Patterns of treatment failure in patients undergoing adjuvant or definitive radiotherapy for vulvar cancer

2019 ◽  
Vol 29 (5) ◽  
pp. 857-862
Author(s):  
Christina Steen Vorbeck ◽  
Anuja Jhingran ◽  
Revathy B Iyer ◽  
Annika Loft ◽  
Ann Klopp ◽  
...  
Keyword(s):  
Adjuvant Radiotherapy ◽  
Clinical Decision Making ◽  
Vulvar Cancer ◽  
Recurrent Disease ◽  
Treatment Strategies ◽  
High Dose ◽  
Definitive Radiotherapy ◽  
Failure Patterns ◽  
Gynecology And Obstetrics ◽  
Dose Planning

ObjectivesKnowledge of the detailed pattern of failure can be useful background knowledge in clinical decision making and potentially drive the development of new treatment strategies by increasing radiotherapy dose prescription to high-risk sub-regions of the target. Here, we analyze patterns of recurrence in patients with vulvar cancer treated with radiotherapy according to original planning target volumes and radiation dose delivered.MethodsWe analyzed dose-planning and post-treatment recurrence scans from patients with vulvar cancer treated at two institutions from January 2009 through October 2014. We delineated the recurrences and merged the dose-planning and recurrence scans for each patient by using deformable co-registration. We estimated the center of each recurrence on the merged scans with the goal of relating them to the original dose plan.ResultsWe evaluated 157 patients who received radiotherapy for vulvar cancer. Median age was 68 years (range 29–91). Patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA-IVB were included. Twenty-nine patients had recurrent disease; 156 patients had squamous cell carcinoma and one patient had adenosquamous carcinoma of the vulva. Among the 157 patients, 37 patients with recurrent disease had recurrence scans available for review, for a total of 80 recurrence sites; 53% of the recurrences were located in the region to which the highest dose (60–70 Gy) had been prescribed. Patients who received definitive radiotherapy developed failure primarily in the high-dose region (80.5%), whereas patients who received adjuvant radiotherapy had a more scattered failure pattern (p<0.0001). Among the latter group, 29.5% failed in the high-dose region.ConclusionsPatients who received definitive versus adjuvant radiotherapy had different failure patterns, indicating that separate approaches are needed to improve both adjuvant and definitive radiotherapy for vulvar cancer.

scholarly journals Impact of Mantle Cell Lymphoma Contamination of Autologous Stem Cell Grafts on Outcome After High-Dose Chemotherapy

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2558
Author(s):  
Malte Roerden ◽  
Stefan Wirths ◽  
Martin Sökler ◽  
Wolfgang A. Bethge ◽  
Wichard Vogel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mantle Cell Lymphoma ◽  
Clinical Decision Making ◽  
Cell Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Mantle Cell ◽  
Autologous Grafts

Novel predictive factors are needed to identify mantle cell lymphoma (MCL) patients at increased risk for relapse after high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HDCT/Auto-HSCT). Although bone marrow and peripheral blood involvement is commonly observed in MCL and lymphoma cell contamination of autologous stem cell grafts might facilitate relapse after Auto-HSCT, prevalence and prognostic significance of residual MCL cells in autologous grafts are unknown. We therefore performed a multiparameter flow cytometry (MFC)-based measurable residual disease (MRD) assessment in autologous stem cell grafts and analyzed its association with clinical outcome in an unselected retrospective cohort of 36 MCL patients. MRD was detectable in four (11%) autologous grafts, with MRD levels ranging from 0.002% to 0.2%. Positive graft-MRD was associated with a significantly shorter progression-free and overall survival when compared to graft-MRD negative patients (median 9 vs. 56 months and 25 vs. 132 months, respectively) and predicted early relapse after Auto-HSCT (median time to relapse 9 vs. 44 months). As a predictor of outcome after HDCT/Auto-HSCT, MFC-based assessment of graft-MRD might improve risk stratification and support clinical decision making for risk-oriented treatment strategies in MCL.

scholarly journals Primary Central Nervous System Lymphoma in Elderly Patients: Management and Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3479
Author(s):  
Andrea Morales-Martinez ◽  
Fernando Lozano-Sanchez ◽  
Alberto Duran-Peña ◽  
Khe Hoang-Xuan ◽  
Caroline Houillier
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Elderly Patients ◽  
Treatment Strategies ◽  
Central Nervous System Lymphoma ◽  
High Dose Chemotherapy ◽  
Current Treatment ◽  
Cns Lymphoma ◽  
High Dose ◽  
Consolidation Phase

The management of elderly patients suffering from primary central nervous system (CNS) lymphoma, who represent a rapidly growing population, is challenging. Despite the advances made in PCNSL treatment, the prognosis in older patients remains unsatisfactory. The high risk of systemic and CNS toxicity induced by a high-dose chemotherapy regimen and radiation therapy, respectively, limits the use of consolidation phase treatments in elderly patients and contributes to the poor outcome of these patients. Here, we review the current treatment strategies and ongoing trials proposed for elderly PCNSL patients.

scholarly journals Refractory constrictive pericarditis caused by an immune checkpoint inhibitor properly managed with infliximab: a case report

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Shohei Moriyama ◽  
Mitsuhiro Fukata ◽  
Ryoma Tatsumoto ◽  
Mihoko Kono
Keyword(s):  
Lung Cancer ◽  
Constrictive Pericarditis ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Rescue Therapy ◽  
Treatment Strategies ◽  
High Dose ◽  
Acute Pericarditis ◽  
Line Therapy ◽  
Steroid Refractory

Abstract Background Immune checkpoint inhibitors (ICIs) can cause cardiac immune-related adverse events (irAEs), including pericarditis. Cardiovascular events related to pericardial irAE are less frequent, but fulminant forms can be fatal. However, the diagnosis and treatment strategies for pericardial irAE have not established. Case summary A 58-year-old man was diagnosed with advanced non-small-cell lung cancer and nivolumab was administered as 5th-line therapy. Eighteen months after the initiation of nivolumab, the patient developed limb oedema and increased body weight. Although a favourable response of the cancer was observed, pericardial thickening and effusion were newly detected. He was diagnosed with irAE pericarditis after excluding other causes of pericarditis. Nivolumab was suspended and a high-dose corticosteroid was initiated. However, right heart failure (RHF) symptoms were exacerbated during the tapering of corticosteroid because acute pericarditis developed to steroid-refractory constrictive pericarditis. To suppress sustained inflammation of the pericardium, infliximab, a tumour necrosis factor-alfa inhibitor, was initiated. After the initiation of infliximab, the corticosteroid dose was tapered without deterioration of RHF. Exacerbation of lung cancer by irAE treatment including infliximab was not observed. Discussion IrAE should be considered when pericarditis develops after the administration of ICI even after a long period from its initiation. Infliximab rescue therapy may be considered as a 2nd-line therapy for steroid-refractory irAE pericarditis even with constrictive physiology.

scholarly journals GCT-65. INCIDENCE AND OUTCOME OF INTRACRANIAL MALIGNANT GERM CELL TUMOURS DIAGNOSED IN WESTERN DENMARK IN THE LAST DECADE

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii341-iii341
Author(s):  
Yasmin Lassen-Ramshad ◽  
Torben Stamm Mikkelsen ◽  
Steen Rosthoej ◽  
Louise Tram Henriksen ◽  
Ruta Tuckuvienne ◽  
...  
Keyword(s):  
Germ Cell ◽  
Chart Review ◽  
Recurrent Disease ◽  
High Dose Chemotherapy ◽  
Salvage Treatment ◽  
High Dose ◽  
Germ Cell Tumours ◽  
Younger Adults ◽  
Multidrug Chemotherapy ◽  
Disseminated Disease

Abstract INTRODUCTION Intracranial malignant germ cell tumours (iGCT) are rare brain tumours mainly diagnosed in children and younger adults. MATERIAL AND METHODS A retrospective analysis was performed by chart review of patients treated for iGCT in the northern and central region of Denmark. Teratoma only patients were not included in the study. RESULTS 20 patients with iGCT were diagnosed from 2008–2019 in Western Denmark. The cumulative incidence was 1.05 per 100.000. The yearly incidence was 0.1 per 100.000. Mean age at diagnosis was 18 years (range 8–36 years), 17 were males and 3 were females. 13 patients presented with germinoma and 7 patients with non germinomateous germ cell tumours (NGGCT). Three patients had disseminated disease, two with germinoma and one with NGGCT. All patients had received radiotherapy and 18 patients were treated with multidrug chemotherapy including platinum and etoposide before irradiation. Two patients experienced recurrent disease, both non disseminated at diagnosis, one patient with germinoma and one patient with NGGCT. Both received salvage treatment including high dose chemotherapy with stem cell transplantation and reirradiation. Two NGGCT patients died, one patient after development of an anaplastic astrocytoma in the radiation field five years after radiotherapy and one patient after intracranial hemorraghe 18 months after salvage treatment for recurrent disease. Overall survival was 90%, 100% for GCT and 71% for NGGCT. CONCLUSION The outcome of patients with iGCT in Western Denmark was comparable to the literature. A nationwide study of epidemiology and outcome of iGCT in Denmark is planned.

scholarly journals MBCL-37. CHEMOTHERAPY STRATEGIES FOR YOUNG CHILDREN NEWLY DIAGNOSED WITH CLASSIC (CLMB) OR ANAPLASTIC/LARGE CELL (A/LCMB) MEDULLOBLASTOMA UP TO THE ERA OF MOLECULAR PROFILING – A COMPARATIVE OUTCOMES ANALYSIS

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii396-iii397
Author(s):  
Jonathan Finlay ◽  
Martin Mynarek ◽  
Girish Dhall ◽  
Claire Mazewski ◽  
Richard Grundy ◽  
...  
Keyword(s):  
Head Start ◽  
Young Children ◽  
Induction Chemotherapy ◽  
Treatment Strategies ◽  
Large Cell ◽  
High Dose ◽  
Event Free Survival ◽  
Standard Chemotherapy ◽  
Outcomes Analysis ◽  
Free Survival

Abstract BACKGROUND/OBJECTIVE The introduction of German regimens, supplementing “standard” chemotherapy with both intravenous high-dose (HD-MTX) and intraventricular (IVENT-MTX) methotrexate, and North American regimens incorporating marrow-ablative chemotherapy with autologous hematopoietic cell rescue (HDCx+AuHCR), report encouraging outcomes for young children with medulloblastoma. We performed a comparative outcomes analysis of treatment strategies for young children with ClMB or A/LCMB. DESIGN/ METHODS Data from 12 prospective multi-center trials published between 2005 and 2019 for children &lt;six-years-old with ClMB or A/LCMB were reviewed; survivals were compared. RESULTS COG-9921, UKCCSG-CNS9204, COG-P9934 and SJYCO7 employing standard chemotherapy with either no or risk-based irradiation, reported 3-5-year event-free survival (EFS) of 17+/-5%, 33+/-28% (ClMB), 14+/-7% and 13.8+/-9% (ClMB) respectively, with reported EFS of 0% for A/LCMB in UKCCSG-CNS9204 and SJYCO7. HIT-SKK’87, HIT-SKK’92 and HIT-SKK’00 incorporating HD-MTX and IVENT-MTX reported 2-10-year EFS of 30–34+/-10–11% for ClMB and 33+/-27% (HIT-SSK’00) for A/LCMB. Head Start HS-I-II combined, CCG-99703 and HS-III employing induction chemotherapy, with or without HD-MTX, followed by single or tandem HDCx+AuHCR reported 3-5-year EFS of 42+/-14%, 50+/-11% and 27+/-6% for ClMB, with EFS for A/LCMB of 38+/-13% (HS-III). Finally, 5-year overall survivals for ACNS0334, without or with induction HD-MTX, are 39% and 69% respectively for ClMB and A/LCMB combined. CONCLUSIONS A trend towards better outcomes for young children with ClMB and A/LCMB is observed in trials including either HD-MTX and IVENT-MTX or including HD-MTX-containing induction chemotherapy and HDCx+AuHCR. Trials excluding HD-MTX, IVENT-MTX and HDCx+AuHCR have poorer outcomes.

Ranscriptome Analysis Reveals the Molecular Mechanism of Yiqi Rougan Decoction in Reducing CCl4-induced Liver Fibrosis in Rats

2021 ◽  
Author(s):  
Yu Xiong ◽  
Jinyuan Hu ◽  
Chen Xuan ◽  
Jiayu Tian ◽  
Kaiyue Tan ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Liver Fibrosis ◽  
Liver Injury ◽  
Molecular Mechanism ◽  
Treatment Strategies ◽  
Specific Treatment ◽  
Mitogen Activated Protein Kinase ◽  
Signalling Pathways ◽  
High Dose ◽  
Peroxisome Proliferator

Abstract BackgroundLiver fibrosis develops from various chronic liver diseases, and there is currently a lack of specific treatment strategies. Yiqi Rougan decoction (YQRG) is a traditional Chinese medicine that has shown durative effects in the treatment of liver fibrosis; however, the mechanism associated with YQRG-related improvements in liver fibrosis remains to be experimentally determined. This study evaluated the therapeutic effect of YQRG on carbon tetrachloride (CCl4)-induced liver fibrosis in rats and its molecular mechanism. MethodsWe used low-, medium-, and high-dose YQRG to treat CCl4-induced liver fibrosis in rats, followed by assessment of liver injury and fibrosis according to liver appearance, body weight, liver mass index, histopathologic examination, and serum testing. Additionally, we performed transcriptome analysis using RNA-sequencing (RNA-seq) technology, including cluster, Gene Ontology (GO), and pathway analyses, to identify differentially expressed genes (DEGs), and protein and gene expression were detected by immunofluorescence (IFC), western blot, and real-time quantitative PCR. ResultsThe results showed that YQRG effectively alleviated CCl4-induced liver injury and fibrosis in rats, including observations of improved liver function, decreased activity of hepatic stellate cells (HSCs), and decreased extracellular matrix (ECM) deposition. Moreover, we identified downregulated and upregulated DEGs in the model group relative to the control and YQRG-treated groups, with GO analysis revealing their enrichment in biological processes, such as endoplasmic reticulum stress (ERS), apoptosis, and autophagy. Furthermore, pathway analysis showed that YQRG treatment downregulated the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase/Akt (PI3K/AKT) signalling pathways and upregulated other signalling pathways, including those related to peroxisome proliferator-activated receptors(PPAR) and AMP-activated protein kinase(AMPK), with these finding subsequently verified experimentally. ConclusionThese findings showed that YQRG improved CCl4-induced liver fibrosis through multiple mechanisms and pathways, offering critical insight into the YQRG-related therapeutic mechanism and promoting further research into its potential application.

Clinical Aspects and Treatment of Rapid Cycling Mood Disorders

1986 ◽  
Vol 31 (5) ◽  
pp. 436-441 ◽  
Author(s):  
J. Mark Levy ◽  
Ronald A. Remick
Keyword(s):  
Mood Disorders ◽  
Medication Compliance ◽  
Treatment Strategies ◽  
Clinical Aspects ◽  
High Dose ◽  
Rapid Cycling ◽  
Cycling Treatment ◽  
Psychotherapeutic Approach ◽  
Bipolar Ii ◽  
Natural Expression

Eight female patients with rapid cycling mood disorders (at least four discrete affective episodes per year) were examined from a clinical perspective. Assessment suggested several different etiologies to the rapid cycling pattern in these patients. These included that the rapid mood swings were: a natural expression of the affective disorder, tricyclic induced, a result of frequent medication changes and/or poor medication compliance, and a combination of the aforementioned etiologies. All patients were helped significantly with treatment. Treatment was individualized for each patient's unique illness and possible etiological factors in the rapid cycling. Treatment strategies and guidelines include: i) A psychotherapeutic approach involving the patient and his family which emphasizes the lengthy nature of treatment before expected results; ii) The necessity of rigorous drug adherence, in) The sole use of “high dose” lithium therapy (> 1.2 MEQ/L) in some patients, and the consideration of “high dose” lithium in conjunction with tricyclics, MAO inhibitors or “adjuvant” medication in certain bipolar II patients; iv) The discontinuation of tricyclics in bipolar l rapid cyclers;v) The combination of lithium salts and carbamazepine or the use of carbamazepine alone in selected patients.

scholarly journals Primary maxillofacial chordoma: a rare case report and literature review

2019 ◽  
Vol 47 (9) ◽  
pp. 4575-4579
Author(s):  
Yu Cui ◽  
Xiang-yan Cui ◽  
Tingting Yu ◽  
Zhan-peng Zhu ◽  
Xin Wang
Keyword(s):  
Adjuvant Radiotherapy ◽  
Rare Case ◽  
Postoperative Radiotherapy ◽  
Eastern Cooperative Oncology Group ◽  
Treatment Strategies ◽  
Comprehensive Treatment ◽  
Neck Lymph Node ◽  
Group Score ◽  
Rare Case Report

Primary maxillofacial chordoma is extremely rare. We herein report a very rare case of a recurrent maxillofacial chordate tumor that was diagnosed in a 56-year-old woman who underwent three tumor resections. After surgical treatment, the patient healed well with an Eastern Cooperative Oncology Group score of 1. She was discharged to a local hospital for adjuvant radiotherapy. Close follow-up was ongoing at the time of this writing. Radical surgery and adjuvant radiotherapy remain the main treatment strategies for chordoma. Postoperative radiotherapy is particularly important. Our experience is to administer a total dose of 50 Gy to a clearly delineated target. If appropriate comprehensive treatment is available, distant metastasis of primary chordoma is rare, and neck dissection is therefore not generally recommended. Neck lymph node dissection is generally not recommended.

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