Proton Pencil Beam Scanning Facilitates the Safe Treatment of Extended Radiation Targets for Hodgkin Lymphoma: A Report from the Proton Collaborative Group Registry.

Because proton beam therapy (PBT) can lower the dose of radiation to the heart, lungs, and breast, it is an established radiation modality for patients with Hodgkin lymphoma (HL). Pencil beam scanning (PBS) PBT facilitates the treatment of more extensive targets. This may be especially of value for lymphoma patients who require RT to both mediastinal and axillary targets, defined here as extended target RT (ETRT), given the target distribution and need to minimize the lung, heart, and breast dose. Using the Proton Collaborative Group registry, we identified patients with HL treated with PBT to both their mediastinum and axilla, for which DICOM-RT was available. All patients were treated with PBS. To evaluate the dosimetric impact of PBS, we compared delivered PBS plans with VMAT butterfly photon plans optimized to have the same target volume coverage, when feasible. Between 2016 and 2021, twelve patients (median 26 years) received PBS ETRT (median 30.6 Gy (RBE)). Despite the large superior/inferior (SI, median 22.2 cm) and left/right (LR, median 22.8 cm) extent of the ETRT targets, all patients were treated with one isocenter except for two patients (both with SI and LR > 30 cm). Most commonly, anterior beams, with or without posterior beams, were used. Compared to photons, PBS had greater target coverage, better conformity, and lower dose heterogeneity while achieving lower doses to the lungs and heart, but not to the breast. No acute grade 3+ toxicities were reported, including pneumonitis. Proton ETRT in this small cohort was safely delivered with PBS and was associated with an improved sparing of the heart and lungs compared to VMAT.

The Accuracy of Artificial Intelligence ChatGPT in Oncology Exam Questions.

The aim of this study is to assess the accuracy of ChatGPT in response to oncology exam questions in the setting of one-shot learning. Consecutive national radiation oncology in-service multiple-choice examinations were collected and inputted into ChatGPT 4o and ChatGPT 3.5 to determine ChatGPT's answers. ChatGPT's answers were then compared to the answer keys to determine whether ChatGPT correctly or incorrectly answered each question, and to determine if improvements in responses were seen with the newer ChatGPT version. A total of 600 consecutive questions were inputted into ChatGPT. ChatGPT 4o answered 72.2% questions correctly, whereas 3.5 answered 53.8% questions correctly. There was a significant difference in performance by question category (p < 0.01). ChatGPT performed poorer with respect to knowledge of landmark studies and treatment recommendations/planning. ChatGPT is a promising technology, with the latest version showing marked improvement. While it still has limitations, with further evolution, it may be considered a reliable resource for medical training and decision making in the oncology space.

Differences in Patterns of Care and Referral Between Proton and Photon Therapy.

Purpose: To report demographic and clinical characteristics of patients who were more likely to receive proton beam therapy (PBT) than photon therapy from facilities with access to proton centers. Materials and Methods: We utilized the national cancer database to identify the facilities with access to PBT between 2004 and 2015 and compared the relative usage of photons and PBT for demographic and clinical scenarios in breast, prostate, and nonsmall cell cancer. Results: In total, 231 facilities with access to proton centers accounted for 168 323 breast, 39 975 lung, and 77 297 prostate cancer patients treated definitively. Proton beam therapy was used in 0.5%, 1.5%, and 8.9% of breast, lung, and prostate cases. Proton beam therapy was correlated with a farther distance traveled and longer start time from diagnosis for each site (P < .05).For breast, demographic correlates of PBT were treatment in the west coast (odds ratio [OR] = 4.81), age <60 (OR = 1.25), white race (OR = 1.94), and metropolitan area (OR = 1.58). Left-sided cancers (OR = 1.28), N2 (OR = 1.71), non-ER+/PR+/Her2Neu- cancers (OR = 1.24), accelerated partial breast irradiation (OR = 1.98), and hypofractionation (OR = 2.35) were predictors of PBT.For nonsmall cell cancer, demographic correlates of PBT were treatment in the south (OR = 2.6), metropolitan area (OR = 1.72), and Medicare insurance (OR = 1.64). Higher comorbid score (OR = 1.36), later year treated (OR = 3.16), and hypofractionation (not SBRT) (OR = 3.7) were predictors of PBT.For prostate, correlates of PBT were treatment in the west coast (OR = 2.48), age <70 (OR = 1.19), white race (OR = 1.41), metropolitan area (OR = 1.25), higher income/education (OR = 1.25), and treatment at an academic center (OR = 33.94). Lower comorbidity score (OR = 1.42), later year treated (OR = 1.37), low-risk disease (OR = 1.45), definitive compared to postoperative (OR = 6.10), and conventional fractionation (OR = 1.64) were predictors of PBT. Conclusion: Even for facilities with established referrals to proton centers, PBT utilization was low; socioeconomic status was potentially a factor. Proton beam therapy was more often used with left-sided breast and low-risk prostate cancers, without a clear clinical pattern in lung cancer.

The potential role of precision medicine to alleviate racial disparities in prostate, bladder and renal urological cancer care.

Background: Racial disparities in oncological outcomes resulting from differences in social determinants of health (SDOH) and tumour biology are well described in prostate cancer (PCa) but similar inequities exist in bladder (BCa) and renal cancers (RCCs). Precision medicine (PM) aims to provide personalized treatment based on individual patient characteristics and has the potential to reduce these inequities in GU cancers. Objective: This article aims to review the current evidence outlining racial disparities in GU cancers and explore studies demonstrating improved oncological outcomes when PM is applied to racially diverse patient populations. Evidence acquisition: Evidence was obtained from Pubmed and Web of Science using keywords prostate, bladder and renal cancer, racial disparity and precision medicine. Because limited studies were found, preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were not applied but rather related articles were studied to explore existing debates, identify the current status and speculate on future applications. Results: Evidence suggests addressing SDOH for PCa can reverse racial inequities in oncological outcomes but differences in incidence remain. Similar disparities in BCa and RCC are seen, and it would be reasonable to suggest achieving parity in SDOH for all races would do the same. Research applying a PM approach to different ethnicities is lacking although in African Americans (AAs) with metastatic castrate-resistant prostate cancer (mCRPCa) better outcomes have been shown with androgen receptor inhibitors, radium-223 and sipuleucel. Exploiting the abscopal effect with targeted radiation therapy (RT) and immunotherapy has promise but requires further study, as does defining actionable mutations in specific patient groups to tailor treatments as appropriate. Conclusion: For all GU cancers, the historical underrepresentation of ethnic minorities in clinical trials still exists and there is an urgent need for recruitment strategies to address this. PM is a promising development with the potential to reduce inequities in GU cancers, however, both improved understanding of race-specific tumour biology, and enhanced recruitment of minority populations into clinical trials are required. Without this, the benefits of PM will be limited.

Reirradiation With Proton Therapy for Recurrent Malignancies of the Esophagus and Gastroesophageal Junction: Results of the Proton Collaborative Group Multi-Institutional Prospective Registry Trial.

Purpose: Treatment options for recurrent esophageal cancer (EC) previously treated with radiation therapy (RT) are limited. Reirradiation (reRT) with proton beam therapy (PBT) can offer lower toxicities by limiting doses to surrounding tissues. In this study, we present the first multi-institutional series reporting on toxicities and outcomes after reRT for locoregionally recurrent EC with PBT. Methods and Materials: Analysis of the prospective, multicenter, Proton Collaborative Group registry of patients with recurrent EC who had previously received photon-based RT and underwent PBT reRT was performed. Patient/tumor characteristics, treatment details, outcomes, and toxicities were collected. Local control (LC), distant metastasis-free survival (DMFS), and overall survival (OS) were estimated using the Kaplan-Meier method. Event time was determined from reRT start. Results: Between 2012 and 2020, 31 patients received reRT via uniform scanning/passive scattering (61.3%) or pencil beam scanning (38.7%) PBT at 7 institutions. Median prior RT, PBT reRT, and cumulative doses were 50.4 Gy (range, 37.5-110.4), 48.6 Gy (relative biological effectiveness) (25.2-72.1), and 99.9 Gy (79.1-182.5), respectively. Of these patients, 12.9% had 2 prior RT courses, and 67.7% received PBT with concurrent chemotherapy. Median follow-up was 7.2 months (0.9-64.7). Post-PBT, there were 16.7% locoregional only, 11.1% distant only, and 16.7% locoregional and distant recurrences. Six-month LC, DMFS, and OS were 80.5%, 83.4%, and 69.1%, respectively. One-year LC, DMFS, and OS were 67.1%, 83.4%, and 27%, respectively. Acute grade ≥3 toxicities occurred in 23% of patients, with 1 acute grade 5 toxicity secondary to esophageal hemorrhage, unclear if related to reRT or disease progression. No grade ≥3 late toxicities were reported. Conclusions: In the largest report to date of PBT for reRT in patients with recurrent EC, we observed acceptable acute toxicities and encouraging rates of disease control. However, these findings are limited by the poor prognoses of these patients, who are at high risk of mortality. Further research is needed to better assess the long-term benefits and toxicities of PBT in this specific patient population.

Prospective evaluation of patient-reported outcomes of invisible ink tattoos for the delivery of external beam radiation therapy: the PREFER trial.

Introduction: Invisible ink tattoos (IITs) avoid cosmetic permanence of visible ink tattoos (VITs) while serving as more reliable landmarks for radiation setup than tattooless setups. This trial evaluated patient-reported preference and feasibility of IIT implementation. Methods and materials: In an IRB-approved, single institution, prospective trial, patients receiving proton therapy underwent IIT-based treatment setup. A survey tool assessed patient preference on tattoos using a Likert scale. Matched patients treated using our institutional standard tattooless setup were identified; treatment times and image guidance requirements were evaluated between tattooless and IIT-based alignment approaches. Distribution differences were estimated using Wilcoxon rank-sum tests or Chi-square tests. Results: Of 94 eligible patients enrolled, median age was 58 years, and 58.5% were female. Most common treatment sites were breast (18.1%), lung (17.0%) and pelvic (14.9%). Patients preferred to receive IITs versus VITs (79.8% pre-treatment and 75.5% post-treatment, respectively). Patients were willing to travel farther from home to avoid VITs versus IITs (p<0.01). Females were willing to travel (45.5% vs. 23.1%; p=0.04) and pay additional money to avoid VITs (34.5% vs. 5.1%; p<0.01). Per-fraction average +treatment time and time from on table/in room to first beam were shorter with IIT-based vs. tattooless setup (12.3min vs. 14.1min; p=0.04 and 24.1min vs. 26.2min; p=0.02, respectively). Discussion: In the largest prospective trial on IIT-based radiotherapy setup to date, we found that patients prefer IITs to VITs. Additionally, IIT-based alignment is an effective and efficient strategy in comparison with tattooless setup. Standard incorporation of IITs for patient setup should be strongly considered.

Combining theranostic/particle therapy with immunotherapy for the treatment of GU malignancies.

Particle therapy and radiopharmaceuticals are emerging fields in the treatment of genitourinary cancers. With these novel techniques and the ever-growing immunotherapy options, the combinations of these therapies have the potential to improve current cancer cure rates. However, the most effective sequence and combination of these therapies is unknown and is a question that is actively being explored in multiple ongoing clinical trials. Here, we review the immunological effects of particle therapy and the available radiopharmaceuticals and discuss how best to combine these therapies.

Pencil Beam Scanning Proton Bragg Peak Conformal FLASH in Prostate Cancer Stereotactic Body Radiotherapy.

Bragg peak FLASH radiotherapy (RT) uses a distal tracking method to eliminate exit doses and can achieve superior OAR sparing. This study explores the application of this novel method in stereotactic body radiotherapy prostate FLASH-RT. An in-house platform was developed to enable intensity-modulated proton therapy (IMPT) planning using a single-energy Bragg peak distal tracking method. The patients involved in the study were previously treated with proton stereotactic body radiotherapy (SBRT) using the pencil beam scanning (PBS) technique to 40 Gy in five fractions. FLASH plans were optimized using a four-beam arrangement to generate a dose distribution similar to the conventional opposing beams. All of the beams had a small angle of two degrees from the lateral direction to increase the dosimetry quality. Dose metrics were compared between the conventional PBS and the Bragg peak FLASH plans. The dose rate histogram (DRVH) and FLASH metrics of 40 Gy/s coverage (V40Gy/s) were investigated for the Bragg peak plans. There was no significant difference between the clinical and Bragg peak plans in rectum, bladder, femur heads, large bowel, and penile bulb dose metrics, except for Dmax. For the CTV, the FLASH plans resulted in a higher Dmax than the clinical plans (116.9% vs. 103.3%). For the rectum, the V40Gy/s reached 94% and 93% for 1 Gy dose thresholds in composite and single-field evaluations, respectively. Additionally, the FLASH ratio reached close to 100% after the application of the 5 Gy threshold in composite dose rate assessment. In conclusion, the Bragg peak distal tracking method can yield comparable plan quality in most OARs while preserving sufficient FLASH dose rate coverage, demonstrating that the ultra-high dose technique can be applied in prostate FLASH SBRT.

Stereotactic Body Radiation Therapy (SBRT) for Hepatocellular Carcinoma (HCC) With Single Photon Emission Computed Tomography (SPECT) Functional Treatment Planning in Patients With Advanced Hepatic Cirrhosis.

Purpose: We report on the feasibility and outcomes of liver stereotactic body radiation therapy (SBRT) for hepatocellular carcinoma (HCC) with single-photon emission computed tomography (SPECT) functional treatment planning in patients with Child-Pugh (CP) B/C cirrhosis. Methods and Materials: Liver SPECT with 99mTc-sulfur colloid was coregistered to treatment planning computed tomography (CT) for the guided avoidance of functional hepatic parenchyma during SBRT. Functional liver volumes (FLVs) obtained from SPECT were compared with anatomic liver volumes defined on the planning CT. Radiation dose constraints were adapted exclusively to FLV. Local control, toxicity, and survival were reported with at least 6 months of radiographic follow-up. Pre- and posttransplant outcomes were analyzed in a subset of patients who completed SBRT as a bridge to liver transplant. Model of End-Stage Liver Disease was used to score hepatic function before and after SBRT completion. Results: With a median follow-up of 32 months, 45 patients (58 lesions) with HCC and CP-B/C cirrhosis received SBRT to a median dose of 45 Gy (3-5 fractions). FLV loss (34%, P < .001) was observed in all patients, and the functional and anatomic liver volumes matched well in a control group of noncirrhotic/non-HCC patients. Despite marked functional parenchyma retraction, the amount of FLV on SPECT exposed to the threshold irradiation was significantly less than the CT liver volumes (P < .001) because of the optimized beam placement during dosimetry planning. Twenty-three patients (51%) successfully completed orthotopic liver transplant, with a median time to transplant of 9.2 months. With 91% in-field local control, the overall 2-year survival was 65% (90% after the orthotopic liver transplant), with no incidence of radiation-induced liver disease observed within 3 to 4 months or accelerated CP class migration from B to C within the first 6 months post-SBRT. Mean Model of End-Stage Liver Disease-Na score was not significantly elevated at 3-month intervals after SBRT completion. Conclusions: Functional treatment planning with 99mTc sulfur colloid SPECT/CT allows identification and avoidance of functional hepatic parenchyma in patients with CP-B/C cirrhosis, leading to low toxicity and satisfactory transplant outcomes.

Prognostic implications of HER2NEU-low in metastatic breast cancer.

INTRODUCTION: We explored characteristics and clinical outcomes of HER2-negative and HER2-low metastatic breast cancers using real-world data. METHODS: We queried the National Cancer Database to identify MBC patients that were HER2-low or HER2-negative per immunohistochemical staining. A binomial regression analysis identified demographic and clinical correlates of each subtype. A Cox multivariable regression analysis (MVA) and propensity-match analysis were performed to identify correlates of survival. RESULTS: Excluding missing data, 24,636 MBC patients diagnosed between 2008 and 2015 were identified; 27.9% were HER2-negative and 72.1% were HER2-low. There were no relevant demographic differences between the groups. HER2-low tumors were half as likely to have concomitant hormone receptor-positive status (p < 0.01). The 3-year survival rate among hormone receptor-negative patients was 33.8% for HER2-low and 32.2% for HER2-negative (p < 0.05), and 60.9% and 55.6% in HER2-low and HER2-negative cases among hormone receptor-positive patients (p < 0.05), respectively. HER2-low cases were associated with better survival on MVA (HR =0.95, 95% CI 0.91-0.99) and remained superior with propensity-matching (HR = 0.92, 95% CI 0.89-0.96). In a subset analysis isolated to hormone receptor-positive cases, HER2-low remained correlated with improved survival (HR = 0.93, 95% CI 0.89-0.98) with propensity-matched MVA. Correlates of worse survival include older age as a continuous variable (HR = 1.02, 95% CI 1.02-1.02) and Black race (HR = 1.26, 95% CI 1.20-1.32) [all p < 0.01]. CONCLUSIONS: In the largest such analysis performed to date, our study demonstrates a small but statistically significant association with improved survival for HER2-low tumors compared to HER2-negative tumors in MBC.