International Journal of Particle Therapy最新文献

Purpose: To determine the rib fracture rate in a cohort of patients with breast cancer treated with proton therapy.

Patient and methods: From a prospective database, we identified 225 patients treated with proton therapy between 2012 and 2020 (223 women; 2 men). Clinical and dosimetric data were extracted, the cumulative incidence method assessed rib fracture rate, and Fine-Gray tests assessed prognostic significance of select variables. In-field rib fracture was defined as a fracture that occurred in a rib located within the 10% isodose line. Out-of-field rib fracture was defined as a fracture occurring in a rib location outside of the 10% isodose line.

Results: Of the patients, 74% had left-sided breast cancer; 5%, bilateral; and 21%, right-sided. Dual-energy x-ray absorptiometry scans showed normality in 20%, osteopenia in 34%, and osteoporosis in 6% (test not performed in 40%). Additionally, 57% received an aromatase inhibitor. Target volumes were breast ± internal mammary nodes (IMNs) (16%), breast and comprehensive regional lymphatics (32%), chest wall ± IMNs (1%), and chest wall/comprehensive regional lymphatics (51%). Passive-scattered proton therapy was used for 41% of patients, 58% underwent pencil-beam scanning (PBS), and 1% underwent a combination (passive scattering/PBS), with 85% of patients receiving a boost. Median follow-up was 3.1 years, with 97% having >12-month follow-up. The 3-year cumulative in-field rib fracture incidence was 3.7%. Eight patients developed in-field rib fractures (1 symptomatic, 7 imaging identified) for a 0.4% symptomatic rib fracture rate. Median time from radiation completion to rib fracture identification was 1.8 years (fractures were identified within 2.2 years for 7 of 8 patients). No variables were associated with rib fracture on univariate analysis. Three fractures developed outside the radiation field (0.9% cumulative incidence of out-of-field rib fracture).

Conclusion: In this series of patients with breast cancer treated with proton therapy, the 3-year rib fracture rates remain low (in-field 3.7%; symptomatic 0.4%). As in photon therapy, the asymptomatic rate may be underestimated owing to a lack of routine surveillance imaging. However, patients experiencing symptomatic rib fractures after proton therapy for breast cancer are rare.

Purpose: When treating esophageal cancer with radiation therapy, it is critical to limit the dose to surrounding structures, such as the lung and/or heart, as much as possible. Proton radiation therapy allows a reduced radiation dose to both the heart and lungs, potentially reducing the risk of cardiopulmonary toxicity. Here, we report disease control, survival, and toxicity outcomes among patients with esophageal cancer treated with proton radiation therapy and concurrent chemotherapy (chemoradiation therapy; CRT) with or without surgery.

Materials and methods: We enrolled 17 patients with thoracic esophageal carcinoma on a prospective registry between 2010 and 2021. Patients received proton therapy to a median dose of 50.4-GyRBE (range, 50.4-64.8) in 1.8-Gy fractions.Acute and late toxicities were graded per the Common Terminology Criteria for Adverse Events, version 4.0 (US National Cancer Institute, Bethesda, Maryland). In addition, disease control, patterns of failure, and survival outcomes were collected.

Results: Nine patients received preoperative CRT, and 8 received definitive CRT. Overall, 88% of patients had adenocarcinoma, and 12% had squamous cell carcinoma. With a median follow-up of 2.1 years (range, 0.5-9.4), the 3-year local progression-free, disease-free, and overall survival rates were 85%, 66%, and 55%, respectively. Two patients (1 with adenocarcinoma and 1 with squamous cell carcinoma) recurred at the primary site after refusing surgery after a complete clinical response to CRT. The most common acute nonhematologic and hematologic toxicities, respectively, were grades 1 to 3 esophagitis and grades 1 to 4 leukopenia, both affecting 82% of patients. No acute cardiopulmonary toxicities were observed in the absence of surgical resection. Reagarding surgical complications, 3 postoperative cardiopulmonary complications occurred as follows: 1 grade 1 pleural effusion, 1 grade 3 pleural effusion, and 1 grade 2 anastomotic leak. Two severe late CRT toxicities occurred: 1 grade 5 tracheoesophageal fistula and 1 grade 3 esophageal stenosis requiring a feeding tube.

Conclusion: Proton radiation therapy is a safe, effective treatment for esophageal cancer with increasing evidence supporting its role in reducing cardiopulmonary toxicity.

Fast neutron therapy has been used for decades. In conjunction with recent advances in photonic techniques, fast neutrons are no longer of much oncologic interest, which is not unequivocally positive, given their undoubted therapeutic value. This mini-review recalls the history of medical research on fast neutrons, considers their physical and radiobiological properties alongside their benefits for cancer treatment, and discusses their place in modern radiation oncology.

Purpose: Proton therapy is an emerging therapy for several malignancies owing to its favorable therapeutic ratio. There are very limited data on the use of proton therapy in the management of thyroid carcinoma. Our objective was to review the safety, feasibility, and outcomes of proton therapy for patients with thyroid cancer treated to the head and neck.

Methods: From our institution's proton database from 2012 to 2021, we identified 22 patients with thyroid cancer treated with proton beam therapy. We evaluated outcomes and toxicities.

Results: Median follow-up was 26 months. Of the 22 patients, 50% were female. The mean age was 65 years. Three patients had anaplastic cancer; 13, papillary carcinoma; 2, follicular carcinoma; and 2, poorly differentiated carcinoma. Forty-six percent had T4 disease. Primary targets were the central neck compartment, level VI, and upper mediastinum. Radiation dose was 60 GyRBE adjuvantly, and 70 GyRBE for gross disease (range, 6000-7600 GyRBE). Eight patients underwent upfront adjuvant radiation, and 3 received definitive radiation for unresectable disease upfront. Eleven patients received either salvage or palliative radiation. Fifty-nine percent of patients had extrathyroidal extension, and 64% of patients had gross disease in the neck before treatment. Fifty percent of patients had metastatic disease before treatment. Sixteen patients received concurrent chemotherapy, 63% of these patients received doxorubicin. For all patients, 1-year local regional recurrence (LRR) was 0%, and overall survival (OS) was 90%. Acute grade 3+ toxicities occurred in 27% of patients, the most frequent being dermatitis (27%). Three patients required a percutaneous endoscopic gastrostomy tube after radiation therapy (RT), 2 owing to progression. There were no grade 4+ toxicities.

Conclusions: Proton therapy for thyroid cancer appears feasible and effective with minimal toxicities. Prospective studies comparing proton therapy with intensity-modulated RT, to evaluate the clinical efficacy of using proton therapy to reduce toxicities in patients undergoing radiation for thyroid cancer, are warranted.

Purpose: Reports of proton beam therapy (PBT) utilization for cutaneous melanoma of the head and neck (HN) region is virtually non-existent. This study reports on the efficacy and acute toxicities of PBT for primary HN cutaneous melanoma.

Materials and methods: We queried the prospectively collected, multi-institutional Proton Collaborative Group registry for all consecutive patients with HN cutaneous melanoma receiving PBT from May 2010 to December 2019. Kaplan-Meier methods were used to estimate overall survival (OS), progression free survival (PFS), and local regional recurrence free survival (LRFS). Toxicity was reported per CTCAE version 4.0.

Results: A total of 8 patients were identified with a median age of 69 (range, 37-88). All patients (100%) underwent surgery followed with postoperative PBT. There were 3 patients (37.5%) with T3 or T4 disease and 4 (50%) with N2 or N3 disease. The median radiation dose was 46 GyRBE (range, 27-70) and median dose per fraction was 2.4 GyRBE (range, 2.0-6.0) with the most common dose fractionation being 44 or 48 GyRBE in 20 fractions (n = 4). At a median follow-up of 40.1 months (range, 1.6-62.4) the 1 and 3 year OS rates were 85.7% and 35.7%, respectively. The median PFS was 25.40 months (95% CI, 2.53-58.70) while PFS at 1 year and 3 years was 85.7% and 35.7%, respectively. LRFS was 100% at 1 year and 85.7% at 3 years. Five of the 8 patients developed distant metastases, of which 3 received immunotherapy. Acute G2+ and G3+ toxicities occurred in 5 of 8 patients and 2 of 8 patients, respectively. G3 toxicities included radiation dermatitis (n = 1) and immunotherapy-related rash (n = 1). No G4+ toxicities were reported.

Conclusion: Single modality PBT for HN melanomas in the definitive setting provides effective and durable local control rates with tolerable acute toxicity. Distant failure remains the primary pattern of failure.

Purpose: We present an analysis of various operational metrics for a novel compact proton therapy system, including clinical case mix, subsystems utilization, and quality assurance trends in beam delivery parameters over a period of 5 years.

Materials and methods: Patient-specific data from a total of 850 patients (25,567 fractions) have been collected and analyzed. The patient mix include a variety of simple, intermediate, and complex cases. Beam-specific delivery parameters for a total of 3585 beams were analyzed. In-room imaging system usage for off-line adaptive purpose is reported. We also report key machine performances metrics based on routine quality assurance in addition to uptime.

Results: Our analysis shows that system subcomponents including gantry and patient positioning system have maintained a tight mechanical tolerance over the 5-year period. Various beam parameters were all within acceptable tolerances with no clear trends. Utilization frequency histograms of gantry and patient positioning system show that only a small fraction of all available angles was used for patient deliveries with cardinal angels as the most usable. Similarly, beam-specific metrics, such as range, modulation, and air gaps, were clustered unevenly over the available range indicating that this compact system was more than capable to treat the complex variety of tumors of our patient mix.

Conclusion: Our data show that this compact system is versatile, robust, and capable of delivering complex treatments like a large full-gantry system. Utilization data show that a fraction of all subcomponents range of angular motion has been used. Compilation of beam-specific metrics, such as range and modulation, show uneven distributions with specific clustering over the entire usable range. Our findings could be used to further optimize the performance and cost-effectiveness of future compact proton systems.

Purpose: To investigate whether volumetric-modulated proton arc therapy (VPAT) plans generate comparable doses to organs at risk (OARs) compared with interstitial high-dose-rate (iHDR) brachytherapy for patients with gynecologic cancer with disease extension to parametrial/pelvic side wall, who are not eligible for the aggressive procedure.

Materials and methods: VPAT delivers proton arc beams by modulated energies at the beam nozzle while maintaining the same incident energy to the gantry during the arc rotation. Plans of 10 patients previously treated with iHDR brachytherapy for high-risk clinical treatment volumes (HRCTV; 31.8-110.6 cm³; lateral dimensions, 4.2-5.6 cm) were selected and compared with VPAT plans. VPAT plans for each patient were designed using a 152- to 245-MeV range of energy-modulated proton beams.

Results: HRCTV coverage of the VPAT plans was comparable to that of the iHDR plans, with V150% showing no statistical differences. On average, the V100% and V90% of VPAT plans were higher than those of the iHDR plans, 95.0% vs 91.9% (P = .02) and 98.6% vs 97.5% (P = .02), respectively. D100 was also 17% higher for the VPAT plans (P = .03). On average, the D_2cm³ of bladder, rectum, and small bowels in the VPAT plans were considerably lower than those in iHDR plans (by 17.4%, 35.2%, and 65.6%, respectively; P < .05 for all OARs).

Conclusion: VPAT-generated plans were dosimetrically superior to those with HDR brachytherapy with interstitial needles for locally advanced gynecologic cancer with parametrial/pelvic side wall disease extension. Dosimetrically, VPAT provides a noninvasive alternative to iHDR brachytherapy with a superior dosimetric profile.

Purpose: Finite proton range affords improved dose conformality of radiation therapy when patient regions-of-interest geometries are well characterized. Substantial changes in patient anatomy necessitate re-planning (RP) to maintain effective, safe treatment. Regularly planned verification scanning (VS) is performed to ensure consistent treatment quality. Substantial resources, however, are required to conduct an effective proton plan verification program, which includes but is not limited to, additional computed tomography (CT) scanner time and dedicated personnel: radiation therapists, medical physicists, physicians, and medical dosimetrists.

Materials and methods: Verification scans (VSs) and re-plans (RPs) of 711 patients treated with proton therapy between June 2015 and June 2018 were studied. All treatment RP was performed with the intent to maintain original plan integrity and coverage. The treatments were classified by anatomic site: brain, craniospinal, bone, spine, head and neck (H&N), lung or chest, breast, prostate, rectum, anus, pelvis, esophagus, liver, abdomen, and extremity. Within each group, the dates of initial simulation scan, number of VSs, number of fractions completed at the time of VS, and the frequency of RP were collected. Data were analyzed in terms of rate of RP and individual likelihood of RP.

Results: A total of 2196 VSs and 201 RPs were performed across all treatment sites. H&N and lung or chest disease sites represented the largest proportion of plan modifications in terms of rate of re-plan (RoR: 54% and 58%, respectively) and individual likelihood of RP on a per patient basis (likelihood of RP [RP%]: 46% and 39%, respectively). These sites required RP beyond 4 weeks of treatment, suggesting continued benefit for frequent, periodic VS. Disease sites in the lower pelvis demonstrated a low yield for RP per VS (0.01-0.02), suggesting that decreasing VS frequency, particularly late in treatment, may be reasonable.

Conclusions: A large degree of variation in RoR and individual RP% was observed between anatomic treatment sites. The present retrospective analysis provides data to help develop anatomic site-based VS protocols.

Purpose: In patients treated with chemoradiation for esophageal cancer (EC), randomized trial data demonstrate that proton beam therapy (PBT) reduces toxicities and postoperative complications (POCs) compared with intensity-modulated radiation therapy (IMRT). However, whether radiation therapy modality affects postoperative health care resource utilization remains unknown.

Materials and methods: We examined 287 patients with EC who received chemoradiation (prescribed 50.4 Gy/GyE) followed by esophagectomy, including a real-world observational cohort of 237 consecutive patients treated from 2007 to 2013 with PBT (n = 81) versus IMRT (n = 156); and an independent, contemporary comparison cohort of 50 patients from a randomized trial treated from 2012 to 2019 with PBT (n = 21) versus IMRT (n = 29). Postoperative complications were abstracted from medical records. Health care charges were obtained from institutional claims and adjusted for inflation (2021 dollars). Charge differences (Δ = $PBT - $IMRT) were compared by treatment using adjusted generalized linear models with the gamma distribution.

Results: Baseline PBT versus IMRT characteristics were not significantly different. In the observational cohort, during the neoadjuvant chemoradiation phase, health care charges were higher for PBT versus IMRT (Δ = +$71,959; 95% confidence interval [CI], $62,274-$82,138; P < .001). There was no difference in surgical charges (Δ = -$2234; 95% CI, -$6003 to $1695; P = .26). However, during postoperative hospitalization following esophagectomy, health care charges were lower for PBT versus IMRT (Δ = -$25,115; 95% CI, -$37,625 to -$9776; P = .003). In the comparison cohort, findings were analogous: Charges were higher for PBT versus IMRT during chemoradiation (Δ = +$61,818; 95% CI, $49,435-$75,069; P < .001), not different for surgery (Δ = -$4784; 95% CI, -$6439 to $3487; P = .25), and lower for PBT postoperatively (Δ = -$27,048; 95% CI, -$41,974 to -$5300; P = .02). Lower postoperative charges for PBT were especially seen among patients with any POCs in the contemporary comparison (Δ = -$176,448; 95% CI, -$209,782 to -$78,813; P = .02).

Conclusion: Higher up-front chemoradiation resource utilization for PBT in patients with EC was partially offset postoperatively, moderated by reduction in POC risks. Results extend existing clinical evidence of toxicity reduction with PBT.

Purpose: To compare the late gastrointestinal (GI) and genitourinary toxicities (GU) estimated using multivariable normal tissue complication probability (NTCP) models, between pencil-beam scanning proton beam therapy (PBT) and helical tomotherapy (HT) in patients of high-risk prostate cancers requiring pelvic nodal irradiation (PNI) using moderately hypofractionated regimen.

Materials and methods: Twelve consecutive patients treated with PBT at our center were replanned with HT using the same planning goals. Six late GI and GU toxicity domains (stool frequency, rectal bleeding, fecal incontinence, dysuria, urinary incontinence, and hematuria) were estimated based on the published multivariable NTCP models. The ΔNTCP (difference in absolute NTCP between HT and PBT plans) for each of the toxicity domains was calculated. A one-sample Kolmogorov-Smirnov test was used to analyze distribution of data, and either a paired t test or a Wilcoxon matched-pair signed rank test was used to test statistical significance.

Results: Proton beam therapy and HT plans achieved adequate target coverage. Proton beam therapy plans led to significantly better sparing of bladder, rectum, and bowel bag especially in the intermediate range of 15 to 40 Gy, whereas doses to penile bulb and femoral heads were higher with PBT plans. The average ΔNTCP for grade (G)2 rectal bleeding, fecal incontinence, stool frequency, dysuria, urinary incontinence, and G1 hematuria was 12.17%, 1.67%, 2%, 5.83%, 2.42%, and 3.91%, respectively, favoring PBT plans. The average cumulative ΔNTCP for GI and GU toxicities (ΣΔNTCP) was 16.58% and 11.41%, respectively, favoring PBT. Using a model-based selection threshold of any G2 ΔNTCP >10%, 67% (8 patients) would be eligible for PBT.

Conclusion: Proton beam therapy plans led to superior sparing of organs at risk compared with HT, which translated to lower NTCP for late moderate GI and GU toxicities in patients of prostate cancer treated with PNI. For two-thirds of our patients, the difference in estimated absolute NTCP values between PBT and HT crossed the accepted threshold for minimal clinically important difference.