[Show abstract][Hide abstract] ABSTRACT: The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at Euro 23 billion per year, a level of cost that is not matched in current European hematology research funding. In recent decades, hematology research has improved our fundamental understanding of the biology of blood disorders, and has improved diagnostics and treatments, sometimes in revolutionary ways. This progress highlights the potential of focused basic research programs such as this EHA Roadmap. The EHA Roadmap identifies nine sections in hematology: normal hematopoiesis, malignant lymphoid and myeloid diseases, anemias and related diseases, platelet disorders, blood coagulation and hemostatic disorders, transfusion medicine, infections in hematology, and hematopoietic stem cell transplantation. These sections span 60 smaller groups of diseases or disorders. The EHA Roadmap identifies priorities and needs across the field of hematology, including those to develop targeted therapies based on genomic profiling and chemical biology, to eradicate minimal residual malignant disease, and to develop cellular immunotherapies, combination treatments, gene therapies, hematopoietic stem cell treatments, and treatments that are better tolerated by elderly patients.
[Show abstract][Hide abstract] ABSTRACT: Chemoradiotherapy is the standard-of-care treatment of squamous-cell carcinoma of the anus (SCCA), and this has not changed in decades. Radiation doses of 50-60 Gy, as used in many phase III trials, result in substantial late morbidities and fail to control larger and node-positive tumours. Technological advances in radiation therapy are improving patient outcomes and quality of life, and should be applied to patients with SCCA. Modern techniques such as intensity-modulated radiotherapy (IMRT), rotational IMRT, image-guided radiotherapy using cone-beam CT, and stereotactic techniques have enabled smaller margins and highly conformal plans, resulting in decreased radiation doses to the organs at risk and ensuring a shorter overall treatment time. In this Perspectives article, the use of novel approaches to target delineation, optimized radiotherapy techniques, adaptive radiotherapy, dose-escalation with external-beam radiotherapy (EBRT) or brachytherapy, and the potential for modified fractionation are discussed in the context of SCCA.
No preview · Article · Jan 2016 · Nature Reviews Clinical Oncology
[Show abstract][Hide abstract] ABSTRACT: High dose rate brachytherapy is a highly conformal method of radiation dose escalation for prostate cancer and one of several treatment options for men with localised disease. The large doses per fraction exploit the low alpha/beta ratio of prostate cancer cells so that biological radiation dose delivered is substantially greater than that achieved with conventional external beam delivery. This review article presents contemporary data on the rationale for high dose rate brachytherapy including treatment technique and future directions.
No preview · Article · Jan 2016 · Cancer/Radiothérapie
[Show abstract][Hide abstract] ABSTRACT: Background and purpose:
Patients treated with low radiotherapy dose or treated at young age are at a risk of developing local relapse. Although data are preliminary, brachytherapy seems an attractive treatment option for recurrent prostate cancer after previous radiotherapy. Therefore, the UroGEC group of the GEC-ESTRO conducted a Delphi study, to explore expert opinion on the management of salvage prostate brachytherapy.
Material and methods:
For this study, a series of digital questionnaires were sent, which enabled data collection from an international group of experienced participants. Consensus was defined as 80% agreement for each question.
Eighteen experts completed all rounds of the Delphi study. After the final round consensus was reached on 17 out of 38 (45%) questions. Consensus was reached in 52% of questions about patient selection, in 50% of the questions about diagnostic tests and in 22% of the questions on performing salvage prostate brachytherapy.
The group was able to find consensus on less than half of the questions. Most consensus was reached on topics involving patient selection and diagnostic tests, where participants could build on their experience of daily practice. However, the way to perform the salvage treatment is less established and results in more disagreement between participants.
No preview · Article · Nov 2015 · Radiotherapy and Oncology
[Show abstract][Hide abstract] ABSTRACT: Extra-nodal sites may be involved in around 40% of patients with non-Hodgkin lymphoma. The general principles for target volume delineation in this setting are presented, together with specific examples. In general, the entire organ affected should be encompassed in the clinical target volume with an expansion of at least 10 mm, increased in some instances to account for patterns of potential lymphatic flow. Adjacent lymph nodes may be treated using standard techniques for nodal irradiation. Doses for extra-nodal lymphoma follow the same principles as nodal lymphoma, delivering 30 Gy in 15 fractions for Hodgkin and aggressive non-Hodgkin lymphoma and 24 Gy in 12 fractions for indolent lymphomas, with the exception of certain palliative situations, mycosis fungoides, central nervous system lymphoma and natural killer/T-cell lymphoma.
Full-text · Article · Oct 2015 · Clinical Oncology
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To establish a survival prediction model in the setting of a randomized trial of re-irradiation for painful bone metastases.
Data were randomly divided into training and testing sets with an approximately 3:2 ratio. Baseline factors of gender, primary cancer site, KPS, worst-pain score and age were included with backward variable selection to derive a model using the training set. A partial score was assigned by dividing the value of each statistically significant regression coefficient by the smallest statistically significant regression coefficient. The survival prediction score (SPS) was obtained by adding together partial scores for the variables that were statistically significant. Three risk groups were modelled.
The training set included 460 patients and the testing set 351 patients. Only KPS and primary cancer site reached the 5%-significance level. Summing up the partial scores assigned to KPS (90-100, 0; 70-80, 1; 50-60, 2) and primary cancer site (breast, 0; prostate, 1.3; other, 2.6; lung, 3) totalled the SPS. The 1/3 and 2/3 percentiles of the SPS were 2 and 3.6. For the testing set, the median survival of the 3 groups was not reached, 11.3 (95% C.I. 8.5 - not reached) and 5.2months (95% C.I. 3.7-6.5). The 3, 6 and 12month survival rates for the worst group were 64.4% (95% C.I. 55.3-72.1%), 43.0% (95% C.I. 34.0-51.8%) and 19.7% (95% C.I. 12.4-28.1%) respectively, similar to that in the training set.
This survival prediction model will assist in choosing dose fractionation. We recommend a single 8Gy in the worst group identified.
No preview · Article · Oct 2015 · Radiotherapy and Oncology
[Show abstract][Hide abstract] ABSTRACT: Purpose:
The objective of our study was to determine the optimal cut points for classification of pain scores as mild, moderate, and severe based on interference with function and quality of life (QOL).
We evaluated 822 patients who completed the Brief Pain Inventory (BPI) and/or the European Organization for Research and Treatment of Cancer (EORTC) QOL Questionnaire Core 30 (QLQ-C30) prior to receiving repeat radiation therapy for previously irradiated painful bone metastases. Optimal cut points for mild, moderate, and severe pain were determined by the MANOVA that yielded the largest F ratio for the between category effect on the seven interference items of BPI and the six functional domains of QOL (physical, role, emotional, cognitive, social functioning, and global QOL) as indicated by Pillai's Trace, Wilk's λ, and Hostelling's Trace F statistics.
For BPI and for QOL domains separately, the two largest F ratios for Wilk's λ, Pillai's Trace, and Hotelling's Trace F statistics were from the cut points 4, 8 and 6, 8. When combining both, the optimal cut points were 4, 8 with 1-4 (mild), 5-8 (moderate), and 9-10 (severe). With this classification, the mean scores of all the seven interference items in BPI and the six functional domains were all highly statistically different. Patients with severe pain survived significantly shorter than those with mild and moderate pain (p < 0.0001).
Our analysis supports the classification of pain scores as follows: 1-4 as mild pain, 5-8 as moderate pain, and 9-10 as severe pain. This may facilitate conduct of future clinical trials.
No preview · Article · Sep 2015 · Supportive Care in Cancer
[Show abstract][Hide abstract] ABSTRACT: It is unclear whether patients with early-stage Hodgkin's lymphoma and negative findings on positron-emission tomography (PET) after three cycles of chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) require radiotherapy.
Patients with newly diagnosed stage IA or stage IIA Hodgkin's lymphoma received three cycles of ABVD and then underwent PET scanning. Patients with negative PET findings were randomly assigned to receive involved-field radiotherapy or no further treatment; patients with positive PET findings received a fourth cycle of ABVD and radiotherapy. This trial assessing the noninferiority of no further treatment was designed to exclude a difference in the 3-year progression-free survival rate of 7 or more percentage points from the assumed 95% progression-free survival rate in the radiotherapy group.
A total of 602 patients (53.3% male; median age, 34 years) were recruited, and 571 patients underwent PET scanning. The PET findings were negative in 426 of these patients (74.6%), 420 of whom were randomly assigned to a study group (209 to the radiotherapy group and 211 to no further therapy). At a median of 60 months of follow-up, there had been 8 instances of disease progression in the radiotherapy group, and 8 patients had died (3 with disease progression, 1 of whom died from Hodgkin's lymphoma); there had been 20 instances of disease progression in the group with no further therapy, and 4 patients had died (2 with disease progression and none from Hodgkin's lymphoma). In the radiotherapy group, 5 of the deaths occurred in patients who received no radiotherapy. The 3-year progression-free survival rate was 94.6% (95% confidence interval [CI], 91.5 to 97.7) in the radiotherapy group and 90.8% (95% CI, 86.9 to 94.8) in the group that received no further therapy, with an absolute risk difference of -3.8 percentage points (95% CI, -8.8 to 1.3).
The results of this study did not show the noninferiority of the strategy of no further treatment after chemotherapy with regard to progression-free survival. Nevertheless, patients in this study with early-stage Hodgkin's lymphoma and negative PET findings after three cycles of ABVD had a very good prognosis either with or without consolidation radiotherapy. (Funded by Leukaemia and Lymphoma Research and others; RAPID ClinicalTrials.gov number, NCT00943423.).
No preview · Article · Apr 2015 · New England Journal of Medicine
[Show abstract][Hide abstract] ABSTRACT: Objectives: A review of SBRT for oligometastases defined as three or fewer sites of isolated metastatic disease. The aim was to identify local control, overall survival (OS) and progression free survival (PFS) of patients receiving SBRT for OM disease. Methods: Data was analysed for SBRT delivered between 1/9/10-31/3/14. End points included local control, progression free survival, overall survival and toxicity. Results: 76 patients received SBRT. Median age was 60 (31-89) years. 44 were male. Median follow-up was 12.3(0.2-36.9) months. Major primary tumour sites included colorectal (38%), breast (18%) and prostate (12%). Treatment sites included lymph nodes (42%), bone and spine (29%) and soft tissue (29%). 42% were previously treated with conventional radiotherapy. 45% were disease free after SBRT. 4% had local relapse, 45% had distant relapse, 6% had local and distant relapse. Local control was 89%. OS was 84.4% at 1 year and 63.2% at 2 years. PFS was 49.1% at 1 year and 26.2% at 2 years. Toxicities included duodenal ulcer and biliary stricture formation. Conclusion: SBRT can achieve durable control of OM lesions and results in minimal radiation-induced morbidity. Advances in knowledge: This cohort is one of the largest reported to date and contributes to the field of SBRT in oligometastases which is emerging as an important research area. It is the only study reported from the UK and uses a uniform technique throughout. The efficacy and low toxicity with durable control of local disease with this approach is shown setting the foundations for future randomised studies.
No preview · Article · Feb 2015 · British Journal of Radiology
[Show abstract][Hide abstract] ABSTRACT: Stereotactic body radiotherapy (SBRT) is often used to treat patients with oligometastases (OM). Yet, patterns of SBRT practice for OM are unknown. Therefore, we surveyed radiation oncologists internationally, to understand how and when SBRT is used for OM.
A 25-question survey was distributed to radiation oncologists. Respondents using SBRT for OM were asked how long they have been treating OM, number of patients treated, organs treated, primary reason for use, doses used, and future intentions. Respondents not using SBRT for OM were asked reasons why SBRT was not used and intentions for future adoption. Data were analyzed anonymously.
We received 1007 surveys from 43 countries. Eighty-three percent began using SBRT after 2005 and greater than one third after 2010. Eighty-four percent cited perceived treatment response/durability as the primary reason for using SBRT in OM patients. Commonly treated organs were lung (90%), liver (75%), and spine (70%). SBRT dose/fractionation schemes varied widely. Most would offer a second course to new OM. Nearly all (99%) planned to continue and 66% planned to increase SBRT for OM. Of those not using SBRT, 59% plan to start soon. The most common reason for not using SBRT was lack of clinical efficacy (48%) or lack of necessary image guidance equipment (34%).
Radiation oncologists are increasingly using SBRT for OM. The main reason for not using SBRT for OM is a perceived lack of evidence demonstrating clinical advantages. These data strengthen the need for robust prospective clinical trials (ongoing and in development) to demonstrate clinical efficacy given the widespread adoption of SBRT for OM.
No preview · Article · Feb 2015 · American Journal of Clinical Oncology
[Show abstract][Hide abstract] ABSTRACT: Background/purpose:
To identify risk factors for vaginal stenosis and to establish a dose-effect relationship for image-guided brachytherapy in locally advanced cervical cancer.
Patients from the ongoing EMBRACE study with prospectively assessed morbidity (CTCAEv3.0) at baseline and at least one follow-up were selected. Patient-, disease- and treatment characteristics were tested as risk factors for vaginal stenosis G⩾2 in univariate and multivariable analyses (Cox proportional hazards model) and a dose-effect curve was deduced from the estimates. The ICRU rectum point was used to derive the recto-vaginal reference point dose.
In 630 patients included (median follow-up 24months), 2-year actuarial estimate for vaginal stenosis G⩾2 was 21%. Recto-vaginal reference point dose (HR=1.025, p=0.029), external beam radiotherapy (EBRT) dose >45Gy/25 fractions (HR=1.770, p=0.056) and tumor extension in the vagina (HR=2.259, p⩽0.001) were risk factors for vaginal stenosis, adjusted for center reporting effects. Based on the model curve, the risk was 20% at 65Gy, 27% at 75Gy and 34% at 85Gy (recto-vaginal reference point dose).
Keeping the EBRT dose at 45Gy/25 fractions and decreasing the dose contribution of brachytherapy to the vagina decrease the risk of stenosis. A planning aim of ⩽65Gy EQD2 (EBRT+brachytherapy dose) to the recto-vaginal reference point is therefore proposed.
No preview · Article · Jan 2015 · Radiotherapy and Oncology
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To validate the feasibility and use of dose points to characterize the bladder wall dose distribution and investigate potential impact of the applicator position in cervical cancer brachytherapy.
Methods and materials:
One hundred twenty-eight optimized MRI plans were evaluated. The International Commission of Radiation Units and Measurements (ICRU-38) point doses (B(ICRU)), surrogate for bladder base doses, were compared with D(2cc). Vaginal source to superior-anterior border of the symphysis distances were measured and compared within two groups, namely Group 1-B(ICRU)/D(2cc) ≥1 and Group 2-B(ICRU)/D(2cc) <1. Additionally, points at 1.5 and 2 cm cranial to the B(ICRU), parallel to the tandem and the body axis were analyzed.
Thirty-seven percent of the patients had the ratio B(ICRU)/D(2cc) of 1 or higher, with the 2cc subvolume at the bladder base (Group 1). In 63%, BICRU/D2cc ratio was lower than 1 and the 2cc, cranial to the bladder base (Group 2). Median vaginal source-to-superior-anterior border of the symphysis line distance was -2 cm (range, -3.7 to +1.2 cm) in Group 1 and +1.8 cm (range, -2 to +4.8 cm) in Group 2 (+ cranial/- caudal direction). There was a high correlation between vaginal sources near the symphysis and the 2cc subvolume at the bladder base. The additional points provided no added value.
Location of the 2cc subvolume varies in cervical cancer brachytherapy. Maximum doses are at the bladder base if vaginal sources are also in the vicinity of the bladder base indicated by B(ICRU)/D(2cc) ratio of 1 or higher. Such variation should be considered in dose-effect analyses and intercomparisons, as the same D(2cc) at different bladder locations may correlate with different morbidity profiles and severity Reporting D(2cc) and B(ICRU) doses together therefore remains essential.