scholarly journals Neoadjuvant concurrent chemoradiotherapy with and without hyperthermia in retroperitoneal sarcomas: feasibility, efficacy, toxicity, and long-term outcome

Author(s):  
A. Willner ◽  
K. Fechner ◽  
A. Agaimy ◽  
F. Haller ◽  
M. Eckstein ◽  
...  

Abstract Purpose Retroperitoneal (RPS) sarcomas are associated with poor local and abdominal tumor control. However, the benefit of preoperative radio- or chemotherapy alone for these entities is currently unclear. Moreover, as intermediate- and high-grade sarcomas have a tendency toward early metastasis, exploration of neoadjuvant strategies is of high importance. This analysis reports the results of our 20-year single-institution experience with preoperative neoadjuvant concurrent chemoradiation. Methods From 2000–2019, 27 patients with intermediate- or high-grade RPS (12 dedifferentiated liposarcoma, 10 leiomyosarcoma, 5 others) were treated with radiotherapy (median dose: 50.4 Gy; range 45–75 Gy) and two cycles of chemotherapy (doxorubicin 50 mg/m2 BSA/d3 q28 and ifosfamide 1.5 g/m2 BSA/d1‑5 q28) in neoadjuvant intent. Chemotherapy consisted of doxorubicin alone in two cases and ifosfamide alone in one case. Fifteen patients (56%) additionally received deep regional hyperthermia. Results The median follow-up time was 53 months (±56.7 months). 92% of patients received two cycles of chemotherapy as planned and 92% underwent surgery. At 5 and 10 years, abdominal-recurrence-free survival was 74.6% (±10.1%) and 66.3% (±11.9%), distant metastasis-free survival was 67.2% (±9.7%) and 59.7% (±11.1%), and overall survival was 60.3% (±10.5%) and 60.3% (±10.5%), respectively. CTC grade III and IV toxicities were leukocytopenia (85%), thrombocytopenia (33%), and anemia (11%). There were no treatment-related deaths. Conclusion Neoadjuvant chemoradiotherapy with and without hyperthermia for retroperitoneal sarcomas is feasible and provided high local control of intermediate- and high-grade sarcoma.

2021 ◽  
Author(s):  
Alexander Willner ◽  
Katja Fechner ◽  
Abbas Agaimy ◽  
Florian Haller ◽  
Markus Eckstein ◽  
...  

Abstract Background Retroperitoneal (RPS) and intra-abdominal sarcomas (IAS) are associated with poor local and abdominal tumor control. Yet, the benefit of preoperative radio- or chemotherapy alone for these entities currently is unclear. Moreover, as intermediate- and high-grade sarcomas have a tendency for early metastasis, exploration of neoadjuvant strategies is of high importance. This analysis reports the results of our 20-year single-institution experience with preoperative neoadjuvant concurrent chemoradiation.Methods From 2000-2019, 27 patients with intermediate- or high-grade RPS or IAS (12 dedifferentiated liposarcoma, 10 leiomyosarcoma, 5 others) were treated with radiotherapy (median dose: 50.4 Gy; range 45-75 Gy) and two cycles of chemotherapy (doxorubicin 50mg/m² BSA/d3 q28 and ifosfamide 1.5g/m2 BSA/d1-5 q28) in neoadjuvant intention. Chemotherapy consisted of doxorubicin alone in two cases and ifosfamide alone in one case. Fifteen patients (56%) received deep regional hyperthermia additionally.Results The median follow-up time was 53 months (± 56.7 months). 92% of patients received two cycles of chemotherapy as planned and 92% underwent surgery. At 5 and 10 years, abdominal-recurrence-free-survival was 74.6% (± 10.1%) and 66.3% (± 11.9%), distant-metastasis-free-survival was 67.2% (± 9.7%) and 59.7% (± 11.1%), and overall-survival was 60.3% (± 10.5%) and 60.3% (± 10.5%), respectively. CTC grade III and IV toxicities were leukocytopenia (85%), thrombocytopenia (33%) and anemia (11%). There were no treatment-related deaths.Conclusions Neoadjuvant chemoradiotherapy with and without hyperthermia for retroperitoneal and intra-abdominal sarcoma is feasible and provided high local control of intermediate - and high-grade sarcoma.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 93.1-93
Author(s):  
Y. Ferfar ◽  
S. Morinet ◽  
O. Espitia ◽  
C. Agard ◽  
M. Vautier ◽  
...  

Background:Aortitis is a group of disorders characterized by the inflammation of the aorta. The most common causes of aortitis are the large-vessel vasculitis i.e. giant cell arteritis (GCA) and Takayasu arteritis (TA). However, aortitis may be isolated. Because of the wide variation in the course of aortitis, predicting outcome is challenging. The optimal management strategy of isolated aortitis (IA) is still unclear as IA is poorly defined, with data consisting of small retrospective and case control studies.Objectives:To assess the long-term outcome and prognosis factors for vascular complications in patients with isolated aortitis.Methods:Retrospective multicenter study of 353 patients with non-infectious aortitis including 136 giant cell arteritis (GCA), 96 Takayasu arteritis (TA) and 73 isolated aortitis (IA). Factors associated with event-free survival, vascular event-free survival and revascularization-free survival were assessed. Risk factors for vascular complications were identified in multivariate analysis.Results:After a median follow up of 52 months, vascular complications were observed in 32.3 %, revascularization in 30 % and death in 7.6%. The 5-year cumulative incidence of vascular complications was 58% (41; 71), 20% (13; 29), and 19 % (11; 28) in IA, GCA and TA, respectively. In multivariate analysis, IA [HR, 1.85 (1.19 to 2.88), p=0.017] and male gender [1.77 (1.26 to 2.49), p<0.0001] were independently associated with vascular events. The 5-year surgery-free survival was 45% (31; 65), 71% (62; 81) and 76% (68; 86) in IA, TA and GCA, respectively.Conclusion:IA has a worse vascular prognosis than GCA and TA. Sixty percent of IA patients will experience a vascular complication within 5 years from diagnosis.Disclosure of Interests:None declared


HPB ◽  
2021 ◽  
Vol 23 ◽  
pp. S58
Author(s):  
K. Nakagawa ◽  
T. Akahori ◽  
K. Nakamura ◽  
T. Takagi ◽  
N. Ikeda ◽  
...  

2005 ◽  
Vol 91 (2) ◽  
pp. 168-172 ◽  
Author(s):  
Mahmut Gumus ◽  
Perran Fulden Yumuk ◽  
Gul Atalay ◽  
Mehmet Aliustaoglu ◽  
Beyza Macunluoglu ◽  
...  

Background Regional lymph node (LN) involvement in colorectal cancer (CRC) identifies the stage and the subset of patients who would benefit from adjuvant chemotherapy. We performed a retrospective analysis to determine if the number of recovered LNs was associated with long-term outcome in patients operated on for stage II and III CRC. Patients and methods Hospital records of 179 patients with CRC followed in our unit from 1997 to April 2003 were reviewed. Results On average 11.68 ± 7.3 LNs were sampled per surgical specimen. Sampling of at least nine LNs appeared to be the minimum number required for accurately predicting LN involvement ( P = 0.002). Three-year rates of disease-free survival (DFS), local recurrence-free survival (LRFS) and overall survival (OS) were lower in patients with fewer than nine LNs sampled ( P = 0.032, P = 0.006 and P = 0.04, respectively). However, this had no impact on the three-year distant metastasis-free survival rate (DMFS) ( P = 0.472). In stage II disease, patients with nine or more LNs dissected had significantly higher three year DFS and LRFS rates than the subgroup with fewer than nine LNs dissected ( P = 0.024 and P = 0.015, respectively), but this did not have any effect on DMFS or OS ( P = 0.406 and P = 0.353, respectively). Conclusion Current protocols provide adjuvant treatment in stage III patients; the problem is to correctly determine stage by recovering as many LNs as possible.


2019 ◽  
Vol 105 (3) ◽  
pp. e660-e675 ◽  
Author(s):  
Ulf Elbelt ◽  
Sven M Schlaffer ◽  
Michael Buchfelder ◽  
Ulrich J Knappe ◽  
Greisa Vila ◽  
...  

Abstract Context Despite growing evidence that temozolomide (TMZ) therapy is effective for the treatment of aggressive pituitary tumors (APTs) or carcinomas (PCs), individual therapy decisions remain challenging. Objective We therefore aimed to report on clinical characteristics leading to initiation of TMZ therapy and to add evidence on TMZ long-term effectiveness. Design and subjects Retrospective survey on TMZ treatment in patients with APTs or PCs. TMZ therapy was initiated in 47 patients (22 females) with APTs (n = 34) or PCs (n = 13). Mean age at diagnosis was 45 ± 15 years. The immunohistochemical subtypes were corticotroph (n = 20), lactotroph (n = 18), and nonfunctioning (n = 9) tumors. TMZ therapy started 8 years after initial diagnosis using a standard regimen (median 6 cycles) for the majority of patients. Results Long-term radiological response to TMZ after a median follow-up of 32 months with 4 patients still on TMZ therapy was tumor regression for 9 (20%), stable disease for 8 (17%), and tumor progression for 29 patients (63%) (outcome data available for 46 patients). Progression occurred 16 months after initiation of TMZ. Median estimated progression-free survival was 23 months. Disease stabilization and median progression-free survival did not differ between patients with APTs or PCs. Predictors of tumor response were not identified. Overall, TMZ was well tolerated. Conclusion We performed a nationwide survey on TMZ therapy in patients with APTs and PCs. While early response rates to TMZ are promising, long-term outcome is less favorable. Prolonged TMZ administration should be considered. We were not able to confirm previously reported predictors of tumor response to TMZ.


Gut ◽  
2017 ◽  
Vol 67 (2) ◽  
pp. 237-243 ◽  
Author(s):  
D Laharie ◽  
A Bourreille ◽  
J Branche ◽  
M Allez ◽  
Y Bouhnik ◽  
...  

ObjectiveCiclosporin and infliximab have demonstrated short-term similar efficacy as second-line therapies in patients with acute severe UC (ASUC) refractory to intravenous steroids. The aim of this study was to assess long-term outcome of patients included in a randomised trial comparing ciclosporin and infliximab.DesignBetween 2007 and 2010, 115 patients with steroid-refractory ASUC were randomised in 29 European centres to receive ciclosporin or infliximab in association with azathioprine. Patients were followed until death or last news up to January 2015. Colectomy-free survival rates at 1 and 5 years and changes in therapy were estimated through Kaplan-Meier method and compared between initial treatment groups through log-rank test.ResultsAfter a median follow-up of 5.4 years, colectomy-free survival rates (95% CI) at 1 and 5 years were, respectively, 70.9% (59.2% to 82.6%) and 61.5% (48.7% to 74.2%) in patients who received ciclosporin and 69.1% (56.9% to 81.3%) and 65.1% (52.4% to 77.8%) in those who received infliximab (p=0.97). Cumulative incidence of first infliximab use at 1 and 5 years in patients initially treated with ciclosporin was, respectively, 45.7% (32.6% to 57.9%) and 57.1% (43.0% to 69.0%). Only four patients from the infliximab group were subsequently switched to ciclosporin. Three patients died during the follow-up, none directly related to UC or its treatment.ConclusionsIn this cohort of patients with steroid-refractory ASUC initially treated by ciclosporin or infliximab, long-term colectomy-free survival was independent from initial treatment. These long-term results further confirm a similar efficacy and good safety profiles of both drugs and do not favour one drug over the other.Trial registration numberEudraCT: 2006-005299-42; ClinicalTrials.gouv number: NCT00542152; post-results.


2014 ◽  
Vol 112 (07) ◽  
pp. 176-182 ◽  
Author(s):  
Michael Humenberger ◽  
Martin Andreas ◽  
Bassam Redwan ◽  
Klaus Distelmaier ◽  
Günter Klappacher ◽  
...  

SummaryEndothelin (ET)-1 is a pro-fibrotic vasoconstrictive peptide causing microvascular dysfunction and cardiac remodelling after acute ST-elevation myocardial infarction (STEMI). It acts via two distinct receptors, ET-A and ET-B, and is involved in inflammation and atherogenesis. Patients with posterior-wall STEMI were randomly assigned to intravenous BQ-123 at 400 nmol/minute (min) or placebo over 60 min, starting immediately prior to primary percutaneous coronary intervention (n=54). Peripheral blood samples were drawn at baseline as well as after 24 hours and 30 days. Myeloperoxidase (MPO), as a marker of neutrophil activation and matrix metalloproteinase 9 (MMP-9), a marker of extracellular matrix degradation were measured in plasma. Clinical follow-up was conducted by an investigator blinded to treatment allocation over three years. During the median follow-up period of 3.6 years (interquartile range [IQR] 3.3–4.1) we observed a longer event-free survival in patients randomised to receive BQ-123 compared with patients randomised to placebo (mean 4.5 years (95% confidence interval: 3.9–5) versus mean 3 years (2.2–3.7), p=0.031). Patients randomised to ET-A receptor blockade demonstrated a greater reduction of MPO levels from baseline to 24 hours compared to placebo-treated patients (-177 ng/ml (IQR 103–274) vs –108 ng/ml (74–147), p=0.006). In addition, a pronounced drop in MMP-9 levels (-568 ng/ml (44–1157) vs –117 ng/ml (57–561), p=0.018) was observed. There was no significant difference in amino-terminal propetide of pro-collagen type III levels. In conclusion, short-term administration of BQ-123 leads to a reduction in MPO, as well as MMP-9 plasma levels and to a longer event-free survival in patients with STEMI.ClinicalTrials.gov Identifier: NCT00502528


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1866-1866
Author(s):  
Min Kyoung Kim ◽  
Chang-Ki Min ◽  
Myung Soo Hyun ◽  
Kihyun Kim ◽  
Sung-Soo Yoon ◽  
...  

Abstract Abstract 1866 Background: In multiple myeloma (MM), the association between the response to induction before autologous stem cell transplantation (ASCT) and long-term outcome is less clear but the situation may change with the introduction of novel agents. We therefore assessed the clinical relevance of response of bortezomib induction treatment or post-ASCT response for patients who received bortezomib-combined induction chemotherapy followed by ASCT. Methods: We retrospectively assessed 183 MM patients who received bortezomib-containing induction therapy (BTZ-IT) followed by ASCT in 24 institutions throughout Korea between 2003 and 2010. Records of these patients were reviewed using the Korean Myeloma Registry database (www.myeloma.or.kr). Each institution was requested to reconfirm the data using additional case report forms. Patients who had overt MM based on International Myeloma Working Group diagnostic criteria were selected. Results: One-hundred seventy eight patients were eligible. Their median age was 56 years (range, 28–69 years) and 96 (53.9%) were male. Forty nine (27.5%) received bortezomib as front-line therapy and 129 (72.5%) as second-line treatment. All patients underwent ASCT and 22 (12.4%) were treated with tandem ASCT. Ninety-seven (54.5%) patients were treated with maintenance therapy after ASCT. After BTZ-IT, the response rates in this selected series of patients were 37.6% CR, 12.4% VGPR, 41.0% PR, 7.3% SD and 1.7% PD (Figure 1A, 1B, 1C); the corresponding post-ASCT rates were 69.2% CR, 14.0% VGPR, 11.0% PR, 2.9% SD and 2.9% PD. At a median follow-up of 46.6 months, the 3-year overall survival (OS) and event-free survival (EFS) rates were 70.0% and 31.9%, respectively. Multivariate analysis showed that factors independently predictive of OS and EFS included achievement of BTZ-IT response °Ã PR (P=0.025 and P=0.014, respectively) and the treatment with maintenance therapy (P=0.048 and P=0.001, respectively). Post-ASCT CR vs. °Â VGPR was also an independent prognostic factor for OS and EFS (P=0.0001 and P=0.002, respectively). Conclusion: At least PR to BTZ-IT and CR after ASCT were predictive of survival. These findings suggest that patients who responded to BTZ-IT may benefit from ASCT due to an enhanced quality of response. Maintenance therapy can also affect patient outcomes. Disclosures: No relevant conflicts of interest to declare.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2756-2756 ◽  
Author(s):  
Gabriele Gugliotta ◽  
Fausto Castagnetti ◽  
Massimo Breccia ◽  
Luciano Levato ◽  
Adele Capucci ◽  
...  

Abstract Abstract 2756 Background: Nilotinib is a potent and selective BCR-ABL inhibitor. The phase 3 ENESTnd trial demonstrated superior efficacy nilotinib vs. imatinib, with higher and faster molecular responses. After 24 months, the rates of progression to accelerated-blastic phase (ABP) were 0.7% and 1.1% with nilotinib 300mg and 400mg BID, respectively, significantly lower compared to imatinib (4.2%). Nilotinib has been approved for the frontline treatment of Ph+ CML. With imatinib 400mg (IRIS trial), the rate of any event and of progression to ABP were higher during the first 3–4 years. Consequently, a confirmation of the durability of responses to nilotinib beyond 3 years is extremely relevant. Aims: To evaluate the long term outcome of patients treated with nilotinib 400mg BID as frontline therapy. Methods: A multicentre phase 2 trial was conducted by the GIMEMA CML WP (ClinicalTrials.gov.NCT00481052). Median 48-month follow-up data for all patients will be presented. Definitions: MR3.0 (Major Molecular Response) as a BCR-ABL/ABL ratio <0,1%IS; MR4.0, undetectable transcript levels with ≥10,000 ABL transcripts; failures: according to the revised ELN recommendations; events: failures and treatment discontinuation for any reason. All the analysis has been made according to the intention-to-treat principle. Results: 73 patients enrolled: median age 51 years; 45% low, 41% intermediate and 14% high Sokal risk. The cumulative incidence of CCgR at 12 months was 100%. CCgR at each milestone: 78%, 96%, 96%, 95%, 92% at 3, 6, 12, 18 and 24 months, respectively. The overall estimated probability of MR3.0 was 99%, while the rates of MR3.0 at 3, 6, 12, 18 and 24 months were 52%, 66%, 85%, 81% and 82%, respectively. Two out of 73 patients never achieved a MR3.0, 1 who progressed to AP/BP (see below) and 1 in stable and confirmed CCgR at 36 months. Three pts had a confirmed loss of MR3.0 due to low adherence (all 3 still on nilotinib). The overall estimated probability of MR4.0 was 79%, while the rates of MR4.0 at 12, 24 and 36 months were 12%, 27% and 25%, respectively. One third (21/73 pts) showed a stable MR4.0 (defined based on 3 consecutive MR4.0 samples 4 months apart). Only one patient progressed at 6 months to ABP and subsequently died (high Sokal risk, T315I mutation). Adverse events were mostly grade 1 or 2 and manageable with appropriate dose adaptations. During the first 12 months, the mean daily dose was 600–800mg in 74% of patients. The nilotinib last daily dose was as follows: 800mg in 46 (63%) patients, 600mg in 3 (4%) patients and 400mg in 18 (25%), 6 permanent discontinuations. Detail of discontinuation: 1 patient progressed to ABP; 3 patients had recurrent episodes of amylase and/or lipase increase (no pancreatitis); 1 patient had atrial fibrillation (unrelated to study drug) and 1 patient died after 32 months of mental deterioration and starvation (unrelated to study drug). Two patients are currently on imatinib second-line and 2 on dasatinib third-line. With a median follow-up of 39 months, the estimated probability of overall survival, progression-free survival and failure-free survival was 97%, the estimated probability of event-free survival was 91%. Conclusions: The rate of failures was very low during the first 3 years. Responses remain stable. The high rates of responses achieved during the first 12–18 months are being translated into optimal outcome for most of patients. Acknowledgments: European LeukemiaNet, COFIN, Bologna University, BolognAIL Disclosures: Gugliotta: Novartis: Honoraria; Bristol-Myers-Squibb: Honoraria. Castagnetti:Novartis: Honoraria; Bristol Myers Squibb: Honoraria. Cuneo:Roche: Consultancy, Speakers Bureau. Soverini:Novartis: Consultancy; ARIAD: Consultancy; Bristol-Myers Squibb: Consultancy. Saglio:Novartis Pharmaceutical: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Speakers Bureau; Pfizer: Consultancy. Rosti:Novartis: Consultancy; Bristol Myers Squibb: Consultancy; Novartis: Research Funding; Novartis: Honoraria; Bristol Myers Squibb: Honoraria.


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