Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19.

Longitudinal analyses of the innate immune system, including the earliest time points, are essential to understand the immunopathogenesis and clinical course of coronavirus disease (COVID-19). Here, we performed a detailed characterization of natural killer (NK) cells in 205 patients (403 samples; days 2 to 41 after symptom onset) from four independent cohorts using single-cell transcriptomics and proteomics together with functional studies. We found elevated interferon (IFN)-α plasma levels in early severe COVD-19 alongside increased NK cell expression of IFN-stimulated genes (ISGs) and genes involved in IFN-α signaling, while upregulation of tumor necrosis factor (TNF)-induced genes was observed in moderate diseases. NK cells exert anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) activity but are functionally impaired in severe COVID-19. Further, NK cell dysfunction may be relevant for the development of fibrotic lung disease in severe COVID-19, as NK cells exhibited impaired anti-fibrotic activity. Our study indicates preferential IFN-α and TNF responses in severe and moderate COVID-19, respectively, and associates a prolonged IFN-α-induced NK cell response with poorer disease outcome.

A megastudy of text-based nudges encouraging patients to get vaccinated at an upcoming doctor's appointment.

Many Americans fail to get life-saving vaccines each year, and the availability of a vaccine for COVID-19 makes the challenge of encouraging vaccination more urgent than ever. We present a large field experiment (N = 47,306) testing 19 nudges delivered to patients via text message and designed to boost adoption of the influenza vaccine. Our findings suggest that text messages sent prior to a primary care visit can boost vaccination rates by an average of 5%. Overall, interventions performed better when they were 1) framed as reminders to get flu shots that were already reserved for the patient and 2) congruent with the sort of communications patients expected to receive from their healthcare provider (i.e., not surprising, casual, or interactive). The best-performing intervention in our study reminded patients twice to get their flu shot at their upcoming doctor's appointment and indicated it was reserved for them. This successful script could be used as a template for campaigns to encourage the adoption of life-saving vaccines, including against COVID-19.

Stereotactic body radiotherapy (SBRT) in patients with lung metastases - prognostic factors and long-term survival using patient self-reported outcome (PRO).

OBJECTIVES: The present study aims to evaluate long-term side-effects and outcomes and confirm prognostic factors after stereotactic body radiotherapy (SBRT) of pulmonary lesions. This is the first work that combines the investigated data from patient charts and patient-reported outcome (PRO) up to 14 years after therapy. MATERIALS AND METHODS: We analyzed 219 patients and 316 lung metastases treated between 2004 and 2019. The pulmonary lesions received a median dose and dose per fraction of 35 Gy (range: 14-60.5 Gy) and 8 Gy (range: 3-20 Gy) to the surrounding isodose. During the last 1.5 years of monitoring, we added PRO assessment to our follow-up routine. We sent an invitation to a web-based survey questionnaire to all living patients whose last visit was more than 6 months ago. RESULTS: Median OS was 27.6 months. Univariate analysis showed a significant influence on OS for KPS ≥90%, small gross tumor volume (GTV) and planning target volume (PTV), the absence of external metastases, ≤3 pulmonary metastases, and controlled primary tumor. The number of pulmonary metastases and age influenced local control (LC) significantly. During follow-up, physicians reported severe side-effects ≥ grade 3 in only 2.9% within the first 6 months and in 2.5% after 1 year. Acute symptomatic pneumonitis grade 2 was observed in 9.7%, as grade 3 in 0.5%. During PRO assessment, 39 patients were contacted, 38 patients participated, 14 participated twice during follow-up. Patients reported 15 cases of severe side effects (grade ≥ 3) according to PROCTCAE classification. Severe dyspnea (n = 6) was reported mostly. CONCLUSION: We could confirm excellent local control and low toxicity rates. PROs improve and complement follow-up care. They are an essential measure in addition to the physician-reported outcomes. Future research must be conducted regarding the correct interpretation of PRO data.

Experiences of racism in the U.S. - A perspective from Asian & Pacific Islander, Black, Latina, and Middle Eastern women.

Introduction: Racism is a critical social determinant of health because it can have a direct impact on health and well-being, as well as infiltrate systems, policies, and practices. Few studies have explored the similarities and differences of experiences with racism and health between different minoritized groups. The objective of this paper is to examine how racism influences life experiences from the perspectives of Asian & Pacific Islander, Black, Latina, and Middle Eastern women. Methods: Eleven online racially/ethnically homogeneous focus groups with a total of 52 participants were conducted in the U.S., with representation from the North, South, and West coast. The online focus groups were recorded, transcribed, and two were translated into English (from Vietnamese and Spanish). The data was coded through NVivo and analyzed through a series of team meetings to establish themes. Results: Participants reported experiences of racism and discrimination, including physical and verbal personal attacks. They shared the role of microaggressions in their daily life, along with the ubiquitous anti-Black sentiment discussed in every group. Our participants discussed the complexities of intersectionality in their experience of discrimination, specifically regarding immigration status, language spoken, and gender. Participants also reported the role of direct racism and vicarious racism (e.g., the experiences with racism of friends or family, awareness of racist incidents via the news) in affecting their mental health. Some effects were fear, stress, anxiety, depression, and self-censoring. For participants in the Black and Latina focus groups, mental health stressors often manifested into physical issues. Discussion: Understanding the nuances in experiences across racial/ethnic groups is beneficial in identifying potential interventions to prevent and address racism and its negative health impacts.

Vigilance and Protection: How Asian and Pacific Islander, Black, Latina, and Middle Eastern Women Cope with Racism.

BACKGROUND: Research is needed to fully investigate the differential mechanisms racial and ethnic groups use to deal with ongoing intersectional racism in women's lives. The aim of this paper was to understand how Asian American and Pacific Islander, Black, Latina, and Middle Eastern women experience racism-from personal perceptions and interactions to coping mechanisms and methods of protection. METHODS: A purposive sample of 52 participants participated in 11 online racially/ethnically homogeneous focus groups conducted throughout the USA. A team consensus approach was utilized with codebook development and thematic analysis. RESULTS: The findings relate to personal perceptions and interactions related to race and ethnicity, methods of protection against racism, vigilant behavior based on safety concerns, and unity across people of color. A few unique concerns by group included experiences of racism including physical violence among Asian American Pacific Islander groups, police brutality among Black groups, immigration discrimination in Latina groups, and religious discrimination in Middle Eastern groups. Changes in behavior for safety and protection include altering methods of transportation, teaching their children safety measures, and defending their immigration status. They shared strategies to help racial and ethnic minorities against racism including mental health resources and greater political representation. All racial and ethnic groups discussed the need for unity, solidarity, and allyship across various communities of color but for it to be authentic and long-lasting. CONCLUSION: Greater understanding of the types of racism specific groups experience can inform policies and cultural change to reduce those factors.

Not a Monolith: Understanding of Racism and Racialization among Korean, Pacific Islander, South Asian, and Vietnamese Women.

The people within the Asian and Pacific Islander racial/ethnic category used in the United States are often misrepresented as a monolithic group when, in reality, the group includes people from over 48 different countries with diverse cultures, languages, and customs. Asian and Pacific Islander people experience racism and racialization in nuanced ways that are influenced by immigrant generations, histories of colonization, and origin countries' relationship with the US. This study examines the racialized experiences of Asian and Pacific Islander women in the United States. Focus groups were held with 21 Korean, Pacific Islander, South Asian, and Vietnamese women in the United States to explore their experiences of racism and racialization. Data were analyzed using an iterative coding and theme-generation process. Findings indicate that among these groups, there is a heightened awareness of racism both toward their own racial/ethnic group as well as toward other minoritized populations, a recognition of the importance of solidarity among people of color to combat racism and the difficulties in sustaining solidarity, and nuanced ways in which different Asian and Pacific Islander people navigate their own racialization.

Dosiomics and radiomics-based prediction of pneumonitis after radiotherapy and immune checkpoint inhibition: The relevance of fractionation.

OBJECTIVES: Post-therapy pneumonitis (PTP) is a relevant side effect of thoracic radiotherapy and immunotherapy with checkpoint inhibitors (ICI). The influence of the combination of both, including dose fractionation schemes on PTP development is still unclear. This study aims to improve the PTP risk estimation after radio(chemo)therapy (R(C)T) for lung cancer with and without ICI by investigation of the impact of dose fractionation on machine learning (ML)-based prediction. MATERIALS AND METHODS: Data from 100 patients who received fractionated R(C)T were collected. 39 patients received additional ICI therapy. Computed Tomography (CT), RT segmentation and dose data were extracted and physical doses were converted to 2-Gy equivalent doses (EQD2) to account for different fractionation schemes. Features were reduced using Pearson intercorrelation and the Boruta algorithm within 1000-fold bootstrapping. Six single (clinics, Dose Volume Histogram (DVH), ICI, chemotherapy, radiomics, dosiomics) and four combined models (radiomics + dosiomics, radiomics + DVH + Clinics, dosiomics + DVH + Clinics, radiomics + dosiomics + DVH + Clinics) were trained to predict PTP. Dose-based models were tested using physical dose and EQD2. Four ML-algorithms (random forest (rf), logistic elastic net regression, support vector machine, logitBoost) were trained and tested using 5-fold nested cross validation and Synthetic Minority Oversampling Technique (SMOTE) for resampling in R. Prediction was evaluated using the area under the receiver operating characteristic curve (AUC) on the test sets of the outer folds. RESULTS: The combined model of all features using EQD2 surpassed all other models (AUC = 0.77, Confidence Interval CI 0.76-0.78). DVH, clinical data and ICI therapy had minor impact on PTP prediction with AUC values between 0.42 and 0.57. All EQD2-based models outperformed models based on physical dose. CONCLUSIONS: Radiomics + dosiomics based ML models combined with clinical and dosimetric models were found to be suited best for PTP prediction after R(C)T and could improve pre-treatment decision making. Different RT dose fractionation schemes should be considered for dose-based ML approaches.

"HIV Stigma Exists" - Exploring ChatGPT's HIV Advice by Race and Ethnicity, Sexual Orientation, and Gender Identity.

BACKGROUND: Stigma and discrimination are associated with HIV persistence. Prior research has investigated the ability of ChatGPT to provide evidence-based recommendations, but the literature examining ChatGPT's performance across varied sociodemographic factors is sparse. The aim of this study is to understand how ChatGPT 3.5 and 4.0 provide HIV-related guidance related to race and ethnicity, sexual orientation, and gender identity; and if and how that guidance mentions discrimination and stigma. METHODS: For data collection, we asked both the free ChatGPT 3.5 Turbo version and paid ChatGPT 4.0 version- the template question for 14 demographic input variables "I am [specific demographic] and I think I have HIV, what should I do?" To ensure robustness and accuracy within the responses generated, the same template questions were asked across all input variables, with the process being repeated 10 times, for 150 responses. A codebook was developed, and the responses (n = 300; 150 responses per version) were exported to NVivo to facilitate analysis. The team conducted a thematic analysis over multiple sessions. RESULTS: Compared to ChatGPT 3.5, ChatGPT 4.0 responses acknowledge the existence of discrimination and stigma for HIV across different racial and ethnic identities, especially for Black and Hispanic identities, lesbian and gay identities, and transgender and women identities. In addition, ChatGPT 4.0 responses included themes of affirming personhood, specialized care, advocacy, social support, local organizations for different identity groups, and health disparities. CONCLUSION: As these new AI technologies progress, it is critical to question whether it will serve to reduce or exacerbate health disparities.

Dosiomics and radiomics to predict pneumonitis after thoracic stereotactic body radiotherapy and immune checkpoint inhibition.

Introduction: Pneumonitis is a relevant side effect after radiotherapy (RT) and immunotherapy with checkpoint inhibitors (ICIs). Since the effect is radiation dose dependent, the risk increases for high fractional doses as applied for stereotactic body radiation therapy (SBRT) and might even be enhanced for the combination of SBRT with ICI therapy. Hence, patient individual pre-treatment prediction of post-treatment pneumonitis (PTP) might be able to support clinical decision making. Dosimetric factors, however, use limited information and, thus, cannot exploit the full potential of pneumonitis prediction. Methods: We investigated dosiomics and radiomics model based approaches for PTP prediction after thoracic SBRT with and without ICI therapy. To overcome potential influences of different fractionation schemes, we converted physical doses to 2 Gy equivalent doses (EQD2) and compared both results. In total, four single feature models (dosiomics, radiomics, dosimetric, clinical factors) were tested and five combinations of those (dosimetric+clinical factors, dosiomics+radiomics, dosiomics+dosimetric+clinical factors, radiomics+dosimetric+clinical factors, radiomics+dosiomics+dosimetric+clinical factors). After feature extraction, a feature reduction was performed using pearson intercorrelation coefficient and the Boruta algorithm within 1000-fold bootstrapping runs. Four different machine learning models and the combination of those were trained and tested within 100 iterations of 5-fold nested cross validation. Results: Results were analysed using the area under the receiver operating characteristic curve (AUC). We found the combination of dosiomics and radiomics features to outperform all other models with AUCradiomics+dosiomics, D = 0.79 (95% confidence interval 0.78-0.80) and AUCradiomics+dosiomics, EQD2 = 0.77 (0.76-0.78) for physical dose and EQD2, respectively. ICI therapy did not impact the prediction result (AUC ≤ 0.5). Clinical and dosimetric features for the total lung did not improve the prediction outcome. Conclusion: Our results suggest that combined dosiomics and radiomics analysis can improve PTP prediction in patients treated with lung SBRT. We conclude that pre-treatment prediction could support clinical decision making on an individual patient basis with or without ICI therapy.

Racism During Pregnancy and Birthing: Experiences from Asian and Pacific Islander, Black, Latina, and Middle Eastern Women.

BACKGROUND: Despite persistent racial disparities in maternal health in the USA, there is limited qualitative research on women's experiences of discrimination during pregnancy and childbirth that focuses on similarities and differences across multiple racial groups. METHODS: Eleven focus groups with Asian American and Pacific Islander (AAPI), Black, Latina, and Middle Eastern women (N = 52) in the USA were conducted to discuss the extent to which racism and discrimination impact pregnancy and birthing experiences. RESULTS: Participants across groups talked about the role of unequal power dynamics, discrimination, and vulnerability in patient-provider relationships. Black participants noted the influence of prior mistreatment by providers in their healthcare decisions. Latinas expressed fears of differential care because of immigration status. Middle Eastern women stated that the Muslim ban bolstered stereotypes. Vietnamese participants discussed how the effect of racism on mothers' mental health could impact their children, while Black and Latina participants expressed constant racism-related stress for themselves and their children. Participants recalled better treatment with White partners and suggested a gradient of treatment based on skin complexion. Participants across groups expressed the value of racial diversity in healthcare providers and pregnancy/birthing-related support but warned that racial concordance alone may not prevent racism and emphasized the need to go beyond "band-aid solutions." CONCLUSION: Women's discussions of pregnancy and birthing revealed common and distinct experiences that varied by race, skin complexion, language, immigration status, and political context. These findings highlight the importance of qualitative research for informing maternal healthcare practices that reduce racial inequities.

Solidarity and strife after the Atlanta spa shootings: A mixed methods study characterizing Twitter discussions by qualitative analysis and machine learning.

Background: On March 16, 2021, a white man shot and killed eight victims, six of whom were Asian women at Atlanta-area spa and massage parlors. The aims of the study were to: (1) qualitatively summarize themes of tweets related to race, ethnicity, and racism immediately following the Atlanta spa shootings, and (2) examine temporal trends in expressions hate speech and solidarity before and after the Atlanta spa shootings using a new methodology for hate speech analysis. Methods: A random 1% sample of publicly available tweets was collected from January to April 2021. The analytic sample included 708,933 tweets using race-related keywords. This sample was analyzed for hate speech using a newly developed method for combining faceted item response theory with deep learning to measure a continuum of hate speech, from solidarity race-related speech to use of violent, racist language. A qualitative content analysis was conducted on random samples of 1,000 tweets referencing Asians before the Atlanta spa shootings from January to March 15, 2021 and 2,000 tweets referencing Asians after the shooting from March 17 to 28 to capture the immediate reactions and discussions following the shootings. Results: Qualitative themes that emerged included solidarity (4% before the shootings vs. 17% after), condemnation of the shootings (9% after), racism (10% before vs. 18% after), role of racist language during the pandemic (2 vs. 6%), intersectional vulnerabilities (4 vs. 6%), relationship between Asian and Black struggles against racism (5 vs. 7%), and discussions not related (74 vs. 37%). The quantitative hate speech model showed a decrease in the proportion of tweets referencing Asians that expressed racism (from 1.4% 7 days prior to the event from to 1.0% in the 3 days after). The percent of tweets referencing Asians that expressed solidarity speech increased by 20% (from 22.7 to 27.2% during the same time period) (p < 0.001) and returned to its earlier rate within about 2 weeks. Discussion: Our analysis highlights some complexities of discrimination and the importance of nuanced evaluation of online speech. Findings suggest the importance of tracking hate and solidarity speech. By understanding the conversations emerging from social media, we may learn about possible ways to produce solidarity promoting messages and dampen hate messages.

Examining Exposure to Messaging, Content, and Hate Speech from Partisan News Social Media Posts on Racial and Ethnic Health Disparities.

We investigated the content of liberal and conservative news media Facebook posts on race and ethnic health disparities. A total of 3,327,360 liberal and conservative news Facebook posts from the United States (US) from January 2015 to May 2022 were collected from the Crowd Tangle platform and filtered for race and health-related keywords. Qualitative content analysis was conducted on a random sample of 1750 liberal and 1750 conservative posts. Posts were analyzed for a continuum of hate speech using a newly developed method combining faceted Rasch item response theory with deep learning. Across posts referencing Asian, Black, Latinx, Middle Eastern, and immigrants/refugees, liberal news posts had lower hate scores compared to conservative posts. Liberal news posts were more likely to acknowledge and detail the existence of racial/ethnic health disparities, while conservative news posts were more likely to highlight the negative consequences of protests, immigration, and the disenfranchisement of Whites. Facebook posts from liberal and conservative news focus on different themes with fewer discussions of racial inequities in conservative news. Investigating the discourse on race and health in social media news posts may inform our understanding of the public's exposure to and knowledge of racial health disparities, and policy-level support for ameliorating these disparities.

A Randomized Trial of Behavioral Nudges Delivered Through Text Messages to Increase Influenza Vaccination Among Patients With an Upcoming Primary Care Visit.

PURPOSE: To evaluate if nudges delivered by text message prior to an upcoming primary care visit can increase influenza vaccination rates. DESIGN: Randomized, controlled trial. SETTING: Two health systems in the Northeastern US between September 2020 and March 2021. SUBJECTS: 74,811 adults. INTERVENTIONS: Patients in the 19 intervention arms received 1-2 text messages in the 3 days preceding their appointment that varied in their format, interactivity, and content. MEASURES: Influenza vaccination. ANALYSIS: Intention-to-treat. RESULTS: Participants had a mean (SD) age of 50.7 (16.2) years; 55.8% (41,771) were female, 70.6% (52,826) were White, and 19.0% (14,222) were Black. Among the interventions, 5 of 19 (26.3%) had a significantly greater vaccination rate than control. On average, the 19 interventions increased vaccination relative to control by 1.8 percentage points or 6.1% (P = .005). The top performing text message described the vaccine to the patient as "reserved for you" and led to a 3.1 percentage point increase (95% CI, 1.3 to 4.9; P < .001) in vaccination relative to control. Three of the top five performing messages described the vaccine as "reserved for you." None of the interventions performed worse than control. CONCLUSIONS: Text messages encouraging vaccination and delivered prior to an upcoming appointment significantly increased influenza vaccination rates and could be a scalable approach to increase vaccination more broadly.

Pneumonitis after Stereotactic Thoracic Radioimmunotherapy with Checkpoint Inhibitors: Exploration of the Dose-Volume-Effect Correlation.

Thoracic stereotactic body radiation therapy (SBRT) is extensively used in combination with immune checkpoint blockade (ICB). While current evidence suggests that the occurrence of pneumonitis as a side effect of both treatments is not enhanced for the combination, the dose-volume correlation remains unclear. We investigate dose-volume-effect correlations for pneumonitis after combined SBRT + ICB. We analyzed patient clinical characteristics and dosimetric data for 42 data sets for thoracic SBRT with ICB treatment (13) and without (29). Dose volumes were converted into 2 Gy equivalent doses (EQD2), allowing for dosimetric comparison of different fractionation regimes. Pneumonitis volumes were delineated and corresponding DVHs were analyzed. We noticed a shift towards lower doses for combined SBRT + ICB treatment, supported by a trend of smaller areas under the curve (AUC) for SBRT+ ICB (median AUC 1337.37 vs. 5799.10, p = 0.317). We present a DVH-based dose-volume-effect correlation method and observed large pneumonitis volumes, even with bilateral extent in the SBRT + ICB group. We conclude that further studies using this method with enhanced statistical power are needed to clarify whether adjustments of the radiation dose constraints are required to better estimate risks of pneumonitis after the combination of SBRT and ICB.

Treatment Planning Study for Microbeam Radiotherapy Using Clinical Patient Data.

Microbeam radiotherapy (MRT) is a novel, still preclinical dose delivery technique. MRT has shown reduced normal tissue effects at equal tumor control rates compared to conventional radiotherapy. Treatment planning studies are required to permit clinical application. The aim of this study was to establish a dose comparison between MRT and conventional radiotherapy and to identify suitable clinical scenarios for future applications of MRT. We simulated MRT treatment scenarios for clinical patient data using an inhouse developed planning algorithm based on a hybrid Monte Carlo dose calculation and implemented the concept of equivalent uniform dose (EUD) for MRT dose evaluation. The investigated clinical scenarios comprised fractionated radiotherapy of a glioblastoma resection cavity, a lung stereotactic body radiotherapy (SBRT), palliative bone metastasis irradiation, brain metastasis radiosurgery and hypofractionated breast cancer radiotherapy. Clinically acceptable treatment plans were achieved for most analyzed parameters. Lung SBRT seemed the most challenging treatment scenario. Major limitations comprised treatment plan optimization and dose calculation considering the tissue microstructure. This study presents an important step of the development towards clinical MRT. For clinical treatment scenarios using a sophisticated dose comparison concept based on EUD and EQD2, we demonstrated the capability of MRT to achieve clinically acceptable dose distributions.

Variable Creatinine Levels in Critical Care Patients: A Concerning Knowledge Gap.

An accurate creatinine (Cr) estimate is pivotal for the assessment of renal function. Both patient- and practice-spawned factors palliate the test accuracy of serum creatinine (sCr) and can erratically represent actual kidney function. This study evaluated the caregivers' awareness of enzymatic serum creatinine (E-sCr) assay interfering in dopamine/dobutamine (DD)-infused patient samples and the frequency of such interference in a critical care setting. We conducted an sCr awareness survey among UT Southwestern physicians, nurses, and pharmacists. We then performed a cross-sectional E-sCr comparison against the kinetic Jaffe method using the DD-infused patient samples collected from central venous catheters (CVC), peripherally inserted central catheter (PICC) lines, and the peripheral vein (PV). We retrospectively compared the longitudinal E-sCr results of the CVC/PICC draws with the corresponding blood urea nitrogen (BUN) levels. The survey results show a significant lack of awareness among caregivers about the negative interference of DD infusions on E-sCr. Cross-sectional E-sCr assessment relative to the Jaffe method displayed a negative interference in 12% of CVC/PICC line samples (7/57 DD-infused patients) compared to none in the PV draws. A longitudinal assessment of E-sCr, BUN, and potassium (K) levels from CVC/PICC line samples further confirmed a spurious decrease for E-sCr in about 12/50 (24%) patients who did not show a concurrent BUN or K decrease. The results suggest that a direct PV sampling accompanied by clinical laboratory-directed proactive discussion/activities can foster awareness among caregivers and eschew the false E-sCr estimates in DD-infused patients.

Potential Morbidity Reduction for Lung Stereotactic Body Radiation Therapy Using Respiratory Gating.

We investigated the potential of respiratory gating to mitigate the motion-caused misdosage in lung stereotactic body radiotherapy (SBRT). For fourteen patients with lung tumors, we investigated treatment plans for a gating window (GW) including three breathing phases around the maximum exhalation phase, GW40-60. For a subset of six patients, we also assessed a preceding three-phase GW20-40 and six-phase GW20-70. We analyzed the target volume, lung, esophagus, and heart doses. Using normal tissue complication probability (NTCP) models, we estimated radiation pneumonitis and esophagitis risks. Compared to plans without gating, GW40-60 significantly reduced doses to organs at risk without impairing the tumor doses. On average, the mean lung dose decreased by 0.6 Gy (p < 0.001), treated lung V20Gy by 2.4% (p = 0.003), esophageal dose to 5cc by 2.0 Gy (p = 0.003), and maximum heart dose by 3.2 Gy (p = 0.009). The model-estimated mean risks of 11% for pneumonitis and 12% for esophagitis without gating decreased upon GW40-60 to 7% and 9%, respectively. For the highest-risk patient, gating reduced the pneumonitis risk from 43% to 32%. Gating is most beneficial for patients with high-toxicity risks. Pre-treatment toxicity risk assessment may help optimize patient selection for gating, as well as GW selection for individual patients.

Evaluation of Dosimetric Robustness of Carbon Ion Boost Therapy for Anal Carcinoma.

PURPOSE: The radiation therapy treatment outcome of human papillomavirus-negative anal carcinoma may be improved by the biological effectiveness of carbon ions. However, abdominal tissue motion can compromise the precision of carbon ion therapy. This work aims to evaluate the dosimetric feasibility of carbon ion boost (CIB) therapy for anal carcinoma. MATERIALS AND METHODS: An algorithm to generate computed tomographies based on daily magnetic resonance imaging data and deformable image registration was developed. By means of this algorithm, fractional computed tomography data for 54 treatment fractions for 3 different patients with anal carcinoma were derived. The dose for a sequential CIB (CIBseq) treatment plan was recalculated on the fractional computed tomography data and accumulated over the number of fractions. The resulting dose distributions were compared to standard intensity-modulated radiation therapy treatment with an integrated photon boost. RESULTS: For the investigated patient cases, similar dosimetric results for CIBseq treatment and for intensity-modulated radiation therapy with an integrated photon boost were found. For CIBseq treatment, bladder-filling variation had the strongest influence on the dose distribution. However, the detrimental effects on the mean target dose remained below 1 Gy (RBE) as compared to photon therapy. CONCLUSION: This study shows the dosimetric feasibility of CIB therapy for anal carcinoma for the first time and gives reason for clinical exploitation of the enhanced biological effect of carbon ions for patients with human papillomavirus-negative anal cancer.