Radiation Therapy for Chemotherapy Refractory Gingival Myeloid Sarcoma.
Ontology highlight
ABSTRACT:
SUBMITTER: Lee DY
PROVIDER: S-EPMC8143974 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Soft-tissue sarcoma (STS) represent a rare tumor entity, accounting for less than 1% of adult malignancies. The cornerstone of curative intent treatment is surgery with free margins, although the extent of the surgical approach has been subject to change in the last decades. Multimodal approaches usually including radiation therapy have replaced extensive surgical procedures in order to preserve functionality while maintaining adequate local control. However, the possibility to apply adequate radiation doses by external beam radiation therapy (EBRT) can be limited in some situation especially in case of directly adjacent organs at risk with low radiation tolerance. Application of at least a part of the total dose via intraoperative radiation therapy (IORT) with a single fraction during the surgical procedure may overcome those limitations, because radiosensitive structures can be moved out of the radiation field resulting in reduced toxicity while the enhanced biological effectivity of the high single dose improves local control. The current review summarizes rationale, techniques, oncological and functional outcomes including possible pitfalls and associated toxicities based on the published literature for IORT focusing on extremity and retroperitoneal STS. In extremity STS, combination of limb-sparing surgery, IORT and pre- or postoperative EBRT with moderate doses consistently achieved excellent local control rates at least comparable to approaches using EBRT alone but usually including patient cohorts with higher proportions of unfavourable prognostic factors. Further on, IORT containing approaches resulted in very high limb preservation rates and good functional outcome, probably related to the smaller high dose volume. In retroperitoneal STS, the combination of preoperative EBRT, surgery and IORT consistently achieved high local control rates which seem superior to surgery alone or surgery with EBRT at least with regard to local control and in some reports even to overall survival. Further on, preoperative EBRT in combination with IORT seems to be superior to the opposite combination with regard to local control and toxicity. No major differences in wound healing disturbances or postoperative complication rates can be observed with IORT compared to non-IORT containing approaches. Neuropathy of major nerves remains a dose limiting toxicity requiring dose restrictions or exclusion from target volume. Gastrointestinal structures and ureters should be excluded from the IORT area whenever possible and the IORT volume should be restricted to the available minimum. Nevertheless, IORT represents an ideal boosting method if combined with EBRT and properly executed by experiences users which should be further evaluated preferably in prospective randomized trials.
| S-EPMC5244699 | biostudies-literature
Project description:Therapy for those with relapsed or refractory acute myeloid leukemia is suboptimal. Studies have suggested that timed sequential salvage combination cytotoxic chemotherapy may have particular utility for that indication. We report here a series of ten such adult patients treated sequentially at a single center with EMA (cytarabine 500 mg/m2/day as continuous infusion on days 1-3 and days 8-10, mitoxantrone 12 mg/m2/day on days 1-3, and etoposide 200 mg/m2/day as continuous infusion on days 8-10). The overall complete remission rate was 40% (including 3 of 4 of those with relapsed disease) but use of this regimen was associated with prolonged cytopenia and a high rate of infectious adverse events. Even with the availability of modern infectious prophylaxis and therapies, the EMA regimen is likely best reserved for those with relapsed disease treated with curative intent prior to an allogeneic hematopoietic cell transplant.
| S-EPMC7079712 | biostudies-literature
Project description:Acute myeloid leukemia (AML) is a group of hematological malignancies causing high mortality around the world. However, the treatment of AML is still one of the most formidable challenges. In this study, we employed a well-established global metabolic profiling platform, which combined ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) with gas chromatography mass spectrometry (GC-MS) to investigate the metabolic alterations associated with salvage chemotherapy on 10 refractory acute myeloid leukemia (RAML) patients. A total of 390 metabolites were identified from 20 serum samples obtained from all 10 patients before and post salvage chemotherapy. The metabolomics profile was found to be very heterogeneous across the RAML patients. The results showed very subtle metabolic differences upon one-time chemotherapy treatment for an individual patient. Only 9 metabolites including imidazole lactate, glycerol 3-phosphate, three fatty acids, and four lysolipids in the blood serum were significantly changed before and post chemotherapy, suggesting their important roles during the development of RAML. This study may not only provide new insight into the metabolomics features in RAML patients, but also have relevance to improve the treatment and outcome of RAML.
| S-EPMC9079900 | biostudies-literature
Project description:Deep sequencing has revealed that epigenetic modifiers are the most mutated genes in acute myeloid leukemia (AML). Thus, elucidating epigenetic dysregulation in AML is crucial to understand disease mechanisms. Here, we demonstrate that metal response element binding transcription factor 2/polycomblike 2 (MTF2/PCL2) plays a fundamental role in the polycomb repressive complex 2 (PRC2) and that its loss elicits an altered epigenetic state underlying refractory AML. Unbiased systems analyses identified the loss of MTF2-PRC2 repression of MDM2 as central to, and therefore a biomarker for, refractory AML. Thus, immature MTF2-deficient CD34+CD38- cells overexpress MDM2, thereby inhibiting p53 that leads to chemoresistance due to defects in cell-cycle regulation and apoptosis. Targeting this dysregulated signaling pathway by MTF2 overexpression or MDM2 inhibitors sensitized refractory patient leukemic cells to induction chemotherapeutics and prevented relapse in AML patient-derived xenograft mice. Therefore, we have uncovered a direct epigenetic mechanism by which MTF2 functions as a tumor suppressor required for AML chemotherapeutic sensitivity and identified a potential therapeutic strategy to treat refractory AML.Significance: MTF2 deficiency predicts refractory AML at diagnosis. MTF2 represses MDM2 in hematopoietic cells and its loss in AML results in chemoresistance. Inhibiting p53 degradation by overexpressing MTF2 in vitro or by using MDM2 inhibitors in vivo sensitizes MTF2-deficient refractory AML cells to a standard induction-chemotherapy regimen. Cancer Discov; 8(11); 1376-89. ©2018 AACR. See related commentary by Duy and Melnick, p. 1348 This article is highlighted in the In This Issue feature, p. 1333.
| S-EPMC7200079 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Deep sequencing has revealed that epigenetic modifiers are the most mutated genes in acute myeloid leukemia (AML). Thus, elucidating epigenetic dysregulation in AML is crucial to understand disease mechanisms. Here, we demonstrate that Metal Response Element Binding Transcription Factor 2/Polycomblike 2 (MTF2/PCL2) plays a fundamental role in the Polycomb repressive complex 2 (PRC2) and that its loss elicits an altered epigenetic state underlying refractory AML. Unbiased systems analyses identified the loss of MTF2-PRC2 repression of MDM2 as central to, and therefore a biomarker for, refractory AML. Thus, immature MTF2- deficient CD34+CD38- cells overexpress MDM2, thereby inhibiting p53 that leads to chemoresistance due to defects in cell cycle regulation and apoptosis. Targeting this dysregulated signaling pathway by MTF2 overexpression or MDM2 inhibitors sensitized refractory patient leukemic cells to induction chemotherapeutics and prevented relapse in AML patient-derived xenograft (PDX) mice. Therefore, we have uncovered a direct epigenetic mechanism by which MTF2 functions as a tumor suppressor required for AML chemotherapeutic sensitivity and identified a potential therapeutic strategy to treat refractory AML.
2018-07-31 | GSE98380 | GEO
Project description:BACKGROUND: Hilar cholangiocarcinoma is a rare tumour which is best managed by an aggressive surgical approach. The role of adjuvant or neoadjuvant radiation therapy, chemotherapy or chemoradiation remains controversial, as no prospective randomized studies have been performed. METHODS: This review summarizes the recent literature regarding the role of radiation, chemotherapy and chemoradiation in hilar cholangiocarcinoma. The results of a biliary cancer questionnaire regarding current treatment strategies are also reported. RESULTS: A number of retrospective studies have shown that patients treated with adjuvant radiation therapy have prolonged survival compared with untreated patients. However, most of these reports did not control for tumour stage or performance status. A carefully controlled trial from the Johns Hopkins Hospital did not demonstrate any benefit for adjuvant radiation therapy. A number of phase II trials of chemotherapy have demonstrated modest response rates (20-40%). The best responses have been reported with 5-fluorouracil (5-FU) in combination with interferon-alpha or with leucovorin and mitomycin C. Recent non-randomized reports of chemoradiation with 5-FU with or without gemcitabine as the radiosensitizer suggest, but do not prove, improved survival. Adjuvant chemoradiation is currently being employed at specialized centres most often in the Americas (71%) and the Asia/Pacific region (55%) and to a lesser degree in Europe (29%). DISCUSSION: The only chance for long-term survival in patients with hilar cholangiocarcinoma is complete resection with negative margins. Neither radiation therapy nor chemotherapy alone has been proven to prolong survival in completely or partially resected patients or in unresected patients. Recent uncontrolled data suggest that chemoradiation may improve survival in resected and locally unresectable patients. However, prospective, randomized multicentre trials need to be performed to confirm efficacy.
| S-EPMC2043100 | biostudies-other
Project description:Assessment of chemo- and radiation therapy-naïve biopsy-confirmed invasive human breast tumors by RNAseq.
2017-07-08 | GSE100925 | GEO
Project description:PurposeDespite anatomical differences, truncal soft tissue sarcomas (STS) often are grouped with extremity sarcomas. We evaluated the clinical outcome of patients with truncal STS who underwent gross total resection (GTR) and radiation therapy (RT), with special emphasis on those treated with intensity modulated radiation therapy (IMRT).MethodsFrom January 1, 2001 to December 31, 2018, 64 patients received GTR and RT, where 48 patients were male, 35 patients were aged ≤ 60 years, and 48 patients had tumors ≤ 10 cm. Sixty-two tumors were high grade, 36 were in the chest wall, 7 in the abdominal wall, and 21 were paraspinal. During surgery, 7 received mesh reconstruction, and 6 received flap closure. R0 resection was achieved in 53 patients. Thirteen patients received chemotherapy.ResultsWith a median follow-up of 57 months, the 5-year actuarial local control (LC) was 71%. In the IMRT subset (50/64, 78%), the 5-year LC for the chest/abdominal wall was 84%, and 69% for the paraspinal subsite. Grade 2+ radiation dermatitis was seen in 21 of 64 (33%) patients, 5 of 64 (8%) developed noninfectious wound complications, 5 of 64 (8%) developed infectious wound complications, and 1 of 64 (2%) developed grade 2 chest wall pain. No additional grade 2+ late toxicity was observed.ConclusionsBased on this study, achieving LC in truncal STS treated with GTR and RT remains challenging even with IMRT (5-year LC: 78%). While the use of IMRT was more promising for tumors of the chest/abdominal wall with 5-year LC of 84%, it was 69% for those located in the paraspinal subsite, indicating a need for further improvement.
| S-EPMC9487906 | biostudies-literature
Project description:Radiation therapy is an integral component of local management with oncologic resection for soft tissue sarcoma. Radiotherapy is indicated in patients at an increased risk of local recurrence so that improved local control may be achieved. Sequencing of radiotherapy and resection should be determined by multidisciplinary input before treatment initiation. For most patients, preoperative delivery of radiation therapy is preferred. In patients initially thought to be at low risk for local recurrence and found to have unexpected adverse pathologic features at resection, postoperative radiation therapy is indicated. The use of radiation therapy for retroperitoneal sarcoma is controversial; when used, preoperative delivery of radiation is recommended.
| S-EPMC9372474 | biostudies-literature
Project description:BackgroundMyeloid sarcoma (MS) is a rare, extramedullary tumor consisting of myeloid blasts. Little is known about the genetic background of MS and the prognostic value of genetic abnormalities in MS. In particular, the broad variety of gene fusions that occur in MS is marginally covered by traditional testing methods due to lack of fresh tumor specimens.MethodsHere, we analyzed the clinical and genetic features of 61 MS cases. We performed RNA sequencing (RNA-seq) on formalin-fixed paraffin-embedded (FFPE) or fresh samples to analyze fusion genes in 26 cases. In addition, we performed genetic abnormalities-based risk stratification using fusion genes and gene mutations.ResultsA total of 305 fusion genes were identified in 22 cases, including the following five recurrent fusion genes: RUNX1-RUNX1T1, CBFβ-MYH11, ETV6-MECOM, FUS-ERG, and PICALM-MLLT10. The prognosis in the adverse-risk group was significantly worse than that in the favorable/intermediate-risk group (median survival: 12 months vs. not reached; p = 0.0004).ConclusionThese results indicated the efficacy of RNA-seq using FFPE-derived RNA as a clinical routine for detecting fusion genes, which can be used as markers for risk stratification in MS.
| S-EPMC10166975 | biostudies-literature