scholarly journals Involved Site Radiotherapy Extends Time to Premature Menopause in Infra-Diaphragmatic Female Hodgkin Lymphoma Patients – An Analysis of GHSG HD14- and HD17-Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Johannes Rosenbrock ◽  
Andrés Vásquez-Torres ◽  
Horst Mueller ◽  
Karolin Behringer ◽  
Matthias Zerth ◽  
...  
Keyword(s):  
Ovarian Function ◽  
Standard Of Care ◽  
Intermediate Stage ◽  
Target Volume ◽  
Multiple Regression Model ◽  
Premature Menopause ◽  
Time Interval ◽  
Gonadal Function ◽  
Consolidation Radiotherapy ◽  
Involved Field

IntroductionConsolidation radiotherapy in intermediate stage Hodgkin´s lymphoma (HL) has been the standard of care for many years as involved field radiotherapy (IFRT) after chemotherapy. It included initially involved region(s). Based on randomized studies, radiation volumes could be reduced and involved site radiation therapy (ISRT) became the new standard. ISRT includes the initially affected lymph nodes. In young adults suffering from HL, infertility and hypogonadism are major concerns. With regard to these questions, we analyzed the influence of modern radiotherapy concepts such as consolidating ISRT in infradiaphragmatic involvement of HL after polychemotherapy.Patients and MethodsFive hundred twelve patients treated within German Hodgkin Study Group (GHSG) HD14 and HD17 trials were evaluated. We analyzed log-adjusted follicle-stimulating-hormone (FSH)- and luteinizing-hormone (LH)-levels of HD14-patients with infradiaphragmatic radiotherapy (IDRT) in comparison with HD14-patients, who had a supradiaphragmatic radiotherapy (SDRT). In a second step, we compared IFRT with ISRT of female HD17 patients regarding the effects on ovarian function and premature menopause.ResultsWe analyzed FSH- and LH-levels of 258 female and 241 male patients, all treated with IFRT. Of these 499 patients, 478 patients had SDRT and 21 patients had IDRT. In a multiple regression model, we could show that log-adjusted FSH (p=0.0006) and LH values (p=0.0127) were significantly higher after IDRT than after SDRT. The effect of IDRT on gonadal function was comparable to two cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPPesc). We compared the effect of IFRT with ISRT in thirteen female HD17 patients with infradiaphragmatic (ID) involvement. The mean ovarian dose after ISRT was significantly lower than after IFRT. The calculated proportion of surviving non-growing follicles (NGFs) increased significantly from 11.87% to 24.48% in ISRT compared to IFRT, resulting in a significantly longer calculated time to menopause. The younger the age at therapy, the greater the absolute time gain until menopause.ConclusionInfradiaphragmatic IFRT impairs gonadal function to a similar extent as two cycles of BEACOPPesc. In comparison, the use of ISRT target volume definition significantly reduced radiation dose to the ovaries and significantly extends the time interval from treatment to premature menopause.

scholarly journals Head-to-head intra-individual comparison of biodistribution and tumor uptake of 68Ga-FAPI and 18F-FDG PET/CT in cancer patients

2021 ◽  
Author(s):  
Frederik L. Giesel ◽  
Clemens Kratochwil ◽  
Joel Schlittenhardt ◽  
Katharina Dendl ◽  
Matthias Eiber ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Standard Of Care ◽  
Blood Pool ◽  
Tracer Uptake ◽  
Time Interval ◽  
Tumor Uptake ◽  
Primary Tumors ◽  
Individual Comparison ◽  
Pet Ct ◽  
Fdg Pet Ct

Abstract Purpose FAPI ligands (fibroblast activation protein inhibitor), a novel class of radiotracers for PET/CT imaging, demonstrated in previous studies rapid and high tumor uptake. The purpose of this study is the head-to-head intra-individual comparison of 68Ga-FAPI versus standard-of-care 18F-FDG in PET/CT in organ biodistribution and tumor uptake in patients with various cancers. Material and Methods This international retrospective multicenter analysis included PET/CT data from 71 patients from 6 centers who underwent both 68Ga-FAPI and 18F-FDG PET/CT within a median time interval of 10 days (range 1–89 days). Volumes of interest (VOIs) were manually drawn in normal organs and tumor lesions to quantify tracer uptake by SUVmax and SUVmean. Furthermore, tumor-to-background ratios (TBR) were generated (SUVmax tumor/ SUVmax organ). Results A total of 71 patients were studied of, which 28 were female and 43 male (median age 60). In 41 of 71 patients, the primary tumor was present. Forty-three of 71 patients exhibited 162 metastatic lesions. 68Ga-FAPI uptake in primary tumors and metastases was comparable to 18F-FDG in most cases. The SUVmax was significantly lower for 68Ga-FAPI than 18F-FDG in background tissues such as the brain, oral mucosa, myocardium, blood pool, liver, pancreas, and colon. Thus, 68Ga-FAPI TBRs were significantly higher than 18F-FDG TBRs in some sites, including liver and bone metastases. Conclusion Quantitative tumor uptake is comparable between 68Ga-FAPI and 18F-FDG, but lower background uptake in most normal organs results in equal or higher TBRs for 68Ga-FAPI. Thus, 68Ga-FAPI PET/CT may yield improved diagnostic information in various cancers and especially in tumor locations with high physiological 18F-FDG uptake.

LONG‐TIME RESPONSE PREDICTED BY EXACT ELASTIC RAY THEORY

Geophysics ◽  
1965 ◽  
Vol 30 (3) ◽  
pp. 363-368 ◽  
Author(s):  
T. W. Spencer
Keyword(s):  
Formal Solution ◽  
Intermediate Stage ◽  
Time Limit ◽  
Time Interval ◽  
Individual Response ◽  
Axially Symmetric ◽  
Long Time ◽  
The Difference ◽  
The Individual ◽  
Significant Figures

The formal solution for an axially symmetric radiation field in a multilayered, elastic system can be expanded in an infinite series. Each term in the series is associated with a particular raypath. It is shown that in the long‐time limit the individual response functions produced by a step input in particle velocity are given by polynomials in odd powers of the time. For rays which suffer m reflections, the degree of the polynomials is 2m+1. The total response is obtained by summing all rays which contribute in a specified time interval. When the rays are selected indiscriminately, the difference between the magnitude of the partial sum at an intermediate stage of computation and the magnitude of the correct total sum may be greater than the number of significant figures carried by the computer. A prescription is stated for arranging the rays into groups. Each group response function varies linearly in the long‐time limit and goes to zero when convolved with a physically realizable source function.

scholarly journals Dosimetric comparison between 3D conformal and intensity-modulated radiation therapy for prostate cancer

2010 ◽  
Vol 9 (2) ◽  
pp. 77-85 ◽  
Author(s):  
Courtney Buckey ◽  
Gregory Swanson ◽  
Sotirios Stathakis ◽  
Nikos Papanikolaou
Keyword(s):  
Radiation Therapy ◽  
Organs At Risk ◽  
External Beam Radiotherapy ◽  
Radiation Therapy Oncology Group ◽  
Intensity Modulated Radiation Therapy ◽  
Standard Of Care ◽  
Target Volume ◽  
Conformal Radiation Therapy ◽  
Intensity Modulated ◽  
3D Crt

AbstractBackground and Purpose: Intensity-modulated radiation therapy (IMRT) is considered by many to be the standard of care in the delivery of external-beam radiotherapy treatments to the prostate. The purpose of this study is to assess the validity of the purported benefits of IMRT.Materials and Methods: Treatment plans were produced for 10 patients using both 3D conformal radiation therapy (3D-CRT) and IMRT, utilising the dose constraints recommended by the Radiation Therapy Oncology Group (RTOG) 0415 protocol. Three IMRT modalities used in this study were linear accelerator based IMRT, helical tomotherapy, and serial tomotherapy. The prescription to the target, 76 Gy, was the same for all plans.Results: In general the 3D-CRT plans satisfied the RTOG criteria for planning target volume (PTV) coverage, and met or bettered the dose criteria for the organs at risk. PTV coverage was more homogeneous for the IMRT plans than the 3D-CRT plans but not significantly improved.Conclusions: Technically, because the IMRT plans required greater effort for the optimisation, longer treatment times and higher monitor units, the use of IMRT for the fulfilment of the protocol’s dosimetric goals was not justified using these constraints.

scholarly journals VEROnA Protocol: A Pilot, Open-Label, Single-Arm, Phase 0, Window-of-Opportunity Study of Vandetanib-Eluting Radiopaque Embolic Beads (BTG-002814) in Patients With Resectable Liver Malignancies (Preprint)

2019 ◽  
Author(s):  
Laura Beaton ◽  
Henry F J Tregidgo ◽  
Sami A Znati ◽  
Sharon Forsyth ◽  
Matthew J Clarkson ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Standard Of Care ◽  
Intermediate Stage ◽  
Window Of Opportunity ◽  
Current Standard ◽  
Open Label ◽  
Liver Malignancies ◽  
Surgical Specimen ◽  
Resected Liver ◽  
Phase 0

BACKGROUND Transarterial chemoembolization (TACE) is the current standard of care for patients with intermediate-stage hepatocellular carcinoma (HCC) and is also a treatment option for patients with liver metastases from colorectal cancer. However, TACE is not a curative treatment, and tumor progression occurs in more than half of the patients treated. Despite advances and technical refinements of TACE, including the introduction of drug-eluting beads-TACE, the clinical efficacy of TACE has not been optimized, and improved arterial therapies are required. OBJECTIVE The primary objectives of the VEROnA study are to evaluate the safety and tolerability of vandetanib-eluting radiopaque embolic beads (BTG-002814) in patients with resectable liver malignancies and to determine concentrations of vandetanib and the N-desmethyl metabolite in plasma and resected liver following treatment with BTG-002814. METHODS The VEROnA study is a first-in-human, open-label, single-arm, phase 0, window-of-opportunity study of BTG-002814 (containing 100 mg vandetanib) delivered transarterially, 7 to 21 days before surgery in patients with resectable liver malignancies. Eligible patients have a diagnosis of colorectal liver metastases, or HCC (Childs Pugh A), diagnosed histologically or radiologically, and are candidates for liver surgery. All patients are followed up for 28 days following surgery. Secondary objectives of this study are to evaluate the anatomical distribution of BTG-002814 on noncontrast-enhanced imaging, to evaluate histopathological features in the surgical specimen, and to assess changes in blood flow on dynamic contrast-enhanced magnetic resonance imaging following treatment with BTG-002814. Exploratory objectives of this study are to study blood biomarkers with the potential to identify patients likely to respond to treatment and to correlate the distribution of BTG-002814 on imaging with pathology by 3-dimensional modeling. RESULTS Enrollment for the study was completed in February 2019. Results of a planned interim analysis were reviewed by a safety committee after the first 3 patients completed follow-up. The recommendation of the committee was to continue the study without any changes to the dose or trial design, as there were no significant unexpected toxicities related to BTG-002814. CONCLUSIONS The VEROnA study is studying the feasibility of administering BTG-002814 to optimize the use of this novel technology as liver-directed therapy for patients with primary and secondary liver cancer. CLINICALTRIAL ClinicalTrial.gov NCT03291379; https://clinicaltrials.gov/ct2/show/NCT03291379 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/13696

scholarly journals Repeated Mechanical Endovascular Thrombectomy for Recurrent Large Vessel Occlusion

Stroke ◽  
2021 ◽  
Author(s):  
Ghada A. Mohamed ◽  
Hassan Aboul Nour ◽  
Raul G. Nogueira ◽  
Mahmoud H. Mohammaden ◽  
Diogo C. Haussen ◽  
...  
Keyword(s):  
Scale Score ◽  
Standard Of Care ◽  
The United States ◽  
Outcome Data ◽  
Large Vessel ◽  
Time Interval ◽  
Modified Rankin Scale ◽  
Large Vessel Occlusion ◽  
Vessel Occlusion ◽  
Previously Treated

Background and Purpose: Mechanical thrombectomy (MT) is now the standard of care for large vessel occlusion (LVO) stroke. However, little is known about the frequency and outcomes of repeat MT (rMT) for patients with recurrent LVO. Methods: This is a retrospective multicenter cohort of patients who underwent rMT at 6 tertiary institutions in the United States between March 2016 and March 2020. Procedural, imaging, and outcome data were evaluated. Outcome at discharge was evaluated using the modified Rankin Scale. Results: Of 3059 patients treated with MT during the study period, 56 (1.8%) underwent at least 1 rMT. Fifty-four (96%) patients were analyzed; median age was 64 years. The median time interval between index MT and rMT was 2 days; 35 of 54 patients (65%) experienced recurrent LVO during the index hospitalization. The mechanism of stroke was cardioembolism in 30 patients (56%), intracranial atherosclerosis in 4 patients (7%), extracranial atherosclerosis in 2 patients (4%), and other causes in 18 patients (33%). A final TICI recanalization score of 2b or 3 was achieved in all 54 patients during index MT (100%) and in 51 of 54 patients (94%) during rMT. Thirty-two of 54 patients (59%) experienced recurrent LVO of a previously treated artery, mostly the pretreated left MCA (23 patients, 73%). Fifty of the 54 patients (93%) had a documented discharge modified Rankin Scale after rMT: 15 (30%) had minimal or no disability (modified Rankin Scale score ≤2), 25 (50%) had moderate to severe disability (modified Rankin Scale score 3–5), and 10 (20%) died. Conclusions: Almost 2% of patients treated with MT experience recurrent LVO, usually of a previously treated artery during the same hospitalization. Repeat MT seems to be safe and effective for attaining vessel recanalization, and good outcome can be expected in 30% of patients.

scholarly journals Management of patients with intermediate stage hepatocellular carcinoma

2020 ◽  
Vol 12 ◽  
pp. 175883592097084
Author(s):  
David Prince ◽  
Ken Liu ◽  
Weiqi Xu ◽  
Minjiang Chen ◽  
Jin-Yu Sun ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Standard Of Care ◽  
Intermediate Stage ◽  
Tumor Burden ◽  
Current Standard ◽  
Current Management ◽  
Heterogenous Group ◽  
Patient Subgroups ◽  
Significant Health ◽  
Systemic Therapies

Hepatocellular carcinoma (HCC) causes a significant health burden globally and its impact is expected to increase in the coming years. Intermediate stage HCC, as defined by the Barcelona Clinic Liver Cancer (BCLC) system stage B, represents up to 30% of patients at diagnosis and encompasses a broad spectrum of tumor burden. Several attempts have been made to further subclassify this heterogenous group. The current standard of care recommended by BCLC for intermediate stage HCC patients is transarterial chemoembolization (TACE), with modest outcomes reported. While refinements have been made to TACE technique and patient selection, it remains non-curative. In the real-world setting, only 60% of patients with intermediate stage HCC receive TACE, with the remainder deviating to a range of other therapies that have shown promise in select patient subgroups. These include curative treatments (resection, ablation, and liver transplantation), radiotherapy (stereotactic and radioembolization), systemic therapies, and their combination. In this review, we summarize the classifications and current management for patients with intermediate stage HCC as well as highlight recent key developments in this space.

scholarly journals The Role of Radiotherapy in Hodgkin’s Lymphoma: What Has Been Achieved during the Last 50 Years?

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Magdalena Witkowska ◽  
Agata Majchrzak ◽  
Piotr Smolewski
Keyword(s):  
Radiation Therapy ◽  
Safety Profile ◽  
Hodgkin’S Lymphoma ◽  
Antitumor Agents ◽  
Standard Of Care ◽  
Hodgkin's Lymphoma ◽  
Field Size ◽  
Field Radiation ◽  
Involved Field

Currently, Hodgkin’s lymphoma (HL) has an excellent clinical outcome, with overall survival of approximately 90% in early stages of the disease. Based on young age of the majority of patients at the time of diagnosis and their long survival time, increased attention has been focused on long-term toxicity of therapy. While novel, directly targeting antitumor agents, with an excellent safety profile, have been developed for HL treatment, the role of radiotherapy is still debated. Radiotherapy may induce cardiovascular disease and impairment of thyroid or pulmonary function and, most importantly, may lead to development of secondary cancers. As a consequence, the current radiation therapy planning paradigm is mainly focused on a reduction of field size. As it was investigated in clinical trials regional therapy is as effective as extended field radiotherapy, but less toxic. Although chemotherapy is the mainstay of HL treatment, consolidative involved field radiation therapy is still considered to be the standard of care in both early and advanced stages. Recently, further field reduction has been investigated to further decrease the late radiation-induced toxicity. In this paper we describe the role and safety profile of radiotherapy in the past and present and hope for the novel techniques in the future.

Limited-Stage Disease: Optimal Use of Chemotherapy and Radiation Treatment

Hematology ◽  
2008 ◽  
Vol 2008 (1) ◽  
pp. 321-325 ◽  
Author(s):  
John Radford
Keyword(s):  
Hodgkin Lymphoma ◽  
Radiation Treatment ◽  
Late Toxicity ◽  
Standard Of Care ◽  
Early Years ◽  
Wide Field ◽  
Current Standard ◽  
Limited Stage ◽  
Stage Disease ◽  
Involved Field

AbstractIn the early years of treatment for limited-stage Hodgkin lymphoma there was an understandable focus on disease elimination. This has been replaced by concerns about the amount and balance of different therapies and eventually, as cure rates improve, a desire to individualize management based on risk factors at presentation and response to initial treatment. In limited stage Hodgkin lymphoma, early success was obtained with wide field radiotherapy but later combined modality approaches were employed to overcome the problem of out of field radiotherapy relapses. The acute and delayed toxicity of alkylating agent based therapies led to their replacement with ABVD and concerns about the late toxicity of radiotherapy resulted in smaller field sizes being first assessed in clinical trial and later introduced into clinical practice. The current standard of care of 3 or 4 cycles of ABVD followed by involved-field radiotherapy in clinically staged patients is the culmination of years of work involving many thousands of patients taking part in clinical trials.Our current focus is on the role of PET imaging and whether a response-adapted approach guided by PET can individualize therapy such that radiotherapy and its attendant late toxicity that impacts on future quality of life and survival can be avoided altogether in a subset of patients.

Temporary Ovarian Suppression in the Prevention of Chemotherapy-induced Premature Menopause in Early-stage Breast Cancer Patients

2013 ◽  
Vol 09 (01) ◽  
pp. 13
Author(s):  
Martina Nunzi ◽  
Silvia Sabatini ◽  
◽  
Keyword(s):  
Breast Cancer ◽  
Ovarian Function ◽  
Early Stage ◽  
Phase Iii ◽  
Premature Menopause ◽  
Gnrh Analogue ◽  
Breast Cancer Patients ◽  
Ovarian Suppression ◽  
Phase Ii Studies ◽  
Randomised Controlled

Infertility and premature menopause are possible side effects of chemotherapy in young women with breast cancer and can affect their compliance to treatment. There is a lot of interest in maintaining ovarian function after chemotherapy in order to ensure fertility and delay the symptoms of early menopause. The use of a gonadotropin-releasing hormone (GnRH) analogue, administered in combination with chemotherapy to protect ovarian reserve against cytotoxic damage, is one of the approaches that has been evaluated, although the rationale for its use is based mainly on hypothesis. Several phase II studies have suggested a decreased incidence of amenorrhoea with the use of GnRH analogue concomitant with chemotherapy. However, the subsequent phase III studies have produced conflicting results. In particular, the temporary ovarian suppression in combination with modern (neo)adjuvant chemotherapy for preventing premature menopause showed no benefit in three studies and an advantage in two studies. This use of a GnRH analogue is appealing but further randomised controlled trials are needed to evaluate its efficacy.

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