[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.).
New England Journal of Medicine 04/2015; 372(17):1598-607. DOI:10.1056/NEJMoa1408648 · 55.87 Impact Factor
[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.
British Journal of Radiology 02/2015; 88(1048):20140712. DOI:10.1259/bjr.20140712 · 2.03 Impact Factor
[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.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
We previously demonstrated that 48% of patients with pain at sites of previously irradiated bone metastases benefit from reirradiation. It is unknown whether alleviating pain also improves patient perception of quality of life (QOL).
Patients and methods:
We used the database of a randomized trial comparing radiation treatment dose fractionation schedules to evaluate whether response, determined using the International Consensus Endpoint (ICE) and Brief Pain Inventory pain score (BPI-PS), is associated with patient perception of benefit, as measured using the European Organisation for Resesarch and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and functional interference scale of the BPI (BPI-FI). Evaluable patients completed baseline and 2-month follow-up assessments.
Among 850 randomly assigned patients, 528 were evaluable for response using the ICE and 605 using the BPI-PS. Using the ICE, 253 patients experienced a response and 275 did not. Responding patients had superior scores on all items of the BPI-FI (ie, general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life) and improved QOL, as determined by scores on the EORTC QLQ-C30 scales of physical, role, emotional and social functioning, global QOL, fatigue, pain, and appetite. Similar results were obtained using the BPI-PS; observed improvements were typically of lesser magnitude.
Patients responding to reirradiation of painful bone metastases experience superior QOL scores and less functional interference associated with pain. Patients should be offered re-treatment for painful bone metastases in the hope of reducing pain severity as well as improving QOL and pain interference.
[Show abstract][Hide abstract] ABSTRACT: Aims:
This single-centre retrospective study evaluated combination external beam radiotherapy and high dose rate brachytherapy for patients in whom radical treatment was appropriate but comorbidity or frailty excluded this as an option.
Materials and methods:
In total, 59 patients were selected for a combined approach and treated between October 2000 and October 2011; 68% were male. The median age was 77 years (range 53-88 years); 66% had adenocarcinoma, 31% squamous cell carcinoma. Tumour stage: I: 20%, II: 43%, III: 32% and IV: 3%. External beam radiotherapy doses of either 27 Gy/six fractions or 30 Gy/10 fractions were delivered, followed by high dose rate brachytherapy at doses of either 10 or 15 Gy utilising an iridium 192 source at 1 cm.
The median overall survival of all treated patients was 12.3 months; 1, 2 and 3 year survival rates were 51, 19 and 7%, respectively. Patients with stage I disease had a median survival of 16 months compared with 10 months for patients with stage III disease (P = 0.036). The pretreatment dysphagia score was associated with survival (P = 0.021).
This study shows the value of a purely radiation-based approach in a selected population. Treatment is deliverable with excellent compliance and the median survival compares favourably with unselected patients treated palliatively in our institution.
[Show abstract][Hide abstract] ABSTRACT: Prostate cancer (PCa) is the second most common disease among men worldwide. It is important to know survival outcomes and prognostic factors for this disease. Recruitment for the largest therapeutic randomised controlled trial in PCa-the Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy: A Multi-Stage Multi-Arm Randomised Controlled Trial (STAMPEDE)-includes men with newly diagnosed metastatic PCa who are commencing long-term androgen deprivation therapy (ADT); the control arm provides valuable data for a prospective cohort.
European Urology 10/2014; 66(6). DOI:10.1016/j.eururo.2014.09.032 · 13.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To investigate the optimal distribution of sources using high dose rate brachytherapy to deliver a focal boost to a dominant lesion within the whole prostate gland based on multi-parametric magnetic resonance imaging (mpMRI).
Sixteen patients with prostate cancer underwent mpMRI each of which demonstrated a dominant lesion. There were single lesions in 6 patients, two lesions in 4 and 3 lesions in 6 patients. Two dosimetric models and parameters were compared in each case. The first model used 10mm intervals between needles, and the second model used additional needles at 5 mm intervals between each needle in the boost area.
Three of thirty-two plans did not achieve the plan objectives. These three plans were in the first model. A higher median urethral volume was seen in the 'unsuccessful' group (2.7 cc, and 1.9 cc, respectively, p-value=0.12). Conformity indices of the second model were also better than the first model (COIN index; 0.716 and 0.643, respectively).
Focal monotherapy based on mpMRI achieves optimal dosimetry by individualizing the needle positions using 5mm spacing rather than 10mm spacing within the boost volume. A larger urethral volume may have an adverse effect on this distribution. Formal clinical evaluation of this approach is currently underway.
Radiotherapy and Oncology 09/2014; 113(1). DOI:10.1016/j.radonc.2014.09.001 · 4.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Modern treatment of Hodgkin's lymphoma (HL) has transformed its prognosis but causes late effects, including premature menopause. Cohort studies of premature menopause risks after treatment have been relatively small, and knowledge about these risks is limited.
Nonsurgical menopause risk was analyzed in 2127 women treated for HL in England and Wales at ages younger than 36 years from 1960 through 2004 and followed to 2003 through 2012. Risks were estimated using Cox regression, modified Poisson regression, and competing risks. All statistical tests were two-sided.
During follow-up, 605 patients underwent nonsurgical menopause before age 40 years. Risk of premature menopause increased more than 20-fold after ovarian radiotherapy, alkylating chemotherapy other than dacarbazine, or BEAM (bis-chloroethylnitrosourea [BCNU], etoposide, cytarabine, melphalan) chemotherapy for stem cell transplantation, but was not statistically significantly raised after adriamycin, bleomycin, vinblastine, dacarbazine (ABVD). Menopause generally occurred sooner after ovarian radiotherapy (62.5% within five years of ≥5 Gy treatment) and BEAM (50.9% within five years) than after alkylating chemotherapy (24.2% within five years of ≥6 cycles), and after treatment at older than at younger ages. Cumulative risk of menopause by age 40 years was 81.3% after greater than or equal to 5Gy ovarian radiotherapy, 75.3% after BEAM, 49.1% after greater than or equal to 6 cycles alkylating chemotherapy, 1.4% after ABVD, and 3.0% after solely supradiaphragmatic radiotherapy. Tables of individualized risk information for patients by future period, treatment type, dose and age are provided.
Patients treated with HL need to plan intended pregnancies using personalized information on their risk of menopause by different future time points.
JNCI Journal of the National Cancer Institute 08/2014; 106(9). DOI:10.1093/jnci/dju207 · 12.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
To evaluate late urinary (GU) and gastrointestinal (GI) adverse events (AEs) and biochemical control of disease after high-dose rate brachytherapy (HDR-BT) in locally advanced prostate cancer.
Patients and methods
227 consecutive patients were treated with 3 × 10.5 Gy (n = 109) or 2 × 13 Gy (n = 118) HDR-BT alone. Biochemical failure was assessed using the Phoenix definition of PSA nadir + 2 μg/l and late AEs using the RTOG scoring system and the International Prostate Symptom Score (IPSS).
Kaplan–Meier estimates and prevalence of late events indicate that urinary, bowel and IPSS symptoms are higher after 31.5 Gy than after 26 Gy, however differences are significant only for Grade 1 and 2 urinary toxicity. Kaplan–Meier estimates of morbidity are consistently and considerably higher than time-point estimates of prevalence; which reflects the transient nature of most symptoms. At 3 years 93% and 97% of patients treated with 26 and 31.5 Gy, respectively, were free from biochemical relapse (p = 0.5) and 91% for the latter regimen at 5 years. In univariate and multivariate analysis risk-category was the only significant predictor of relapse (p < 0.03).
These HDR-BT schedules achieved high levels of biochemical control of disease in patients with advanced prostate cancer with few severe complications seen throughout the first 3 years.
Radiotherapy and Oncology 07/2014; 112(1). DOI:10.1016/j.radonc.2014.06.007 · 4.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction
Radiation therapy has been shown to successfully palliate bone metastases. A number of systematic reviews and large clinical trials have reported response rates for initial treatment and retreatment.
To determine overall response rates of patients with painful uncomplicated bone metastases undergoing initial treatment and retreatment.
Intent-to-treat and evaluable patient statistics from a systematic review of palliative radiotherapy trials for initial treatment of bone metastases and a randomized clinical trial of retreatment were pooled and analyzed to determine the overall response rates for patients receiving initial treatment and retreatment.
In the intent-to-treat calculation, 71–73% of patients had an overall response to radiation treatment and in the evaluable patient population; 85–87% of patients did so. Response rates varied slightly whether patients underwent single or multiple fractions in initial treatment or retreatment.
Single and multiple fraction radiation treatment yielded very similar overall response rates. Patients treated with a single fraction for both initial and repeat radiation experience almost identical overall response to those patients treated with multiple fraction treatment. It is therefore recommended that patients with uncomplicated painful bone metastases be treated with a single 8 Gy fraction of radiation at both the initial treatment and retreatment.
Radiotherapy and Oncology 07/2014; 112(1). DOI:10.1016/j.radonc.2014.06.015 · 4.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
The addition of carbogen and nicotinamide (CON) to radiotherapy (RT) improves overall survival in invasive bladder cancer. We explored whether expression of the hypoxia marker hypoxia-inducible factor-1α (HIF-1α) alone or in combination with other markers predicted benefit from CON.
A retrospective study was carried out using material from patients with high-grade invasive bladder carcinoma enrolled in the BCON phase III trial of RT alone or with CON (RT+CON). HIF-1α expression was studied in 137 tumours using tissue microarrays and immunohistochemistry. Data were available from other studies for carbonic anhydrase IX and glucose transporter 1 protein and gene expression and tumour necrosis.
Patients with high HIF-1α expression had improved 5-year local relapse-free survival with RT+CON (47%) compared with RT alone (21% hazard ratio (HR) 0.48, 95% CI 0.26–0.8, P=0.02), no benefit was seen with low HIF-1α expression (HR 0.81, 95% CI 0.43–1.50, P=0.5). Combinations of markers including necrosis also predicted benefit but did not improve on prediction using necrosis alone.
HIF-1α may be used to predict benefit from CON in patients with bladder cancer but does not improve on use of necrosis.
British Journal of Cancer 06/2014; 111(3). DOI:10.1038/bjc.2014.315 · 4.84 Impact Factor