancer surgery.

Prognostic Factors of Patients with Gastric Gastrointestinal Stromal Tumor after Curative Resection: A Retrospective Analysis of 406 Consecutive Cases in a Multicenter Study

2015 ◽  
Vol 55 (1-2) ◽  
pp. 12-23 ◽  
Author(s):  
In-Hwan Kim ◽  
Sang-Gyu Kwak ◽  
Hyun-Dong Chae
Keyword(s):  
Prognostic Factors ◽  
Multicenter Study ◽  
Tumor Size ◽  
Curative Resection ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Free Survival ◽  
Gastric Gists ◽  
Disease Free

Background/Purpose: Gastric gastrointestinal stromal tumors (GISTs) have a highly variable clinical course, and recurrent disease sometimes develops despite curative surgery. This study was undertaken to investigate the surgical role in treating gastric GISTs and evaluate the clinicopathological features of a large series of patients who underwent curative resection for gastric GISTs to clarify which features were independent prognostic factors. Methods: The clinicopathological data of 406 patients with gastric GISTs who underwent curative resection at 4 university hospitals in Daegu, South Korea, from March 1998 to March 2012 were reviewed. All cases were confirmed as gastric GISTs by immunohistochemical staining, in which CD117 or CD34 was positive. Clinical follow-up was performed periodically, and disease-free survival rates were retrospectively investigated using the medical records. Results: The mean follow-up period was 42.9 months (range: 2-166). There were 11 recurrent patients (2.7%). Due to the small number of recurrences, age, sex and location were controlled using propensity score matching before performing any statistical analysis. Tumor size, mitotic count, NIH classification, and cellularity were judged to be independent prognostic factors for recurrence by univariate analysis. In a multivariate analysis, tumor size and mitotic count were significantly and independently related to recurrence, and tumor size was determined to be the most important prognostic factor for recurrence after curative resection (hazard ratio: 1.204; p < 0.01). Conclusions: The results of this multicenter study demonstrate that disease-free survival rates are good. Tumor size was disclosed as the most important factor for recurrence in gastric GIST patients who underwent radical resection.

BiovaxID™ Vaccine Therapy of Follicular Lymphoma in First Remission: Long-Term Follow-Up of a Phase II Trial and Status of a Controlled, Randomized Phase III Trial.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2441-2441 ◽  
Author(s):  
Carlos Santos ◽  
Lee Stern ◽  
Laura Katz ◽  
Thelma Watson ◽  
Gause Barry
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Disease Free Survival ◽  
T Cell Response ◽  
Phase Iii ◽  
Patient Specific ◽  
Free Survival ◽  
The Impact ◽  
Disease Free

Abstract Malignant B-cells in Follicular Non-Hodgkin’s Lymphoma expresses a clonal idiotype immunoglobulin which can serve as the basis for a patient-specific anti-idiotype vaccine. In a previous single-arm Phase II study by Bendandi, et al (Nature Med5:1171–1177, 1999), we evaluated the ability of tumor-specific idiotype (Id) conjugated to keyhole limpet hemocyanin (KLH) administered concurrently with granulocyte-monocyte colony-stimulating factor (GM-CSF) adjuvant to induce complete remissions and molecular remissions in treated patients. The vaccine formulation induced a tumor-specific cytotoxic CD8+ and CD4+ T-cell response in patients in first complete remission after standard chemotherapy, as well as achieved molecular remissions in 8 of 11 of these patients. Data available at the time of this abstract for the 20-patient cohort, indicates a median follow-up of 9.167 years. 9 patients (45 %) remain in continuous first CR at their most recent follow-up (either in 2004 or 2005), and overall survival is 95%. The data further indicates the median disease free survival for the cohort is 96.5 months (8.04 years). To date there have been no additional reported mortalities in this cohort. As of August 2005, we report the progress of the Phase III clinical trial for this vaccine, opened in January 2000 by the NCI to evaluate the impact of this hybridoma-based Id vaccine on disease-free survival in a group of up to 375 previously untreated patients who have attained a CR or CRu from PACE [Prednisone, Doxorubicin, Cyclophosphamide, and Etoposide (ProMACE without methotrexate)] chemotherapy, and who are randomized to receive either vaccine or control. To date, 187 patients have been accrued onto the study. Of those patients, 145 (77.5%) achieved a CR or Cru and are being followed in this ongoing clinical trial.

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