Abstract
Background
Recent advances in radiotherapy techniques have allowed ablative doses to be safely delivered to inoperable liver tumors. In this setting, proton beam radiotherapy (PBT) provides ...the means to escalate radiation dose to the target volume while sparing the uninvolved liver. This study evaluated the safety and efficacy of hypofractionated PBT for liver tumors, predominantly hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).
Methods
We evaluated the prospective registry of the Proton Collaborative Group for patients undergoing definitive PBT for liver tumors. Demographic, clinicopathologic, toxicity, and dosimetry information were compiled.
Results
To date, 63 patients have been treated at 9 institutions between 2013 and 2019. Thirty (48%) had HCC and 25 (40%) had ICC. The median dose and biological equivalent dose (BED) delivered was 58.05 GyE (range 32.5–75) and 80.5 GyE (range 53.6–100), respectively. The median mean liver BED was 13.9 GyE. Three (4.8%) patients experienced at least one grade ≥ 3 toxicity. With median follow-up of 5.1 months (range 0.1–40.8), the local control (LC) rate at 1 year was 91.2% for HCC and 90.9% for ICC. The 1-year LC was significantly higher (95.7%) for patients receiving BED greater than 75.2 GyE than for patients receiving BED of 75.2 GyE or lower (84.6%,
p
= 0.029). The overall survival rate at 1 year was 65.6% for HCC and 81.8% for ICC.
Conclusions
Hypofractionated PBT results in excellent LC, sparing of the uninvolved liver, and low toxicity, even in the setting of dose-escalation. Higher dose correlates with improved LC, highlighting the importance of PBT especially in patients with recurrent or bulky disease.
Abstract
BACKGROUND
Atypical and anaplastic meningiomas have reduced progression-free/overall survival (PFS/OS) compared to benign meningiomas. Stereotactic radiosurgery (SRS) for atypical ...meningiomas (AMs) and anaplastic meningiomas (malignant meningiomas, MMs) has not been adequately described.
OBJECTIVE
To define clinical/radiographic outcomes for patients undergoing SRS for AM/MMs.
METHODS
An international, multicenter, retrospective cohort study was performed to define clinical/imaging outcomes for patients receiving SRS for AM/MMs. Tumor progression was assessed with response assessment in neuro-oncology (RANO) criteria. Factors associated with PFS/OS were assessed using Kaplan-Meier analysis and a Cox proportional hazards model.
RESULTS
A total of 271 patients received SRS for AMs (n = 233, 85.9%) or MMs (n = 38, 14.0%). Single-fraction SRS was most commonly employed (n = 264, 97.4%) with a mean target dose of 14.8 Gy. SRS was used as adjuvant treatment (n = 85, 31.4%), salvage therapy (n = 182, 67.2%), or primary therapy (1.5%). The 5-yr PFS/OS rate was 33.6% and 77.0%, respectively. Increasing age (hazard ratio (HR) = 1.01, P < .05) and a Ki-67 index > 15% (HR = 1.66, P < .03) negatively correlated with PFS. MMs (HR = 3.21, P < .05), increased age (HR = 1.04, P = .04), and reduced KPS (HR = 0.95, P = .04) were associated with shortened OS. Adjuvant versus salvage SRS did not impact PFS/OS. A shortened interval between surgery and SRS improved PFS for AMs (HR = 0.99, P = .02) on subgroup analysis. Radiation necrosis occurred in 34 (12.5%) patients. Five-year rates of repeat surgery/radiation were 33.8% and 60.4%, respectively.
CONCLUSION
AM/MMs remain challenging tumors to treat. Elevated proliferative indices are associated with tumor recurrence, while MMs have worse survival. SRS can control AM/MMs in the short term, but the 5-yr PFS rates are low, underscoring the need for improved treatment options for these patients.
Graphical Abstract
Graphical Abstract
•High dose rate brachytherapy reduces rectal toxicity in prostate cancer treatment.•Rectal toxicity lower with brachytherapy than external beam radiotherapy.•Biochemical control similar for ...brachytherapy and external beam radiotherapy.
Using a prospectively collected institutional database, we compared rectal toxicity following high dose rate (HDR) brachytherapy as monotherapy relative to dose-escalated external beam radiotherapy (EBRT) for patients with localized prostate cancer.
2683 patients treated with HDR or EBRT between 1994 and 2017 were included. HDR fractionation was 38 Gy/4 fractions (n = 321), 24 Gy/2 (n = 96), or 27 Gy/2 (n = 128). EBRT patients received a median dose of 75.6 Gy in 1.8 Gy fractions range 70.2–82.8 Gy, using either 3D conformal or intensity modulated radiotherapy (IMRT). EBRT patients underwent 3D image guidance via an off-line adaptive process.
Median follow-up was 7.5 years (7.4 years for EBRT and 7.9 years for HDR). 545 patients (20.3%) received HDR brachytherapy and 2138 (79.7%) EBRT. 69.1% of EBRT patients received IMRT. Compared to EBRT, HDR was associated with decreased rates of acute grade ≥2 diarrhea (0.7% vs. 4.5%, p < 0.001), rectal pain/tenesmus (0.6% vs. 7.9%, p < 0.001), and rectal bleeding (0% vs. 1.6%, p = 0.001). Rates of chronic grade ≥2 rectal bleeding (1.3% vs. 8.7%, p < 0.001) and radiation proctitis (0.9% vs. 3.3%, p = 0.001) favored HDR over EBRT. Rates of any chronic rectal toxicity grade ≥2 were 2.4% vs. 10.5% (p < 0.001) for HDR versus EBRT, respectively. In those treated with IMRT, acute and chronic rates of any grade ≥2 GI toxicity were significantly reduced but remained significantly greater than those treated with HDR.
In appropriately selected patients with localized prostate cancer undergoing radiation therapy, HDR brachytherapy as monotherapy is an effective strategy for reducing rectal toxicity.
Vestibular schwannomas (VSs) related to neurofibromatosis type 2 (NF2) are challenging tumors. The increasing use of stereotactic radiosurgery (SRS) necessitates further investigations of its role ...and safety.
To evaluate tumor control, freedom from additional treatment (FFAT), serviceable hearing preservation, and radiation-related risks of patients with NF2 after SRS for VS.
We performed a retrospective study of 267 patients with NF2 (328 VSs) who underwent single-session SRS at 12 centers participating in the International Radiosurgery Research Foundation. The median patient age was 31 years (IQR, 21-45 years), and 52% were male.
A total of 328 tumors underwent SRS during a median follow-up time of 59 months (IQR, 23-112 months). At 10 and 15 years, the tumor control rates were 77% (95% CI: 69%-84%) and 52% (95% CI: 40%-64%), respectively, and the FFAT rate were 85% (95% CI: 79%-90%) and 75% (95% CI: 65%-86%), respectively. At 5 and 10 years, the serviceable hearing preservation rates were 64% (95% CI: 55%-75%) and 35% (95% CI: 25%-54%), respectively. In the multivariate analysis, age (hazards ratio: 1.03 95% CI: 1.01-1.05; P = .02) and bilateral VSs (hazards ratio: 4.56 95% CI: 1.05-19.78; P = .04) were predictors for serviceable hearing loss. Neither radiation-induced tumors nor malignant transformation were encountered in this cohort.
Although the absolute volumetric tumor progression rate was 48% at 15 years, the rate of FFAT related to VS was 75% at 15 years after SRS. None of the patients with NF2-related VS developed a new radiation-related neoplasm or malignant transformation after SRS.
•Higher BED was associated with improved OS in SCC lung patients undergoing SBRT.•BED escalation was not advantageous in patients with non-SCC NSCLC.•BED > 150 Gy may confer a survival benefit in ...patients with SCC.
Multiple studies have suggested that patients with early-stage SCC of the lung treated with SBRT are more susceptible to local failure compared to other NSCLC histologies. It is unknown if higher BED leads to improved outcomes in this patient population. We evaluated the effect of “high” BED versus “low” BED SBRT on overall survival (OS) in SCC and non-SCC NSCLC patients.
The National Cancer Database was used to identify patients with cT1-2N0M0 NSCLC diagnosed between 2006–2016 treated with 3–5 fraction SBRT. Patients were grouped by BEDhigh (>150 Gy) and BEDlow (≤132 Gy). Univariate and multivariable analysis using Kaplan-Meier and Cox proportional hazards regression modeling were performed. Propensity-score matched analysis with inverse probability of treatment (IPTW) weighting was used to account for selection bias.
We identified 4,717 eligible SCC patients and 8,807 eligible non-SCC NSCLC patients. In SCC patients, BEDhigh was associated with improved OS in both univariate and multivariate analysis (MVA HR 0.84 95% CI 0.76–0.92, p < 0.001), with estimated IPTW-adjusted 3-year OS of 49% compared to 41% for the BEDlow group. In contrast, BEDhigh was not associated with improved OS compared to BEDlow for non-SCC NSCLC patients (MVA HR 0.94 95% CI 0.86–1.04, p = 0.23), with estimated IPTW-adjusted 3-year OS of 54% and 53%, respectively.
Our analysis suggests that in patients with early-stage NSCLC, SBRT regimens with BED > 150 Gy may confer a survival benefit in patients with SCC histology. Histology-based dose modification should be considered, and prospective validation may be warranted.
Background:Skull-base chordomas and chondrosarcomas are rare tumors that arise directly adjacent to important critical structures. Appropriate management consists of maximal safe resection followed ...by postoperative dose-escalated radiation therapy. Proton beam therapy is often employed in this context to maximize the sparing of organs at risk, such as the brainstem and optic apparatus. METHODSThis is a single-institutional experience treating skull-base chordomas and chondrosarcomas with postoperative pencil beam scanning proton therapy. We employed a simultaneous integrated boost to the gross tumor volume (GTV) for increased conformality. Demographic, clinicopathologic, toxicity, and dosimetry information were collected. Toxicity was assessed according to Common Terminology Criteria for Adverse Events (CTCAE), v. 4.0. RESULTSBetween 2017 and 2020, 13 patients were treated with postoperative proton therapy. There were 10 patients with chordoma (77%) and three with chondrosarcoma (23%). A gross total resection was achieved in six (60%) patients with chordoma and one patient with chondrosarcoma (33%). Nine patients (69%) received postoperative therapy, whereas four (31%) received treatment at recurrence/progression following re-excision. The median dose to the GTV was 72.4 cobalt-Gray equivalents (range, 70.0 to 75.8). The mean GTV was 3.4 cc (range, 0.2-38.7). There were no grade 3 or greater toxicities. One patient developed grade 2 temporal lobe necrosis. At 10.7 months' median follow-up (range, 2.1-30.6), the rates of local control and overall survival were 100%. CONCLUSIONSProton beam therapy with pencil beam scanning and simultaneous integrated boost to the GTV affords excellent early local control with the suggestion of low morbidity. This method deserves consideration as an optimal method for limiting dose to adjacent organs at risk and delivering clinically effective doses to the treatment volume.
Preoperative chemoradiation represents the standard of care in patients with locally advanced rectal cancer. Robustness is often compromised in the setting of proton beam therapy owing to the ...sensitivity of proton particles to tissue heterogeneity, such as with intestinal gas. The ideal beam arrangement to mitigate the anatomic uncertainty caused by intestinal gas is not well defined.
We developed pencil beam scanning plans using (1) 1-beam posteroanterior (PA) plans, (2) 2-beam with right and left posterior oblique (RPO and LPO) plans, (3) 3-beam with PA and opposed lateral plans, and (4) 5-beam with PA, RPO, LPO, and opposed lateral plans. We created 12 plans with robustness optimization and ran a total of 60 plan evaluations for varying degrees of intestinal gas distension to evaluate which plans would maintain clinical goals to the greatest degree.
A single PA beam resulted in considerable loss of target coverage to the clinical target volume prescribed 50 Gy (volume receiving 100% of the prescribed dose V100% < 90%) with rectal distension ≥3 cm in diameter in the short axis. In contrast, the other field designs maintained coverage with up to 5 cm of distension. On plans generated based on a 5-cm distended rectum with air medium, the 1-beam, 3-beam, and 5-beam arrangements resulted in loss of target coverage (V100% < 90%) with rectal contraction ≤3 cm, whereas the 2-beam arrangement maintained coverage to as low as 2 cm. On plans generated based on a 3-cm distension of the rectum, both the 2-beam and 3-beam arrangements maintained V100% > 90% even with collapsed rectum to as low as 1 cm, simulating a patient treatment scenario without any rectal gas.
A single PA beam should be avoided when using proton beam therapy for rectal cancer. RPO/LPO and PA/opposed lateral arrangements may both be considered; RPO/LPO is favored to reduce integral dose and avoid beams traversing the hips. In patients for whom the plan CT has rectal distension of ≥3 cm, resimulation or strategies to reduce intestinal gas should be strongly considered.
Concurrent chemoradiation plays an integral role in the treatment of esophageal cancer. Proton beam radiation therapy has the potential to spare adjacent critical organs, improving toxicity profiles ...and potentially improving clinical outcomes.
We evaluated the REG001-09 registry for patients undergoing proton radiation therapy for esophageal cancer. Demographic, clinicopathologic, toxicity, and dosimetry information were compiled.
We identified 155 patients treated at 10 institutions between 2010 and 2019. One hundred twenty (77%) had adenocarcinoma and 34 (22%) had squamous cell carcinoma. One hundred thirty-seven (88%) received concurrent chemotherapy. The median delivered dose was 50.51 Gy-equivalent (GyE; range, 41.4-70.1). Grade ≥3 toxicities occurred in 22 (14%) of patients and were most commonly dysphagia (6%), esophagitis (4%), anorexia (4%), and nausea (2%). There were no episodes of grade ≥4 lymphopenia and no grade 5 toxicities. The average mean heart, lung, and liver doses and average maximum spinal cord dose were 10.0 GyE, 4.8 GyE, 3.8 GyE, and 34.2 GyE, respectively. For gastroesophageal junction tumors, 8% of patients developed acute grade ≥3 toxicity and the mean heart, liver, right kidney, and left kidney doses were 10.5 GyE, 3.9 GyE, 0.4 GyE, and 4.9 GyE, respectively. Gastroesophageal junction location was protective against development of grade ≥3 toxicity on univariate (P = .0009) and multivariate (P = .004) analysis.
Proton beam radiation therapy affords excellent dosimetric parameters and low toxicity in patients with esophageal cancer treated with curative intent. Prospective trials are underway investigating the comparative benefit of proton-based therapy.
The optimal management of patients with stage I-II squamous cell carcinoma (SCC) of the anus is controversial. The current study evaluates the efficacy of combined chemotherapy and radiation therapy ...(CRT) versus radiation therapy (RT) alone in the treatment of these patients using the Surveillance, Epidemiology, and End Results (SEER) registries.
SEER 18 Custom Data registries were queried for patients with stage I-II SCC of the anus. Univariate analysis (UVA) and multivariable analysis (MVA) using Kaplan-Meier and Cox proportional hazards regression modeling were performed. Propensity-score matched analysis with inverse probability of treatment weighting (IPTW) was used to account for indication bias.
A total of 4,288 patients with stage I-II disease were identified, of whom 3,982 (93%) underwent CRT and 306 (7%) underwent RT. Median follow-up was 42 months. Approximately 30.8% had T1 disease and 69.2% had T2-T3 disease. The IPTW-adjusted 5-year overall survival (OS) was 76.7%, with no significant differences between the CRT and RT groups (77%
73.5%, P=0.33). On multivariate IPTW-adjusted analysis, the lack of association between CRT use and OS was upheld (HR, 0.84, 95% CI, 0.65-1.08, P=0.2). On subgroup analyses, 5-year OS was 86% with CRT (n=1,216) and 84.2% with RT (n=103) (P=0.74) in stage I (T1N0) patients, while 5-year OS was 72.8% with CRT (n=2,766) and 66.4% with RT (n=203) (P=0.13) in stage II (T2-3N0) patients. CRT was associated with improved median OS in stage II patients (119 months
not reached, P=0.04).
The current study suggests that omission of concurrent chemotherapy is not associated with inferior OS in patients with stage I SCC of the anus. However, combined chemoradiation was superior to radiation alone in patients with stage II disease. Prospective evidence is needed to optimize clinical decision-making in this patient population.
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