scholarly journals Radiotherapy in Medulloblastoma—Evolution of Treatment, Current Concepts and Future Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 5945
Author(s):  
Clemens Seidel ◽  
Sina Heider ◽  
Peter Hau ◽  
Annegret Glasow ◽  
Stefan Dietzsch ◽  
...  
Keyword(s):  
Survival Rates ◽  
Current Evidence ◽  
Future Perspectives ◽  
Survival Times ◽  
Treatment Needs ◽  
Therapeutic Landscape ◽  
Risk Patients ◽  
Standard Risk ◽  
Review Current ◽  
Current Risk

Medulloblastoma is the most frequent malignant brain tumor in children. During the last decades, the therapeutic landscape has changed significantly with craniospinal irradiation as the backbone of treatment. Survival times have increased and treatments were stratified according to clinical and later molecular risk factors. In this review, current evidence regarding the efficacy and toxicity of radiotherapy in medulloblastoma is summarized and discussed mainly based on data of controlled trials. Current concepts and future perspectives based on current risk classification are outlined. With the introduction of CSI, medulloblastoma has become a curable disease. Due to combination with chemotherapy, survival rates have increased significantly, allowing for a reduction in radiation dose and a decrease of toxicity in low- and standard-risk patients. Furthermore, modern radiotherapy techniques are able to avoid side effects in a fragile patient population. However, high-risk patients remain with relevant mortality and many patients still suffer from treatment related toxicity. Treatment needs to be continually refined with regard to more efficacious combinatorial treatment in the future.

Six Months of Maintenance Chemotherapy After Intensified Treatment for Acute Lymphoblastic Leukemia of Childhood

2000 ◽  
Vol 18 (7) ◽  
pp. 1508-1516 ◽  
Author(s):  
Yasunori Toyoda ◽  
Atsushi Manabe ◽  
Masahiro Tsuchida ◽  
Ryohji Hanada ◽  
Koichiro Ikuta ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Lymphoblastic Leukemia ◽  
Survival Rates ◽  
Remission Induction ◽  
Maintenance Chemotherapy ◽  
Risk Patients ◽  
Standard Risk ◽  
Overall Survival Rates

PURPOSE: We postulated that intensification of chemotherapy immediately after remission induction might reduce the leukemic cell burden sufficiently to allow an abbreviated period of antimetabolite therapy. PATIENTS AND METHODS: Three hundred forty-seven children (ages 1 to 15 years) with previously untreated acute lymphoblastic leukemia (ALL) were enrolled onto the Tokyo L92–13 study, which excluded patients with mature B-cell ALL and patients less than 1 year old. One hundred twenty-four patients were classified as standard risk, 122 as high risk, and 101 as extremely high risk, according to age, peripheral-blood leukocyte count, selected genetic abnormalities, and immunophenotype. All subjects received four drugs for remission induction, followed by a risk-directed multidrug intensification phase and therapy for presymptomatic leukemia in the CNS. Maintenance chemotherapy with oral mercaptopurine and methotrexate was administered for 6 months, with all treatment stopped by 1 year after diagnosis. RESULTS: The mean (± SD) event-free survival (EFS) and overall survival rates for all patients were 59.5% ± 3.4% and 81.5% ± 2.2%, respectively, at 5.5 years after diagnosis. EFS rates by risk category were similar (60.2% ± 6.0% for standard risk, 57.7% ± 5.6% for high risk, and 62.5% ± 5.7% for extremely high risk), whereas overall survival rates differed significantly (91.2% ± 2.7%, 80.0% ± 4.1%, and 72.1% ± 4.5%, respectively, P < .0001 by the log-rank test). There were 107 relapses. Eighty-five (79.4%) of these 107 patients achieved second complete remissions, with subsequent EFS rates of 61.5% ± 7.9% (standard risk), 42.6% ± 8.1% (high risk), and 9.6% ± 6.4% (extremely high risk). Of the five risk factors analyzed, only the response to prednisolone monotherapy among extremely high-risk patients proved important. CONCLUSION: Early treatment intensification did not compensate for a truncated phase of maintenance chemotherapy in children with standard- or high-risk ALL. However, 6 months of antimetabolite treatment seemed adequate for extremely high-risk patients who were good responders to prednisolone and received intensified chemotherapy that included high-dose cytarabine early in the clinical course.

Transapical versus Conventional Aortic Valve Replacement�A Propensity-Matched Comparison

2012 ◽  
Vol 15 (1) ◽  
pp. 4 ◽  
Author(s):  
David M. Holzhey ◽  
William Shi ◽  
A. Rastan ◽  
Michael A. Borger ◽  
Martin H�nsig ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Survival Rates ◽  
Long Term Results ◽  
Term Survival ◽  
Kaplan Meier ◽  
Risk Patients ◽  
Short And Long Term ◽  
Good Treatment Option ◽  
Matched Comparison

<p><b>Introduction:</b> The goal of this study was to compare the short- and long-term outcomes after aortic valve (AV) surgery carried out via standard sternotomy/partial sternotomy versus transapical transcatheter AV implantation (taTAVI).</p><p><b>Patients and Methods:</b> All 336 patients who underwent taTAVI between 2006 and 2010 were compared with 4533 patients who underwent conventional AV replacement (AVR) operations between 2001 and 2010. Using propensity score matching, we identified and consecutively compared 2 very similar groups of 167 patients each. The focus was on periprocedural complications and long-term survival.</p><p><b>Results:</b> The 30-day mortality rate was 10.8% and 8.4% (<i>P</i> = .56) for the conventional AVR patients and the TAVI patients, respectively. The percentages of postoperative pacemaker implantations (15.0% versus 6.0%, <i>P</i> = .017) and cases of renal failure requiring dialysis (25.7% versus 12.6%, <i>P</i> = .004) were higher in the TAVI group. Kaplan-Meier curves diverged after half a year in favor of conventional surgery. The estimated 3-year survival rates were 53.5% � 5.7% (TAVI) and 66.7% � 0.2% (conventional AVR).</p><p><b>Conclusion:</b> Our study shows that even with all the latest successes in catheter-based AV implantation, the conventional surgical approach is still a very good treatment option with excellent long-term results, even for older, high-risk patients.</p>

scholarly journals What Has Clinical Research in Suicide Prevention Done for You Lately?

CNS Spectrums ◽  
2006 ◽  
Vol 11 (6) ◽  
pp. 440-441 ◽  
Author(s):  
Jan Fawcett
Keyword(s):  
Suicidal Ideation ◽  
Suicide Risk ◽  
Clinical Status ◽  
Panic Attacks ◽  
Current Evidence ◽  
Suicide Risk Assessment ◽  
Short Term ◽  
The Past ◽  
Standard Risk ◽  
Suicide Plan

What have you heard or read over the past 10 years that has improved you ability to assess and manage suicide risk in your patients?There has been a paucity of data. What little data there is reviewed in this month's articles.They highlight findings that you should know about. Clinicians seem to cling to the familiar, unless some intense marketing is done.For instance, are you aware that the current evidence shows that a denial of suicide thoughts, plans, or intent—even a contract for safety—means absolutely nothing in the absence of a full suicide risk assessment?Yet clinicians seem to rely on these ’reassurances“ from their patients and are shocked when the patient later commits suicide. Why should a patient who is deciding that life is too painful to live tell you the truth? Robert I. Simon, MD, and Daniel W. Shuman, JD, review these facts.Are you aware that severe psychic anxiety, panic attacks, agitation, and severe insomnia often precede suicide within hours, days, or weeks and can be rapidly modified with treatment?On the other hand, standard risk factors for suicide such as suicidal ideation, hopelessness, and past suicidal attempts are not good predictors of suicide in the short term. A suicide plan, recent high intent attempt, or refusal to contract for safety may well indicate immediate risk, but a denial of suicidal ideation or intent and a contract for no harm mean absolutely nothing without a full suicide assessment that takes current clinical status, past suicidal tendencies, social support, and willingness to accept help into account.

Clonal Diversity of Ig and T-Cell–Receptor Gene Rearrangements Identifies a Subset of Childhood B-Precursor Acute Lymphoblastic Leukemia With Increased Risk of Relapse

Blood ◽  
1998 ◽  
Vol 92 (3) ◽  
pp. 952-958 ◽  
Author(s):  
Elaine Green ◽  
Carmel M. McConville ◽  
Judith E. Powell ◽  
Jillian R. Mann ◽  
Philip J. Darbyshire ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
T Cell Receptor ◽  
Lymphoblastic Leukemia ◽  
Clonal Diversity ◽  
Cell Receptor ◽  
Prognostic Indicators ◽  
Gene Rearrangements ◽  
Risk Patients ◽  
Standard Risk

Abstract Current prognostic indicators such as age, sex, and white blood cell count (WBC) fail to identify all children with more aggressive forms of B-precursor acute lymphoblastic leukemia (ALL), and a proportion of patients without poor prognostic indicators still relapse. Results obtained from an analysis of 65 pediatic B-precursor ALL patients indicated that subclone formation leading to clonal diversity, as detected by Ig and T-cell receptor (TCR) gene rearrangements, may represent a very useful prognostic indicator, independent of age, sex, and WBC. Disease-free survival was significantly shorter in those patients showing clonal diversity at presentation. Furthermore, clonal diversity was detected not only in the majority of high-risk patients who relapsed but was also associated with a high probability of relapse in standard-risk patients. Sixty-five percent (13/20) of standard-risk patients who also showed clonal diversity subsequently relapsed, whereas the percentage of relapses among standard-risk patients without clonal diversity was much lower at 19% (7/36). Continued clonal evolution during disease progression is an important feature of aggressive B-precursor ALL. All 5 patients with clonal diversity who were followed up in our study showed a change in the pattern of clonality between presentation and relapse. This implies an important role for clonal diversity as a mechanism of disease progression through the process of clonal variation and clonal selection. © 1998 by The American Society of Hematology.

scholarly journals LINC-28. EPIDEMIOLOGICAL CHARACTERISTICS AND SURVIVAL OUTCOMES OF CHILDREN WITH MEDULLOBLASTOMA TREATED AT THE NATIONAL CANCER INSTITUTE (INCA) IN RIO DE JANEIRO, BRAZIL

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii383-iii384
Author(s):  
Gabriela Oigman ◽  
Diana Osorio ◽  
Joseph Stanek ◽  
Jonathan Finlay ◽  
Denizar Vianna ◽  
...  
Keyword(s):  
High Risk ◽  
Maternal Education ◽  
Survival Outcomes ◽  
Middle Income ◽  
Female Ratio ◽  
High Risk Patients ◽  
Presenting Symptoms ◽  
Risk Patients ◽  
Epidemiological Characteristics ◽  
Standard Risk

Abstract BACKGROUND Medulloblastoma (MB), the most malignant brain tumor of childhood has survival outcomes exceeding 80% for standard risk and 60% for high risk patients in high-income countries (HIC). These results have not been replicated in low-to-middle income countries (LMIC), where 80% of children with cancer live. Brazil is an upper-middle income country according to World Bank, with features of LMIC and HIC. METHODS We conducted a retrospective review of 126 children (0–18 years) diagnosed with MB from 1997 to 2016 at INCA. Data on patients, disease characteristics and treatment information were retrieved from the charts and summarized descriptively; overall survival (OS) and event-free survival (EFS) were calculated using the Kaplan-Meier Method. RESULTS The male/female ratio was 1.42 and the median age at diagnosis was 7.9 years. Headache (79%) and nausea/vomiting (75%) were the most common presenting symptoms. The median time from onset of symptoms to surgery was 50 days. The OS for standard-risk patients was 69% and 53% for high-risk patients. Patients initiating radiation therapy within 42 days after surgery (70.6% versus 59.6% p=0.016) experienced better OS. Forty-five patients (35%) had metastatic disease at admission. Lower maternal education correlated with lower OS (71.3% versus 49% p=0.025). Patients who lived &gt;40km from INCA fared better (OS= 68.2% versus 51.1% p=0.032). Almost 20% of families lived below the Brazilian minimum wage. CONCLUSIONS These findings suggest that socioeconomic factors, education, early diagnosis and continuous data collection, besides oncological treatment must be adressed to improve the survival of children with MB.

Back-Table Modified Stent-Graft for Endovascular Repair of Ascending Aorta

2021 ◽  
pp. 152660282110282
Author(s):  
Juan Shi ◽  
Ligang Liu ◽  
Xiang Wei ◽  
Mingjia Ma
Keyword(s):  
Endovascular Repair ◽  
Survival Rates ◽  
Ascending Aorta ◽  
Cerebellar Infarction ◽  
Type Ia ◽  
Risk Patients ◽  
Aorta Replacement ◽  
Aortic Dissections ◽  
Event Rates

Objectives To investigate the effectiveness of modified stent-grafts (SGs) for the management of ascending aortic pathologies. Materials and Methods From January 2015 to December 2019, 31 individuals were treated by ascending aortic endovascular repair with a back-table modified SG for acute (n=4) or chronic (n=1) type A aortic dissections, penetrating aortic ulcers (n=18), pseudoaneurysms (n=2), anastomotic fistula (n=1), and endoleaks after thoracic endovascular aortic repair (TEVAR) (n=5). The commercially available thoracic aortic SGs were modified with a fenestration or truncation technique on the back-table according to aortography during the operation. Results The 30-day mortality and aorta-related mortality rates were 12.9% and 6.5%, respectively. There were 2 strokes, 3 respiratory insufficiencies, and 6 endoleaks during hospitalization. During a mean follow-up of 28.8±16.6 months, the overall survival rates at 1 year and 3 years were both 80.6%. Free from adverse event rates at 1 year and 3 years were 88.9% and 84.7%, respectively. There were 2 deaths during follow-up: One patient died of cachexia 1 month after discharge, and the other patient died of acute myocardial infarction 3 months after discharge. One patient with a pseudoaneurysm underwent open ascending aorta replacement 3 months after discharge for a type Ia endoleak. Another patient suffered from cerebellar infarction 17 months after discharge. Conclusion The modified SG for endovascular repair of the ascending aorta is a practicable alternative and presents acceptable outcomes in high-risk patients.

scholarly journals Therapeutic Role of Tocilizumab in SARS-CoV-2-Induced Cytokine Storm: Rationale and Current Evidence

2021 ◽  
Vol 22 (6) ◽  
pp. 3059
Author(s):  
Corrado Pelaia ◽  
Cecilia Calabrese ◽  
Eugenio Garofalo ◽  
Andrea Bruni ◽  
Alessandro Vatrella ◽  
...  
Keyword(s):  
Review Article ◽  
Lung Damage ◽  
Current Evidence ◽  
Therapeutic Effects ◽  
Cytokine Storm ◽  
Future Perspectives ◽  
Pathogenic Role ◽  
Refractory Rheumatoid Arthritis ◽  
Life Threatening

Among patients suffering from coronavirus disease 2019 (COVID-19) syndrome, one of the worst possible scenarios is represented by the critical lung damage caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced cytokine storm, responsible for a potentially very dangerous hyperinflammatory condition. Within such a context, interleukin-6 (IL-6) plays a key pathogenic role, thus being a suitable therapeutic target. Indeed, the IL-6-receptor antagonist tocilizumab, already approved for treatment of refractory rheumatoid arthritis, is often used to treat patients with severe COVID-19 symptoms and lung involvement. Therefore, the aim of this review article is to focus on the rationale of tocilizumab utilization in the SARS-CoV-2-triggered cytokine storm, as well as to discuss current evidence and future perspectives, especially with regard to ongoing trials referring to the evaluation of tocilizumab’s therapeutic effects in patients with life-threatening SARS-CoV-2 infection.

scholarly journals Perioperative Systemic Treatment for Muscle-Invasive Bladder Cancer: Current Evidence and Future Perspectives

2021 ◽  
Vol 22 (13) ◽  
pp. 7201
Author(s):  
In-Ho Kim ◽  
Hyo-Jin Lee
Keyword(s):  
Bladder Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Systemic Treatment ◽  
Checkpoint Inhibitors ◽  
Invasive Bladder Cancer ◽  
Current Evidence ◽  
Future Perspectives ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

Radical cystectomy is the primary treatment for muscle-invasive bladder cancer; however, approximately 50% of patients develop metastatic disease within 2 years of diagnosis, which results in dismal prognosis. Therefore, systemic treatment is important to improve the prognosis of muscle-invasive bladder cancer. Currently, several guidelines recommend cisplatin-based neoadjuvant chemotherapy before radical cystectomy, and adjuvant chemotherapy is recommended in patients who have not received neoadjuvant chemotherapy. Immune checkpoint inhibitors have recently become the standard treatment option for metastatic urothelial carcinoma. Owing to their clinical benefits, several immune checkpoint inhibitors, with or without other agents (including other immunotherapy, cytotoxic chemotherapy, and emerging agents such as antibody drug conjugates), are being extensively investigated in perioperative settings. Several studies for perioperative immunotherapy have shown that immune checkpoint inhibitors have promising efficacy with relatively low toxicity, and have explored the predictive molecular biomarkers. Herein, we review the current evidence and discuss the future perspectives of perioperative systemic treatment for muscle-invasive bladder cancer.

scholarly journals SEOM clinical guideline for management of adult medulloblastoma (2020)

2021 ◽  
Author(s):  
R. Luque ◽  
M. Benavides ◽  
S. del Barco ◽  
L. Egaña ◽  
J. García-Gómez ◽  
...  
Keyword(s):  
Residual Tumor ◽  
Large Cell ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Molecular Alterations ◽  
Adult Medulloblastoma ◽  
Group 4 ◽  
Risk Patients ◽  
Standard Risk

AbstractRecent advances in molecular profiling, have reclassified medulloblastoma, an undifferentiated tumor of the posterior fossa, in at least four diseases, each one with differences in prognosis, epidemiology and sensibility to different treatments. The recommended management of a lesion with radiological characteristics suggestive of MB includes maximum safe resection followed by a post-surgical MR < 48 h, LCR cytology and MR of the neuroaxis. Prognostic factors, such as presence of a residual tumor volume > 1.5 cm2, presence of micro- or macroscopic dissemination, and age > 3 years as well as pathological (presence of anaplastic or large cell features) and molecular findings (group, 4, 3 or p53 SHH mutated subgroup) determine the risk of relapse and should guide adjuvant management. Although there is evidence that both high-risk patients and to a lesser degree, standard-risk patients benefit from adjuvant craneoespinal radiation followed by consolidation chemotherapy, tolerability is a concern in adult patients, leading invariably to dose reductions. Treatment after relapse is to be considered palliative and inclusion on clinical trials, focusing on the molecular alterations that define each subgroup, should be encouraged. Selected patients can benefit from surgical rescue or targeted radiation or high-dose chemotherapy followed by autologous self-transplant. Even in patients that are cured by chemorradiation presence of significant sequelae is common and patients must undergo lifelong follow-up.

Phase I Study of Fludarabine Plus Cyclophosphamide in Patients With Previously Untreated Low-Grade Lymphoma: Results and and Long-Term Follow-Up—A Report From the Eastern Cooperative Oncology Group

2000 ◽  
Vol 18 (5) ◽  
pp. 987-987 ◽  
Author(s):  
Howard S. Hochster ◽  
Martin M. Oken ◽  
Jane N. Winter ◽  
Leo I. Gordon ◽  
Bruce G. Raphael ◽  
...  
Keyword(s):  
Phase Ii ◽  
Bone Marrow Involvement ◽  
Survival Rates ◽  
Eastern Cooperative Oncology Group ◽  
Disease Free Survival ◽  
Low Grade ◽  
Survival Times ◽  
Free Survival ◽  
Disease Free

PURPOSE: To determine the toxicity and recommended phase II doses of the combination of fludarabine plus cyclophosphamide in chemotherapy-naive patients with low-grade lymphoma. PATIENTS AND METHODS: Previously untreated patients with low-grade lymphoma were entered onto dosing cohorts of four patients each. The cyclophosphamide dose, given on day 1, was increased from 600 to 1,000 mg/m2. Fludarabine 20 mg/m2 was administered on days 1 through 5. The first eight patients were treated every 21 days; later patients were treated every 28 days. Prophylactic antibiotics were required. RESULTS: Prolonged cytopenia and pulmonary toxicity each occurred in three of eight patients treated every 3 weeks. The 19 patients treated every 28 days, who were given granulocyte colony-stimulating factor as indicated, did not have undue nonhematologic toxicity. Dose-limiting toxicity was hematologic. At the recommended phase II/III dose (cyclophosphamide 1,000 mg/m2), grade 4 neutropenia was observed in 17% of all cycles and 31% of first cycles. Grade 3 or 4 thrombocytopenia was seen in only 1% of all cycles. The median number of cycles per patient was six (range, two to 11) for all patients enrolled. The response rate was 100% of 27 patients entered; 89% achieved a complete and 11% a partial response. Nineteen of 22 patients with bone marrow involvement had clearing of the marrow. Median duration of follow-up was more than 5 years; median overall and disease-free survival times have not been reached. Kaplan-Meier estimated 5-year overall survival and disease-free survival rates were 66% and 53%, respectively. CONCLUSION: The recommended dosing for this combination in patients with previously untreated low-grade lymphoma is cyclophosphamide 1,000 mg/m2 day 1 and fludarabine 20 mg/m2 days 1 through 5. The regimen has a high level of activity, with prolonged complete remissions providing 5-year overall and disease-free survival rates as high as those reported for other therapeutic approaches in untreated patients.

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