Impact of cytogenetic abnormalities on the risk of disease progression in solitary bone plasmacytomas.

Most patients with solitary bone plasmacytomas (SBP) progress to multiple myeloma (MM) after definitive radiation therapy as their primary treatment. Whether the presence of high-risk (HR) cytogenetic abnormalities by fluorescence in situ hybridization (FISH) in the clonal plasma cells, obtained either directly from the diagnostic SBP tissue or the corresponding bone marrow examination at the time of diagnosis, is associated with a shorter time to progression (TTP) to MM is unknown. This study evaluated all patients diagnosed with SBP at the Mayo Clinic from January 2012 to July 2022. The presence of del(17p), t(14;16), t(4;14), or +1q (gain or amplification) by FISH in clonal plasma cells was defined as HR. A total of 114 patients were included in this cohort, and baseline FISH was available for 55 patients (48%), of which 22 were classified as HR (40%). The median TTP to MM for patients with SBP and HR FISH was 8 months (95% confidence interval [CI], 6.3-26) compared with 42 months (95% CI, 25-not reached [NR]) in patients with SBP without HR FISH (P < .001). In a multivariate analysis, only HR FISH was a significant predictor for shorter TTP to MM, independent of minimal marrow involvement and an abnormal serum free light chain ratio at diagnosis. Deletion (17p) and gain 1q abnormalities were the most common FISH abnormalities responsible for the short TTP to MM. Thus, assessing for HR FISH abnormalities in clonal plasma cells derived from either the diagnostic SBP tissue or the staging bone marrow examination of patients with newly diagnosed SBP is feasible and prognostic for a shorter TTP to MM.

Incorporating radiation with anti-CD19 chimeric antigen receptor T-cell therapy for relapsed/refractory non-Hodgkin lymphoma: A multicenter consensus approach.

Anti-CD19 chimeric antigen receptor T-cell therapy (CART) has revolutionized the outcomes of relapsed and/or refractory B-cell non-Hodgkin lymphoma. However, CART is still limited by its availability, toxicity, and response durability. Not all patients make it to the CART infusion phase due to disease progression. Among those who receive CART, a significant number of patients experience life-threatening cytokine release syndrome toxicity, and less than half maintain a durable response with the majority relapsing in pre-existing sites of disease present pre-CART. Radiation therapy stands as a promising peri-CART and salvage treatment that can improve the outcomes of these patients. Evidence suggests that bridging radiotherapy prior to CART controls the disease during the manufacturing period, augments response rates and local control, cytoreduces/debulks the disease and decreases the severity of cytokine release syndrome, and may prolong disease-free intervals and survival especially in patients with bulky disease. Consolidative radiotherapy for residual post-CART disease alters the pattern of relapse and improves local recurrence-free and progression-free survivals. Salvage radiotherapy for relapsed post-CART disease has favorable survival outcomes when delivered comprehensively for patients with limited relapsed disease and palliates symptoms for patients with diffuse relapsed disease. The biology of the disease during the peri-CART period is poorly understood, and further studies investigating the optimal timing and dosing of radiation therapy (RT) are needed. In this review, we tackle the most significant challenges of CART, review and propose how RT can help mitigate these challenges, and provide The Mayo Clinic experts' approach on incorporating RT with CART.

Consolidative radiotherapy for residual fluorodeoxyglucose activity on day +30 post CAR T-cell therapy in non-Hodgkin lymphoma.

Majority of non-Hodgkin lymphoma (NHL) patients who achieve partial response (PR) or stable disease (SD) to CAR T-cell therapy (CAR T) on day +30 progress and only 30% achieve spontaneous complete response (CR). This study is the first to evaluate the role of consolidative radiotherapy (cRT) for residual fluorodeoxyglucose (FDG) activity on day +30 post- CAR T in NHL. We retrospectively reviewed 61 patients with NHL who received CAR T and achieved PR or SD on day +30. Progression-free survival (PFS), overall survival (OS), and local relapse-free survival (LRFS) were assessed from CAR T infusion. cRT was defined as comprehensive - treated all FDG-avid sites - or focal. Following day +30 positron emission tomography scan, 45 patients were observed and 16 received cRT. Fifteen (33%) observed patients achieved spontaneous CR, and 27 (60%) progressed with all relapses involving initial sites of residual FDG activity. Ten (63%) cRT patients achieved CR, and four (25%) progressed with no relapses in the irradiated sites. The 2-year LRFS was 100% in the cRT sites and 31% in the observed sites (P<0.001). The 2-year PFS was 73% and 37% (P=0.025) and the 2-year OS was 78% and 43% (P=0.12) in the cRT and observation groups, respectively. Patients receiving comprehensive cRT (n=13) had superior 2- year PFS (83% vs. 37%; P=0.008) and 2-year OS (86% vs. 43%; P=0.047) compared to observed or focal cRT patients (n=48). NHL patients with residual FDG activity following CAR T are at high risk of local progression. cRT for residual FDG activity on day +30 post-CAR T appears to alter the pattern of relapse and improve LRFS and PFS.

Development of transparent eye shields for total skin electron beam radiotherapy.

PURPOSE: For total skin electron (TSE) beam radiation therapy, the anterior eye and conjunctiva can be protected with eye shields to prevent keratitis, xerophthalmia, and cataractogenesis. Conventional metal eye shields can reduce patient balance by obscuring vision and thus increasing the risk for falls. We report on the design, fabrication, and clinical use of transparent acrylic eye shields for TSE. METHODS: The primary design goals were a seven-fold reduction in the dose to the anterior eye and conjunctiva to meet published dose-recommendations, preservation of vision for the wearer, and biocompatibility for external use. Resembling thick swim goggles, the design features 23 mm thick acrylic lenses that are mounted in a 3-D printed support structure that conforms to the eye socket and can be worn with a strap. Dose measurements were performed in a simulated Stanford-technique treatment with an anthropomorphic phantom using Gafchromic EBT film RESULTS: The transparent eye shields were manufactured using a 3D-printer and CNC-machine. Based on measurements from the simulated treatments for each of the eye shields, the eye shields provided a 12-fold reduction in dose to the lens. After use in more than 200 fractions, the shields were well tolerated by patients, and there were no reports of any incidents or adverse events. CONCLUSION: Transparent TSE eye shields are able to reduce the dose to the eyes while maintaining vision during treatment at a reasonable cost.

Outcomes in primary cutaneous diffuse large B-cell lymphoma, leg type.

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL, LT) is a rare, aggressive lymphoma characterized by skin involvement predominantly in the lower extremities. Immunochemotherapy with or without involved-site radiation therapy (ISRT) is considered standard front-line therapy. Over-expression of PD-L1/PD-L2 is seen in a high proportion of PCDLBCL, LT cases, but efficacy of immune checkpoint inhibitors (ICI) in relapsed/refractory, PCDLBCL, LT has not been thoroughly studied. We conducted a retrospective cohort study of patients diagnosed with PCDLBCL, LT seen at Mayo Clinic from 1 January 2000 to 31 December 2020. Using the Kaplan-Meier method, we calculated progression-free survival, duration of response, and overall survival in patients who received front-line rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with and without ISRT, and salvage ICI therapy for relapsed/refractory disease. A total of 28 patients with PCDLBCL, LT were identified. The median PFS in patients treated with R-CHOP plus ISRT was 58 months (95% CI: 18-112) compared to 14 months (95% CI: 5-not reached; p = 0.04) in those treated with R-CHOP without ISRT. The median PFS from salvage ICI therapy was 10 months (95% CI: 4-not reached), and median DOR from salvage ICI therapy was 23 months [95% CI: 4-26]. R-CHOP with ISRT had a significantly longer median PFS compared to R-CHOP without ISRT as front-line therapy for PCDLBCL, LT. ICIs may have a role in treating relapsed/refractory disease as reasonable activity in heavily pre-treated patients was observed in this study.

How to Sequence Therapies in Mycosis Fungoides.

OPINION STATEMENT: Choice of therapy in mycosis fungoides is based on both patient- and lymphoma-specific factors, such as disease characteristics, comorbidities, symptoms and effect on quality of life, potential associated toxicities of therapy, response and tolerance to prior lines of therapy, and convenience and practicality. Generally, we sequence therapies from least toxic, targeted, nonimmunosuppressive to more toxic, immunosuppressive and from single agent to multiple agents, as necessary. If more toxic, immunosuppressive agents are required to alleviate disease burden or symptoms, we generally use them just long enough to control the disease, then transition to a maintenance regimen with less toxic, less immunosuppressive agents.

Skin-directed radiation therapy for cutaneous lymphoma: The Mayo Clinic experience.

BACKGROUND: Focal or total skin radiation therapy can be used to treat mild to refractory cutaneous T-cell lymphoma. OBJECTIVE: To report the broad therapeutic benefit of radiation therapy for cutaneous T-cell lymphoma. METHODS: Retrospective, single-institution review of outcomes for skin-directed radiation therapy. RESULTS: Skin-directed radiation therapy showed a 99% response rate and 80% complete response rate after treatment regardless of involvement, severity, histopathologic subtype, dose, or fractionation. The overall in-field recurrence rate was 15%, and median time to recurrence was 296 days (range, 1-1884 days). Focal and hypofractionated regimens were similarly associated with disease response and rare toxicity. Short-term rates of secondary skin cancer after treatment were comparable to expected incidence in a patient population without radiation. LIMITATIONS: Large total number of treatments courses compared with overall number of patients. Heterogenous mix of treatment regimens (no standardization of dose or fraction number). CONCLUSIONS: Radiation therapy is a well-tolerated treatment option for properly selected patients with cutaneous T-cell lymphoma.

Use of topical nasal anesthesia during flexible endoscopic evaluation of swallowing in dysphagic patients.

OBJECTIVE: This study aimed to determine the effect of topical lidocaine on Penetration-Aspiration Scale (PAS) scores and patient comfort and tolerance of flexible endoscopic evaluation of swallowing (FEES) examinations in dysphagic patients. METHODS: Adults with dysphagia referred for swallowing evaluation were recruited to participate in consecutive nonanesthetized and then anesthetized FEES examinations. Under endoscopic visualization, participants consumed 6 swallows consisting of graduated volumes of milk, pudding, and cracker in each condition and recorded their discomfort and tolerance in the 2 conditions. Penetration-Aspiration Scale scores were assigned in blinded fashion for each swallow. RESULTS: Twenty-five adults participated in the study. Although there was no statistically significant effect of anesthesia on PAS scores (P=.065), the odds of a higher PAS score were 33% higher during anesthetized swallows. The anesthetized condition yielded significantly less discomfort and pain during the examination, significantly less pain and discomfort during insertion and removal of the endoscope, and significantly greater overall tolerance than the nonanesthetized condition. CONCLUSION: The use of topical lidocaine during FEES may impair swallowing ability in patients with dysphagia, but this result does not achieve statistical significance. Topical nasal anesthesia significantly reduces subjective pain and discomfort and improves tolerance during FEES.

Clinical and economic outcomes of patients with brain metastases based on symptoms: an argument for routine brain screening of those treated with upfront radiosurgery.

BACKGROUND: Insurers have started to deny reimbursement for routine brain surveillance with magnetic resonance imaging (MRI) after stereotactic radiosurgery (SRS) for brain metastases in favor of symptom-prompted imaging. The authors investigated the clinical and economic impact of symptomatic versus asymptomatic metastases and related these findings to the use of routine brain surveillance. METHODS: Between January 2000 and December 2010, 442 patients underwent upfront SRS for brain metastases. In total, 127 asymptomatic patients and 315 symptomatic patients were included. Medical records were used to determine the presenting symptoms, distant and local brain failure, retreatment, and need for hospital and rehabilitative care. Cost-of-care estimates were based on Medicare payment rates as of January 2013. RESULTS: Symptomatic patients had an increased hazard for all-cause mortality (hazard ratio, 1.448) and were more likely to experience neurologic death (42% vs 20%; P < .0001). Relative to asymptomatic patients, symptomatic patients required more craniotomies (43% vs 5%; P < .0001), had more prolonged hospitalization (2 vs 0 days; P < .0001), were more likely to have Radiation Therapy Oncology Group grade 3 and 4 post-treatment symptoms (24% vs 5%; P < .0001), and required $11,957 more on average to manage per patient. Accounting for all-cause mortality rates and the probability of diagnosis at each follow-up period, the authors estimated that insurers would save an average $1326 per patient by covering routine surveillance MRI after SRS to detect asymptomatic metastases. CONCLUSIONS: Patients who presented with symptomatic brain metastases had worse clinical outcomes and cost more to manage than asymptomatic patients. The current findings argue that routine brain surveillance after radiosurgery has clinical benefits and reduces the cost of care.

Radiotherapy for aseptic granulomatous dermatitis: A case report.

Granulomatous dermatitis is a common tissue reaction pattern seen in the skin or systematically in various presentations. Granulomatous dermatitis can be subclassified into infectious and non-infectious categories. This article focuses on a patient with non-infectious granulomatous dermatitis followed for many years. Past medical history included bilateral total shoulder arthroplasty complicated by prosthetic joint infections. In its early stages, the axillary rash was painful and had many fluid-filled blisters. Ultimately, the histology of the rash deemed the lesion non-infectious and mostly due to an inflammatory process. Specifically, ionizing radiation was used for this patient. The category of granulomatous processes is broad and there are many subtypes. Other treatment options for non-infectious granulomatous processes may include corticosteroids, phototherapy, and interferon-gamma injections. The differential for granulomatous processes is extensive and treatment should be decided on a case-by-case basis.

Should All Patients With Stage IE Gastric Mucosa-Associated Lymphoid Tissue Lymphoma Receive Antibiotic Eradication Therapy for Helicobacter pylori?

PURPOSE: H. pylori eradication therapy (HPE) can lead to tumor regression in H. pylori-positive (HPP) gastric mucosa-associated lymphoid tissue (MALT) lymphoma. However, some patients do not have detectable H. pylori (HP) infection (H. pylori-negative [HPN]) and the guidelines differ in their initial approach to HPN patients. The National Comprehensive Cancer Network (NCCN) recommends proceeding to radiation therapy, whereas European Society for Medical Oncology suggests HPE for every patient, even those who are HPN. To address this issue, we evaluated the effectiveness of HPE in limited-stage gastric MALT lymphoma. MATERIALS AND METHODS: We retrospectively reviewed patients newly diagnosed with stage IE gastric MALT lymphoma between January 2002 and December 2022. The primary outcome was the complete remission (CR) rate defined as no macroscopic findings of lymphoma and negative gastric biopsy at the follow-up gastric endoscopy. RESULTS: Fifty-two patients were reviewed, and HP infection was detected in 19 (36.5%) patients-14 by immunostaining, three by serology, and one each by stool antigen and urea breath test. All 19 HPP and eight of the 33 HPN patients received HPE treatment. The CR rate was 63% (12/19) in HPP patients and 13% (1/8) in HPN patients (P = .033). After a median follow-up of 89.7 months, only two of the 12 HPP patients achieving CR have relapsed; the one HPN patient who received HPE remains in CR at 12+ months. CONCLUSION: For limited-stage HPP gastric MALT lymphoma, HPE is an effective and durable first-line treatment and should be used. For HPN patients, the CR rate with HPE is very low in our experience and is thus in support of the NCCN guideline.

Fine-Tuning Low-Dose Total Skin Electron Therapy for Optimal Management of Cutaneous T-Cell Lymphoma: A Comparative Analysis of Regimens.

Purpose: Low-dose total skin electron beam therapy (TSEBT) is a proven treatment for managing cutaneous T-cell lymphoma (CTCL) and Sezary syndrome with skin burden. We performed a retrospective comparison of response rates and time to progression for patients receiving low-dose TSEBT based on dose per fractionation, total dose, and stage. Methods and Materials: One hundred and ten patients with CTCL and Sezary syndrome were treated with 135 courses of low-dose (400-1500 cGy) TSEBT or subtotal skin electron therapy at multiple centers of a single institution between August 2003 and June 2023. Patients were stratified according to total dose, dose per fraction, and stage. Results: The median follow-up was 301 days (IQR, 141, 767). The median age at treatment was 69.9 years (range, 29.7-96.5). T-stage distribution was as follows: 3 (2.7%) T1, 74 (67.3%) T2, 16 (14.5%) T3, and 17 (15.5%) T4. American Joint Committee on Cancer eighth edition stage distribution was as follows: 3 (2.7%) IA, 53 (48.2%) IB, 3 (2.7%) IIA, 16 (14.5%) IIB, 8 (7.3%) IIIA, 19 (17.3%) IVA, and 8 (7.3%) IVB. There was no significant difference in disease distribution between patients treated with different fractionation schemes. The overall response rate was 89.6%. Forty-four courses (32.6%), 34 courses (25.2%), and 43 (31.9%) resulted in a complete, near-complete, and partial response, respectively. Fourteen courses (10.4%) resulted in no clinical response. For all patients, the median time to response was 43.0 days (IQR, 23.0-70). The median time to skin progression for all patients was 107.5 days (IQR, 67.8-233.5). Conclusions: This analysis demonstrated that CTCL patients treated with low-dose radiation therapy delivered over various fractionation schemes had similar overall response rates and median time to progression.

Impact of Relative Biologic Effectiveness for Proton Therapy for Head and Neck and Skull-Base Tumors: A Technical and Clinical Review.

Proton therapy has emerged as a crucial tool in the treatment of head and neck and skull-base cancers, offering advantages over photon therapy in terms of decreasing integral dose and reducing acute and late toxicities, such as dysgeusia, feeding tube dependence, xerostomia, secondary malignancies, and neurocognitive dysfunction. Despite its benefits in dose distribution and biological effectiveness, the application of proton therapy is challenged by uncertainties in its relative biological effectiveness (RBE). Overcoming the challenges related to RBE is key to fully realizing proton therapy's potential, which extends beyond its physical dosimetric properties when compared with photon-based therapies. In this paper, we discuss the clinical significance of RBE within treatment volumes and adjacent serial organs at risk in the management of head and neck and skull-base tumors. We review proton RBE uncertainties and its modeling and explore clinical outcomes. Additionally, we highlight technological advancements and innovations in plan optimization and treatment delivery, including linear energy transfer/RBE optimizations and the development of spot-scanning proton arc therapy. These advancements show promise in harnessing the full capabilities of proton therapy from an academic standpoint, further technological innovations and clinical outcome studies, however, are needed for their integration into routine clinical practice.

Impact of radiation dose distribution on nutritional supplementation needs in head and neck cancer radiotherapy: a voxel-based machine learning approach.

Objectives: To investigate the relationship between nutritional supplementation and radiation dose to the pharyngeal constrictor muscles and larynx for head and neck (HN) cancer patients undergoing radiotherapy. Methods: We retrospectively analyzed radiotherapy (RT) dose for 231 HN cancer patients, focusing on the pharyngeal constrictors and larynx. We defined nutritional supplementation as feeding tube utilization or >10% weight loss from baseline within 90 days after radiotherapy completion. Using deformable image registration (DIR), we mapped each patient's anatomical structures to a reference coordinate system, and corresponding deformations were applied to dose matrices. Voxel doses were utilized as features for ridge logistic regression models, optimized through 5-fold cross-validation. Model performance was assessed with area under the curve of a receiver operating curve (AUC) and F1 score. We built and compared models using 1) pharyngeal constrictor voxels, 2) larynx voxels, 3) clinical factors and mean regional dose metrics, and 4) clinical factors and dose-volume histogram metrics. Test set AUCs were compared among the models, and feature importance was evaluated. Results: DIR of the pharyngeal constrictors and larynx yielded mean Dice coefficients of 0.80 and 0.84, respectively. Pharyngeal constrictors voxels and larynx voxel models had AUC of 0.88 and 0.82, respectively. Voxel-based dose modeling identified the superior to middle regions of the pharyngeal constrictors and the superior region of larynx as most predictive of feeding tube use/weight loss. Univariate analysis found treatment setting, treatment laterality, chemotherapy, baseline dysphagia, weight, and socioeconomic status predictive of outcome. An aggregated model using mean doses of pharyngeal constrictors and larynx subregions had an AUC of 0.87 and the model using conventional DVH metrics had an AUC of 0.85 with p-value of 0.04. Feature importance calculations from the regional dose model indicated that mean doses to the superior-middle pharyngeal constrictor muscles followed by mean dose to the superior larynx were most predictive of nutritional supplementation. Conclusions: Machine learning modeling of voxel-level doses enables identification of subregions within organs that correlate with toxicity. For HN radiotherapy, doses to the superior-middle pharyngeal constrictors are most predictive of feeding tube use/weight loss followed by the doses to superior portion of the larynx.

Tailoring Radiation Therapy for Patients With Limited Cutaneous T Cell Lymphoma: Preliminary Clinical Experience With Subtotal Skin Electron Therapy.

BACKGROUND/AIM: Total skin electron beam therapy (TSEBT) is an effective treatment for managing cutaneous T-cell lymphoma (CTCL), but may result in unnecessary toxicity. With the production of a custom rolling shield holding a configurable stack of plastic slats to block uninvolved skin, we implemented a program for subtotal skin electron beam therapy (STSEBT). We report our preliminary experience with STSEBT vs. TSEBT to manage CTCL. PATIENTS AND METHODS: A retrospective review of 32 CTCL patients who were treated at a single institution between February 28th, 2017, and May 25th, 2022, was completed. Of these cases, seven patients received STSEBT and 25 received TSEBT. RESULTS: Thirty-two patients underwent a course of STSEBT or TSEBT. The median follow-up was 465 days and the median age at diagnosis was 70.8 years. Stage distribution was as follows: one (3%) IA, 16 (50%) IB, 6 (19%) IIB, two (6%) IIIA, five (16%) IVA, and two (6%) IVB. The overall response rate was 96%. For patients receiving TSEBT (n=25), three (12%), 10 (40%), and 11 (44%) had a CR, NCR, and PR, respectively. For the patients receiving STSEBT, four (57.1%), three (42.9%), and zero (0%) had a CR, NCR, and PR, respectively. There was one patient (4%) with no response. Cumulative incidence of progressive skin disease requiring additional electron therapy at three months was 21.1% [IQR=8.6, 51.5%], 36.8% [IQR=20, 68%] at six months, and 57.9% [IQR=38.5, 87.1%] at one year. Low rates of toxicities were recorded. CONCLUSION: This analysis demonstrated that treatment of CTCL patients with low disease burden with STSEBT results in similar overall response and time to progression compared to treatment with TSEBT.

Radiation Dose Sensitivity of Subregions of the Larynx to Patient-Reported Swallowing Outcomes.

Purpose: To assess any correlation between swallowing dysfunction and radiation dose to 5 subregions of the larynx. Methods and Materials: A cohort of 136 patients with head and neck cancer, treated with either photon or proton radiation therapy, was assessed using an endpoint of patient-reported swallowing scores, evaluated with the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-H&N35 survey, within 1 month after treatment. Five subregions of the larynx were contoured, and dosimetric metrics were extracted for each subregion as well as the total larynx. Univariate and multivariate logistic regression statistical analyses were used to determine statistical correlation with the dose metrics and clinical variables. Univariate regression models were statistically compared using a non-nested model test. Results: Under univariate analysis, unilateral versus bilateral nodal irradiation (P = .004), concurrent chemotherapy (P = .007), and surgery (P = .015) were statistically significant predictors of poor swallowing score. Unilateral versus bilateral irradiation was statistically significant under multivariate analysis (P = .039). The epiglottis was the most predictive subregion of swallowing score, with a majority (21 of 25) of dosimetric variables being identified as statistically significant. The maximum dose to the epiglottis was the most significant dosimetric variable tested for poor swallowing score in both univariate (P = .003) and multivariate (P = .051) analyses. Comparison of univariate models indicated a general preference for epiglottic variables with the mean dose to the epiglottis being preferred at a statistically significant level in many cases. Conclusions: These results show the relatively increased sensitivity of the epiglottis compared with the rest of the larynx when considering patient-reported decrements in quality-of-life swallowing score and support both the inclusion of the epiglottis in standard larynx contours and the assessment of the epiglottis dose during plan evaluation. Our data suggest that keeping the mean and max doses to the epiglottis <20 to 37 Gy and <53 to 60 Gy, respectively, will reduce swallowing difficulties.

Cancer in Patients With Incidental Asymmetric Oropharynx Positron Emission Tomography Uptake.

Importance: Asymmetric oropharynx uptake on positron emission tomography (PET)/computed tomography (CT) is a common incidental finding and often prompts otolaryngology referral to rule out malignancy; however, the true risk of malignancy based on this finding is unknown. Objective: To identify the incidence of oropharynx cancer in patients with incidental asymmetric oropharynx PET uptake. Design, Setting, and Participants: In this retrospective cohort study, patients 18 years and older undergoing PET/CT scans at Mayo Clinic between January 2001 and December 2018 were included. Patients with a history or pretest suspicion of oropharynx cancer were excluded. Data were analyzed from March 2021 to December 2023. Exposure: Blinded radiologic review of imaging studies, including measurement of maximum standardized uptake values (SUVmax) of the ipsilateral side of concern and contralateral side. Retrospective medical record review for associated clinical data. Main Outcomes and Measures: The primary study outcome was the incidence of oropharynx cancer diagnosis in patients with asymmetric oropharynx PET uptake. The primary outcome was formulated before data collection. Results: Of the 1854 patients identified with asymmetric oropharynx PET uptake, 327 (17.6%) met inclusion criteria. Of these, 173 (52.9%) were male, and the median (range) age was 65.0 (24.8-90.7) years. The mean (SD) follow-up interval was 52.1 (43.4) months. A total of 18 of 327 patients (5.5%) were newly diagnosed with oropharynx cancer. The most common diagnosis was squamous cell carcinoma (n = 9), followed by lymphoma (n = 8), and sarcoma (n = 1). Patients with an incidental diagnosis of oropharynx cancer had higher mean (SD) ipsilateral SUVmax (8.7 [3.7] vs 5.3 [1.9]) and SUVmax ratio (3.0 [1.6] vs 1.6 [0.6]) compared with patients with normal examination findings. SUVmax ratio and difference were found to be good discriminators of oropharynx cancer, with areas under the receiver operating characteristic curve of 86.3% (95% CI, 76.4-94.6) and 85.8% (95% CI, 74.8-94.6), respectively. Patients with a new diagnosis of oropharynx cancer were more likely to have a corresponding CT abnormality than those with normal examination findings (6 of 18 [33%] vs 24 of 295 [8.1%]). Patients with concerning lesions on oropharynx palpation by an otolaryngology health care professional were significantly more likely to be diagnosed with oropharynx cancer compared with patients with normal examination findings (odds ratio, 28.4; 95% CI, 6.6-145.8). Conclusions and Relevance: In this cohort study, while incidental asymmetric oropharynx PET uptake was common, a new diagnosis of oropharynx cancer was not and potentially results in a large volume of unnecessary referrals and work-up. Using SUVmax ratio, SUVmax difference, and CT correlation may increase the benefit of referral. Patients with a palpable oropharynx lesion and asymmetric oropharynx PET uptake should undergo confirmatory biopsy.

Minibeam Radiation Therapy Treatment (MBRT): Commissioning and First Clinical Implementation.

PURPOSE: Minibeam radiation therapy (MBRT) is characterized by the delivery of submillimeter-wide regions of high "peak" and low "valley" doses throughout a tumor. Preclinical studies have long shown the promise of this technique, and we report here the first clinical implementation of MBRT. METHODS AND MATERIALS: A clinical orthovoltage unit was commissioned for MBRT patient treatments using 3-, 4-, 5-, 8-, and 10-cm diameter cones. The 180 kVp output was spatially separated into minibeams using a tungsten collimator with 0.5 mm wide slits spaced 1.1 mm on center. Percentage depth dose (PDD) measurements were obtained using film dosimetry and plastic water for both peak and valley doses. PDDs were measured on the central axis for offsets of 0, 0.5, and 1 cm. The peak-to-valley ratio was calculated at each depth for all cones and offsets. To mitigate the effects of patient motion on delivered dose, patient-specific 3-dimensional-printed collimator holders were created. These conformed to the unique anatomy of each patient and affixed the tungsten collimator directly to the body. Two patients were treated with MBRT; both received 2 fractions. RESULTS: Peak PDDs decreased gradually with depth. Valley PDDs initially increased slightly with depth, then decreased gradually beyond 2 cm. The peak-to-valley ratios were highest at the surface for smaller cone sizes and offsets. In vivo film dosimetry confirmed a distinct delineation of peak and valley doses in both patients treated with MBRT with no dose blurring. Both patients experienced prompt improvement in symptoms and tumor response. CONCLUSIONS: We report commissioning results, treatment processes, and the first 2 patients treated with MBRT using a clinical orthovoltage unit. While demonstrating the feasibility of this approach is a crucial first step toward wider translation, clinical trials are needed to further establish safety and efficacy.