Frontline treatment of localized osteosarcoma without methotrexate: Results of the St. Jude Children's Research Hospital OS99 trial

10036 Background: Standard treatment of osteosarcoma includes cisplatin and high-dose methotrexate (HD-MTX), but both agents are associated with significant toxicity and MTX administration requires complex pharmacokinetic monitoring. In our previous OS91 trial, the combination of carboplatin and ifosfamide with doxorubicin and HD-MTX yielded outcomes comparable to those of cisplatin-based regimens with less long-term toxicity in localized osteosarcoma. Methods: Between 1999 and 2006, we conducted a multi-institutional trial (OS99) to evaluate the activity of carboplatin, ifosfamide, and doxorubicin without HD-MTX in newly-diagnosed patients with localized osteosarcoma. Treatment comprised 12 cycles of chemotherapy given every 3 weeks: 3 consecutive cycles of carboplatin (dose targeted to AUC 8 mg/ml×min on day 1) and ifosfamide (2.65 g/m2 daily for 3 days) and one cycle of doxorubicin (25 mg/m2 daily for 3 days) followed by definitive surgery (week 12) and 2 additional cycles of carboplatin/ifosfamide and 3 cycles each of ifosfamide/doxorubicin and carboplatin/doxorubicin for a total of 35 weeks. The log rank test was used to compare survival and event-free survival (EFS) distributions. Results: A total of 72 eligible patients were enrolled. The median age was 13.4 years and 41 (57%) were male. The most common tumor site was the femur (n = 46; 64%). The median follow-up for survivors was 4.4 years. Forty of the 66 (60.6%) evaluable patients had good histologic response (tumor necrosis > 90%) to preoperative chemotherapy. There was no difference in EFS or survival distributions between OS99 and OS91. Four-year estimates of EFS were 68.1 ± 6.7% for OS99 compared to 70.2 ± 6.6% for OS91 (p = 0.89). The 4-year OS was 82.4% ± 5.7% for OS99 compared to 74.5% ± 6.3 for OS91 (p = 0.25). Conclusions: OS99 produced outcomes similar to cisplatin or HD-MTX containing regimens and offers an alternative treatment regimen especially for patients with renal compromise and institutions where pharmacokinetic monitoring of MTX is not available. No significant financial relationships to disclose.

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Timing of Second Autologous Transplantations in Multiple Myeloma: Results of a Multicenter Sequential Randomized Clinical Trial.

Blood ◽

10.1182/blood.v108.11.59.59 ◽

2006 ◽

Vol 108 (11) ◽

pp. 59-59 ◽

Cited By ~ 5

Author(s):

Abderrahman Abdelkefi ◽

Saloua Ladeb ◽

Tarek Ben Othman ◽

Lamia Torjman ◽

Amel Lakhal ◽

...

Keyword(s):

Overall Survival ◽

Randomized Trial ◽

Rank Test ◽

Optimal Timing ◽

High Dose ◽

Consolidation Therapy ◽

Event Free Survival ◽

Free Survival ◽

Log Rank Test

Abstract Background: Autologous stem cell transplantation (ASCT) is now considered standard therapy in young patients (<65 years) with multiple myeloma (MM). The Intergroupe Francophone du Myelome conducted a randomized trial of the treatment of MM with high-dose chemotherapy followed by either one or two successive ASCTs. The probabilities of event-free-survival and overall survival were doubled with a double transplant. However, no randomized trial has compared tandem transplant up-front with a strategy including planned second ASCT at relapse or progression. Therefore, we performed a multicenter, sequential, randomized trial designed to assess the optimal timing of a second ASCT. Methods: From May 2003 to April 2006, 140 patients with symptomatic MM (de novo) and less than 60 years of age, were randomly assigned to receive either tandem transplantation up-front (within 6 months of the first transplantation) [Arm A, n=69] or one ASCT followed by a consolidation therapy with thalidomide (day +90, 100 mg/per day during 5 months) [Arm B, n=71]. Patients included in the arm B received a second transplant in case of disease progression on consolidation therapy, or in case of relapse in responders. Clinical characteristics of each group were similar. In both arms of the study, ASCT was preceded by first-line therapy with thalidomide-dexamethasone and subsequent collection of peripheral blood stem cells with high-dose cyclophosphamide (4 g/m2) and G-CSF. Data were analyzed on an intent-to-treat basis. Results: With a median follow-up of 23 months (range: 6–34), the 2-year overall survival was 55% in the arm A and 75% in the arm B. Survival curves were not different (P=0.28, log-rank test). The 2-year event-free survival was 41% in the arm A and 60% in the arm B (P=0.4, log-rank-test). In the arm B, relapse-free survival of ≥ 16 months following the first transplantation was an important predictor of overall survival (p< 0.001). Conclusion: Data from the present study suggest that up-front single ASCT followed by a consolidation therapy with thalidomide and a second ASCT after relapse or progression is a safe and effective global strategy to treat MM patients. Longer follow-up is needed before definite conclusions can be given concerning the optimal timing of second autologous transplantations in patients with MM.

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Re-bleeding and its predictors after capsule endoscopy in patients with obscure gastrointestinal bleeding in long-term follow-up

BMC Gastroenterology ◽

10.1186/s12876-019-1137-3 ◽

2019 ◽

Vol 19 (1) ◽

Author(s):

Panu Wetwittayakhlang ◽

Jirapat Wonglhow ◽

Nisa Netinatsunton ◽

Naichaya Chamroonkul ◽

Teerha Piratvisuth

Keyword(s):

Specific Treatment ◽

Rank Test ◽

Gi Bleeding ◽

Free Survival ◽

Log Rank Test ◽

Negative Study ◽

Long Term Follow Up ◽

Bleeding Episodes

Abstract Background Capsule endoscopy (CE) is the preferred diagnostic test of choice in the investigation of obscure gastrointestinal bleeding (OGIB). Although, a conservative strategy is recommended in the short-term, for cases with a negative result from CE, the impact of CE on long-term re-bleeding still remains unclear. Hence, the aim of this study was to determine the long-term re-bleeding rate along with predictors after CE in patients with OGIB. Methods We retrospectively reviewed 216 patients with OGIB, whom had received a CE examination, so as to investigate the cause of obscure GI bleeding; between July 2008 and March 2018. The patient’s characteristics, medication use, CE finding, treatments strategy, re-bleeding episodes and follow-up information were collected from the institutional electronic medical chart and CE database. Re-bleeding free survival was evaluated using Kaplan-Meier curves with log rank test, whilst predictors associated with the re-bleeding episodes were analyzed via the use of Cox proportional hazard model. Results One hundred and thirty-three patients with OGIB, having received CE were enrolled in the analysis. The pool rate of re-bleeding was 26.3% (35/133) during a follow-up duration of 26 months after CE. Patients with positive CE study, without specific treatment, had higher rates of re-bleeding (47.6%) than those with positive study whom received specific treatment (25.7%), and negative study (20.8%) (p = 0.042). Although, the re-bleeding free survival was not significantly different among the groups (log rank test; P = 0.10). Re-bleeding events occurring within 6, 12, and 24 months after CE were 36, 64 and 92%, respectively. The high-frequency re-bleeding etiologies were the small bowel angiodysplasias and abnormal vascular lesions. Furthermore, independent predictors for re-bleeding after CE were patients with cirrhosis (hazard ratio, HR 4.06), incomplete CE visualization (HR 2.97), and a history of previous GI bleeding (HR 2.80). Conclusions The likelihood of re-bleeding after CE was higher in patients with positive CE study than those with negative study. Specific treatments, or therapeutic interventions for patients with detectable lesions reduced the probability of re-bleeding episodes in long-term follow-up. Close follow-up for recurrent bleeding is recommeded for at least 2 years after CE.

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Robot-assisted minimally invasive thoracolaparoscopic esophagectomy versus open esophagectomy: long-term follow-up of a randomized clinical trial

Diseases of the Esophagus ◽

10.1093/dote/doaa079 ◽

2020 ◽

Vol 33 (Supplement_2) ◽

Author(s):

Eline M de Groot ◽

Sylvia van der Horst ◽

B Feike Kingma ◽

Lucas Goense ◽

Pieter C van der Sluis ◽

...

Keyword(s):

Overall Survival ◽

Disease Free Survival ◽

Rank Test ◽

Robot Assisted ◽

Short Term ◽

Free Survival ◽

Log Rank Test ◽

Disease Free

ABSTRACT Initial results of the ROBOT, which randomized between robot-assisted minimally invasive esophagectomy (RAMIE) and open transthoracic esophagectomy (OTE), showed significantly better short-term postoperative outcomes in favor of RAMIE. However, it is not yet clarified if RAMIE is equivalent to OTE regarding long-term outcomes. The aim of this study was to report the long-term oncological results of the ROBOT trial in terms of survival and disease-free survival. This study is a follow-up study of the ROBOT trial, which was a randomized controlled trial comparing RAMIE to OTE in 112 patients with intrathoracic esophageal cancer. Both the trial protocol and short-term results were previously published. The primary outcome of the current study was 5-year overall survival. Secondary outcomes were disease-free survival and recurrence patterns. Analysis was by intention to treat. During the recruitment period, 109 patients were included in the survival analysis (RAMIE n = 54, OTE n = 55). Majority of patients had clinical stage III or IV (RAMIE 63%, OTE 55%) and received neoadjuvant chemoradiotherapy (80%). Median follow-up was 60 months (range 31–60). The combined 5-year overall survival rates for RAMIE and OTE were 41% (95% CI 27–55) and 40% (95% CI 26–53), respectively (log rank test P = 0.827). The 5-year disease-free survival rate was 42% (95% CI 28–55) in the RAMIE group and 43% (95% CI 29–57) in the OTE group (log rank test P = 0.749). Out of 104 patients, 57 (55%) developed recurrent disease detected at a median of 10 months (range 0–56) after surgery. No statistically difference in recurrence rate nor recurrence pattern was observed between both groups. Overall survival and disease-free survival of RAMIE are comparable to OTE. These results continue to support the use of robotic surgery for esophageal cancer.

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Rituximab Maintenance Treatment for a Maximum of 5 Years in Follicular Lymphoma: Final Results of the Randomized Phase III Trial SAKK 35/03

Blood ◽

10.1182/blood-2018-99-116864 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1601-1601 ◽

Cited By ~ 1

Author(s):

Christian Taverna ◽

Giovanni Martinelli ◽

Felicitas Hitz ◽

Walter Mingrone ◽

Thomas Pabst ◽

...

Keyword(s):

Follicular Lymphoma ◽

Phase Iii ◽

Rank Test ◽

Short Term ◽

Free Survival ◽

Rituximab Maintenance ◽

Log Rank Test ◽

Term Maintenance

Abstract Background: Follicular lymphoma is usually a disase with a prolonged course and a chemotherapy-free regimen might be a favourable treatment strategy. SAKK 35/03 investigated two different durations of rituximab maintenance (5 years vs. 6 months) in patients with follicular lymphoma after induction with 4 weekly doses of rituximab monotherapy. With a median follow-up of 6.4 years we were not able to show a benefit with long-term rituximab maintenance up to five years in event-free survival (EFS) or overall survival (OS ). Here we report the final results with a median follow-up of 10 years. Methods: 270 patients (median age 57 years: range 25-82) with untreated, relapsed, stable or chemotherapy resistant follicular lymphoma were treated with 4 doses of rituximab monotherapy in weekly intervals (375 mg/m²). Patients achieving at least a partial response were randomly assigned to receive maintenance therapy with one infusion of rituximab every 2 months, either on a short-term schedule (four administrations) or a long-term schedule (maximum of five years or until disease progression or unacceptable toxicity). The primary endpoint was EFS . Progression-free survival (PFS), OS, and toxicity were secondary endpoints. Comparisons between the two treatment arms were performed using the log-rank test for survival endpoints. Results: 165 patients were randomly assigned to short-term (n=82) or long-term (n=83) maintenance. At a median follow-up period of 10 years, the median EFS is 3.4 years (95% CI 2.1-5.5) in the short-term arm and 5.3 years (95% CI 3.5-7.5) in the long-term arm. Using the pre-specified log-rank test this difference is statistically not significant (p=0.39 ). There is no significant difference in PFS and OS. Median OS in the short-term arm is 11.0 years (95% CI 11.0, NA ) and not reached in the long-term arm (p=0.80). The incidence of subsequent cancers increased in both arms over time, nine patients developed a subsequent cancer in the short-term maintenance arm and 10 in the long-term maintenance arm. There was no major additional toxicity with longer follow-up. Conclusions : Even with a long follow-up of 10 years we were not able to show a significant benefit of long-term compared to short-term rituximab maintenance in EFS, PFS and OS. Treatment strategies and study designs need to take these results into consideration in order to guarantee optimal medical and scientific results. Disclosures Zucca: Celltrion: Consultancy; AstraZeneca: Consultancy. Ghielmini:Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau.

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Phase I/II study incorporating intravenous hydroxyurea into high-dose chemotherapy for patients with primary refractory or relapsed and refractory intermediate-grade and high-grade malignant lymphoma.

Journal of Clinical Oncology ◽

10.1200/jco.1995.13.5.1089 ◽

1995 ◽

Vol 13 (5) ◽

pp. 1089-1095 ◽

Cited By ~ 8

Author(s):

W P Vaughan ◽

E Kris ◽

J Vose ◽

P J Bierman ◽

P Gwilt ◽

...

Keyword(s):

Phase I ◽

Continuous Infusion ◽

Progression Free Survival ◽

High Dose Chemotherapy ◽

Rank Test ◽

High Dose ◽

Hematopoietic Stem ◽

Free Survival ◽

Stem Cell Rescue

PURPOSE A phase I/II study was performed to evaluate the incorporation of hydroxyurea (HU) into high-dose chemotherapy of non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS Thirty-eight patients with primary refractory and refractory relapsed NHL were treated with carmustine (BCNU) (300 mg/m2 on day -8), cyclophosphamide (Cy) (2.5 g/m2/d on days -8 and -7), etoposide (E) (150 mg/m2 every 12 hours on days -6, -5, and -4), and HU (BCHE) with autologous hematopoietic stem-cell rescue. Twenty-one patients received HU in a dose escalation of 2 to 12 g/m2 intravenously (IV) by 72-hour continuous infusion. When the IV formulation was not available, 17 patients were given 18 g/m2 of HU orally in divided doses every 6 hours over the same 72-hour period. RESULTS The dose-limiting toxicity of 72-hour continuous infusion HU in this regimen was mucositis. Endotracheal intubation was necessary to protect the airway in two thirds of patients treated at 12 g/m2. Six patients (oral BCHE, five of 17; IV BCHE, one of 21) died with nonresponding or progressive disease and, at least in part, from the complications of the high-dose chemotherapy. Seventeen patients (45%) achieved complete remission (CR). More patients treated with IV BCHE achieved CR than patients treated with oral BCHE (12 of 21 v five of 17; P < .1, chi 2 test). Nine patients (two of 17 oral BCHE and seven of 21 IV BCHE) remain disease-free as of January 31, 1994, with a minimum follow-up time of 3 years. The lower mortality and higher response rate with IV BCHE translated into a significantly superior probability of progression-free survival (PFS) (33% at 4 year v 12% for oral BCHE; P = .048, log-rank test). CONCLUSION High-dose BCHE is effective treatment for primary refractory and refractory relapsed NHL. Continuous IV HU appears to be less toxic and more effective than intermittent oral HU in this regimen.

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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 ◽

10.1182/blood.v104.11.1883.1883 ◽

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

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Long Term Follow-Up of 4-Hydroperoxycyclophosphamide Purged Autologous Bone Marrow Transplantation in Non-Hodgkin’s Lymphoma Patients with High Risk of Bone Marrow Involvement.

Blood ◽

10.1182/blood.v104.11.5234.5234 ◽

2004 ◽

Vol 104 (11) ◽

pp. 5234-5234

Author(s):

Elise A. Chong ◽

Charalambos Andreadis ◽

Stephen J. Schuster ◽

Selina M. Luger ◽

David L. Porter ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

High Risk ◽

B Cell ◽

Tumor Cells ◽

Platelet Transfusion ◽

High Dose ◽

Free Survival

Abstract Introduction: High-dose chemotherapy and autologous stem cell transplant (ASCT) can result in long term survival for patients with advanced non-Hodgkin’s lymphoma (NHL) but relapse remains a common cause of treatment failure. Bone marrow (BM) involvement is common in NHL and there is controversy over whether or not reinfusion of BM stem cells contaminated by clonogenic tumor cells is a major cause of relapse following ASCT. Bone marrow purging can reduce the number of tumor cells in vitro, but the impact on relapse and disease free survival (DFS) remains unknown. Methods: Between 1990 and 1993, 20 pts with poor prognosis NHL (B-symptoms, high LDH, bulky adenopathy, stage III or IV, or relapsed disease) at high risk for BM involvement underwent 4-hydroperoxycyclophosphamide (4-hc) purged BM transplantation. Thirteen pts had low grade B-cell NHL, 6 had an intermediate grade B-cell NHL with a small B-cell component, and 1 had T-lymphoblastic lymphoma. Seven of 20 pts had received ≥3 prior chemotherapeutic regimens. Three pts underwent transplantation in first complete remission and 17 pts were in chemotherapy-responsive relapse. At diagnosis, 11 of 20 pts had documented BM involvement, and at ASCT, 6 of 20 pts had BM involvement (all < 5% involvement at BM harvest). Eighteen pts (90%) received 4-hc purged autologous BM, and 2 pts (10%) received 4-hc purged autologous BM and peripheral stem cell support. High dose regimens included Cytoxan/TBI (85%), BCV(10%), and Melphalan/TBI (5%). The median age was 45 yrs (range: 20–57 yrs). The median nucleated cell count of 4-hc marrow that was reinfused was 2.4 × 108 /kg (range: 0.87–5.5). The median time to granulocyte recovery was 26 days (range: 14–59). Two pts died at days 31 and 35 without achieving platelet transfusion independence. In the remaining 18 pts, the last platelet transfusion was given at a median of 29 days post-marrow infusion (range 18–149), and the median in-patient hospital days was 27 (range: 16–82 days). Results: There were 2 deaths (fungal infection and CNS relapse) during ASCT. One pt died in CR after developing secondary AML 5.34 yrs after ASCT. Post-ASCT, 18 of 20 pts achieved CR (including 1 pt who had no evidence of disease at autopsy), 1 pt had a PR, and 1 pt died during BMT and was not evaluable for response. Median follow-up for the group was 8.2 yrs (range: 0.1–12.4 yrs). At last follow-up, 9 pts remain in CR (1 died of AML in CR), 5 pts had relapsed and remain alive, and 5 pts died of progressive disease. Median follow-up for survivors was 11.1 yrs (range: 5.2–12.4 yrs). 65% of pts remain alive at last follow-up. The median EFS was 9.4 yrs (range: 0.1–12.4 yrs). Those who achieved a CR post-ASCT had a median DFS of 10.6 yrs (range: 1.1–12.4 yrs). At 8.2 yrs, 4/6 pts with involved BM at the time of harvest had relapsed or died compared to 7/14 pts with negative BM which is not significantly different. Conclusion: ASCT using 4-hc BM purging is feasible and can result in long term relapse free survival, even for pts with subtypes of NHL at high risk for BM involvement. Whether 4-hc BM purging is equivalent or superior to immunologic approaches to stem cell processing remains to be determined.

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Necessity of Intraventricular Chemotherapy with the Modified Bonn Protocol in Primary CNS Lymphoma (PCNSL) Patients.

Blood ◽

10.1182/blood.v108.11.2452.2452 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2452-2452

Author(s):

Ingo G.H. Schmidt-Wolf ◽

Hendrik Pels ◽

Annika Juergens ◽

Axel Glasmacher ◽

Holger Schulz ◽

...

Keyword(s):

Primary Cns Lymphoma ◽

Progression Free Survival ◽

Cns Lymphoma ◽

High Dose ◽

Free Survival ◽

Intraventricular Chemotherapy ◽

High Infection ◽

Intraventricular Treatment

Abstract Background: Treatment of primary CNS lymphoma (PCNSL) with a combined systemic and intraventricular chemotherapy (Bonn protocol) has achieved an overall response rate (ORR) of 84% and long term complete remissions in a substantial fraction of patients younger than 60 years. Purpose: Due to a high infection rate of the Ommaya reservoir the question was addressed if intraventricular treatment is dispensable in this polychemotherapy protocol. Patients and Methods: Fifty patients with histologically confirmed PCNSL were enrolled onto a phase II-study evaluating chemotherapy without radiotherapy and without intraventricular treatment. A high-dose methotrexate (MTX) (cycles 1,2,4,5) and cytarabine (ara-C) (cycles 3,6) based systemic therapy (including dexamethasone, vinca-alkaloids, ifosfamide and cyclophosphamide) was administered. Results: In an ongoing trial thirty-five of 50 patients (18 pat. < 60 years, 17 pat. over 60 years) are yet assessable for response after a median follow up of nine months (range: 1 to 26 months). In 18 patients < 60 years, the ORR was 78%. However, median time to treatment failure (TTF) was eight months, and median progression free survival (PFS) only 7 months according to frequent early relapses. Conclusions: Early relapses are frequent in younger patients treated with the modified Bonn protocol without intraventricular treatment despite a high ORR. These preliminary results support the assumption that intraventricular treatment is essential to achieve sustained remissions after successful treatment of PCNSL.

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A single-center retrospective study of patients treated with trabectedin (TRB) with long-term follow up.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.11061 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 11061-11061

Author(s):

Brett A. Schroeder ◽

Chad He ◽

Yuzheng Zhang ◽

Michael Wagner ◽

Robin Lewis Jones ◽

...

Keyword(s):

Demographic Variables ◽

Rank Test ◽

Prior Chemotherapy ◽

Pairwise Correlation ◽

Log Rank Test ◽

Long Term Follow Up ◽

Line Of Therapy ◽

Clinical Trial Information

11061 Background: TRB is FDA approved drug for the treatment of liposarcoma (Lipo) and leiomyosarcoma (LMS). The aim of this study was to evaluate potential biomarkers associated with prolonged benefit in patients treated with TRB at our center prior to 2016. Methods: We performed a retrospective search of UW/FHCRC CASIS database to identify patients treated with TRB prior to 2016. Demographic variables and clinical variables (such as histology and treatment) were retrieved. Statistics were performed with R 3.4.1 software. Pairwise Pearson’s correlation was calculated for the # of prior chemotherapy regimens with # of TRB cycles. The Kaplan-Meir method was used to evaluate overall survival (OS). Log-rank test was conducted to compare groups in terms of OS. Results: 145 sarcoma patients treated with TRB were identified with a mean follow up of 5 years (generally on NCT01427582 or NCT01343277). Patients averaged 1.9 prior chemotherapy regimens prior to TRB (range 0-7 regimens) and received an average of 5.6 TRB doses (range 1-25 doses). Subtypes are listed on table. The # of prior regimens was negatively correlated with the # of TRB cycles that patients received (pairwise correlation coefficient = -1.77; p=0.034), suggesting that multiple prior treatment lines either made TRB less tolerable or made sarcoma less sensitive to TRB. The median OS for this heavily treated metastatic population was 0.5 years. However, patients who were able to stay on TRB for more than 5 cycles had a significantly higher OS (p=0.001). While only 23% of patients who received less than 5 cycles of TRB were alive at 5 years (95% CI: 0.15, 0.32), 53% of those who received 5 or more cycles of (95% CI: 0.39, 0.65) were alive at 5 years. Conclusions: TRB may be more effective when administered as an earlier line of therapy. Patients who are able to stay on TRB for a longer duration had a significant improvement in OS. Detailed subset analysis will be presented as will initial findings of our biomarker work. These retrospective data warrant further evaluation. Clinical trial information: NCT01427582 or NCT01343277. [Table: see text]

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10-year clinical outcomes after radiofrequency catheter ablation for atrial fibrillation. A single center experience

European Heart Journal ◽

10.1093/eurheartj/ehab724.0518 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

J.F Alderete Martinez ◽

S Shizuta ◽

F Yoneda ◽

S Nishiwaki ◽

M Tanaka ◽

...

Keyword(s):

Atrial Fibrillation ◽

Catheter Ablation ◽

Adverse Events ◽

Confidence Interval ◽

Clinical Outcomes ◽

Radiofrequency Catheter Ablation ◽

Rank Test ◽

Log Rank Test

Abstract Background Radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) is becoming a routine procedure to treat patients with drug-refractory symptomatic AF. However, data regarding very long-term clinical outcomes is limited. The aim of the present study was to evaluate the 10-year clinical outcomes of patients who underwent RFCA for paroxysmal and persistent AF. Methods We retrospectively enrolled 503 consecutive patients (mean age 66,9±9,51 years; 71,6% male) who underwent RFCA for drug-refractory symptomatic AF between February 2004 and June 2011. Follow-up information was obtained using medical records and/or telephonic interviews with the patient, relatives and/or referring physicians. Results Among 503 patients enrolled in this study, 362 had paroxysmal atrial fibrillation (PAF) and 141 had persistent atrial fibrillation (PeAF) (72% and 28%, respectively). Mean follow-up was 8,84±3,05 years. The 10-year event-free rate for recurrent atrial tachyarrhythmia (AT) after the first procedure was 44,5% (49,4% for PAF vs 31,9% for PeAF; p=0,002 by log-rank test) and 81,9% after the last procedure (87,3% for PAF and 67,9% for PeAF; p≤0,001 by log-rank test). AT recurrence was observed most commonly during the first 12 months of the initial procedure (56%), with only 18% of them occurring after 60 months. Multivariate analysis revealed that persistent AF (hazard ratio=1,366; 95% confidence interval 1,058–1,76; p=0,017) and duration of AF >5 years (hazard ratio=1,357; 95% confidence interval 1,064–1,732; p=0,005) were independent risk factors for AT recurrence. Regarding adverse events, there were 24 (4,8%) hospitalizations for acute decompensated heart failure, 20 (4%) ischemic strokes and 14 (2,8%) bleeding complications requiring hospital admissions. Patients taking oral anticoagulation and antiarrhythmic drugs at the end of the study accounted for 32,8% and 16,7% respectively. Conclusions RFCA for AF provided favorable results in terms of arrhythmia event-free survival in long-term follow-up with better results in patients with paroxysmal AF. Persistent AF and long-standing AF (beyond 5 years) were associated with AT recurrence. Despite the large number of patients who discontinued oral anticoagulation, thromboembolic adverse events were rare. FUNDunding Acknowledgement Type of funding sources: None.

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