scholarly journals Prospective evaluation of multitarget treatment of pediatric patients with helical intensity-modulated radiotherapy

2020 ◽  
Vol 196 (12) ◽  
pp. 1103-1115
Author(s):  
Maria-Elena A. Salfelder ◽  
Kerstin A. Kessel ◽  
Uwe Thiel ◽  
Stefan Burdach ◽  
Severin Kampfer ◽  
...  

Abstract Background and purpose Radiotherapy (RT) is persistently gaining significance in the treatment of pediatric tumors. However, individual features of a growing body and multifocal stages complicate this approach. Tomotherapy offers advantages in the treatment of anatomically complex tumors with low risks of side effects. Here we report on toxicity incidence and outcome of tomotherapy with a focus on multitarget RT (mtRT). Materials and methods From 2008 to 2017, 38 children diagnosed with sarcoma were treated with tomotherapy. The median age was 15 years (6–19 years). Toxicity was graded according to the Common Terminology Criteria for Adverse Events v.4.03 and classified into symptoms during RT, acutely (0–6 months) and late (>6 months) after RT, and long-term sideeffects (>24 months). Results The main histologies were Ewing sarcoma (n = 23 [61%]) and alveolar rhabdomyosarcoma (n = 5 [13%]). RT was performed with a median total dose of 54 Gy (40.5–66.0 Gy) and a single dose of 2 Gy (1.80–2.27 Gy). Twenty patients (53%) received mtRT. Median follow-up was 29.7 months (95% confidence interval 15.3–48.2 months) with a 5-year survival of 55.2% (±9.5%). The 5‑year survival rate of patients with mtRT (n = 20) was 37.1 ± 13.2%, while patients who received single-target RT (n = 18) had a 5-year survival rate of 75 ± 10.8%. Severe toxicities (grade 3 and 4) emerged in 14 patients (70%) with mtRT and 7 patients (39%) with single-target RT. Two non-hematological grade 4 toxicities occurred during RT: one mucositis and one radiodermatitis. After mtRT 5 patients had grade 3 toxicities acute and after single-target RT 4 patients. One patient had acute non-hematological grade 4 toxicities (gastritis, pericarditis, and pericardial effusion) after mtRT. Severe late effects of RT occurred in 2 patients after mtRT and in none of the single-target RT patients. No severe long-term side effects appeared. Conclusion Our results showed acceptable levels of acute and late toxicities, considering the highly advanced diseases and multimodal treatment. Hence, tomotherapy is a feasible treatment method for young patients with anatomically complex tumors or multiple targets. Especially mtRT is a promising and innovative treatment approach for pediatric sarcomas, delivering unexpectedly high survival rates for patients with multifocal Ewing sarcomas in this study, whereby the limited number of patients should invariably be considered in the interpretation.

2019 ◽  
Vol 47 (5) ◽  
pp. 1307-1325 ◽  
Author(s):  
Caroline Busch ◽  
Helen Wheadon

Abstract Chronic myeloid leukaemia (CML) is a paradigm of precision medicine, being one of the first cancers to be treated with targeted therapy. This has revolutionised CML therapy and patient outcome, with high survival rates. However, this now means an ever-increasing number of patients are living with the disease on life-long tyrosine kinase inhibitor (TKI) therapy, with most patients anticipated to have near normal life expectancy. Unfortunately, in a significant number of patients, TKIs are not curative. This low-level disease persistence suggests that despite a molecularly targeted therapeutic approach, there are BCR-ABL1-independent mechanisms exploited to sustain the survival of a small cell population of leukaemic stem cells (LSCs). In CML, LSCs display many features akin to haemopoietic stem cells, namely quiescence, self-renewal and the ability to produce mature progeny, this all occurs through intrinsic and extrinsic signals within the specialised microenvironment of the bone marrow (BM) niche. One important avenue of investigation in CML is how the disease highjacks the BM, thereby remodelling this microenvironment to create a niche, which enables LSC persistence and resistance to TKI treatment. In this review, we explore how changes in growth factor levels, in particular, the bone morphogenetic proteins (BMPs) and pro-inflammatory cytokines, impact on cell behaviour, extracellular matrix deposition and bone remodelling in CML. We also discuss the challenges in targeting LSCs and the potential of dual targeting using combination therapies against BMP receptors and BCR-ABL1.


2020 ◽  
Vol 9 (12) ◽  
pp. 3943
Author(s):  
João Caramês ◽  
Ana Catarina Pinto ◽  
Gonçalo Caramês ◽  
Helena Francisco ◽  
Joana Fialho ◽  
...  

This retrospective study evaluated the survival rate of short, sandblasted acid-etched surfaced implants with 6 and 8 mm lengths with at least 120 days of follow-up. Data concerning patient, implant and surgery characteristics were retrieved from clinical records. Sandblasted and acid-etched (SLA)-surfaced tissue-level 6 mm (TL6) or 8 mm (TL8) implants or bone-level tapered 8 mm (BLT8) implants were used. Absolute and relative frequency distributions were calculated for qualitative variables and mean values and standard deviations for quantitative variables. A Cox regression model was performed to verify whether type, length and/or width influence the implant survival. The cumulative implant survival rate was assessed by time-to-event analyses (Kaplan–Meier estimator). In all, 513 patients with a mean age of 58.00 ± 12.44 years received 1008 dental implants with a mean follow-up of 21.57 ± 10.77 months. Most implants (78.17%) presented a 4.1 mm diameter, and the most frequent indication was a partially edentulous arch (44.15%). The most frequent locations were the posterior mandible (53.97%) and the posterior maxilla (31.55%). No significant differences were found in survival rates between groups of type, length and width of implant with the cumulative rate being 97.7% ± 0.5%. Within the limitations of this study, the evaluated short implants are a predictable option with high survival rates during the follow-up without statistical differences between the appraised types, lengths and widths.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 33-34
Author(s):  
Paula A. Lengerke Diaz ◽  
Michael Y. Choi ◽  
Eider F. Moreno Cortes ◽  
Jose V. Forero ◽  
Juliana Velez-Lujan ◽  
...  

Single oral targeted therapies have emerged as a standard of care in chronic lymphocytic leukemia (CLL). However, accessibility, side effects, and financial burden associated with long term administration limit their clinical use. Mainly, it is unclear in what clinical situation discontinuation of oral therapy can be recommended. The combination of type II anti-CD20 antibody obinutuzumab-Gazyva® with ibrutinib (GI) has shown a significant progression-free survival benefit in patients (pts) with CLL, including those with high-risk genomic aberrations. We conducted a phase 1b/2, single-arm, open-label trial to evaluate the safety and efficacy of GI as first-line treatment in 32 CLL pts. We report the outcome in pts that discontinued ibrutinib (either after 3 years of sustained complete response (CR) as stipulated in the clinical protocol, or due to other reasons). CLL pts enrolled in this protocol were ≥65 years old, or unfit/unwilling to receive chemotherapy. Pts received GI for six cycles, followed by daily single-agent ibrutinib. The protocol was designed to ensure that pts with a sustained CR after 36 months were allowed to discontinue ibrutinib. The median age was 66 years (IQR 59-73), and 6% of the evaluated pts had 17p deletion. All pts were able to complete the six planned cycles of obinutuzumab. The combination regimen was well-tolerated, and the most common adverse events (>5% CTCAE grade 3-4) were neutropenia, thrombocytopenia, and hyperglycemia. The rate and severity of infusion-related reactions (IRR) were much lower than expected (Grade≥ 3, 3%), and pts without IRR had lower serum levels of cytokines/chemokines CCL3 (P=0.0460), IFN-γ (P=0.0457), and TNF-α (P=0.0032) after infusion. The overall response rate was 100%, with nine pts (28%) achieving a CR, and four pts (12.5%) with undetectable minimal residual disease (uMRD) in the bone marrow, defined as <10-4 CLL cells on multicolor flow cytometry. At a median follow-up of 35.5 months (IQR 24.5-42.7) after starting treatment, 91% of the enrolled pts remain in remission with a 100% overall survival. Sixteen pts have completed a long-term follow-up of 36 months. Six pts showed CR, with three of them achieving uMRD in the bone marrow. Ten of these pts were in PR, and only one had disease progression and started treatment for symptomatic stage I disease with obinutuzumab plus venetoclax. In total, thirteen pts (41%) have stopped ibrutinib, with a median time on treatment prior to discontinuation of 35 months. Five (16%) of these pts had CRs and discontinued after 36 months. Eight additional pts (25%) had PRs and discontinued ibrutinib without being eligible: three pts discontinued prior to 36 months due to toxicities, and five pts discontinued after 36 months (3 due to side effects, and 2 due to financially driven decision). One patient eligible to discontinue ibrutinib, decided to remain on treatment despite sustained CR. After a median follow up time following ibrutinib discontinuation of 8 months (IQR 3.5-17), only two out of 13 pts have progressed (10 and 17 months after Ibrutinib discontinuation). None of the pts that stopped ibrutinib after achieving a CR have shown signs of disease progression. Of note, the pharmaceutical sponsor provided ibrutinib for the first 36 months, after which pts or their insurer became financially responsible. This particular scenario could bias the discontinuation pattern compared to a real world experience. It also provided us with a perspective about diverse factors affecting the treatment choices of pts. In summary, the obinutuzumab plus ibrutinib combination therapy was well-tolerated, with a much lower IRR rate. Efficacy compares favorably with historical controls with all pts responding to therapy, no deaths associated with treatment or disease progression, and a longer than expected time-to-progression after discontinuation of ibrutinib. The rate of ibrutinib discontinuation was higher than reported in the literature, most likely influenced by the protocol design and financial decisions driven by the switch from sponsor-provided ibrutinib to insurance or self-paid medication. Our observations regarding safety, efficacy and lack of disease progression after ibrutinib discontinuation are encouraging, and warrant confirmation in long-term prospective studies. Clinicaltrials.gov Identifier NCT02315768. Funding: Pharmacyclics LLC. Disclosures Choi: AbbVie: Consultancy, Speakers Bureau. Amaya-Chanaga:AbbVie: Ended employment in the past 24 months, Other: Research performed while employed as an investigator of this study at UCSD.. Kipps:Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Castro:Kite Pharma: Research Funding; Pharmacyclics: Research Funding; Fate Therapeutics: Research Funding.


Author(s):  
Petri Bellova ◽  
Jens Goronzy ◽  
Roman Riedel ◽  
Tim Grothe ◽  
Albrecht Hartmann ◽  
...  

AbstractDual-mobility cups (DMCs) were introduced in France more than 40 years ago and are increasingly used not only in hip revision but also primary hip arthroplasty. Due to a simulated large-head articulation and increased jumping distance, DMCs can contribute to a high range of motion in the hip joint and reduce the risk of instability. Numerous studies have reported low dislocation rates and high survival rates in the mid-term follow-up. Nevertheless, long-term data, especially on primary hip replacement, remain limited, and the effect of recent designs and material innovations is still unclear. Therefore, primary DMCs are mainly proposed in patients at high risk for dislocation (i.e. pelvitrochanteric insufficiency, compromised spinopelvic mobility, neuromuscular disorders, obesity and femoral neck fractures). Based on a review of recently published studies referring to these indications, the current study discusses the advantages and disadvantages of DMCs.


Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Ziad Alkutobi ◽  
Deena Laila ◽  
Mohammad Tariq

Abstract Background Denosumab and zoledronate are increasingly prescribed for primary and secondary osteoporosis long-term management. Methods A retrospective audit was conducted at Basildon Hospital during 2012-2019 using the NICE guidelines standards to evaluate the long term safety and efficacy of denosumab and zoledronate. Number of patients was 84, diagnosed with osteoporosis or osteopenia, 34 of them received 10 or more denosumab injections and 50 patients planned to receive 5 zoledronate infusions (9 patients received 5 and 38 patients received 4). Results Forty percent of the patients were at their 8th decade followed by 28.57% and 21.42 % at their 9th and 7th decades respectively. More than 90% were Caucasian females. Primary prevention was in 39.28% and secondary prevention in 60.71%. The commonest sites of fracture were the wrist and vertebrae at 34.37% for each; followed by the neck of femur and humerous at 12.5% for each. Denosumab was the 1st, 2nd, 3rd or 4th line of treatment in 9.52%, 13.09%, 16.66% and 1.19% respectively; whereas zoledronate was the 1st, 2nd or 3rd line of treatment in 13.09%, 40.47% and 5.95% respectively. The commonest reason for choosing denosumab as the first line was chronic kidney disease, whereas the reason for choosing it as the 2nd or 3rd line was inefficacy of bisphosphonate in 69% or gastrointestinal side effects in 14%. Zoledronate was chosen in all cases because of intolerability to oral bisphosphonate or gastrointestinal side effects. Repeat DXA scan was performed after the 5th, 10th denosumab injections and the 3rd zoledronate infusions. After the 5th Denosumab, DXA scan showed improvement or stability in 100% and 85.29% at the spine and hip respectively whilst deterioration was seen in 14.7% at the hip. After the 10th denosumab, the rate of improvement or stability at the spine was reduced to 88.23% and decline was seen in 2.94%. At the hip area, 73.52% continued to show improvement or stability, whilst 17.66 % showed deterioration. After the 3rd zoledronate, 98% and 88% showed improvement or stability at the spine and hip respectively whilst deterioration seen in 2% and 12% at the spine and hip respectively. One patient on zoledronate experienced dental issues after the 4th injection and stopped treatment. There were no jaw osteonecrosis, no new fractures and no significant side effects with either denosumab or zoledronate. Ninety percent of patients who completed 10 denosumab injections were planned to continue for another 5 injections. Conclusion After the period of 3-5 years, denosumab and zoledronate were well tolerated and BMD was either stable or improved at both spinal and hip sites. There were few cases of deterioration mainly at the hip area with both zoledronate and denosumab. Future researches are needed to stratify guidelines on discontinuation of denosumab. Disclosures Z. Alkutobi None. D. Laila None. M. Tariq None. A. Nandagudi None.


Author(s):  
Hsiao ◽  
Chen ◽  
Meir ◽  
Tan ◽  
Hsiao ◽  
...  

To determine the comparative efficacy and safety of penetrating keratoplasty (PK) and Descemet stripping automated endothelial keratoplasty (DSAEK) in the Asian population receiving imported donor corneas, our single-center retrospective study provides analysis supporting the transition from PK to DSAEK in the Asian population using imported American donor corneas. We analyzed 259 patients with 241 and 57 cases of PK and DSAEK respectively during 2008 to 2017 using imported corneas at Chang Gung Memorial Hospital, Linkou, Taiwan. In terms of long-term graft survival analysis, there was no difference between PK and DSAEK (log-rank p = 0.386, HR = 0.920, 95% CI: [0.641–1.380]). However, Cox proportional regression analysis revealed that corneal survival rate of DSAEK group in the first 100 days after transplantation was inferior than that of PK group (log-rank p < 0.001, HR = 2.733, 95% CI: [1.501–4.977])]. Despite the inferior survival rate, there were significantly less neovascularization and Descemet membrane folds in the DSAEK group. Importantly, the non-complication rate of DSAEK was much higher than that of PK with significant difference (PK, 25.7% vs DSAEK 42.0%, p = 0.022). Collectively, DSAEK is suggested as an alternative surgical modality in Asian patients using imported American donor corneas because of less complication, and no difference in long-term corneal graft survival rates between PK and DSAEK.


Materials ◽  
2020 ◽  
Vol 13 (8) ◽  
pp. 1883 ◽  
Author(s):  
Marco Tallarico ◽  
Roberto Scrascia ◽  
Marco Annucci ◽  
Silvio Mario Meloni ◽  
Aurea Immacolata Lumbau ◽  
...  

The achievement of the optimal implant position is a critical consideration in implant surgery, as it can facilitate the ideal prosthesis design and allow adequate oral hygiene maintenance. The switch from bone-driven to prosthetic-driven implant placement, through a comprehensive diagnosis and adequate treatment plan, is a prerequisite for long-term successful implant-based therapy. The aim of the present case report is to describe a step-by-step prosthetic retreatment of a patient with primary treatment failure due to incorrect dental implant placement. Although dental implants achieve high survival rates, the success of implant prosthetic therapy significantly relies on an appropriate implant position. Malpositioned implants can cause damage to vital structures, like nerves or vessels. Moreover, improper implant positioning can result in esthetic, biological, and technical complications and can, in extreme situations, render the desired prosthetic rehabilitation impossible to achieve.


2019 ◽  
Vol 48 (4) ◽  
pp. 030006051989238
Author(s):  
Su Pei ◽  
Kaihua Chen ◽  
Yunli Yang ◽  
Long Chen ◽  
Xiaodong Zhu

Objective To evaluate the efficacy and toxicity of intensity-modulated radiotherapy (IMRT) for the treatment of unresectable liver metastases. Methods Twenty-five patients with unresectable liver metastases treated with IMRT were enrolled from January 2003 to September 2016. The median longest diameter of the lesions was 3.3 cm (range, 1.6–16.7 cm). The fraction dose ranged from 2 to 5.2 Gy, with a median total dose of 50 Gy (range, 30–60 Gy). Results The median follow-up was 9.2 months (range, 2.1–48.8 months). The overall survival rates at 1 and 2 years were 46.4% and 27.4%, respectively. The 1-year local control rate was 69.8%. The 1-year progression-free survival rate was 26.3%. One patient had grade 4 liver dysfunction. One case of grade 4 leukopenia and one case of grade 3 leukopenia occurred, and one case of grade 3 leukopenia and thrombocytopenia was observed. Conclusion IMRT may be a promising and safe treatment for unresectable liver metastases and can be used as a treatment option.


Blood ◽  
2001 ◽  
Vol 97 (4) ◽  
pp. 863-866 ◽  
Author(s):  
Elizabeth C. Storen ◽  
Ayalew Tefferi

Abstract Anagrelide is a novel platelet-lowering agent that has recently been approved for use in essential thrombocythemia (ET) and related disorders. Short-term drug efficacy and toxicity data have previously been presented. The purpose of this study was to obtain additional information regarding long-term anagrelide use. This is a retrospective series of 35 young patients (17 to 48 years) with ET who received anagrelide treatment before 1992. Initial drug dosage ranged between 1 and 10 mg/d, and the median maintenance dosage was 2.5 mg/d. The overall initial response rate of 94% included 74% complete remissions and 20% partial remissions. Of the 33 responding patients, 27 (82%) remained on anagrelide therapy for a median of 10.8 years (range, 7 to 15.5). Of these, 66% maintained a complete and 34% a partial remission over the study period. In general, the reporting of somatic side effects decreased over time, and anemia was the only new side effect that emerged after long-term therapy. Eight patients (24%) experienced a more than 3 g/dL decrease in hemoglobin level. Despite active therapy, 20% of the patients experienced a total of 10 thrombotic episodes, and a similar proportion experienced major hemorrhagic events. All thrombohemorrhagic complications occurred at a platelet count of more than 400 × 109/L. It is concluded that long-term treatment of ET with anagrelide is associated with decreased reporting of initial side effects and the development of mild-to-moderate anemia. Complete normalization of platelet counts may be needed to minimize residual thrombohemorrhagic risk during therapy.


2020 ◽  
Vol 15 (1) ◽  
Author(s):  
L. Pisecky ◽  
J. Allerstorfer ◽  
B. Schauer ◽  
G. Hipmair ◽  
R. Hochgatterer ◽  
...  

Abstract Purpose The aim of this retrospective observational study of one cohort was to evaluate the long-term outcome in patients younger than 60 years after total hip arthroplasty using a straight uncemented stem and an uncemented threaded cup. Methods Between 1986 and 1987, 75 hips of 75 patients (mean age, 53.35 ± 6.17 years) were consecutively implanted with an Alloclassic Zweymüller/Alloclassic SL stem and an Alloclassic CSF cup. Forty-four patients had died over the last 30 years. The remaining 31 patients (mean age, 82.9 ± 6.4 years) were reinvited for follow-up examinations. Clinical and radiographic evaluations were carried out. Results At a mean follow-up of 29.5 (28.8–30.2), 4 patients (5.3%) were lost to follow-up. For the endpoint aseptic loosening (defined as the removal of stem or the cup for 2 cases), the overall survival rate is 97.3%. For the endpoint revision for any reason (22 patients), the survival rate is 70.6%. Eleven patients needed an exchange of head and liner, caused by wear. The average time from implantation until change of head and liner was 21.44 years (SD 5.92). Other reasons for revision surgery were septic loosening (3 cases), aseptic loosening of stem and cup (1 case), aseptic loosening of stem (1 case), periprosthetic calcification (2 cases), implant fracture (1 case), periprosthetic fracture (1 case), intraoperative fissure of stem (1 case), and total wear of liner including cup (1 case). Conclusion The combination of a straight stem (Alloclassic) and a screw cup (CSF) shows excellent results in young patients under the age of 60 at ultra-long-term follow-up at 30 years. Revisions due to wear of the polyethylene liner are more likely than in the older patients.


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