Simultaneous dose and dose rate optimization via dose modifying factor modeling for FLASH effective dose.

BACKGROUND: Although the FLASH radiotherapy (FLASH) can improve the sparing of organs-at-risk (OAR) via the FLASH effect, it is generally a tradeoff between the physical dose coverage and the biological FLASH coverage, for which the concept of FLASH effective dose (FED) is needed to quantify the net improvement of FLASH, compared to the conventional radiotherapy (CONV). PURPOSE: This work will develop the first-of-its-kind treatment planning method called simultaneous dose and dose rate optimization via dose modifying factor modeling (SDDRO-DMF) for proton FLASH that directly optimizes FED. METHODS: SDDRO-DMF models and optimizes FED using FLASH dose modifying factor (DMF) models, which can be classified into two categories: (1) the phenomenological model of the FLASH effect, such as the FLASH effectiveness model (FEM); (2) the mechanistic model of the FLASH radiobiology, such as the radiolytic oxygen depletion (ROD) model. The general framework of SDDRO-DMF will be developed, with specific DMF models using FEM and ROD, as a demonstration of general applicability of SDDRO-DMF for proton FLASH via transmission beams (TB) or Bragg peaks (BP) with single-field or multi-field irradiation. The FLASH dose rate is modeled as pencil beam scanning dose rate. The solution algorithm for solving the inverse optimization problem of SDDRO-DMF is based on iterative convex relaxation method. RESULTS: SDDRO-DMF is validated in comparison with IMPT and a state-of-the-art method called SDDRO, with demonstrated efficacy and improvement for reducing the high dose and the high-dose volume for OAR in terms of FED. For example, in a SBRT lung case of the dose-limiting factor that the max dose of brachial plexus should be no more than 26 Gy, only SDDRO-DMF met this max dose constraint; moreover, SDDRO-DMF completely eliminated the high-dose (V70%) volume to zero for CTV10mm (a high-dose region as a 10 mm ring expansion of CTV). CONCLUSION: We have proposed a new proton FLASH optimization method called SDDRO-DMF that directly optimizes FED using phenomenological or mechanistic models of DMF, and have demonstrated the efficacy of SDDO-DMF in reducing the high-dose volume or/and the high-dose value for OAR, compared to IMPT and a state-of-the-art method SDDRO.

Why is a small sample size not enough?

BACKGROUND: Clinical studies are often limited by resources available, which results in constraints on sample size. We use simulated data to illustrate study implications when the sample size is too small. METHODS AND RESULTS: Using 2 theoretical populations each with N = 1000, we randomly sample 10 from each population and conduct a statistical comparison, to help make a conclusion about whether the 2 populations are different. This exercise is repeated for a total of 4 studies: 2 concluded that the 2 populations are statistically significantly different, while 2 showed no statistically significant difference. CONCLUSIONS: Our simulated examples demonstrate that sample sizes play important roles in clinical research. The results and conclusions, in terms of estimates of means, medians, Pearson correlations, chi-square test, and P values, are unreliable with small samples.

Differences in Rural Versus Urban Patients With Prostate Cancer in Diagnosis and Treatment: An Analysis of a Population-Based Cohort.

PURPOSE: Patients living in rural communities have greater barriers to cancer care and poorer outcomes. We hypothesized that rural patients with prostate cancer have less access and receive different treatments compared with urban patients. METHODS: We used a population-based prospective cohort, the North Carolina Prostate Cancer Comparative Effectiveness and Survivorship Study, to compare differences in prostate cancer diagnosis, access to care, and treatment in patients by geographic residence. The 2013 rural-urban continuum code (RUCC) was used to determine urban (RUCC 1-3) versus rural (RUCC 4-9) location of residence. RESULTS: Patients with rural residence comprised 25% of the cohort (364 of 1,444); they were less likely to be White race and had lower income and educational attainment. Rural patients were more likely to have <12 cores on biopsy (47.1% v 35.7%; P < .001) and less likely (40.8% v 47.6%; P = .04) to receive multidisciplinary consultation. We observed significant differences in treatment between urban and rural patients, including rural patients receiving less active surveillance or observation (22.6% v 28.7%), especially in low-risk cancer (33.2% v 40.7%). On multivariable analysis that adjusted for patient and diagnostic factors, rural residence was associated with less use of active surveillance or observation over radical treatment (ie, surgery or radiation therapy; odds ratio, 0.49 v urban; P < .001) in patients with low-risk cancer. CONCLUSION: Patients with prostate cancer who live in rural versus urban areas experience several differences in care that are likely clinically meaningful, including fewer cores in the diagnostic biopsy, less utilization of multidisciplinary consultation, less use of active surveillance, or observation for low-risk disease. Future studies are needed to assess the efficacy of interventions in mitigating these disparities.

Biological optimization for hybrid proton-photon radiotherapy.

Objective.Hybrid proton-photon radiotherapy (RT) is a cancer treatment option to broaden access to proton RT. Additionally, with a refined treatment planning method, hybrid RT has the potential to offer superior plan quality compared to proton-only or photon-only RT, particularly in terms of target coverage and sparing organs-at-risk (OARs), when considering robustness to setup and range uncertainties. However, there is a concern regarding the underestimation of the biological effect of protons on OARs, especially those in close proximity to targets. This study seeks to develop a hybrid treatment planning method with biological dose optimization, suitable for clinical implementation on existing proton and photon machines, with each photon or proton treatment fraction delivering a uniform target dose.Approach.The proposed hybrid biological dose optimization method optimized proton and photon plan variables, along with the number of fractions for each modality, minimizing biological dose to the OARs and surrounding normal tissues. To mitigate underestimation of hot biological dose spots, proton biological dose was minimized within a ring structure surrounding the target. Hybrid plans were designed to be deliverable separately and robustly on existing proton and photon machines, with enforced uniform target dose constraints for the proton and photon fraction doses. A probabilistic formulation was utilized for robust optimization of setup and range uncertainties for protons and photons. The nonconvex optimization problem, arising from minimum monitor unit constraint and dose-volume histogram constraints, was solved using an iterative convex relaxation method.Main results.Hybrid planning with biological dose optimization effectively eliminated hot spots of biological dose, particularly in normal tissues surrounding the target, outperforming proton-only planning. It also provided superior overall plan quality and OAR sparing compared to proton-only or photon-only planning strategies.Significance.This study presents a novel hybrid biological treatment planning method capable of generating plans with reduced biological hot spots, superior plan quality to proton-only or photon-only plans, and clinical deliverability on existing proton and photon machines, separately and robustly.

Bladder Cancer Survivors Who Do Not Smoke Have Better Longitudinal Health-Related Quality of Life Measures: An Assessment of the Comparative Effectiveness and Survivorship Health in Bladder Cancer (CEASE-BC) Study.

PURPOSE: Cigarette smoking is the most common risk factor for the development of bladder cancer (BC), yet there is a paucity of data characterizing the relationship between smoking status and longitudinal health-related quality of life (HRQoL) outcomes in patients with BC. We examined the association between smoking status and HRQoL among patients with BC. MATERIALS AND METHODS: Data were sourced from a prospective, longitudinal study open between 2014 and 2017, which examined HRQoL in patients aged ≥ 18 years old diagnosed with BC across North Carolina. The QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core instrument) was administered at 3, 12, and 24 months after BC diagnosis. Our primary exposure of interest was current smoking status. Linear regression using generalized estimating equations was used to analyze the relationship between smoking status and various domains of the QLQ-C30. RESULTS: A total of 154 patients enrolled in the study. Eighteen percent were classified as smoking at 3 months from diagnosis, and packs per day ranged from < 0.5 to 2. When controlling for time from diagnosis, demographic covariates, cancer stage, and treatment type, mean differences for physical function (7.4), emotional function (5.6), and fatigue measures (-8.2) were significantly better for patients with BC who did not smoke. CONCLUSIONS: Patients with BC who do not smoke have significantly better HRQoL scores in the domains of physical function, emotional function, and fatigue. These results underscore the need to treat smoking as an essential component of BC care.

Noninferiority of Hypofractionated vs Conventional Postprostatectomy Radiotherapy for Genitourinary and Gastrointestinal Symptoms: The NRG-GU003 Phase 3 Randomized Clinical Trial.

Importance: No prior trial has compared hypofractionated postprostatectomy radiotherapy (HYPORT) to conventionally fractionated postprostatectomy (COPORT) in patients primarily treated with prostatectomy. Objective: To determine if HYPORT is noninferior to COPORT for patient-reported genitourinary (GU) and gastrointestinal (GI) symptoms at 2 years. Design, Setting, and Participants: In this phase 3 randomized clinical trial, patients with a detectable prostate-specific antigen (PSA; ≥0.1 ng/mL) postprostatectomy with pT2/3pNX/0 disease or an undetectable PSA (<0.1 ng/mL) with either pT3 disease or pT2 disease with a positive surgical margin were recruited from 93 academic, community-based, and tertiary medical sites in the US and Canada. Between June 2017 and July 2018, a total of 296 patients were randomized. Data were analyzed in December 2020, with additional analyses occurring after as needed. Intervention: Patients were randomized to receive 62.5 Gy in 25 fractions (HYPORT) or 66.6 Gy in 37 fractions (COPORT). Main Outcomes and Measures: The coprimary end points were the 2-year change in score from baseline for the bowel and urinary domains of the Expanded Prostate Cancer Composite Index questionnaire. Secondary objectives were to compare between arms freedom from biochemical failure, time to progression, local failure, regional failure, salvage therapy, distant metastasis, prostate cancer-specific survival, overall survival, and adverse events. Results: Of the 296 patients randomized (median [range] age, 65 [44-81] years; 100% male), 144 received HYPORT and 152 received COPORT. At the end of RT, the mean GU change scores among those in the HYPORT and COPORT arms were neither clinically significant nor different in statistical significance and remained so at 6 and 12 months. The mean (SD) GI change scores for HYPORT and COPORT were both clinically significant and different in statistical significance at the end of RT (-15.52 [18.43] and -7.06 [12.78], respectively; P < .001). However, the clinically and statistically significant differences in HYPORT and COPORT mean GI change scores were resolved at 6 and 12 months. The 24-month differences in mean GU and GI change scores for HYPORT were noninferior to COPORT using noninferiority margins of -5 and -6, respectively, rejecting the null hypothesis of inferiority (mean [SD] GU score: HYPORT, -5.01 [15.10] and COPORT, -4.07 [14.67]; P = .005; mean [SD] GI score: HYPORT, -4.17 [10.97] and COPORT, -1.41 [8.32]; P = .02). With a median follow-up for censored patients of 2.1 years, there was no difference between HYPORT vs COPORT for biochemical failure, defined as a PSA of 0.4 ng/mL or higher and rising (2-year rate, 12% vs 8%; P = .28). Conclusions and Relevance: In this randomized clinical trial, HYPORT was associated with greater patient-reported GI toxic effects compared with COPORT at the completion of RT, but both groups recovered to baseline levels within 6 months. At 2 years, HYPORT was noninferior to COPORT in terms of patient-reported GU or GI toxic effects. HYPORT is a new acceptable practice standard for patients receiving postprostatectomy radiotherapy. Trial Registration: ClinicalTrials.gov Identifier: NCT03274687.

Demographic and Clinical Factors Associated With Health-Related Quality-of-Life Profiles Among Prostate Cancer Survivors.

PURPOSE: Our purpose was to describe the prevalence and predictors of symptom and function clusters related to physical, emotional, and social components of general health-related quality of life (HRQOL) in a population-based sample of prostate cancer (PCa) survivors. METHODS: Participants (N = 1,162) completed a baseline survey at a median of 9 months after diagnosis to ascertain the co-occurrence of eight symptom and functional domains that are common across all cancers and not treatment-specific. We used latent profile analysis (LPA) to identify subgroup profiles of survivors with low, moderate, or high HRQOL levels. Multinomial logistic regression models were used to identify clinical and sociodemographic factors associated with survivors' membership in the low versus moderate or high HRQOL profile. RESULTS: The LPA identified 16% of survivors who were categorized in the low HRQOL profile at baseline, indicative of the highest symptom burden and lowest functioning. Factors related to survivors' membership in the low versus higher HRQOL profile groups included less than age 65 years at diagnosis, identifying as non-Hispanic Black race, not working, being a former versus never smoker, systemic therapy, less companionship, more comorbidities, lower health care financial well-being, or less spirituality. Several factors remained associated with remaining in the low versus higher HRQOL profiles on the follow-up survey (n = 699), including younger age, Black race, comorbidity, and lower financial and spiritual well-being. CONCLUSION: About one of six PCa survivors experienced elevated physical and psychosocial symptoms that were independent of local curative therapy, but with younger age, race, comorbidity, and lower financial and spiritual well-being as stable risk factors for poor HRQOL over time.

Salvage Therapy for Prostate Cancer: AUA/ASTRO/SUO Guideline Part III: Salvage Therapy After Radiotherapy or Focal Therapy, Pelvic Nodal Recurrence and Oligometastasis, and Future Directions.

PURPOSE: The summary presented herein covers recommendations on salvage therapy for recurrent prostate cancer intended to facilitate care decisions and aid clinicians in caring for patients who have experienced a recurrence following prior treatment with curative intent. This is Part III of a three-part series focusing on evaluation and management of suspected non-metastatic recurrence after radiotherapy (RT) and focal therapy, evaluation and management of regional recurrence, management for molecular imaging metastatic recurrence, and future directions. Please refer to Part I for discussion of treatment decision-making and Part II for discussion of treatment delivery for non-metastatic biochemical recurrence (BCR) after radical prostatectomy (RP). MATERIALS AND METHODS: The systematic review that informs this Guideline was based on searches in Ovid MEDLINE (1946 to July 21, 2022), Cochrane Central Register of Controlled Trials (through August 2022), and Cochrane Database of Systematic Reviews (through August 2022). Update searches were conducted on July 26, 2023. Searches were supplemented by reviewing electronic database reference lists of relevant articles. RESULTS: In a collaborative effort between AUA, ASTRO, and SUO, the Salvage Therapy for Prostate Cancer Guideline Panel developed evidence- and consensus-based guideline statements to provide guidance for the care of patients who experience BCR after initial definitive local therapy for clinically localized disease. CONCLUSIONS: Continuous and deliberate efforts for multidisciplinary care in prostate cancer will be required to optimize and improve the oncologic and functional outcomes of patients treated with salvage therapies in the future.

Salvage Therapy for Prostate Cancer: AUA/ASTRO/SUO Guideline Part I: Introduction and Treatment Decision-Making at the Time of Suspected Biochemical Recurrence after Radical Prostatectomy.

PURPOSE: The summary presented herein covers recommendations on salvage therapy for recurrent prostate cancer intended to facilitate care decisions and aid clinicians in caring for patients who have experienced a recurrence following prior treatment with curative intent. This is Part I of a three-part series focusing on treatment decision-making at the time of suspected biochemical recurrence (BCR) after radical prostatectomy (RP). Please refer to Part II for discussion of treatment delivery for non-metastatic BCR after RP and Part III for discussion of evaluation and management of recurrence after radiotherapy (RT) and focal therapy, regional recurrence, and oligometastasis. MATERIALS AND METHODS: The systematic review that informs this Guideline was based on searches in Ovid MEDLINE (1946 to July 21, 2022), Cochrane Central Register of Controlled Trials (through August 2022), and Cochrane Database of Systematic Reviews (through August 2022). Update searches were conducted on July 26, 2023. Searches were supplemented by reviewing electronic database reference lists of relevant articles. RESULTS: In a collaborative effort between AUA, ASTRO, and SUO, the Salvage Therapy for Prostate Cancer Panel developed evidence- and consensus-based statements to provide guidance for the care of patients who experience BCR after initial definitive local therapy for clinically localized disease. CONCLUSIONS: Advancing work in the area of diagnostic tools (particularly imaging), biomarkers, radiation delivery, and biological manipulation with the evolving armamentarium of therapeutic agents will undoubtedly present new opportunities for patients to experience long-term control of their cancer while minimizing toxicity.

Salvage Therapy for Prostate Cancer: AUA/ASTRO/SUO Guideline Part II: Treatment Delivery for Non-metastatic Biochemical Recurrence After Primary Radical Prostatectomy.

PURPOSE: The summary presented herein covers recommendations on salvage therapy for recurrent prostate cancer intended to facilitate care decisions and aid clinicians in caring for patients who have experienced a recurrence following prior treatment with curative intent. This is Part II of a three-part series focusing on treatment delivery for non-metastatic biochemical recurrence (BCR) after primary radical prostatectomy (RP). Please refer to Part I for discussion of treatment decision-making and Part III for discussion of evaluation and management of recurrence after radiotherapy (RT) and focal therapy, regional recurrence, and oligometastasis. MATERIALS AND METHODS: The systematic review that informs this Guideline was based on searches in Ovid MEDLINE (1946 to July 21, 2022), Cochrane Central Register of Controlled Trials (through August 2022), and Cochrane Database of Systematic Reviews (through August 2022). Update searches were conducted on July 26, 2023. Searches were supplemented by reviewing electronic database reference lists of relevant articles. RESULTS: In a collaborative effort between AUA, ASTRO, and SUO, the Salvage Therapy for Prostate Cancer Panel developed evidence- and consensus-based guideline statements to provide guidance for the care of patients who experience BCR after initial definitive local therapy for clinically localized disease. CONCLUSIONS: Optimizing and personalizing the approach to salvage therapy remains an ongoing area of work in the field of genitourinary oncology and represents an area of research and clinical care that requires well-coordinated, multi-disciplinary efforts.

PRESTO: A Phase III, Open-Label Study of Intensification of Androgen Blockade in Patients With High-Risk Biochemically Relapsed Castration-Sensitive Prostate Cancer (AFT-19).

PURPOSE: Patients with biochemically recurrent prostate cancer (BRPC) after radical prostatectomy and a short PSA doubling time are at risk for distant metastases. Apalutamide, an androgen receptor antagonist, and abiraterone acetate plus prednisone (AAP) prolong survival in the metastatic setting. We evaluated whether intensification of androgen-deprivation therapy (ADT) improves outcomes in BRPC. PATIENTS AND METHODS: PRESTO is a randomized phase III, open-label trial in patients with BRPC and PSA doubling time ≤9 months (ClinicalTrials.gov identifier: NCT03009981). Patients were randomly assigned 1:1:1 to receive a finite 52-week treatment course with ADT control, ADT + apalutamide, or ADT + apalutamide + AAP. The primary end point was PSA progression-free survival (PSA-PFS), defined as serum PSA >0.2 ng/mL after treatment completion. RESULTS: Five hundred three patients were enrolled. The median PSA was 1.8 ng/mL (IQR, 1.0-3.6). At the first planned interim analysis, both experimental arms significantly prolonged PSA-PFS compared with the control arm (median, 24.9 months for ADT + apalutamide v 20.3 months for ADT; hazard ratio [HR], 0.52 [95% CI, 0.35 to 0.77]; P = .00047; median, 26.0 months for ADT + apalutamide + AAP v 20.0 months for ADT; HR, 0.48 [95% CI, 0.32 to 0.71]; P = .00008). Median time to testosterone recovery did not differ across treatment arms. The most common grade ≥3 adverse event was hypertension (7.5%, 7.4%, and 18% in ADT, ADT + apalutamide, and ADT + apalutamide + AAP arms, respectively). CONCLUSION: Intensified AR blockade for a finite duration prolongs PSA-PFS with a manageable safety profile, without adversely affecting time to testosterone recovery. The addition of apalutamide to ADT should be considered in patients with high-risk BRPC.

Roadmap to engagement: Bringing patient partners into cancer research and beyond.

The University of Kansas Cancer Center (KU Cancer Center) initiated an engagement program to leverage the lived experience of individuals and families with cancer. KU Cancer Center faculty, staff, and patient partners built an infrastructure to achieve a patient-designed, patient-led, and research-informed engagement program called Patient and Investigator Voices Organizing Together (PIVOT). This special communication offers an engagement roadmap that can be replicated, scaled, and adopted at other cancer centers and academic health systems. PIVOT demonstrates that collaboration among academic leaders, investigators, and people with a lived experience yields a patient-centered, vibrant environment that enriches the research enterprise.

Ten fraction hypofractionated stereotactic body radiotherapy for the management of ultracentral lung tumors: a retrospective analysis of dosimetry, outcomes, and toxicity.

BACKGROUND: The management of ultracentral thoracic tumors with ablative dose of radiotherapy remains challenging given proximity to critical central structures. We report patient outcomes, toxicity, and dosimetry for ultracentrally located tumors with hypofractionated stereotactic body radiotherapy (hfSBRT). METHODS: Seventy-eight individuals (50 initial radiotherapy, 28 re-irradiation) undergoing 10 fraction hfSBRT for ultracentrally located thoracic tumors treated between 2009 and 2020 at a single institution were retrospectively reviewed. Overall survival (OS), progression free survival (PFS), and local control (LC) were calculated. Incidence and grade of treatment related toxicity were evaluated. Dosimetric analysis of treatment plans and critical adjacent OARs was performed. RESULTS: At a median follow up time of 13 months, 1- and 3-year OS, PFS, and LC were 89%/63%, 37%/18%, and 84%/65%, respectively. Median dose was 65 Gy (BED10 = 107.25 Gy). Median primary bronchial tree maximum dose (Dmax) was 60 Gy (V50 = 0.96 cc). Median esophageal Dmax was 38 Gy (V40 = 0 cc). Median great vessel Dmax was 68 Gy (V50 = 3.53 cc). The most common ≥ grade 2 adverse event was pneumonitis, in 15 individuals (20%). Grade 3 or higher toxicity was observed in 9 individuals (12%): three cases of grade 3 pneumonitis (two re-irradiation, one initial radiotherapy), one grade 3 esophageal stricture following re-irradiation, two grade 3 endobronchial obstructions both following initial radiotherapy, and three grade 5 hemoptysis events (two re-irradiation, one initial radiotherapy). One hemoptysis event was categorized as "possibly" related to treatment, while the remaining two events were categorized as "unlikely" related to treatment in patients with clear evidence of disease progression. CONCLUSIONS: hfSBRT to ultracentral lung tumors delivered over 10 fractions is a safe and effective treatment option, with acceptable rates of toxicity and good rates of tumor control. TRIAL REGISTRATION: IRB registration number 12573.

A community engagement training program for basic and translational cancer researchers.

PURPOSE: There is an increasing awareness of the importance of patient engagement in cancer research, but many basic and translational researchers have never been trained to do so. To address this unmet need, a 1-year patient engagement training program for researchers was developed. METHODS: Eleven researchers and eleven paired research advocates participated. This program, designed for virtual delivery, included 3 didactic modules focused on (1) Community Outreach and Engagement principles and methods, (2) Communication skills, and (3) Team Science. This was followed by longitudinal projects to be completed by the researcher/advocate pairs, including learning about the research project, and co-authoring abstracts, manuscripts and grant proposals. Monthly group meetings allowed pairs to share their experiences. The program culminated in the pairs creating and presenting oral abstracts for the University of Kansas Cancer Center's Annual Research Symposium. RESULTS: All participants indicated that the modules had a positive impact on their ability to collaborate in research. Both researcher self-evaluations and patient advocate evaluations of their researcher partner showed an improvement in researcher communication competency. Results from the Patient Engagement in Research Scale showed that advocates were highly engaged. Within 1 year after program completion, participating pairs have completed four abstracts and 9 grant proposals. CONCLUSION: The program will be modified based on participant feedback, and can be adapted for future cohorts if an increased number of sessions per month and shortened program duration are desired. The program's virtual format allows scalability across institutions to potentially benefit large cohorts of researchers.

Lattice position optimization for LATTICE therapy.

BACKGROUND: LATTICE radiation therapy delivers 3D heterogenous dose of high peak-to-valley dose ratio (PVDR) to the tumor target, with peak dose at lattice vertices inside the target and valley dose for the rest of the target. Although the lattice vertex positions can impact PVDR inside the target and sparing of organs-at-risk (OAR), they are fixed as constants and not optimized during treatment planning in current clinical practice. PURPOSE: This work proposes a new LATTICE plan optimization method that can optimize lattice vertex positions during LATTICE treatment planning, which is the first lattice position optimization study to the best of our knowledge. METHODS: The new LATTICE treatment planning method optimizes lattice vertex positions as well as other plan variables (e.g., photon fluences or proton spot weights), with optimization objectives for target PVDR and OAR sparing. To satisfy mathematical differentiability, the lattice vertices are approximated in sigmoid functions. For geometric feasibility, proper geometry constraints are enforced onto lattice vertex positions. The lattice position optimization problem is solved by iterative convex relaxation (ICR) method and alternating direction method of multipliers (ADMM), and lattice vertex positions and photon/proton plan variables are jointly updated via the Quasi-Newton method. RESULTS: Both photon and proton LATTICE RT were considered, and the optimal lattice vertex positions in terms of plan objectives were found by solving all possible combinations on given discrete positions via exhaustive searching based on standard IMRT/IMPT, which served as the ground truth for validating the new LATTICE method. The results show that the new method indeed provided the optimal lattice vertex positions with the smallest optimization objective, the largest target PVDR, and the best OAR sparing. CONCLUSIONS: A new LATTICE treatment planning method is proposed and validated that can optimize lattice vertex positions as well as other photon or proton plan variables for improving target PVDR and OAR sparing.

Income level and treatment selection in prostate cancer: analysis of a North Carolina population-based cohort.

BACKGROUND: Disparities in treatment selection based on socioeconomic status for prostate cancer exist. However, the association between patient-level income with treatment selection priorities and treatment received has not been studied. METHODS: A population-based cohort of 1382 individuals with newly diagnosed prostate cancer was enrolled throughout North Carolina prior to treatment. Patients self-reported household income and were asked about the importance of 12 factors contributing to their treatment decision-making process. Diagnosis details and primary treatment received were abstracted from medical records and cancer registry data. RESULTS: Patients with lower income were diagnosed with more advanced disease (P < .01). Cure was deemed to be "very important" by more than 90% of patients at all income levels. However, patients with lower vs higher household income were more likely to rate factors beyond cure as "very important" such as cost (P < .01), effect on daily activities (P = .01), duration of treatment (P < .01), recovery time (P < .01), and burden on family and friends (P < .01). On multivariable analysis, high vs low income was associated with increased utilization of radical prostatectomy (odds ratio = 2.01, 95% confidence interval = 1.33 to 3.04; P < .01) and decreased use of radiotherapy (odds ratio = 0.48, 95% confidence interval = 0.31 to 0.75; P < .01). CONCLUSIONS: New insights from this study on the association between income and treatment decision-making priorities provide potential avenues for future interventions to reduce disparities in cancer care.

A treatment plan optimization method with direct minimization of number of energy jumps for proton arc therapy.

Objective. The optimization of energy layer distributions is crucial to proton arc therapy: on one hand, a sufficient number of energy layers is needed to ensure the plan quality; on the other hand, an excess number of energy jumps (NEJ) can substantially slow down the treatment delivery. This work will develop a new treatment plan optimization method with direct minimization of (NEJ), which will be shown to outperform state-of-the-art methods in both plan quality and delivery efficiency.Approach. The proposed method jointly optimizes the plan quality and minimizes the NEJ. To minimize NEJ, (1) the proton spotsxis summed per energy layer to form the energy vectory; (2)yis binarized via sigmoid transform intoy1; (3)y1is multiplied with a predefined energy order vector via dot product intoy2; (4)y2is filtered through the finite-differencing kernel intoy3in order to identify NEJ; (5) only the NEJ ofy3is penalized, whilexis optimized for plan quality. The solution algorithm to this new method is based on iterative convex relaxation.Main results. The new method is validated in comparison with state-of-the-art methods called energy sequencing (ES) method and energy matrix (EM) method. In terms of delivery efficiency, the new method had fewer NEJ, less energy switching time, and generally less total delivery time. In terms of plan quality, the new method had smaller optimization objective values, lower normal tissue dose, and generally better target coverage.Significance. We have developed a new treatment plan optimization method with direct minimization of NEJ, and demonstrated that this new method outperformed state-of-the-art methods (ES and EM) in both plan quality and delivery efficiency.