Feasibility and clinical implementation of MRI-guided surface brachytherapy.

Purpose: Best practices for high-dose-rate surface applicator brachytherapy treatment (SABT) have long relied on computed tomography (CT)-based imaging to visualize diseased sites for treatment planning. Compared with magnetic resonance (MR)-based imaging, CT provides insufficient soft tissue contrast. This work described the feasibility of clinical implementation of MR-based imaging in SABT planning to provide individualized treatment optimization. Material and methods: A 3D-printed phantom was used to fit Freiberg flap-style (Elekta, The Netherlands) applicator. Images were taken using an optimized pointwise encoding time reduction with radial acquisition (PETRA) MR sequence for catheter visualization, and a helical CT scan to generate parallel treatment plans. This clinical study included three patients undergoing SABT for Dupuytren's contracture/palmar fascial fibromatosis imaged with the same modalities.SABT planning was performed in Oncentra Brachy (Elekta Brachytherapy, The Netherlands) treatment planning software. A geometric analysis was conducted by comparing CT-based digitization with MR-based digitization. CT and MR dwell positions underwent a rigid registration, and average Euclidean distances between dwell positions were calculated. A dosimetric comparison was performed, including point-based dose difference calculations and volumetric segmentations with Dice similarity coefficient (DSC) calculations. Results: Euclidean distances between dwell positions from CT-based and MR-based plans were on average 0.68 ±0.05 mm and 1.35 ±0.17 mm for the phantom and patients, respectively. The point dose difference calculations were on average 0.92% for the phantom and 1.98% for the patients. The D95 and D90 DSC calculations were both 97.9% for the phantom, and on average 93.6% and 94.2%, respectively, for the patients. Conclusions: The sub-millimeter accuracy of dwell positions and high DSC's (> 0.95) of the phantom demonstrated that digitization was clinically acceptable, and accurate treatment plans were produced using MR-only imaging. This novel approach, MRI-guided SABT, will lead to individualized prescriptions for potentially improved patient outcomes.

Phototherapy Restores Deficient Type I IFN Production and Enhances Antitumor Responses in Mycosis Fungoides.

Transcriptional profiling demonstrated markedly reduced type I IFN gene expression in untreated mycosis fungoides (MF) skin lesions compared with that in healthy skin. Type I IFN expression in MF correlated with antigen-presenting cell-associated IRF5 before psoralen plus UVA therapy and epithelial ULBP2 after therapy, suggesting an enhancement of epithelial type I IFN. Immunostains confirmed reduced baseline type I IFN production in MF and increased levels after psoralen plus UVA treatment in responding patients. Effective tumor clearance was associated with increased type I IFN expression, enhanced recruitment of CD8+ T cells into skin lesions, and expression of genes associated with antigen-specific T-cell activation. IFNk, a keratinocyte-derived inducer of type I IFNs, was increased by psoralen plus UVA therapy and expression correlated with upregulation of other type I IFNs. In vitro, deletion of keratinocyte IFNk decreased baseline and UVA-induced expression of type I IFN and IFN response genes. In summary, we find a baseline deficit in type I IFN production in MF that is restored by psoralen plus UVA therapy and correlates with enhanced antitumor responses. This may explain why MF generally develops in sun-protected skin and suggests that drugs that increase epithelial type I IFNs, including topical MEK and EGFR inhibitors, may be effective therapies for MF.

Salvage brachytherapy for multiply recurrent metastatic brain tumors: A matched case analysis.

Background: Patients with recurrent brain metastases who have exhausted external radiation options pose a treatment challenge in the setting of advances in systemic disease control which have improved quality of life and survival. Brachytherapy holds promise as salvage therapy given its ability to enforce surgical cytoreduction and minimize regional toxicity. This study investigates the role of salvage brachytherapy in maintaining local control for recurrent metastatic lesions. Methods: We retrospectively reviewed our institution's experience with brachytherapy in patients with multiply recurrent cerebral metastases who have exhausted external radiation treatment options (14 cases). The primary outcome of the study was freedom from local recurrence (FFLR). To capture the nuances of tumor biology, we compared FFLR achieved by brachytherapy to the preceding treatment for each patient. We further compared the response to brachytherapy in patients with lung cancer (8 cases) against a matched cohort of maximally radiated lung brain metastases (10 cases). Results: Brachytherapy treatment conferred significantly longer FFLR compared to prior treatments (median 7.39 vs 5.51 months, P = .011) for multiply recurrent brain metastases. Compared to an independent matched cohort, brachytherapy demonstrated superior FFLR (median 8.49 vs 1.61 months, P = .004) and longer median overall survival (11.07 vs 5.93 months, P = .055), with comparable side effects. Conclusion: Brachytherapy used as salvage treatment for select patients with a multiply recurrent oligometastatic brain metastasis in the setting of well-controlled systemic disease holds promise for improving local control in this challenging patient population.

Characterization of clinical outcomes after shorter course hypofractionated and standard-course radiotherapy for stage I-III curatively-treated Merkel cell carcinoma.

BACKGROUND: Limited data exists regarding the efficacy of curative hypofractionated radiotherapy (hypo-RT) regimens compared to conventionally-fractionated radiotherapy (conv-RT) for Merkel cell carcinoma (MCC). METHODS: A retrospective analysis of 241 patients diagnosed with non-metastatic MCC from 2005-2021 and who received RT at Dana-Farber/Brigham & Women's Cancer Center. The primary outcome was cumulative incidence of in-field locoregional relapse using Gray's test with competing risks of death and isolated out-of-field recurrence. Secondary outcomes included overall survival (OS) and MCC-specific survival using log-rank tests, and risk factors of recurrence using Cox-proportional hazards regression. RESULTS: There were 50 (20.6 %) and 193 (79.4 %) courses of hypo-RT and conv-RT, respectively. The hypo-RT cohort was older (≥73 years at diagnosis: 78.0 % vs 41.5 %, p < 0.01), and received a lower equivalent total RT dose in 2 Gy per fraction (<50 Gy: 58.0 % vs 5.2 %, p < 0.01). Median follow-up was 65.1 months (range: 1.2-194.5) for conv-RT and 25.0 months (range: 1.6-131.3) for hypo-RT cohorts. Two-year cumulative incidence of in-field locoregional relapse was low in both groups (1.1 % conv-RT vs 4.1 % hypo-RT, p = 0.114). While two-year OS was lower for the hypo-RT group (62.6 % vs 84.4 %, p = 0.0008), two-year MCC-specific survival was similar (84.7 % vs 86.6 %, p = 0.743). On multivariable analysis, immunosuppression, clinical stage III disease, and lymphovascular invasion were associated with any-recurrence when controlling for sex, age, and hypo-RT. CONCLUSIONS AND RELEVANCE: There was no difference in cumulative incidence of in-field locoregional relapse or MCC-specific survival between hypo-RT and conv-RT. Prospective studies are needed to confirm hypo-RT as an efficacious treatment option for MCC.

ACR-ABS-ASTRO Practice Parameter for the Performance of Low-Dose-Rate Brachytherapy.

AIM/OBJECTIVES/BACKGROUND: The American College of Radiology (ACR), the American Brachytherapy Society (ABS), and the American Society for Radiation Oncology (ASTRO) have jointly developed the following practice parameter for the performance of low-dose-rate (LDR) brachytherapy. LDR brachytherapy is the application of radioactive sources in or on tumors in a clinical setting with therapeutic intent. The advantages of LDR brachytherapy include improving therapeutic ratios with lower doses to nontarget organs-at-risk and higher doses to a specific target. METHODS: This practice parameter was developed according to the process described under the heading. The Process for Developing ACR Practice Parameters and Technical Standards on the ACR website (https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters-Radiation Oncology of the Commission on Radiation Oncology, in collaboration with ABS and ASTRO. RESULTS: This practice parameter was developed to serve as a tool in the appropriate application of this evolving technology in the care of cancer patients or other patients with conditions where radiation therapy is indicated. It addresses clinical implementation of LDR brachytherapy including personnel qualifications, quality assurance standards, indications, and suggested documentation. This includes a contemporary literature search. CONCLUSIONS: This practice parameter is a tool to guide the use of LDR brachytherapy and does not assess relative clinical indication for LDR brachytherapy when compared with other forms of brachytherapy or external beam therapy, but to focus on the best practices required to deliver LDR brachytherapy safely and effectively, when clinically indicated. Comparative costs of versus other modalities therapy may also need to be considered.

Feasibility of magnetic resonance-only high-dose-rate surface brachytherapy for clinical application.

PURPOSE: In this article, we investigate the feasibility of magnetic resonance (MR)-only imaging for high-dose-rate (HDR) surface brachytherapy (SABT). We examined whether a standard CT-based planning can be replaced with an MR-only planning. For this purpose, the MRI digitization and plan quality check processes were compared against the standard CT-based processes. A prospective clinical implementation of the MR-only planning was evaluated on a clinical data set. METHODS: A pointwise encoding time reduction with radial acquisition (PETRA) sequence was optimized for visualization of Freiburg flap (FF) on MR images. MR and conventional CT images were acquired with a FF applicator (Elekta, Stockholm, Sweden) placed on the following phantoms: (1) flat styrofoam (FST), FF locked-in placed with supporting structure; (2) cast-made facemask, and (3) porcine leg (PL). Catheters were digitized and activated with 10 mm step size on Oncentra Brachy 4.5.3 Treatment Planning System. The CT-only and MR-only treatment plans were generated by optimizing the dose to the target defined as volume at 3 mm skin depth. To compare the plans, the MRI-to-CT alignment was performed via rigid registration. Positional displacements of dwell positions between CT and MR plans were compared on the FST phantom and the relative percent dose difference in 2210 different points from CT or MR-only plans was compared. For all three phantoms, the comparabilities between CT and MR-only plans were assessed by calculating dice similarity coefficient (DSC) for volumes enclosing 150%, 125%, 100%, 95%, 90%, 80%, and 65% isodose lines (V150  -V65 ). The MR images of FF placed on the forearm of a healthy subject were acquired with this optimized PETRA sequence and used for treatment planning. The relative percent dose was calculated on 140 representative points placed at 3 mm skin depth to evaluate the dose to the skin. RESULTS: Using the optimized PETRA sequence, MRTP digitization accuracy was < 1 mm in each dimension and on three-dimensional (3D) displacement for the FST phantom. In each phantom and clinical data set, it was possible to generate MR-only treatment plans with the 3 mm skin depth prescription. In the FST phantom, the mean relative dose at the points was not significantly different (< 0.1% difference) for CT or MR-based plans. The assessment of similarities in dose profiles between CT and MR-only plans' provided DSC values greater than 0.96, 0.92, and 0.73 for all volumes enclosing up to 100%, 125%, and 150% isodose lines, respectively. CONCLUSION: The feasibility of generating a HDR treatment plan with FF using MR-only has been evaluated in phantoms with varying geometry and for a clinical data set. The optimization of a standard MRI sequence-PETRA-implemented in this study showed that FF-based catheters can be digitized and a plan can be generated using only MRI. The resulting MR-only plans were comparable to the conventional CT-based plans, suggesting that MRI alone can generate clinically acceptable plans for FF in phantoms and on a clinical data set. Reliable MR-only treatment planning could improve treatment prescription through more accurate characterization of soft tissue targets.

Acute and late complications and toxicities of skin brachytherapy.

Skin cancer is the most prevalent malignancy, and its incidence is rising. Surgery is the primary treatment, however, morbidity of surgical resection in certain parts of the body warrant alternate treatment options such as radiation therapy. Complex topology of the skin can pose a challenge for treatment with photon and electron external beam radiotherapy techniques. Brachytherapy can be an attractive radiotherapy technique for these regions. Furthermore, brachytherapy results in lower dose to the underlying deep organs. The goal of this manuscript is to provide a brief overview of the role of brachytherapy for skin malignancies and to outline potential acute and long-term toxicities.

Clinical outcomes following high-dose-rate surface applicator brachytherapy for angiosarcoma of scalp and face.

PURPOSE: Angiosarcoma is a sub-type of soft tissue sarcoma, often presenting as a multifocal or diffuse disease process with poor prognosis. This study presents outcomes of a single institution cohort of patients with angiosarcoma of the scalp and face following treatment with multimodality therapy, including high-dose-rate surface applicator (HDR-SA) brachytherapy, and represents the largest cohort utilizing this therapeutic approach. MATERIAL AND METHODS: Twenty patients with primary or recurrent angiosarcoma of the face or scalp were treated with HDR-SA brachytherapy between 2003-2018, with clinical characteristics and outcomes collected from medical records and used to identify prognostic features. RESULTS: Median follow-up was 45 months. Patients treated with HDR-SA brachytherapy had a 4-year local control rate of 63%, a 4-year progression-free survival (PFS) rate of 20%, and a 4-year overall survival rate of 54%. Disease features associated with worse loco-regional control (LRC) included location on the scalp (vs. face, p = 0.04) and tumor size ≥ 5 cm (p = 0.0099). Outcomes after HDR-SA brachytherapy for salvage therapy vs. HDR-SA brachytherapy as a component of an initial treatment approach were also significantly different, with worse LRC (p = 0.0084) and worse overall survival (OS) (p = 0.0019) in a setting of salvage therapy. CONCLUSIONS: Local control rates following HDR-SA brachytherapy for scalp or face angiosarcoma are moderate and similar to what is described in the literature using a variety of local control treatment modalities. Smaller tumors and those involving the face rather than scalp had better outcomes. PFS rates were poor and there is a pressing need for treatment intensification and novel therapeutic options.

Selection criteria for high-dose-rate surface brachytherapy and electron beam therapy in cutaneous oncology.

PURPOSE: High-dose-rate (HDR) brachytherapy is an alternative treatment to electron external beam radiation therapy (EBRT) of superficial skin lesions. The purpose of this study was to establish the selection criteria for HDR brachytherapy technique (HDR-BT) and EBRT in cutaneous oncology for various clinical scenarios. MATERIAL AND METHODS: The study consists of two parts: a) EBRT and HDR-BT treatment plans comparison analyzing clinical target volumes (CTVs) with different geometries, field sizes, and topologies, and b) development of a prediction model capable of characterization of dose distributions in HDR surface brachytherapy for various geometries of treatment sites. RESULTS: A loss of CTV coverage for the electron plans (D90, D95) was recorded up to 45%, when curvature of the applicator increased over 30°. Values for D2 cm3 for both plans were comparable, and they were in range of ±8% of prescription dose. An increase in higher doses (D0.5 cm3 and D0.1 cm3) was observed in HDR-BT plans, and it was greater for larger lesions. The average increase was 3.8% for D0.5 cm3 and 12.3% for D0.1 cm3. When CTV was approximately flat, electron plans were comparable with HDR-BT plans, having lower average D2 cm3, D0.5 cm3, and D0.1 cm3 of 7.7%. Degradation of quality of electron plans was found to be more dependent on target curvature than on CTV size. CONCLUSIONS: Both EBRT and HDR-BT could be used in treatments of superficial lesions. HDR-BT revealed superior CTV coverage when the surface was very large, complex, curvy, or rounded, and when the topology was complicated. The prediction model can be used for an approximate calculation and quick assessment of radiation dose to organs-at-risk (OARs), at a depth or at a lateral distance from CTV.

ACR-ABS-ACNM-ASTRO-SIR-SNMMI practice parameter for selective internal radiation therapy or radioembolization for treatment of liver malignancies.

PURPOSE: The American College of Radiology (ACR), American Brachytherapy Society (ABS), American College of Nuclear Medicine (ACNM), American Society for Radiation Oncology (ASTRO), Society of Interventional Radiology (SIR), and Society of Nuclear Medicine and Molecular Imaging (SNMMI) have jointly developed a practice parameter on selective internal radiation therapy (SIRT) or radioembolization for treatment of liver malignancies. Radioembolization is the embolization of the hepatic arterial supply of hepatic primary tumors or metastases with a microsphere yttrium-90 brachytherapy device. MATERIALS AND METHODS: The ACR -ABS -ACNM -ASTRO -SIR -SNMMI practice parameter for SIRT or radioembolization for treatment of liver malignancies was revised in accordance with the process described on the ACR website (https://www.acr.org/ClinicalResources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters-Interventional and Cardiovascular Radiology of the ACR Commission on Interventional and Cardiovascular, Committee on Practice Parameters and Technical Standards-Nuclear Medicine and Molecular Imaging of the ACR Commission on Nuclear Medicine and Molecular Imaging and the Committee on Practice Parameters-Radiation Oncology of the ACR Commission on Radiation Oncology in collaboration with ABS, ACNM, ASTRO, SIR, and SNMMI. RESULTS: This practice parameter is developed to serve as a tool in the appropriate application of radioembolization in the care of patients with conditions where indicated. It addresses clinical implementation of radioembolization including personnel qualifications, quality assurance standards, indications, and suggested documentation. CONCLUSIONS: This practice parameter is a tool to guide clinical use of radioembolization. It focuses on the best practices and principles to consider when using radioemboliozation effectively. The clinical benefit and medical necessity of the treatment should be tailored to each individual patient.

Pediatric primary cutaneous anaplastic large cell lymphoma treated with brachytherapy.

Primary cutaneous anaplastic large cell lymphoma (PC-ALCL) is a CD30+ lymphoproliferative disorder that rarely occurs in children. Although there are currently no consensus guidelines for the treatment of cutaneous lymphoma in the pediatric population, the isolated form of PC-ALCL is typically managed by surgical excision or external beam radiation therapy. We report the case of a 6-year-old girl with primary cutaneous anaplastic large cell lymphoma that was treated with brachytherapy with no recurrence after 21 months of follow-up, suggesting that brachytherapy may be considered as a treatment for pediatric cutaneous large cell anaplastic lymphoma.

Angiosarcoma of the Scalp and Face: A Dosimetric Comparison of HDR Surface Applicator Brachytherapy and VMAT.

PURPOSE: Angiosarcoma of the face and scalp is a rare disease with high rates of recurrence. The optimal treatment approach is not well defined. This study presents a dosimetric comparison of high-dose-rate surface applicator (HDR-SA) brachytherapy to volumetric-modulated arc therapy (VMAT). METHODS: Between 2011 and 2018, 12 patients with primary or recurrent angiosarcoma of the face or scalp were treated with HDR-SA brachytherapy using CT-based planning at our institution. For comparison, deliverable VMAT plans for each patient were generated, and dose distribution was compared to the delivered HDR-SA brachytherapy plans. RESULTS: Both VMAT and HDR-SA brachytherapy plans delivered good coverage of the clinical target. However, the dose distribution of VMAT was significantly different from HDR-SA brachytherapy across a variety of parameters. Mean doses to the lacrimal gland, orbit, lens, and cochlea were significantly higher with HDR-SA brachytherapy vs. VMAT. Brain Dmax, V80%, and V50% were also significantly higher with HDR-SA brachytherapy. CONCLUSIONS: There may be dosimetric advantages to VMAT over HDR-SA brachytherapy for many patients. However, individual tumor location, patient anatomy, and treatment reproducibility may result in HDR-SA brachytherapy being the preferred technique in a subset of patients. Ultimately, a personalized approach is likely to be the optimal treatment plan.

Management of primary skin cancer during a pandemic: Multidisciplinary recommendations.

During the coronavirus disease 2019 (COVID-19) pandemic, providers and patients must engage in shared decision making regarding the pros and cons of early versus delayed interventions for localized skin cancer. Patients at highest risk of COVID-19 complications are older; are immunosuppressed; and have diabetes, cancer, or cardiopulmonary disease, with multiple comorbidities associated with worse outcomes. Physicians must weigh the patient's risk of COVID-19 complications in the event of exposure against the risk of worse oncologic outcomes from delaying cancer therapy. Herein, the authors have summarized current data regarding the risk of COVID-19 complications and mortality based on age and comorbidities and have reviewed the literature assessing how treatment delays affect oncologic outcomes. They also have provided multidisciplinary recommendations regarding the timing of local therapy for early-stage skin cancers during this pandemic with input from experts at 11 different institutions. For patients with Merkel cell carcinoma, the authors recommend prioritizing treatment, but a short delay can be considered for patients with favorable T1 disease who are at higher risk of COVID-19 complications. For patients with melanoma, the authors recommend delaying the treatment of patients with T0 to T1 disease for 3 months if there is no macroscopic residual disease at the time of biopsy. Treatment of tumors ≥T2 can be delayed for 3 months if the biopsy margins are negative. For patients with cutaneous squamous cell carcinoma, those with Brigham and Women's Hospital T1 to T2a disease can have their treatment delayed for 2 to 3 months unless there is rapid growth, symptomatic lesions, or the patient is immunocompromised. The treatment of tumors ≥T2b should be prioritized, but a 1-month to 2-month delay is unlikely to worsen disease-specific mortality. For patients with squamous cell carcinoma in situ and basal cell carcinoma, treatment can be deferred for 3 months unless the individual is highly symptomatic.

Combined interstitial and surface high-dose-rate brachytherapy treatment of squamous cell carcinoma of the hand.

PURPOSE: We present a case report of treatment using interstitial and surface high-dose-rate (HDR) brachytherapy for cutaneous squamous cell carcinoma (SCC) involving the interspace of the third and fourth digits. The patient refused two-ray amputation and the lesion was not amenable for external beam radiation therapy (EBRT). This is the first report detailing combined interstitial and surface HDR brachytherapy for a hand SCC. MATERIAL AND METHODS: The patient received 4050 cGy in 9 fractions, twice daily using 6 interstitial catheters and 8 Freiburg flap catheters. The clinical target was defined by MRI and ultrasound as a dorsal mass to the interspace between the heads of the third and fourth metacarpals measuring approximately 7 mm transverse × 5 mm volar-dorsal × 16 mm proximal-distal. RESULTS: The treatment resulted in radiographic and clinical tumor control. The patient retained functional use of her hand. However, there were both acute and late treatment-related side effects. Acutely, inpatient admission for pain control with a nerve block was needed. Long-term toxicity was notable for grade 2 skin necrosis treated with hyperbaric oxygen. CONCLUSIONS: The first interstitial and surface HDR brachytherapy for cutaneous squamous cell carcinoma of a finger interspace for hand function preservation is presented. The initial experience revealed that brachytherapy was tolerated but with notable acute and late side effects. Treatment did result in tumor shrinkage with organ preservation and function of two rays. A larger cohort of patients will be required for additional conclusions related to long-term clinical benefits in patients who refuse ray amputation.