Evaluation of time,attendance of medical staff,and resources during interstitial brachytherapy for prostate cancer

Introduction

The German Society of Radiation Oncology initiated a multicenter trial to evaluate core processes and subprocesses of radiotherapy by prospective evaluation of all important procedures in the most frequent malignancies treated by radiation therapy. The aim of this analysis was to assess the required resources for interstitial high-dose-rate (HDR) and low-dose-rate (LDR) prostate brachytherapy (BRT) based on actual time measurements regarding allocation of personnel and room occupation needed for specific procedures.

Patients and methods

Two radiotherapy centers (community hospital of Offenbach am Main and community hospital of Eschweiler) participated in this prospective study. Working time of the different occupational groups and room occupancies for the workflow of prostate BRT were recorded and methodically assessed during a 3-month period.

Results

For HDR and LDR BRT, a total of 560 and 92 measurements, respectively, were documented. The time needed for treatment preplanning was median 24 min for HDR (n?=?112 measurements) and 6 min for LDR BRT (n?=?21). Catheter implantation with intraoperative HDR real-time planning (n?=?112), postimplantation HDR treatment planning (n?=?112), and remotely controlled HDR afterloading irradiation (n?=?112) required median 25, 39, and 50 min, respectively. For LDR real-time planning (n?=?39) and LDR treatment postplanning (n?=?32), the assessed median duration was 91 and 11 min, respectively. Room occupancy and overall mean medical staff times were 194 and 910 min respectively, for HDR, and 113 and 371 min, respectively, for LDR BRT.

Conclusion

In this prospective analysis, the resource requirements for the application of HDR and LDR BRT of prostate cancer were assessed methodically and are presented for first time.     

Anmerkungen zum Problem der Dosierung in der HDR-Brachytherapie

Background

In HDR brachytherapy activity distributions can be achieved which were unknown in LDR brachytherapy. For this reason the classical dosage systems can only be used with caution in HDR brachytherapy.

Methods

Different simple applications are used to investigate the effect of various activity distributions on dose and integrated reference air kerma.

Results

Within the classical LDR dosage systems dose and integrated reference air kerma were equivalent. Due to the possibility to “opotimize” the activity distribution in HDR brachytherapy this is not longer the case. Different optimization algorithms and different optimization goals may lead to quite different activity distributions and different integrated reference air kerma values even if the source positions are the same. For target volume oriented optimization schemes a dosage system is described which is based on dose-volume-histograms.

Conclusions

A widely accepted dosage system in HDR brachytherapy is missing. The dosage system described in this paper may be useful in solving this problem.     

HDR and MDR intracavitary treatment for carcinoma of the uterine cervix

Aim

Treatment of carcinoma of the uterine cervix by remote afterloading brachytherapy has been accompanied with new isotopes having dose rates different from the classical low-dose rate (LDR) radium source. The dose rate conversion factor from LDR to high-dose rate (HDR) found to be around 0.54 in most studies. As regards medium-dose rate (MDR) brachytherapy, the published data are very few and the experience is still short. In this study the experience of Osaka University Hospital with micro-HDR-Selectron and Selectron-MDR, as a preliminary report of the clinical trial, is presented.

Patients and Method

From August 1991 through April 1993, a total of 45 patients with carcinoma of the uterine cervix were randomly allocated to either microSelectron-HDR or Selectron-MDR at the Osaka University Hospital. As regards HDR, dose to point A was adjusted to 32 Gy (for stages I and II), 30 Gy/4 fractions, and 22.5 Gy/3 fractions, for stages III, and IV, respectively. The corresponding values in case of MDR were 35.6, 34 Gy/4 fractions, and 25.5 Gy/3 fractions. External irradiation, according to the stage, was the same in the 2 groups. Nucletron Planning System (NPS) was used for pre-treatment dose calculation at point A, rectal and bladder wall. The dose rate at point A ranged from 24 to 75.6 cGy/min for the HDR group, while for the MDR group ranged among 174.8 to 229.6 cGy/h.

Results

The 3-year survival and loco-regional control rates for both modalities were nearly equivalent (62% and 67% for HDR and 68% and 74% for MDR). The cumulative rectal and bladder complication rates were the same in both groups (29% at 3 years), with only 1 patient (MDR-group) developed grade 3 rectal and bladder complication. In this study, point A dose rate correction factor from LDR to HDR was 0.53 and 0.6 from LDR to MDR.

Conclusion

From the previous reports from Osaka University Medical School, as well as others, HDR was proposed as an alternative to LDR brachytherapy for treatment of carcinoma of the uterine cervix. In this report, Selectron-MDR was nearly equivalent to the microSelectron-HDR as regards survival and loco-regional control rates as well as radiation-induced complication. This is a preliminary report, and the study still needs larger number of patients, and longer follow-up period.     

Computed tomography-guided interstitial high dose rate brachytherapy for centrally located liver tumours: a single institution study

Objectives

To evaluate the clinical outcome of computed tomography (CT)-guided interstitial (IRT) high-dose-rate (HDR) brachytherapy (BRT) in the treatment of unresectable primary and secondary liver malignancies. This report updates and expands our previously described experience with this treatment technique.

Methods

Forty-one patients with 50 tumours adjacent to the liver hilum and bile duct bifurcation were treated in 59 interventions of CT-guided IRT HDR BRT. The tumours were larger than 4 cm with a median volume of 84 cm³ (38–1,348 cm³). The IRT HDR BRT delivered a median total physical dose of 20.0 Gy (7.0–32.0 Gy) in twice daily fractions of median 7.0 Gy (4.0–10.0 Gy) in 19 patients and in once daily fractions of median 8.0 Gy (7.0–14.0 Gy) in 22 patients.

Results

With a median follow-up of 12.4 months, the local control for metastatic hepatic tumours was 89 %, 73 % and 63 % at 6, 12 and 18 months respectively. The local control for primary hepatic tumours was 90 %, 81 % and 50 % at 6, 12 and 18 months respectively. Severe side effects occurred in 5.0 % of interventions with no treatment-related deaths.

Conclusions

CT-guided IRT HDR BRT is a promising procedure for the radiation treatment of centrally located liver malignancies.

Key points

? Interstitial high-dose-rate brachytherapy (IRT HDR BRT) is a promising treatment for central liver tumours ? CT-guided IRT HDR BRT is safe for treating extensive tumours ? CT-guided IRT HDR BRT could play a role in managing unresectable hepatic malignancies     

Salvagebehandlung fortgeschrittener Plattenepithelkarzinome der Mundhöhle und des Oropharynx

Purpose

The clinical effect of high-dose-rate (HDR) interstitial brachytherapy combined with tumor resection was investigated in this retrospective study on patients with recurrent oral and oropharyngeal squamous cell carcinoma.

Patients and Methods

Oral and oropharyngeal squamous cell carcinoma in 38 patients were treated over a period of 7 years (1988–1994) by HDR interstitial brachytherapy using Gammamed 12i^® equipment. Pretreatment of patients in terms of irradiation and surgery differed (33 irradiated with a total dose between 60.0 and 75.6 Gy, including 8 patients with additional surgery; 1 patient with surgery alone, and 4 patients without any pretreatment). Indications for interstitial brachytherapy differed according to individual responses to treatment and medical histories.

Results

Interstitial brachytherapy was successful in the majority of patients, i. e. complete remission: 12, partial remission: 19, no change: 2, progression: 5. Local control and overall survival including patients with surgical treatment was 59% and 81% at 6 months and 47% and 49% after 12 months, respectively.

Conclusion

Interstitial HDR brachytherapy with Iridium 192 is recommended in patients with local recurrences or second primary carcinomas after previous external radiotherapy in the head and neck region. Combination of interstitial brachytherapy and surgery is preferable for these patients.     

Levodopa and pramipexole effects on presynaptic dopamine PET markers and estimated dopamine release

Purpose

Levodopa and dopamine (DA) agonist therapy are two common treatments for Parkinson’s disease (PD). There is controversy about the effects of these treatments on disease progression and imaging markers. Here we used multi-tracer positron emission tomography imaging and a unilateral 6-hydroxydopamine (6-OHDA) rat model of PD to evaluate in vivo the effects of chronic levodopa and pramipexole treatments on measurements of vesicular monoamine transporter type 2 (VMAT2), dopamine transporter (DAT) levels, and on levodopa-induced changes in synaptic DA levels [Δ(DA)].

Methods

Twenty-three unilaterally 6-OHDA lesioned rats underwent an ¹¹C-dihydrotetrabenazine (DTBZ, VMAT2 marker), an ¹¹C-methylphenidate (MP, DAT marker), and a double ¹¹C-raclopride (RAC, D₂-type receptor marker) scan. They were assigned to three treatment groups: saline (N?=?7), pramipexole (N?=?8), and levodopa (N?=?8). After 4 weeks of treatment, imaging was repeated.

Results

Results showed (1) a significant treatment effect on DTBZ, with pramipexole decreasing DTBZ binding compared to levodopa, (2) significant side and treatment-striatal side interaction effects for MP, indicating that levodopa tends to decrease MP binding compared to pramipexole, and (3) no treatment effect on Δ(DA).

Conclusion

These data indicate that while chronic dopaminergic pharmacological treatment affects DTBZ and MP binding, it does not affect levodopa-induced changes in synaptic DA level.     

Dynamic contrast–enhanced ultrasonographic (DCE-US) assessment of the early response after combined gemcitabine and HIFU with low-power treatment for the mouse xenograft model of human pancreatic cancer

Purpose

To assess therapeutic efficacy of gemcitabine and HIFU for a mouse model of pancreatic cancer, and the role of DCE-US for predicting early treatment response compared with pathology.

Materials and methods

In 48 PANC-1- nude mice (G1, HIFU_higher power [n?=?14]; G2, gemcitabine [n?=?12]; G3, combined gemcitabine and HIFU_low power [n?=?12]; and G4, control [n?=?10]), pulsed HIFU or gemcitabine therapy was used. DCE-US was performed 1 day before and after first treatment. Seven DCE-US perfusion parameters were obtained. Therapeutic efficacy was estimated using necrotic fraction and apoptosis. Correlation between tumour size and US perfusion parameters was analysed.

Results

Pathology results showed that combined gemcitabine and HIFU using low-power treatment had a more effective response than other treatments, including in the control group, i.e. necrotic fraction: 40.5?±?4.9 vs. 16.9?±?8.0, p?=?0.000 and apoptosis: 44.3?±?29.4 vs. 7.9?±?4.9, p?=?0.002. In this group, US perfusion parameters, including peak intensity (22.6?±?22.6 vs. 9.6?±?6.3, p?=?0.002), AUC (961.8?±?96.9 vs. 884.4?±?91.4, p?=?0.000), and AUC_out (799.9?±?75.6 vs. 747.1?±?77.9, p?=?0.000), had significantly decreased 1 day following first treatment (p?out showed a tendency to decrease in treated groups. Alternatively, peak intensity, AUC, and AUC_out showed a tendency to increase in control group.

Conclusion

Gemcitabine and HIFU were more effective and safer than other treatments. US perfusion parameters were useful for predicting early therapeutic response 1 day following treatment.

Key points

? Recently, treatment of pancreatic cancer has changed based on a multidisciplinary approach. ? Combined gemcitabine_HIFU demonstrated more effective therapeutic response than other treatments. ? DCE-US is useful for predicting early therapeutic response 1 day after treatment. ? In the combined group, PI, AUC, and AUC ^out decreased 1 day after treatment.     

Locally advanced verrucous carcinoma of the oral cavity

Background

Oral verrucous carcinomas are locally invasive but rarely metastasize. Current treatment options include surgery and external beam radiotherapy (EBRT). In medical inoperable patients or irresectable tumors, high-dose-rate (HDR) brachytherapy is a valid alternative.

Case

We present an 85-year-old man with functionally irresectable cT3N0M0 verrucous carcinoma superficially spreading along the upper alveolar ridge to the retro-alveolar triangle, with infiltration of the left soft and hard palate and buccal mucosa. Using a customized intraoral mold, this patient was treated with HDR brachytherapy delivering a dose of 48 Gy in 12 fractions three times per week. Treatment was well tolerated, and after prolonged confluent mucositis the tumor is in complete remission.

Review of literature and conclusion

The scarce literature on customized mold HDR brachytherapy in maxillary tumors is reviewed and recommendations for other head and neck tumors are given.     

High-dose rate intracavitary irradiation for carcinoma of the uterine cervix

Aim

To investigate the adverse effect of treatment prolongation on the local control and survival of the cervical carcinoma of the uterus.

Patients and Method

Two hundred and sixteen patients with stages IIB and III cervical carcinoma treated with a combination of external radiation and high-dose rate (HDR) intracavitary irradiation between 1978 and 1989 were retrospectively studied. A multivariate analysis was used to determine the effect of treatment time on local control and survival.

Results

Overall treatment time was the most highly significant factors for local control in the multivariate analysis (p=0.0005). The 5-year cumulative relapse rates were significantly different with the treatment times 35 to 42 days: 9% versus 43 to 49 days: 19% versus 50 to 62 days: 42% (p=0.001). The second most significant parameter was stage classification (p=0.02). Concerning relapse-free survival, stage classification (p=0.0001), overall treatment time (p=0.0035) and hemoglobin level (p=0.0174) were the 3 most important prognostic factors, although there was no relationship between treatment time and late complications.

Conclusion

These results suggest that prolongation of treatment time is associated with decreased local control and survival in patients treated with external radiation and HDR intracavitary irradiation.     

Beckenwandrezidive des Zervixkarzinoms

Purpose

The prognosis of patients with pelvic wall recurrences after primary therapy of cervical cancer is bad. In selected patients treated exclusively by surgery as primary therapy the 5-year survival rate was between 5 and 25%. Additionally the combination of operation and radiotherapy (CORT) improved the survival so far. We developed a new concept for the treatment of pelvic wall recurrences. This concept includes the combination of radical surgery, interstitial radiation and chemotheray — CORCT (combined operative- and radiochemotherapy).

Patients and Methods

After radical surgery, interstitial HDR (Ir-192) brachytherapy in afterloading technique (2.5 Gy, 2 fractions/day in 5 days) was performed. Additionally a chemotherapy with cisplatin 25 mg/m²/day in 5 days and 5-fluorouracil 1000 mg/day in 5 days was applicated.

Results

After combined operative- and radiotherapy 3 of 3 patients died after treatment within 8 months (median) because of distant metastases. After additive radiochemotherapy 3 of 4 patients had no evidence of disease (NED) after a follow-up period of 14 (12 to 30) months.

Conclusion

The first treatment results of the new designed combined operative- and radiochemotherapy concept (CORCT) led us to expect an improvement of the prognosis of patients with recurrences of cervical cancer at the pelvic wall.     

18F-Fluorodeoxyglucose PET/CT predicts tumour progression after transarterial chemoembolization in hepatocellular carcinoma

Purpose

¹⁸F-FDG PET monitoring of FDG uptake may be a useful tool for assessment of the biological behaviour of hepatocellular carcinoma (HCC). We evaluated the correlation between FDG uptake on ¹⁸F-FDG PET and clinical characteristics and prognosis.

Methods

In total, 58 HCC patients undergoing ¹⁸F-FDG PET before transarterial chemoembolization (TACE) between May 2007 and May 2010 at Seoul St. Mary’s Hospital were evaluated retrospectively. The predictive value of the ratio of maximal tumour standardized uptake value (SUV) to mean liver SUV (Tsuv _max/Lsuv _mean) was tested. Primary endpoints were the clinical characteristics and treatment response according to Tsuv _max/Lsuv _mean. The secondary endpoint was time to progression (TTP).

Results

A high SUV ratio (cutoff value 1.70) correlated significantly with tumour size (≥5 cm) and serum AFP level (≥400 ng/mL). Objective response rates were significantly different between those with a ratio above (15.7 %) and those with a ratio below (66.6 %) the cutoff value (P?=?0.023). Patients in the low SUV ratio group had a median TTP of 16.8 months compared with 8.1 months in the high SUV ratio group (P?=?0.011). Overall survival in the high SUV ratio group was worse than in the low SUV ratio group (median 56.5 vs. 23.3 months), although the difference was not statistically significant in a multivariate analysis.

Conclusion

Tumour metabolic activity (Tsuv _max/Lsuv _mean), assessed by PET/CT, is an independent predictor of response to TACE in patients with intermediate-stage HCC. Tsuv _max/Lsuv _mean can be used to predict tumour progression. Thus, ¹⁸F-FDG PET can provide valuable information for prediction of prognosis and aid in decisions regarding treatment strategy.     

A comparative analysis of overall survival between high-dose-rate and low-dose-rate brachytherapy boosts for unfavorable-risk prostate cancer

Purpose

External beam radiation therapy (EBRT) with low-dose-rate (LDR) brachytherapy boost has been associated with improved biochemical progression–free survival and overall survival (OS) compared with dose-escalated EBRT (DE-EBRT) alone for unfavorable-risk prostate cancer. However, it is not known whether high-dose-rate (HDR) boost provides a similar benefit. We compare HDR boost against LDR boost and DE-EBRT with respect to OS.

Intracavitary brachytherapy for carcinoma of the uterine cervix—Comparison of HDR (Ir-192) and MDR (Cs-137)—

Purpose

To compare the results of high dose rate (HDR) (Ir-192) and medium dose rate (MDR) (Cs-137) intracavitary brachytherapy (ICRT) for carcinoma of the uterine cervix.

Materials and Methods

Between May 1991 and March 2001, a total of 206 patients with Stage I-IVA previously untreated cervical cancer were treated with ICRT combined with external beam radiotherapy (EBRT). HDR was administered to a total of 135 patients: 22 patients in Stage I, 49 in Stage II, 56 in Stage III, and eight in Stage IVA. MDR was administered to a total of 71 patients: six patients in Stage I, 27 in Stage II, 33 in Stage III, and five in Stage IVA. The MDR at point A was 30 Gy/hour for HDR and 1.7 Gy/hour for MDR treatment, and the corresponding median follow-up periods for survivors were 55 and 68 months.

Results

For the HDR group, 5-year cause-specific survival rates were 90%, 78%, 53% and 33% for Stages I, II, III, and IVA, respectively. For the MDR group, the corresponding rates were 100%, 76%, 51%, and 40%. In the HDR group, 19 patients (14%) developed Grade 2 or higher late complications, and, in the MDR group, four patients (6%) did.

Conclusions

There was no statistically significant difference in cause-specific survivals between the results of HDR and MDR brachytherapy for cervical cancer. The incidence of late complications tended to be higher for the HDR group than for the MDR group, but did not show a statistically significant difference (p=0.07).     

11C-Choline PET/CT as a guide to radiation treatment planning of lymph-node relapses in prostate cancer patients

Purpose

To evaluate, in prostate cancer (PCa) patients the potential of ¹¹C-choline PET/CT as a guide to helical tomotherapy (HTT) of lymph-node (LN) relapses with simultaneous integrated boost (SIB). The efficacy and feasibility of HTT in terms of acute toxicity were assessed.

Methods

We enrolled 83 PCa patients (mean age 68 years, range 51 – 82 years) with biochemical recurrence after radical primary treatment (mean serum PSA 7.61 ng/ml, range 0.37 – 187.00 ng/ml; PSA₀) who showed pathological findings on ¹¹C-choline PET/CT only at the LN site. ¹¹C-Choline PET/CT was performed for restaging and then for radiation treatment planning (PET/CT₀). Of the 83 patients, 8 experienced further LN relapse, of whom 5 were retreated once and 3 were retreated twice (total 94 radiotherapy treatments). All pelvic and/or abdominal LNs positive on PET/CT₀ were treated with high doses using SIB. Doses were in the range 36 – 74 Gy administered in 28 fractions. After the end of HTT (mean 83 days, range 16 – 365 days), serum PSA was measured in all patients (PSA₁) and compared with PSA₀ to evaluate early biochemical response. In 47 patients PET/CT was repeated (PET/CT₁) to assess metabolic responses at the treated areas. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) were used to assess acute toxicity.

Results

PET/CT₀ revealed pathological LNs in the pelvis in 49 patients, pathological LNs in the abdomen in 15 patients pathological LNs in both the pelvis and abdomen in 18 patients, and pathological LNs in the pelvis or abdomen and other sites in 12 patients. All these sites were treated with HTT. With respect to PSA₀, PSA₁ (mean 6.28 ng/ml, range 0.00 – 220.46 ng/ml) showed a complete biochemical response after 66 of the 94 HTT treatments, a partial response after 12 treatments, stable disease after 1 treatment and progression of disease after 15 treatments. Of the 47 patients receiving PET/CT₁, 20 showed a complete metabolic response at the treated area, 22 a partial metabolic response, 3 progression of disease and 2 stable disease. HTT with SIB was well tolerated in all patients. Grade 3 acute toxicity in the genitourinary tract was observed in two patients.

Conclusion

¹¹C-Choline PET/CT is a valuable tool for planning and monitoring HTT in LN relapse after primary treatment. High-dose hypofractionated ¹¹C-choline PET/CT-guided HTT with SIB is well tolerated and is associated with a high early biochemical response rate.     

Interstitial hyperthermia of the prostate in combination with brachytherapy

Objective

A retrospective study to evaluate the feasibility and toxicity of interstitial hyperthermia (IHT) combined with high-dose-rate (HDR) brachytherapy as the initial treatment for low- and intermediate-risk prostate cancer, and as a salvage therapy in previously irradiated patients with local recurrence.

Patients and methods

Between 18 December 2008 and 5 September 2012, 73  prostate cancer patients were treated with interstitial HDR brachytherapy of the prostate combined with IHT. In 54 patients this was the initial therapy for prostate cancer, while the other 19 were treated for local recurrence after previously undergoing external beam radiotherapy (EBRT). Toxicity for the organs of the genitourinary system and rectum was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) v. 4.03 within 3 months after treatment.

Results

Median follow-up was 15 months (range 3–46). The combination of HDR brachytherapy and IHT was well tolerated. The toxicity profile was similar to that of HDR brachytherapy when not combined with hyperthermia. The most common minor complications were urinary frequency (grade 1: 37?%; grade 2: 22?%), nocturia (three times per night: 29?%; four- or more times per night: 20?%) and transient weakening of the urine stream (grade 1: 36?%; grade 2: 11?%). No early rectal complications were observed in the patient group and the severity of genitourinary toxicity was only grade 1–2.

Conclusion

Early tolerance of IHT in combination with HDR brachytherapy is good. Further prospective clinical studies should focus on the effects of combining IHT with HDR brachytherapy and the influence of this adjuvant therapy on biochemical disease-free survival, local control and overall survival.     

Influence of manipulating hypoxia in solid tumors on the radiation dose-rate effect in vivo, with reference to that in the quiescent cell population

Purpose

The aim of this study was to clarify the effect of manipulating intratumor hypoxia on radiosensitivity under reduced dose-rate (RDR) irradiation.

Materials and methods

Tumor-bearing mice were continuously given 5-bromo-2′-deoxyuridine (BrdU) to label all proliferating (P) cells. They received γ-rays or accelerated carbon-ion beams at high dose-rate (HDR) or RDR with or without tumor clamping to induce hypoxia. Some mice without clamping received nicotinamide, an acute hypoxia-releasing agent or misonidazole, a hypoxic cell radio-sensitizer before irradiation. The responses of quiescent (Q) and total (= P + Q) cells were assessed by the micronucleus frequency using immunofluorescence staining for BrdU.

Results

The clearer decrease in radiosensitivity in Q than total cells after RDR γ-ray irradiation was suppressed with carbon-ion beams, especially with a higher linear energy transfer value. Repressing the decrease in the radiosensitivity under RDR irradiation through keeping tumors hypoxic during irradiation and enhancing the decrease in the radiosensitivity by nicotinamide were clearer with γ-rays and in total cells than with carbon-ion beams and in Q cells, respectively. Inhibiting the decrease in the radiosensitivity by misonidazole was clearer with γ-rays and in Q cells than with carbon-ion beams and in total cells, respectively.

Conclusion

Manipulating hypoxia during RDR as well as HDR irradiation influences tumor radiosensitivity, especially with γ-rays.     

A comprehensive,targeted approach to the clinical care of athletes following sport-related concussion

Purpose

The purpose of this paper is to discuss risk and prognostic factors for concussion outcomes, review comprehensive approaches to assessment, and describe a new method for conceptualizing treatment for sport-related concussion using clinical experience.

Methods

Based on the current literature of sport-related concussion and clinical experience, an approach for conceptualizing concussion care using clinical trajectories and targeted treatments was developed.

Results

A comprehensive approach to assessment and targeted treatments for sport-related concussion was developed using specific clinical trajectories.

Conclusion

Sport-related concussions are heterogeneous and require an individualized clinical approach. The use of a comprehensive approach for assessing specific clinical trajectories following a sport-related concussion will help clinicians better conceptualize this injury. Clinicians can then match targeted treatment pathways to specific clinical trajectories to accelerate safe return to play for athletes following a sport-related concussion.

Level of evidence

V.