This phase III trial compared adjuvant whole-brain radiotherapy (WBRT) with observation after either surgery or radiosurgery of a limited number of brain metastases in patients with stable solid ...tumors. Here, we report the health-related quality-of-life (HRQOL) results.
HRQOL was a secondary end point in the trial. HRQOL was assessed at baseline, at 8 weeks, and then every 3 months for 3 years with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and Brain Cancer Module. The following six primary HRQOL scales were considered: global health status; physical, cognitive, role, and emotional functioning; and fatigue. Statistical significance required P ≤ .05, and clinical relevance required a ≥ 10-point difference.
Compliance was 88.3% at baseline and dropped to 45.0% at 1 year; thus, only the first year was analyzed. Overall, patients in the observation only arm reported better HRQOL scores than did patients who received WBRT. The differences were statistically significant and clinically relevant mostly during the early follow-up period (for global health status at 9 months, physical functioning at 8 weeks, cognitive functioning at 12 months, and fatigue at 8 weeks). Exploratory analysis of all other HRQOL scales suggested worse scores for the WBRT group, but none was clinically relevant.
This study shows that adjuvant WBRT after surgery or radiosurgery of a limited number of brain metastases from solid tumors may negatively impact some aspects of HRQOL, even if these effects are transitory. Consequently, observation with close monitoring with magnetic resonance imaging (as done in the EORTC trial) is not detrimental for HRQOL.
Summary The management of primary CNS lymphoma is one of the most controversial topics in neuro-oncology because of the complexity of the disease and the very few controlled studies available. In ...2013, the European Association of Neuro-Oncology created a multidisciplinary task force to establish evidence-based guidelines for immunocompetent adults with primary CNS lymphoma. In this Review, we present these guidelines, which provide consensus considerations and recommendations for diagnosis, assessment, staging, and treatment of primary CNS lymphoma. Specifically, we address aspects of care related to surgery, systemic and intrathecal chemotherapy, intensive chemotherapy with autologous stem-cell transplantation, radiotherapy, intraocular manifestations, and management of elderly patients. The guidelines should aid clinicians in their daily practice and decision making, and serve as a basis for future investigations in neuro-oncology.
The management of patients with brain metastases has become a major issue due to the increasing frequency and complexity of the diagnostic and therapeutic approaches. In 2014, the European ...Association of Neuro-Oncology (EANO) created a multidisciplinary Task Force to draw evidence-based guidelines for patients with brain metastases from solid tumors. Here, we present these guidelines, which provide a consensus review of evidence and recommendations for diagnosis by neuroimaging and neuropathology, staging, prognostic factors, and different treatment options. Specifically, we addressed options such as surgery, stereotactic radiosurgery/stereotactic fractionated radiotherapy, whole-brain radiotherapy, chemotherapy and targeted therapy (with particular attention to brain metastases from non-small cell lung cancer, melanoma and breast and renal cancer), and supportive care.
Summary Background Most patients with glioblastoma are older than 60 years, but treatment guidelines are based on trials in patients aged only up to 70 years. We did a randomised trial to assess the ...optimum palliative treatment in patients aged 60 years and older with glioblastoma. Methods Patients with newly diagnosed glioblastoma were recruited from Austria, Denmark, France, Norway, Sweden, Switzerland, and Turkey. They were assigned by a computer-generated randomisation schedule, stratified by centre, to receive temozolomide (200 mg/m2 on days 1–5 of every 28 days for up to six cycles), hypofractionated radiotherapy (34·0 Gy administered in 3·4 Gy fractions over 2 weeks), or standard radiotherapy (60·0 Gy administered in 2·0 Gy fractions over 6 weeks). Patients and study staff were aware of treatment assignment. The primary endpoint was overall survival. Analyses were done by intention to treat. This trial is registered, number ISRCTN81470623. Findings 342 patients were enrolled, of whom 291 were randomised across three treatment groups (temozolomide n=93, hypofractionated radiotherapy n=98, standard radiotherapy n=100) and 51 of whom were randomised across only two groups (temozolomide n=26, hypofractionated radiotherapy n=25). In the three-group randomisation, in comparison with standard radiotherapy, median overall survival was significantly longer with temozolomide (8·3 months 95% CI 7·1–9·5; n=93 vs 6·0 months 95% CI 5·1–6·8; n=100, hazard ratio HR 0·70; 95% CI 0·52–0·93, p=0·01), but not with hypofractionated radiotherapy (7·5 months 6·5–8·6; n=98, HR 0·85 0·64–1·12, p=0·24). For all patients who received temozolomide or hypofractionated radiotherapy (n=242) overall survival was similar (8·4 months 7·3–9·4; n=119 vs 7·4 months 6·4–8·4; n=123; HR 0·82, 95% CI 0·63–1·06; p=0·12). For age older than 70 years, survival was better with temozolomide and with hypofractionated radiotherapy than with standard radiotherapy (HR for temozolomide vs standard radiotherapy 0·35 0·21–0·56, p<0·0001; HR for hypofractionated vs standard radiotherapy 0·59 95% CI 0·37–0·93, p=0·02). Patients treated with temozolomide who had tumour MGMT promoter methylation had significantly longer survival than those without MGMT promoter methylation (9·7 months 95% CI 8·0–11·4 vs 6·8 months 5·9–7·7; HR 0·56 95% CI 0·34–0·93, p=0·02), but no difference was noted between those with methylated and unmethylated MGMT promoter treated with radiotherapy (HR 0·97 95% CI 0·69–1·38; p=0·81). As expected, the most common grade 3–4 adverse events in the temozolomide group were neutropenia (n=12) and thrombocytopenia (n=18). Grade 3–5 infections in all randomisation groups were reported in 18 patients. Two patients had fatal infections (one in the temozolomide group and one in the standard radiotherapy group) and one in the temozolomide group with grade 2 thrombocytopenia died from complications after surgery for a gastrointestinal bleed. Interpretation Standard radiotherapy was associated with poor outcomes, especially in patients older than 70 years. Both temozolomide and hypofractionated radiotherapy should be considered as standard treatment options in elderly patients with glioblastoma. MGMT promoter methylation status might be a useful predictive marker for benefit from temozolomide. Funding Merck, Lion's Cancer Research Foundation, University of Umeå, and the Swedish Cancer Society.
This European Organisation for Research and Treatment of Cancer phase III trial assesses whether adjuvant whole-brain radiotherapy (WBRT) increases the duration of functional independence after ...surgery or radiosurgery of brain metastases.
Patients with one to three brain metastases of solid tumors (small-cell lung cancer excluded) with stable systemic disease or asymptomatic primary tumors and WHO performance status (PS) of 0 to 2 were treated with complete surgery or radiosurgery and randomly assigned to adjuvant WBRT (30 Gy in 10 fractions) or observation (OBS). The primary end point was time to WHO PS deterioration to more than 2.
Of 359 patients, 199 underwent radiosurgery, and 160 underwent surgery. In the radiosurgery group, 100 patients were allocated to OBS, and 99 were allocated to WBRT. After surgery, 79 patients were allocated to OBS, and 81 were allocated to adjuvant WBRT. The median time to WHO PS more than 2 was 10.0 months (95% CI, 8.1 to 11.7 months) after OBS and 9.5 months (95% CI, 7.8 to 11.9 months) after WBRT (P = .71). Overall survival was similar in the WBRT and OBS arms (median, 10.9 v 10.7 months, respectively; P = .89). WBRT reduced the 2-year relapse rate both at initial sites (surgery: 59% to 27%, P < .001; radiosurgery: 31% to 19%, P = .040) and at new sites (surgery: 42% to 23%, P = .008; radiosurgery: 48% to 33%, P = .023). Salvage therapies were used more frequently after OBS than after WBRT. Intracranial progression caused death in 78 (44%) of 179 patients in the OBS arm and in 50 (28%) of 180 patients in the WBRT arm.
After radiosurgery or surgery of a limited number of brain metastases, adjuvant WBRT reduces intracranial relapses and neurologic deaths but fails to improve the duration of functional independence and overall survival.
Using moderate or ultra-hypofractionation, which is also known as stereotactic body radiotherapy (SBRT) for treatment of localized prostate cancer patients has been increased. We present our ...preliminary results on the clinical utilization of MRI-guided adaptive radiotherapy (MRgRT) for prostate cancer patients with the workflow, dosimetric parameters, toxicities and prostate-specific antigen (PSA) response.
50 prostate cancer patients treated with ultra-hypofractionation were included in the study. Treatment was performed with intensity-modulated radiation therapy (step and shoot) technique and daily plan adaptation using MRgRT. The SBRT consisted of 36.25 Gy in 5 fractions with a 7.25 Gy fraction size. The time for workflow steps was documented. Patients were followed for the acute and late toxicities and PSA response.
The median follow-up for our cohort was 10 months (range between 3 and 29 months). The median age was 73.5 years (range between 50 and 84 years). MRgRT was well tolerated by all patients. Acute genitourinary (GU) toxicity rate of Grade 1 and Grade 2 was 28 and 36%, respectively. Only 6% of patients had acute Grade 1 gastrointestinal (GI) toxicity and there was no Grade ≥ 2 GI toxicity. To date, late Grade 1 GU toxicity was experienced by 24% of patients, 2% of patients experienced Grade 2 GU toxicity and 6% of patients reported Grade 2 GI toxicity. Due to the short follow-up, PSA nadir has not been reached yet in our cohort.
In conclusion, MRgRT represents a new method for delivering SBRT with markerless soft tissue visualization, online adaptive planning and real-time tracking. Our study suggests that ultra-hypofractionation has an acceptable acute and very low late toxicity profile.
MRgRT represents a new markerless method for delivering SBRT for localized prostate cancer providing online adaptive planning and real-time tracking and acute and late toxicity profile is acceptable.
Abstract
Background
The ESTRO-ACROP Consensus Guideline (EACG) recommends implant excluded clinical target volume (CTVp) definitions for post-mastectomy radiation therapy after implant-based ...immediate breast reconstruction (IBR). The purpose of this study is to investigate the effectiveness of Helical Tomotherapy (HTp) and Volumetric Modulated Arc Therapy (VMATp) treatment techniques in terms of CTVp coverage and reduced organ at risk (OAR), normal tissue and implant doses when CTVp was used for treatment planning as the target structure instead of conventional CTV.
Methods
Eight left-sided and eight right-sided breast cancer patients who underwent IBR after mastectomy were included in this study. Planning CT data sets were acquired during free breathing and patients were treated with HT technique targeted to conventional CTV. Retrospectively, CTVp was delineated based on EACG by the same radiation oncologist, and treatment plans with HTp and VMATp techniques were generated based on CTVp. For each patient, relevant dosimetric parameters were obtained from three different treatment plans.
Results
There was no statistically significant difference on target coverage in terms of, PTVp-D95, PTVp-Vpres, homogeneity index (
p
> 0.05) between HTp and VMATp plans. But, the conformity numbers were significantly higher (HTp vs VMATp, 0.69 ± 0.15 vs 0.79 ± 0.12) for VMATp (Z = − 2.17,
p
= 0.030). While HTp significantly lowered Dmax and Dmean for LAD (LAD-D
max
: χ
2
= 12.25,
p
= 0.002 and LAD-D
mean
: χ
2
= 12.30,
p
= 0.002), neither HTp nor VMATp could reduce maximum and mean dose to heart (
p
> 0.05). Furthermore, heart volume receiving 5 Gy was significantly higher for VMATp when compared to HTp (21.2 ± 9.8 vs 42.7 ± 24.8,
p
: 0.004). Both techniques succeeded in reducing the mean dose to implant (HTp vs HT,
p
< 0.001; VMATp vs HT,
p
< 0.001; VMATp vs HTp,
p
= 0.005).
Conclusion
Both HTp and VMATp techniques succeeded to obtain conformal and homogeneous dose distributions within CTVp while reducing the mean implant dose. HTp was found to be superior to VMATp with regards to lowering all OAR doses except for CB.
To present the radiation therapy quality assurance results from a prospective multicenter phase 2 randomized trial of short versus protracted urethra-sparing stereotactic body radiation therapy ...(SBRT) for localized prostate cancer.
Between 2012 and 2015, 165 patients with prostate cancer from 9 centers were randomized and treated with SBRT delivered either every other day (arm A, n = 82) or once a week (arm B, n = 83); 36.25 Gy in 5 fractions were prescribed to the prostate with (n = 92) or without (n = 73) inclusion of the seminal vesicles (SV), and the urethra planning-risk volume received 32.5 Gy. Patients were treated either with volumetric modulated arc therapy (VMAT; n = 112) or with intensity modulated radiation therapy (IMRT; n = 53). Deviations from protocol dose constraints, planning target volume (PTV) homogeneity index, PTV Dice similarity coefficient, and number of monitor units for each treatment plan were retrospectively analyzed. Dosimetric results of VMAT versus IMRT and treatment plans with versus without inclusion of SV were compared.
At least 1 major protocol deviation occurred in 51 patients (31%), whereas none was observed in 41. Protocol violations were more frequent in the IMRT group (P < .001). Furthermore, the use of VMAT yielded better dosimetric results than IMRT for urethra planning-risk volume D
(31.1 vs 30.8 Gy, P < .0001), PTV D
(37.9 vs 38.7 Gy, P < .0001), homogeneity index (0.09 vs 0.10, P < .0001), Dice similarity coefficient (0.83 vs 0.80, P < .0001), and bladder wall V
(24.5% vs 33.5%, P = .0001). To achieve its goals volumetric modulated arc therapy required fewer monitor units than IMRT (2275 vs 3378, P <.0001). The inclusion of SV in the PTV negatively affected the rectal wall V
(9.1% vs 10.4%, P = .0003) and V
(13.2% vs 15.7%, P = .0003).
Protocol deviations with potential impact on tumor control or toxicity occurred in 31% of patients in this prospective clinical trial. Protocol deviations were more frequent with IMRT. Prospective radiation therapy quality assurance protocols should be strongly recommended for SBRT trials to minimize potential protocol deviations.
We aimed to present our initial clinical experience on the implementation of a stereotactic MR-guided online adaptive radiation therapy (SMART) for the treatment of liver metastases in ...oligometastatic disease.
Twenty-one patients (24 lesions) with liver metastasis treated with SMART were included in this retrospective study. Step-and-shoot intensity-modulated radiotherapy technique was used with daily plan adaptation. During delivery, real-time imaging was used by acquiring planar magnetic resonance images in sagittal plane for monitoring and gating. Acute and late toxicities were recorded both during treatment and follow-up visits.
The median follow-up time was 11.6 months (range, 2.2 to 24.6 months). The median delivered total dose was 50 Gy (range, 40 to 60 Gy); with a median fraction number of 5 (range, 3 to 8 fractions) and the median fraction dose was 10 Gy (range, 7.5 to 18 Gy). Ninety-three fractions (83.7%) among 111 fractions were re-optimized. No patients were lost to follow-up and all patients were alive except one at the time of analysis. All of the patients had either complete (80.9%) or partial (19.1%) response at irradiated sites. Estimated 1-year overall survival was 93.3%. Intrahepatic and extrahepatic progression-free survival was 89.7% and 73.5% at 1 year, respectively. There was no grade 3 or higher acute or late toxicities experienced during the treatment and follow-up course.
SMART represents a new, noninvasive and effective alternative to current ablative radiotherapy methods for treatment of liver metastases in oligometastatic disease with the advantages of better visualization of soft tissue, real-time tumor tracking and potentially reduced toxicity to organs at risk.
Background
To present the 18 months results from a prospective multicenter phase II randomized trial of short vs protracted urethra‐sparing stereotactic body radiotherapy (SBRT) for localized ...prostate cancer (PCa).
Methods
Between 2012 and 2015, a total of 170 PCa patients were randomized to 36.25 Gy in 5 fractions (6.5 Gy × 5 to the urethra) delivered either every other day (EOD, arm A, n = 84) or once a week (QW, arm B, n = 86). Genitourinary (GU) and gastrointestinal (GI) toxicity (CTCAE v4.0 scale), IPSS, and QoL scores were assessed at baseline, at the 5th fraction (5fx), 12th weeks (12W), and every 6 months after SBRT. The primary endpoint was biochemical control at 18 months and grade ≥ 3 toxicity (including grade ≥ 2 for urinary obstruction/retention) during the first 3 months.
Results
Among the 165 patients analyzed, the toxicity stopping rule was never activated during the acute phase. Maximum acute grade 2 GU toxicity rates at 5fx were 17% and 19% for arms A and B, respectively, with only 2 cases of grade 2 GI toxicity at 5fx in arm A. At month 18, grade ≥ 2 GU and GI toxicity decreased below 5% and 2% for both arms. No changes in EORTC QLQ‐PR25 scores for GU, GI, and sexual domains were observed in both arms between baseline and month 18. Four biochemical failures were observed, 2 in each arm, rejecting the null hypothesis of an unfavorable response rate ≤ 85% in favor of an acceptable ≥ 95% rate.
Conclusions
At 18 months, urethra‐sparing SBRT showed a low toxicity profile, with minimal impact on QoL and favorable biochemical control rates, regardless of overall treatment time (EOD vs QW).
Dose per fraction and overall treatment time can impact tolerance of prostate SBRT. Urethra‐sparing SBRT showed a low toxicity profile and minimal impact on QoL. An EOD or QW SBRT schedule had a comparable tolerance and efficacy at 18 months.
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