Although most meningiomas will be benign, a small proportion will have atypical or anaplastic histologic features and will exhibit more aggressive behavior. The treatment of these tumors has been ...controversial, especially for patients with recurrence after resection and radiotherapy. We have presented a large series of atypical and anaplastic meningiomas treated with stereotactic radiosurgery (SRS).
We performed a retrospective review of a single-institution radiosurgery database and identified 48 patients with 183 lesions who had undergone 99 SRS sessions from 1999 to 2019. The median dose was 15 Gy prescribed to the 50% isodose line. The center of the failures was plotted, and the distance from the treated tumor to the center of the failure was measured. Simulated treatment volumes for external beam radiotherapy were generated according to the target, and failures were characterized as local, marginal, or distant according to the simulated volume.
The 5-year disease-free and overall survival rate measured from the initial SRS session was 45.8% and 74.7%, respectively. The 5-year lesional control rate was 68.9%. The most common pattern of first failure was isolated distant failure, followed by isolated local or marginal failure. The incidence of distant failure was significantly greater after treatment of >2 lesions in a single SRS session. Isolated local/marginal failure was associated with grade III tumors and an increasing tumor size.
High-risk meningiomas are a heterogeneous group of tumors with a propensity for multiple failures. The most common pattern of relapse after SRS was distant. However, local control remains an issue. Further studies evaluating dose-escalation strategies are warranted.
The ideal timing for the initiation of chemotherapy and radiation therapy (RT) in the use of definitive chemoradiation (CRT) for patients with head and neck cancer is not well established. We sought ...to evaluate the impact of the timing of initiating these two modalities on clinical outcomes.
Patients with squamous cell carcinoma of the head and neck who were treated using definitive chemoradiation from 2012 to 2018 were identified. Patients undergoing re-irradiation, post-op CRT, had recurrent or second primaries, or ECOG 3-4 were excluded. Outcomes including locoregional control (LRC), distant control (DC), progression-free survival (PFS), and overall survival (OS) were estimated and compared between subgroups of the cohort based on the timing in which chemotherapy or RT were initiated: chemotherapy first, same day start, within 24 h, or start on Monday/Tuesday/Wednesday.
A total of 131 patients were included for analysis consisting of oropharynx (64%), larynx (22.9%), nasopharynx (6.9%), hypopharynx (3.1%), oral cavity (1.5%), and unknown primary (1.5%). Chemotherapy was administered as bolus cisplatin every 3 weeks in 40% of patients and weekly cisplatin in 60% with a median cumulative dose of 240 mg/m
2
. In the multivariable analysis (MVA), starting chemotherapy before RT was associated with improved LRC (HR 0.33, 95% CI: 0.11-0.99). Three-year LRC for patients starting chemotherapy first was 90.9% compared to 78.2% in those starting RT first. In the MVA, cisplatin regimen and cumulative cisplatin dose were associated with improved OS, while no factors were significantly associated with DC or PFS.
Starting chemotherapy prior to radiation therapy improves LRC, but did not impact DC, PFS, or OS. Clinical outcomes were not different when stratifying by the other differences in the timing of initiating chemotherapy or RT.
Background
To describe intensity‐modulated radiotherapy (IMRT) with Gamma Knife Radiosurgery (GKRS) boost for locally advanced head and neck cancer (HNC) with disease near dose‐limiting structures.
...Methods
Patients with HNC treated with IMRT/GKRS as part of a combined modality approach between 2011 and 2021 were reviewed. Local control, overall survival and disease‐specific survival were estimated using the Kaplan Meier method.
Results
Twenty patients were included. Nineteen patients had T3‐4 tumors. Median follow‐up was 26.3 months. GKRS site control was 95%. Two patients progressed at the treated primary site, one patient failed at the edge of the GKRS treatment volume, with no perineural or intracranial failure. 2‐year OS was 94.7% (95% CI: 85.2%–100%). Concurrent chemotherapy was given in nine patients (45%). One patient (5%) received induction/concurrent chemotherapy. Brain radionecrosis occurred in three patients, one of which was biopsy‐proven.
Conclusions
IMRT plus GKRS boost results in excellent disease control near critical structures with minimal toxicity.
Introduction
A data‐driven index of dementia risk based on magnetic resonance imaging (MRI), the Alzheimer's Disease Pattern Similarity (AD‐PS) score, was estimated for participants in the ...Atherosclerosis Risk in Communities (ARIC) study.
Methods
AD‐PS scores were generated for 839 cognitively non‐impaired individuals with a mean follow‐up of 4.86 years. The scores and a hypothesis‐driven volumetric measure based on several brain regions susceptible to AD were compared as predictors of incident cognitive impairment in different settings.
Results
Logistic regression analyses suggest the data‐driven AD‐PS scores to be more predictive of incident cognitive impairment than its counterpart. Both biomarkers were more predictive of incident cognitive impairment in participants who were White, female, and apolipoprotein E gene (APOE) ε4 carriers. Random forest analyses including predictors from different domains ranked the AD‐PS scores as the most relevant MRI predictor of cognitive impairment.
Conclusions
Overall, the AD‐PS scores were the stronger MRI‐derived predictors of incident cognitive impairment in cognitively non‐impaired individuals.
Effective treatments for advanced/recurrent head and neck squamous-cell carcinoma are limited. For cases not curable by conventional local therapies, the immune checkpoint inhibitor pembrolizumab ...shows modest response rates. Quad-shot, a hypofractionated palliative radiotherapy regimen (14.8 Gy in four twice-daily fractions), can provide symptomatic relief, contributes to local control and may potentiate the effects of immune checkpoint inhibitors. In this study, 15 patients with advanced/recurrent head and neck squamous-cell carcinoma will be treated with pembrolizumab combined with up to three administrations of quad-shot before cycles four, eight and 13. Outcomes include disease response, survival and treatment toxicity. Correlative multiomics analysis of blood and saliva will identify molecular biomarkers of response to immune checkpoint inhibitor and the immune-related impact of quad-shot.
: This study (WFBCCC 60320) is registered on NCT04454489 (ClinicalTrials.gov).
Ionizing radiation is a critical aspect of current cancer therapy. While classically mature bone was thought to be relatively radio-resistant, more recent data have shown this to not be the case. ...Radiation therapy (RT)-induced bone loss leading to fracture is a source of substantial morbidity. The mechanisms of RT likely involve multiple pathways, including changes in angiogenesis and bone vasculature, osteoblast damage/suppression, and increased osteoclast activity. The majority of bone loss appears to occur rapidly after exposure to ionizing RT, with significant changes in cortical thickness being detectable on computed tomography (CT) within three to four months. Additionally, there is a dose-response relationship. Cortical thinning is especially notable in areas of bone that receive >40 gray (Gy). Methods to mitigate toxicity due to RT-induced bone loss is an area of active investigation. There is an accruing clinical trial investigating the use of risderonate, a bisphosphonate, to prevent rib bone loss in patients undergoing lung stereotactic body radiation therapy (SBRT). Additionally, several other promising therapeutic/preventative approaches are being explored in preclinical studies, including parathyroid hormone (PTH), amifostine, and mechanical loading of irradiated bones.
The role of consolidative radiation therapy (RT) in patients with advanced Hodgkin lymphoma with initial bulk is unclear. GITIL/FIL HD0607 and FIL HD0801, 2 randomized controlled trials with similar ...design and methodologies, did not identify a benefit to consolidative RT after a metabolic complete response to 6 cycles of doxorubicin, bleomycin, vinblastine and dacarbazine. However, their limited sample sizes reduced statistical power to detect a small but clinically meaningful benefit to RT.
In a secondary analysis of these 2 phase 3 trials, reconstructed patient data were used to compare outcomes for early and complete responders randomized to no RT or RT to the site(s) of initial bulk. Estimates of progression-free survival (PFS) in the intent-to-treat (ITT) and per-protocol (PP) analyses were generated using the combined data and compared between groups using the log-rank test.
A total of 412 patients were included in the ITT analysis, and 373 patients were included in the PP analysis. Median age was 30 to 32 years, 42% of patients were stage IIB, and 73% of bulky sites were located in the mediastinum. For the no RT versus RT groups, 5-year ITT PFS estimates were 90.1% versus 90.1%, respectively (P = .81). Five-year PP PFS rates were 90.9% versus 92.9%, respectively (P = .31). There was no observed difference between no RT and RT groups in subgroups according to size of bulky disease: 5 to 7 cm (P = .78), 7 to 10 cm (P = .25), and >10 cm (P = .69).
In this combined analysis of 2 randomized phase 3 clinical trials, consolidative RT to initial sites of bulky nodal involvement was not associated with a PFS benefit in patients with advanced Hodgkin lymphoma in metabolic complete response after 2 and 6 cycles of doxorubicin, bleomycin, vinblastine and dacarbazine.
In patients with non-small cell lung cancer (NSCLC) who present with multiple pulmonary nodules, it is often difficult to distinguish metastatic disease from synchronous primary lung cancers (SPLC). ...We sought to evaluate clinical outcomes after stereotactic body radiotherapy (SBRT) alone to synchronous primary lesions.
Patients with synchronous AJCC 8
th
Edition Stage IA-IIA NSCLC and treated with stereotactic body radiation therapy (SBRT) to all lesions between 2009-2018 were reviewed. SPLC was defined as patients having received two courses of SBRT within 180 days for treatment of separate early stage tumors. In total, 36 patients with 73 lesions were included. Overall survival (OS), progression-free survival (PFS), cumulative incidence of local failure (LF), and regional/distant failure (R/DF) were estimated and compared with a control cohort of solitary early stage NSCLC patients.
Median PFS was 38.8 months (95% CI 14.3-not reached NR); 3-year PFS rates were 50.6% (35.6-72.1). Median OS was 45.9 months (95% CI: 35.9-NR); 3-year OS was 63.0% (47.4-83.8). Three-year cumulative incidence of LF and R/DF was 6.6% (3.7-13.9) and 35.7% (19.3-52.1), respectively. Patients with SPLC were compared to a control group (n = 272) of patients treated for a solitary early stage NSCLC. There was no statistically significant difference in PFS (p = .91) or OS (p = .43). Evaluation of the patterns of failure showed a trend for worse cumulative incidence of R/DF in SPLC patients as compared to solitary early stage NSCLC (p = .06).
SBRT alone to multiple lung tumors with SPLC results in comparable PFS, OS, and LF rates to a cohort of patients treated for solitary early stage NSCLC. Those with SPLC had non-significantly higher R/DF. Patients with SPLC should be followed closely for failure and possible salvage therapy.
At our institution, stereotactic body radiotherapy (SBRT) has commonly been prescribed with 50 Gy in 5 fractions and in select cases, 50 Gy in 10 fractions. We sought to evaluate the impact of these ...2 fractionation schedules on local control and survival outcomes.
We reviewed patients treated with SBRT with 50 Gy/5 fraction or 50 Gy/10 fraction for early-stage non–small cell lung cancer (NSCLC) and metastatic NSCLC. Cumulative incidence of local failure (LF) was estimated using competing risk methodology. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method only for patients with stage I disease.
Of the 353 lesions, 300 (85%) were treated with 50 Gy in 5 fractions and 53 (15%) with 10 fractions. LFs at 3 years were 6.5% and 23.9% and Kaplan-Meier estimate of median time to LF was 17.5 months and 26.2 months, respectively. Multivariable analysis revealed increasing planning target volume (hazard ratio 1.01, P = .04) as an independent predictor of increased LF, but tumor size, ultracentral location, and 10 fractions were not. Among patients with stage I NSCLC (n = 298), overall median PFS was 35.6 months and median OS was 42.4 months. There was no difference in PFS or OS between the 2 treatment regimens for patients with stage I NSCLC. Low rates of grade 3+ toxicity were observed, with 1 patient experiencing grade 3 pneumonitis after a 5-fraction regimen of SBRT.
Dose-fractionation schemes with BED10 ≥ 100 Gy provide superior local control and should be offered when meeting commonly accepted constraints. If those regimens appear unsafe, 50 Gy in 10 fractions may provide acceptable compromise between tumor control and safety with relatively durable control, and minimal negative impact on long-term survival.
We retrospectively reviewed patients with early-stage and metastatic non–small cell lung cancer (NSCLC) treated with stereotactic body radiotherapy using 2 fractionation regimens, 50 Gy in 5 fractions and 10 fractions. Local control was worse with the 10-fraction regimen but was not detrimental to progression-free or overall survival in patients with early NSCLC. Although suboptimal for local control, 50 Gy in 10 fractions could potentially be useful for reasonably durable control when dose-fractionation schemes with BED10 ≥ 100 Gy are considered unsafe.
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