Recurrent Disease and Long-Term Survivorship

2016 ◽  
pp. 499-505
Author(s):  
Denice Economou
Keyword(s):  
Recurrent Disease

Analysis of Molecular Predictors of Response to 5-Azacitine Treatment in AML and MDS Patients Preemptively Treated for Molecular Relapse of Disease

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2384-2384
Author(s):  
Meredith Lilly ◽  
Beatrice Haack ◽  
Anne Otto ◽  
Katja Sockel ◽  
Jan Moritz Middeke ◽  
...  
Keyword(s):  
Clinical Response ◽  
Recurrent Disease ◽  
Molecular Evidence ◽  
Loss Of Function ◽  
Research Support ◽  
Free Survival ◽  
Predictors Of Response ◽  
Epigenetic Regulator ◽  
Regulator Genes

Abstract Background: Relapse of disease remains the major cause of treatment failure in patients with acute myeloid leukemia (AML) or advanced myelodysplastic syndrome (MDS), even after allogeneic hematopoietic stem cell transplantation (HSCT). Treatment of relapsed AML or MDS is difficult, especially after HSCT, and long-term prognosis of patients suffering from relapse is dismal. One approach to overcome this problem is to use sensitive molecular diagnostic strategies to detect recurring disease already at the level of minimal residual disease (MRD), thus avoiding the development of overt hematologic relapse by treatment of patients at the stage of molecular relapse. We have recently implemented preemptive treatment with the demethylating drug 5-Azacitidine (AZA) in patients with molecular evidence of recurrent disease in a prospective Phase II study (RELAZA). In this study, 80% of the patients showed responses, with reduction of MRD and prolonged leukemia free survival, 20% of patients even showed molecular clearance of their leukemia and long-term disease free survival. More recently, results from several groups studying demethylating agents in MDS or AML suggested that patients with mutations in genes involved in epigenetic DNA-modification, such as TET2, DNMT3A or IDH1 or IDH2 might be more responsive to treatment with these drugs. Since we observed varying clinical response in the patients treated preemptively with AZA for molecular evidence of recurrent disease, we correlated the clinical response in these patients with the presence of mutations in epigenetic regulator genes in order to identify potential predictors of response. Patients and Methods: A cohort of 44 patients (23 f/21 m), median age 55.6 years (range 21-75 years), in hematological remission with AML (N=40) or MDS (N=4) were given AZA to treat molecular relapse defined by mutant NPM1 (N=23) or CD34+ chimerism (N=21). Patients were monitored post allogeneic HSCT (N=26) or standard chemotherapy (N=18). The cohort received a median of 5 cycles of AZA (ranging from 1-18 cycles). DNA taken at first diagnosis was analyzed using amplicon based resequencing on a MiSeq next generation sequencing system for the following genes, either analyzing the complete coding region (EZH1, EZH2, DNMT3A, TET1 and TET2) or hot-spot regions (ASXL1, ASXL2, IDH1, IDH2). First diagnosis samples were unavailable for 4 patients. In these, DNA from sorted CD34+ cells taken at the time of molecular relapse was used as a substitute. Results: Amplicon sequencing revealed mutations in one or more genes in 25/44 patients (56.8%). With 15 mutations (34%), DNMT3A was the most frequently mutated gene, the majority of the alterations (9; 60%) were located in exon 23. Mutations in TET2 were found in 8 patients, IDH1 was mutated twice, ASXL2, EZH2 and TET1 were mutated once each. In 20 of the 44 patients (45.5%), no mutations in the investigated genes were found. A comparison of primary response to AZA-treatment (defined as stabilization or decrease of the MRD-marker) between patients with and without mutations revealed no significant difference (79.2 vs 66.6%; P=.48). Likewise, the rate of hematologic relapse was comparable in both cohorts (54% vs. 56%). However, a more detailed look at the patients with mutations revealed differences. The highest initial response rate was observed in patients with DNMT3A mutations (87%), whereas patients with isolated TET2 mutations were less likely to respond (50%). Also, the rate of hematologic relapse was highest in patients with TET2-mutations (75%) compared to patients with DNMT3A-mutations alone (41.6%). In support of a role of TET2-mutations in mediating resistance, an analysis of matched diagnosis and relapse samples in three patients indicated persistence of TET2-loss of function mutations in one patient as well as an acquisition of a second mutant TET2- allele or a switch to a loss-of function-mutation in two patients, indicating that a clonal evolution favoring a subclone with an inactivating TET2-allele under treatment with AZA occurred. Conclusions: Our data confirm that mutations in epigenetic regulator genes are common in patients with AML. Although based on small numbers, these preliminary data do not support that mutations in these genes are associated per se with an improved response to treatment with AZA, but might indicate a differential effect of certain alterations, i.e. DNMT3A-mutations or mutations of TET2. Disclosures Middeke: Genzyme: Speakers Bureau. Thiede:AgenDix GmbH: Equity Ownership, Research Funding; Illumina: Research Support, Research Support Other.

Efficacy of systemic chemotherapy (CT) for the patients (pts) with unresectable liver metastasis (LM) of colorectal cancer (CRC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13567-13567
Author(s):  
K. Mera ◽  
A. Ohtsu ◽  
T. Doi ◽  
M. Muto ◽  
Y. Sano ◽  
...  
Keyword(s):  
Colorectal Adenocarcinoma ◽  
Recurrent Disease ◽  
Survival Rates ◽  
R0 Resection ◽  
Term Survival ◽  
Long Term Survival ◽  
Unresectable Liver Metastasis ◽  
Age Range

13567 Background: Surgical resection of colorectal LM is the only treatment which provides long-term survival for pts with advanced disease confined to the liver. However, most of LM are initially unresectable. The aim of this retrospective study was to evaluate the efficacy of systemic CT for the pts with initially unresectable LM from CRC. Methods: Subjects of this study were advanced CRC with unresectable LM treated by systemic CT at our institution between Aug ’92 and Dec ’03, and fulfilled the following criteria; Age ≤ 75, PS ≤ 2, histologically confirmed colorectal adenocarcinoma, no extrahepatic disease, no prior CT and no serious complication. Results: A total of 349 pts with metastatic CRC were managed by systemic CT between the period. Among these, there were 47 pts who met the recruitment criteria. Their characteristics were; male/female: 32/15, median age (range): 59 (34–75), PS 0/1/2: 33/12/2, primary tumor: colon/rectum: 26/21, sinchronous/metachronous: 26/21, number of LM: 4 ≥ / 5 ≤: 9/38. Regimens of CT were; 5FU/5FU+LV/CPT-11+5FU/CPT-11+5FU+LV/Others: 4/11/7/18/7. In all 47 pts, response rate was 53%, median survival time and 3-year survival rate were 14.6 month and 14.6%, respectively, at a median follow-up of 43.4 month. Seven of 47 (15%) could be secondarily resected after response to CT and all had R0 resection. Estimated 3-year survival rates in resected and non-resected pts were 57.1% and 0%, respectively. Prior CT before liver resection was CPT-11+5FU+LV (IFL)/CPT-11 alone: 6/1. Of the 7 resected pts, 2 pts are alive with no evidence of disease for 38 and 40 month after initiation of CT. Five of 7 pts relapsed (liver 3, liver and lung 2) and all treated with systemic CT for recurrence. Although recurrent disease is persisting, 2 of 5 are still alive for 34 and 48 month by continuing CT. Conclusions: Effective systemic CT allows some pts with unrsectable colorectal LM to be rescued by hepatic resection and provides a chance of long-term survival. No significant financial relationships to disclose.

Mandibular Lingual Releasing Approach

1992 ◽  
Vol 107 (3) ◽  
pp. 395-398 ◽  
Author(s):  
Scott P. Stringer ◽  
J. Randall Jordan ◽  
William M. Mendenhall ◽  
James T. Parsons ◽  
Nicholas J. Cassisi ◽  
...  
Keyword(s):  
Oral Cavity ◽  
Complication Rate ◽  
Recurrent Disease ◽  
High Dose ◽  
Postoperative Radiation ◽  
Mandibular Arch ◽  
Floor Of Mouth ◽  
Oral Diet

The mandibular lingual releasing approach to oral cavity and oropharyngeal tumors provides excellent visualization for resection while integrity of the mandibular arch is preserved. A lingual floor-of-mouth flap is created, which allows delivery of these structures directly into the neck without lip splitting, MAndibulotomy, or mandibulectomy. The procedure was carried out on 15 patients between 1987 and 1991, with followup ranging from 2 to 50 months. Nine patients had received previous radiation, whereas planned postoperative radiation was administered to five patients. The visualization afforded by this technique was very good, in that 12 patients had clear margins of resection. Three patients had close margins; recurrent disease developed in one of these patients 18 months later. Twelve of the patients were able to maintain their weight with an oral diet alone. Four postoperative fistulae occurred, three of these were in patients who had not been previously irradiated. The single fistula that did not spontaneously heal occurred in a patient who had received previous radiation and was also on long-term corticosteroids. Mandibular osteoradionecrosis developed in two patients who received postoperative radiation. The complication rate after previous radiation is acceptable; however, there is risk of mandibular osteoradionecrosis after high-dose postoperative radiation.

scholarly journals LONG-TERM FOLLOW-UP STUDY OF JUVENILE DIFFERENTIATED THYROID CARCINOMA TREATED BY RADIOACTIVE IODINE

2018 ◽  
pp. 87-95
Author(s):  
J. Mihailovic
Keyword(s):  
Prognostic Factors ◽  
Initial Treatment ◽  
Radioactive Iodine ◽  
Recurrent Disease ◽  
Differentiated Thyroid Carcinoma ◽  
Follow Up Study ◽  
Tumor Multifocality ◽  
Long Term Follow Up

The overall prognosis in pediatric differentiated thyroid carcinoma (DTC) is excellent. Recurrent disease is frequent, however, and requires additional treatment. In this study we retrospectively analyzed the outcome of juvenile DTC treated by radioactive iodine (I-131) during the long-term follow-up study of 29 years. Methods: 54 DTC patients (34 females, 20 males; ≤20 years old, mean age, 16,5 years) were treated with 131I (RAI) with a median follow-up of 13 years. Patients (pts) underwent different initial treatment: 49 pts, TTx+RAI; 2 pts, TTx; and 3 pts, STTx. The probability of recurrence and prognostic factors were tested by Kaplan-Meier’s method. Results: Initially, 37/54 pts achieved complete remission (CR), 16/54 pts partial remission (PR), 1/54 had progressive disease (PG). During the follow-up 11 pts (20,4%) who achieved CR developed recurrent disease (RD); median appearance time, 4 years (range, 1–25 years). Probability of recurrence was 15,8% at 5 years; 20,3% at 10 years, 25,6% at 15, 20 and 26 years after initial treatment. Strong predictive factors of recurrence were age (p=0,0001), initial treatment (p=0,0001), and tumor multifocality (p=0,004), while gender, nodal metastases at presentation, distal metastases at presentation, histological type of the tumor, tumor or T stage and clinical stage showed no influence on relapse (p=0,176; p=0,757; p=0,799; and p=0,822, respectively). Patients with RD, PR and PG were retreated, with surgery or surgery plus RAI, receiving cumulative activity up to 40 GBq. The overall outcome in our patients was excellent: 88,9% CR, 5,55% SD, 1,85% PG, 1,85% DRD, and 1,85% OCD. Conclusion: Younger age at diagnosis, less radical primary surgery without subsequent RAI, and tumor multifocality are strong prognostic factors for recurrence. In order to reduce relapse rate and to improve surveillance for recurrent disease, TTx followed by RAI appears to be the most beneficial initial treatment for patients with juvenile DTC. The use of RAI seems to be safe without adverse effects on subsequent fertility and pregnancy or secondary malignancy.

Multimodality salvage therapy for anal cancer failing standard chemoradiation

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15635-e15635
Author(s):  
Y. N. You ◽  
D. W. Larson ◽  
E. J. Dozois ◽  
H. Nelson ◽  
E. Antpack Filho ◽  
...  
Keyword(s):  
Overall Survival ◽  
Recurrent Disease ◽  
Perineal Wound ◽  
External Beam Radiation ◽  
Intraoperative Radiation Therapy ◽  
Beam Radiation ◽  
Intraoperative Radiation ◽  
Multimodality Approach ◽  
Pelvic Resection

e15635 Background: Most squamous cell carcinomas of the anal canal (SCC) respond to chemoradiation, but effective therapy for locally-invasive(T4) or recurrent disease that fails standard chemoradiation and/or salvage abdominoperineal resection (APR) has not been clearly delineated. A multimodality approach including chemoradiation, extended pelvic resection and intraoperative radiation therapy (IORT) was assessed for survival impact and treatment morbidity.morbidities. Methods: A prospective registry including 26 patients with locally-invasive or recurrent disease treated between 1993 and 2007 was reviewed. Primary endpoint was overall survival (OS), obtained from prospectively collected patient questionnaires and medical record review, and analyzed by the Kaplan-Meier method. Short (60-day postoperative) and long-term (median followup: 1.6 years; 5.3 years among survivors) complications were assessed. Results: Patients (median age: 51 years) presented with (1) locally-invasive disease that persisted despite initial standard chemoradiation (n=10, 39%), (2) disease that recurred after initial standard chemoradiation (n=10, 39%; median 1.7 years to recurrence), or (3) re-recurrence after a salvage APR (n=6, 23%; median 1.3 years since APR). All patients received chemotherapy and external beam radiation preoperatively, and 19% received additional postoperative chemoradiation. Gross pelvic disease was completely resected in all (R0 in 73%; R1 in 27%). IORT (750–3250cGy) was delivered at single (92%) or two sites (8%). Median overall survival (OS) was 1.7 years. Five-year OS were: 50%, 10%, and 22% for patients with locally-invasive, recurrent, and re-recurrent disease respectively. Short-term complications predominantly related to the perineal wound. Fifteen patients reported long-term complications (>grade3): bowel obstruction in 8 (1 requiring operation), perineal wound fistula/non-healing in 9, leg paresthesia in 5, hydronephrosis in 3. Conclusions: For select patients with locally-persistent or recurrent SCC who fail standard primary treatment, a multimodality approach involving chemoradiation, extended pelvic resection and IORT offers a chance for improved survival. No significant financial relationships to disclose.

Surgery for acquired cholesteatoma in children: long-term results and recurrence of cholesteatoma

1998 ◽  
Vol 112 (8) ◽  
pp. 742-749 ◽  
Author(s):  
Sven-Eric Stangerup ◽  
Dominika Drozdziewicz ◽  
Mirko Tos ◽  
Franco Trabalzini
Keyword(s):  
Recurrent Disease ◽  
Ossicular Chain ◽  
Observation Time ◽  
Long Term Results ◽  
Kaplan Meier ◽  
Tube Function ◽  
Acquired Cholesteatoma ◽  
Rate Calculation ◽  
Special Risk

AbstractThe aim of the study was to evaluate the long-term results after surgery for acquired cholesteatoma in children and to contribute to the search for predictors of recurrence. During a 15-year period, 114 children underwent surgery. The patients were re-evaluated with a median observation time of 5.8 years. At the last re-evaluation 85 per cent of the ears were dry with an intact drum. Recurrence of cholesteatoma developed in 27 ears. The cumulated total recurrence rate was 24 per cent using the incidence rate calculation, applying Kaplan-Meier survival analysis the corresponding recurrence was 33 per cent. Recurrent disease occurred significantly more frequently in children younger than eight years, with a negative pre-operative Valsalva, with ossicular resorption and with large cholesteatomas. In conclusion, young children with poor Eustachian tube function and a large cholesteatoma with erosion of the ossicular chain, are at special risk of recurrence and should be observed for several years after surgery.

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