Cancer Institute Research Articles

Testosterone and the risk of incident atrial fibrillation in older men: further analysis of the ASPREE study

A cardiovascular safety trial of testosterone in men with cardiovascular risk factors or disease found no difference in rates of major adverse cardiovascular events (MACE) or death but noted more atrial fibrillation (AF) events in testosterone-treated men. We investigated the relationship between endogenous testosterone concentrations with risk of developing AF in healthy older men. Post-hoc analysis of 4570 male participants in the ASPirin in Reducing Events in the Elderly (ASPREE) study. Men were aged ≥ 70 years, had no history of cardiovascular disease (including AF), thyroid disease, prostate cancer, dementia, or life-threatening illnesses. Risk of AF was modelled using Cox proportional hazards regression. Median (IQR) age was 73.7 (71.6-77.1) years and median (IQR) follow-up 4.4 (3.3-5.5) years, during which 286 men developed AF (15.3 per 1000 participant-years). Baseline testosterone was higher in men who developed incident AF compared men who did not [17.0 (12.4-21.2) vs 15.7 (12.2-20.0) nmol/L]. There was a non-linear association of baseline testosterone with incident AF. The risk for AF was higher in men with testosterone in quintiles (Q) 4&5 (Q4:Q3, HR=1.91; 95%CI=1.29-2.83 and Q5:Q3HR=1.98; 95%CI=1.33-2.94). Results were similar after excluding men who experienced MACE or heart failure during follow-up. Circulating testosterone concentrations within the high-normal range are independently associated with an increased risk of incident AF amongst healthy older men. This suggests that AF may be an adverse consequence of high-normal total testosterone concentrations. National Institute on Aging and National Cancer Institute at the National Institutes of Health; Australian Government (NHMRC, CSIRO); Monash University; and AlfredHealth.

Deciphering Trends in Cancer Mortality: A Comprehensive Analysis of Brazilian Data From 1979 to 2021 With Emphasis on Breast and Prostate Cancers.

This study examined cancer mortality trends in Brazil from 1979 to 2021, emphasizing breast and prostate cancers. Utilizing data from the Brazilian Mortality Information System and the Brazilian Institute of Geography and Statistics, it analyzed cancer deaths nationally and regionally, highlighting gender-specific and regional disparities. The research finds that cancer death rates have been growing at an average of 12% per year, contrasting with the population growth rate of 2.2%. This trend is more pronounced in the southern and southeastern regions of Brazil. A comparison of cancer mortality rates between Brazil, the USA, and China reveals that while the Brazilian and Chinese rates exhibit slower growth, the US rate shows a continuous decline since the 1990s. The study adopts a novel approach by focusing on growth rates and employing polynomial interpolation, revealing a deceleration in cancer death growth over the last 15 years across all malignant neoplasms. The study also contextualizes these findings within Brazil's cancer control policies, tracing the evolution of preventive measures and treatment advancements. It highlights the significant role of the National Cancer Institute and the Unified Health System in implementing effective strategies. The decreasing trend in cancer mortality rates in Brazil, despite population growth, illustrates the effectiveness of comprehensive cancer control and prevention measures, underlining their importance in public health policy.

A framework and process for community-engaged, mixed-methods cancer needs assessments.

Community health needs assessments are required for most state and local public health agencies and non-profit hospitals. Typically based on community health improvement planning models, these assessments encompass overall community health and multiple diseases to inform program planning. National Cancer Institute (NCI)-designated Cancer Centers and community-based cancer-focused programs share the goal of reducing cancer burden in the catchment areas they serve. However, to date, no published models exist to guide cancer-specific needs assessments for a determined geographic area that can inform both public health and research initiatives. The purpose of this article is to outline a cancer needs assessment (CNA) framework and community-engaged, mixed-methods process, along with a case study of how we applied it in Kentucky. We convened a steering committee of key organizational partners to provide input throughout the process. We developed a conceptual framework of multi-level determinants affecting cancer-related outcomes. We incorporated both quantitative and qualitative data gathered through a variety of means, including a novel application of group concept mapping to guide definition of priorities. The resulting CNA has helped guide strategic planning and priorities for Kentucky's Cancer Action Plan, Markey Cancer Center, state agencies, and community-based organizations. This framework and process can be used collaboratively by cancer center Community Outreach and Engagement offices, public health agencies, oncology programs, and community partners to plan impactful cancer control programs and research in their catchment areas. Universities can also use them to inform the planning of community engagement and health equity research efforts.

Analysis of BRCA1 germline variants (exons 5, 11 and 20) in breast cancer families from Libya

ABSTRACT Breast cancer (BC) is a leading cause of cancer deaths in Libyan women. BRCA1 variants differ globally due to the diversity of genetic makeup and populations history. Their distribution, prevalence, and significance in Libyans remain largely unexplored. This study investigated the characteristics and distribution of BRCA1 variants in exons 5, 11, and 20 in Libyan families with BC. Thirty-six BC patients at ≤ 45 years, between 46–50 years and with a family history of breast, ovarian, pancreatic or prostate cancer in close relatives, or with triple-negative BC, were selected from 33 unrelated families during 2018–2020 at the National Cancer Institute, Sabratha, Libya. From these 33 families, 20 women (18 BC patients and two unaffected) were screened for BRCA1 exons 5, 11 and 20 using Sanger sequencing. All families completed an epidemiology and family history questionnaire. Twenty-seven variants (26 in exon 11 and 1 in exon 20, minor allele frequency of < 0.01) were detected in 10 of 18 unrelated families (55.6%.) Among the 27 variants, 26 (96%) were heterozygous. A frameshift pathogenic variant, c.2643del, and one novel variant c.1366A>G were identified. Furthermore, seven variants with unknown clinical significance were detected: c.1158T>A, c.1346C>G, c.1174C>G, c.3630 G>T, c.3599A>T, and c.3400 G>C in exon 11, and c.5244T>A in exon 20. Six variants with conflicting pathogenicity interpretations, c. 3460T>A, c. 3572 G>A, c. 3700 G>C, c. 1246C>G, c. 1344C>G, and c. 1054 G>A, were also identified. Twelve benign/likely benign variants were identified. Rare BRCA1 variants that have not been reported in North Africa were found in Libyan patients. These findings provide preliminary insights into the BRCA1 variants that could contribute to hereditary BC risk in Libyans. Further functional, computational, and population analyses are essential to determine their significance and potential impact on BC risk, which could ultimately lead to more personalized management strategies.

Shooting the moon: the National Cancer Institute's implementation framework for data sharing policies.

Shooting the moon: the National Cancer Institute's implementation framework for data sharing policies.

Fertility-Sparing Surgery for Stage I Epithelial Ovarian Cancer.

To describe population-level utilization of fertility-sparing surgery and outcome of reproductive-aged patients with early epithelial ovarian cancer who underwent fertility-sparing surgery in the United States. This retrospective study queried the National Cancer Institute's Surveillance, Epidemiology, and End Result Program. The study included 3,027 patients younger than age 50 years with stage I epithelial ovarian cancer receiving primary surgical therapy from 2007 to 2020. Fertility-sparing surgery was defined as preservation of one ovary and the uterus for unilateral lesion and preservation of the uterus for bilateral lesions. Temporal trend of fertility-sparing surgery was assessed with linear segmented regression with log-transformation. Overall survival associated with fertility-sparing surgery was assessed with Cox proportional hazard regression model. A total of 534 patients (17.6%) underwent fertility-sparing surgery. At the cohort level, the utilization of fertility-sparing surgery was 13.4% in 2007 and 21.8% in 2020 (P for trend=.009). Non-Hispanic White individuals (2.8-fold), those with high-grade serous histology (2.2-fold), and individuals with stage IC disease (2.3-fold) had a more than twofold increase in fertility-sparing surgery utilization during the study period (all P for trend<.05). After controlling for the measured clinicopathologic characteristics, patients who received fertility-sparing surgery had overall survival comparable with that of patients who had nonsparing surgery (5-year rates 93.6% vs 92.1%, adjusted hazard ratio 0.87, 95% CI, 0.57-1.35). This survival association was consistent in high-grade serous (5-year rates 92.9% vs 92.4%), low-grade serous (100% vs 92.2%), clear cell (97.5% vs 86.1%), mucinous (92.1% vs 86.6%), low-grade endometrioid (95.7% vs 97.7%), and mixed (93.3% vs 83.7%) histology (all P>.05). In high-grade endometrioid tumor, fertility-sparing surgery was associated with decreased overall survival (5-year rates 71.9% vs 93.8%, adjusted hazard ratio 2.90, 95% CI, 1.09-7.67). Among bilateral ovarian lesions, fertility-sparing surgery was not associated with overall survival (5-year rates 95.8% vs 92.5%, P=.364). Among 41,914 patients who had epithelial ovarian cancer with any age and stage, those younger than age 50 years with stage I disease increased from 8.6% to 10.9% during the study period (P for trend=.002). Nearly one in five reproductive-aged patients with stage I epithelial ovarian cancer underwent fertility-sparing surgery in recent years in the United States. More than 90% of reproductive-aged patients with stage I epithelial ovarian cancer who underwent fertility-sparing surgery were alive at the 5-year timepoint, except for those with high-grade endometrioid tumors.

Identifying Patterns of Smoking Cessation App Feature Use That Predict Successful Quitting: Secondary Analysis of Experimental Data Leveraging Machine Learning

Background Leveraging free smartphone apps can help expand the availability and use of evidence-based smoking cessation interventions. However, there is a need for additional research investigating how the use of different features within such apps impacts their effectiveness. Objective We used observational data collected from an experiment of a publicly available smoking cessation app to develop supervised machine learning (SML) algorithms intended to distinguish the app features that promote successful smoking cessation. We then assessed the extent to which patterns of app feature use accounted for variance in cessation that could not be explained by other known predictors of cessation (eg, tobacco use behaviors). Methods Data came from an experiment (ClinicalTrials.gov NCT04623736) testing the impacts of incentivizing ecological momentary assessments within the National Cancer Institute’s quitSTART app. Participants’ (N=133) app activity, including every action they took within the app and its corresponding time stamp, was recorded. Demographic and baseline tobacco use characteristics were measured at the start of the experiment, and short-term smoking cessation (7-day point prevalence abstinence) was measured at 4 weeks after baseline. Logistic regression SML modeling was used to estimate participants’ probability of cessation from 28 variables reflecting participants’ use of different app features, assigned experimental conditions, and phone type (iPhone [Apple Inc] or Android [Google]). The SML model was first fit in a training set (n=100) and then its accuracy was assessed in a held-aside test set (n=33). Within the test set, a likelihood ratio test (n=30) assessed whether adding individuals’ SML-predicted probabilities of cessation to a logistic regression model that included demographic and tobacco use (eg, polyuse) variables explained additional variance in 4-week cessation. Results The SML model’s sensitivity (0.67) and specificity (0.67) in the held-aside test set indicated that individuals’ patterns of using different app features predicted cessation with reasonable accuracy. The likelihood ratio test showed that the logistic regression, which included the SML model–predicted probabilities, was statistically equivalent to the model that only included the demographic and tobacco use variables (P=.16). Conclusions Harnessing user data through SML could help determine the features of smoking cessation apps that are most useful. This methodological approach could be applied in future research focusing on smoking cessation app features to inform the development and improvement of smoking cessation apps. Trial Registration ClinicalTrials.gov NCT04623736; https://clinicaltrials.gov/study/NCT04623736

Exploring the risk of second primary malignancies in laryngeal cancer survivors: insights from the SEER database.

We intended to investigate the risk for second primary malignancy (SPM) development in Laryngeal Cancer (LC) survivors. We conducted a population-based analysis of SPM risk using the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. Data of selected LC survivors from the SEER database between 2000 and 2020 were examined. Standardized Incidence ratios (SIRs) for SPM development were calculated, followed by detailed stratification according to anatomical site and different latency periods. A total of 8413 SPMs were observed in our extracted cohort. The collective standardized incidence of SPMs was 2.12 (95% CI 2.07-2.17) compared to the US population, with an absolute excess risk (AER) of 201.73 per 10,000 individuals. The highest SPM risks were observed in patients with young age at diagnosis, females, and American Indians/Alaska natives. Increased SPM risks were reported in patients receiving all modalities of treatment including surgery, chemotherapy, and radiotherapy. Most SPMs were detected in solid organs such asthe lungs and bronchus, oral cavity and pharynx, and prostate. The highest increased risks of developing SPMs were observed in Trachea, larynx, oral cavity and pharynx, lung and bronchus, and esophagus. The risk of SPMs in LC survivors was significantly increased compared to the general US population. Accordingly, a more impactful cancer surveillance strategy for LC patients should be implemented.

Digital phantom versus patient-specific radiation dosimetry in adult routine thorax CT examinations.

The aim of this study was to compare the organ doses assessed through a digital phantom-based and a patient specific-based dosimetric tool in adult routine thorax computed tomography (CT) examinations with reference to physical dose measurements performed in anthropomorphic phantoms. Two Monte Carlo based dose calculation tools were used to assess organ doses in routine adult thorax CT examinations. These were a digital phantom-based dosimetry tool (NCICT, National Cancer Institute, USA) and a patient-specific individualized dosimetry tool (ImpactMC, CT Imaging GmbH, Germany). Digital phantoms and patients were classified in four groups according to their water equivalent diameter (Dw). Normalized to volume computed tomography dose index (CTDIvol), organ dose was assessed for lungs, esophagus, heart, breast, active bone marrow, and skin. Organ doses were compared to measurements performed using thermoluminescent detectors (TLDs) in two physical anthropomorphic phantoms that simulate the average adult individual as a male (Alderson Research Labs, USA) and as a female (ATOM Phantoms, USA). The average percent difference of NCICT to TLD and ImpactMC to TLD dose measurements across all organs in both sexes was 13% and 6%, respectively. The average±1 standard deviation in dose values across all organs with NCICT, ImpactMC, and TLDs was±0.06 (mGy/mGy),±0.19 (mGy/mGy), and±0.13 (mGy/mGy), respectively. Organ doses decreased with increasing Dw in both NCICT and ImpactMC. Organ doses estimated with ImpactMC were in closer agreement to TLDs compared to NCICT. This may be attributed to the inherent property of ImpactMC methodology to generate phantoms that resemble the realistic anatomy of the examined patient as opposed to NCICT methodology that incorporates an anatomical discrepancy between phantoms and patients.

Clinical Practice Guideline-Inconsistent Management of Fertility Preservation in Pediatric Cancer Patients in Community Settings: A Children's Oncology Group Study.

Background: The primary objective was to measure adherence to clinical practice guideline (CPG) recommendations for fertility preservation (FP) in pediatric cancer patients treated in National Cancer Institute Community Oncology Research Program (NCORP) sites. Secondary objectives were to describe factors such as site size associated with CPG-inconsistent care delivery and cryopreservation completion. Methods: This retrospective, multicenter study included patients 15 to 21 years old with a first cancer diagnosis from January 2014 through December 2015 who were previously enrolled to a Children's Oncology Group (COG) study and received care at a participating NCORP site. Patients were randomly selected from a list generated by the COG for chart review by participating sites. Primary outcome was care delivery that was inconsistent with a strong CPG recommendation on FP, namely discussion and offering of FP options before cancer treatment initiation, as adjudicated centrally by a panel. Results: A total of 129 patients from 25 sites were included. Among these, 48% (62/129) received CPG-inconsistent care. Most CPG-inconsistent care was due to lack of FP discussion documentation (93.5%, 58/62). Small site size, treatment at a pediatric (vs mixed adult/pediatric) site, and female sex were associated with higher odds of CPG-inconsistent care delivery. Conclusions: Newly diagnosed pediatric cancer patients often received CPG-inconsistent care for FP, with disproportionate gaps noted for females, and those treated at smaller or pediatric NCORP sites. The primary reason for CPG-inconsistent care is lack of FP discussion from clinicians. Opportunities to improve FP CPG implementation are highlighted.

Optimizing abemaciclib-induced diarrhea management in patients with breast cancer: a pragmatic 2-group study using a postbiotic microbiota stabilizer.

Abemaciclib-induced diarrhea is a relevant concern in clinical practice. Postbiotics have emerged as a promising option for managing it. We conducted a retrospective-prospective, 2-group, observational study to assess the impact of the postbiotic PostbiotiX-Restore, derived by Lactobacillus paracasei CNCM I-5220, on abemaciclib-induced diarrhea in patients with hormone receptor-positive HER2-negative breast cancer. The prospective population (Postbio group) received postbiotic during the first cycle of abemaciclib, while the retrospective one received standard care (Standard group). Diarrhea grading was defined according to the National Cancer Institute's Common Terminology Criteria for Adverse Events. During the first cycle, diarrhea occurred in 78.9% of patients in the Standard cohort and 97.1% in the Postbio one, with most cases being G1-G2. Severe (G3) diarrhea was significantly less frequent in the Postbio group (0%) compared to the Standard one (7.9%; P = .029). Over the entire study period, while the grading difference was not statistically significant, G3 events were less frequent in the Postbio population (5.9%) than the Standard one (15.4%). Moreover, Postbio patients required fewer dose reductions due to diarrhea compared to the Standard group (P = .002). Notably, in the Postbio population, G1 and G2 events had short median durations (3 and 1 days, respectively) and, for the 2 patients experiencing G3 events during the second abemaciclib cycle (off postbiotic), diarrhea lasted only 1 day. Our study demonstrates the effect of PostbiotiX-Restore in mitigating abemaciclib-induced diarrhea, resulting in reduced severity, fewer dose reductions, and shorter duration. Further exploration and validation in larger cohorts are needed.

Benefits of cardiopulmonary resuscitation in cancer patients.

According to meta-analytic data, the prognosis of a cancer patient post-cardiopulmonary resuscitation (CPR) is relatively similar to the general population. However, preselection of patients, the details of CPR, patient-specific characteristics, and post-CPR care are poorly described. The aim of this study is to identify prognostic factors in order to recognize cancer patient profiles more likely to benefit from CPR. This is a retrospective study on a series of patients with solid or hematological malignancies who received CPR between January 2010 and December 2020 in a cancer institute. Sixty-eight patients were included. The ratio of solid to hematological malignancy was 44/24, of which 32 were metastatic solid tumors. Median age was 61years. Hypoxemia (29%) was the primary factor for cardiac arrest, followed by septic shock (21%). ICU mortality and hospital mortality were 87% and 88% respectively. Younger age, the presence of hematological malignancy, or a metastatic solid tumor were poor predictors for in-hospital mortality. Similarly, cardiac arrest in the ICU, as the final consequence of a pathological process, and a resuscitation time of more than 10min have a negative influence on prognosis. This study shows that CPR is a useful intervention in cancer patients, even in the elderly patient, especially in non-metastatic solid tumors where cardiac arrest is the consequence of an acute event and not a terminal process.

Patterns of chemotherapy use with primary radiotherapy for localized bladder cancer in patients 65 or older

IntroductionBladder preservation with concurrent chemoradiotherapy after maximum transurethral resection of bladder tumor is an alternative to radical cystectomy in select patients with muscle invasive bladder cancer (MIBC). Concurrent administration of radio-sensitizing chemotherapy and radiation therapy (RT) has been shown to have superior disease control compared with RT alone and can often be administered with modest added toxicity. We sought to describe national patterns of chemotherapy use.MethodsThe linked surveillance, epidemiology, and end results (SEER)-Medicare database was used to identify patients with cT2-4, N0/X, M0/X BC who received radiation between 2004 and 2018. Data on demographics, clinicopathologic factors, therapy and outcomes were extracted. Concurrent utilization of chemotherapy with RT was also identified (CRT). Multivariate logistic regression (MVA) models were used to explore factors associated with receipt of chemotherapy and overall survival (OS).Results2190 patients met inclusion criteria. Of these, 850 (38.8%) received no chemotherapy. Among those receiving chemotherapy, the most frequent regimens were single agent carboplatin, cisplatin, or gemcitabine. Factors that were independently associated with decreased likelihood of chemotherapy use were increasing age (OR 0.93, CI 0.92 – 0.95), Hispanic race (compared with White, OR 0.62, CI 0.39 – 0.99), cT3 or T4 (compared with cT2, OR 0.70, CI 0.55 – 0.90), and lower National Cancer Institute comorbidity index (OR 0.60, CI 0.51 – 0.70) (p &amp;lt; 0.05). Variables independently associated with increased likelihood of receipt of chemotherapy were married status (OR 1.28, CI 1.06 – 1.54), higher socioeconomic status (OR 1.31, CI 1.06 – 1.64), and later year of diagnosis (OR 1.09, CI 1.06 – 1.12). Receipt of concurrent chemotherapy with RT was associated with superior OS compared with RT alone.ConclusionOver a third of patients &amp;gt;/65 years old receiving curative-intent RT for MIBC do not receive concurrent chemotherapy. Considering the improvement in oncologic outcomes with CRT over RT alone and more options, such as low dose gemcitabine which can be administered with modest toxicity, efforts are needed to identify barriers to utilization and increase the use of radio-sensitizing chemotherapy.

Why location matters: Associations between county-level characteristics and availability of NCORP and NCI sites.

The majority of patients with cancer seek care at community oncology sites; however, most clinical trials are available at National Cancer Institute (NCI)-designated sites. While the NCI National Cancer Oncology Research Program (NCORP) was designed to address this problem, little is known about the county-level characteristics of NCORP site locations. This cross-sectional analysis determined the association between availability of NCORP or NCI sites and county-level characteristic theme percentile scores from the CDC's Social Vulnerability Index themes. Health Resources and Services Administration's Area Health Resource Files were used to determine contiguous counties. We estimated risk ratios and 95% confidence intervals (CI) using modified Poisson regression models to evaluate the association between county-level characteristics and site availability within singular and singular & contiguous counties. Of 3141 included counties, 14% had an NCORP, 2% had an NCI, and 1% had both sites. Among singular counties, for a standard deviation (SD) increase in the racial and ethnic theme score there was a 22% higher likelihood of NCORP site availability (95% CI 1.10-1.36); for a SD increase in the socioeconomic status theme score there was a 24% lower likelihood of NCORP site availability (95% CI 0.67-0.87). Associations were of smaller magnitude when including contiguous counties. NCI sites were located in more vulnerable counties. NCORP sites were more often in racially diverse counties, and less often in socioeconomically vulnerable counties. Research is needed to understand how clinical trial representation will increase if NCORP sites strategically increase their locations in more vulnerable counties.

Genome-wide interaction study of dietary intake of fibre, fruits, and vegetables with risk of colorectal cancer

Consumption of fibre, fruits and vegetables have been linked with lower colorectal cancer (CRC) risk. A genome-wide gene-environment (G×E) analysis was performed to test whether genetic variants modify these associations. A pooled sample of 45 studies including up to 69,734 participants (cases: 29,896; controls: 39,838) of European ancestry were included. To identify G×E interactions, we used the traditional 1--degree-of-freedom (DF) G×E test and to improve power a 2-step procedure and a 3DF joint test that investigates the association between a genetic variant and dietary exposure, CRC risk and G×E interaction simultaneously. The 3-DF joint test revealed two significant loci with p-value <5×10-8. Rs4730274 close to the SLC26A3 gene showed an association with fibre (p-value: 2.4×10-3) and G×fibre interaction with CRC (OR per quartile of fibre increase=0.87, 0.80, and 0.75 for CC, TC, and TT genotype, respectively; G×E p-value: 1.8×10-7). Rs1620977 in the NEGR1 gene showed an association with fruit intake (p-value: 1.0×10-8) and G×fruit interaction with CRC (OR per quartile of fruit increase=0.75, 0.65, and 0.56 for AA, AG, and GG genotype, respectively; G×E -p-value: 0.029). We identified 2 loci associated with fibre and fruit intake that also modify the association of these dietary factors with CRC risk. Potential mechanisms include chronic inflammatory intestinal disorders, and gut function. However, further studies are needed for mechanistic validation and replication of findings. National Institutes of Health, National Cancer Institute. Full funding details for the individual consortia are provided in acknowledgments.

Prospective phase II trial of preoperative hypofractionated proton therapy for extremity and truncal soft tissue sarcoma: the PRONTO study rationale and design

BackgroundOncologic surgical resection is the standard of care for extremity and truncal soft tissue sarcoma (STS), often accompanied by the addition of pre- or postoperative radiation therapy (RT). Preoperative RT may decrease the risk of joint stiffness and fibrosis at the cost of higher rates of wound complications. Hypofractionated, preoperative RT has been shown to provide acceptable outcomes in prospective trials. Proton beam therapy (PBT) provides the means to decrease dose to surrounding organs at risk, such as the skin, bone, soft tissues, and adjacent joint(s), and has not yet been studied in patients with extremity and truncal sarcoma.MethodsOur study titled “PROspective phase II trial of preoperative hypofractionated protoN therapy for extremity and Truncal soft tissue sarcOma (PRONTO)” is a non-randomized, prospective phase II trial evaluating the safety and efficacy of preoperative, hypofractionated PBT for patients with STS of the extremity and trunk planned for surgical resection. Adult patients with Eastern Cooperative Group Performance Status ≤ 2 with resectable extremity and truncal STS will be included, with the aim to accrue 40 patients. Treatment will consist of 30 Gy radiobiological equivalent of PBT in 5 fractions delivered every other day, followed by surgical resection 2–12 weeks later. The primary outcome is rate of major wound complications as defined according to the National Cancer Institute of Canada Sarcoma2 (NCIC-SR2) Multicenter Trial. Secondary objectives include rate of late grade ≥ 2 toxicity, local recurrence-free survival and distant metastasis-free survival at 1- and 2-years, functional outcomes, quality of life, and pathologic response.DiscussionPRONTO represents the first trial evaluating the use of hypofractionated PBT for STS. We aim to prove the safety and efficacy of this approach and to compare our results to historical outcomes established by previous trials. Given the low number of proton centers and limited availability, the short course of PBT may provide the opportunity to treat patients who would otherwise be limited when treating with daily RT over several weeks. We hope that this trial will lead to increased referral patterns, offer benefits towards patient convenience and clinic workflow efficiency, and provide evidence supporting the use of PBT in this setting.Trial registration: NCT05917301 (registered 23/6/2023).

A scoping review evaluating physical and cognitive functional outcomes in cancer survivors treated with chemotherapy: charting progress since the 2018 NCI think tank on cancer and aging phenotypes.

The primary goal of this scoping review was to summarize the literature published after the 2018 National Cancer Institute think tank, "Measuring Aging and Identifying Aging Phenotypes in Cancer Survivors," on physical and cognitive functional outcomes among cancer survivors treated with chemotherapy. We focused on the influence of chemotherapy on aging-related outcomes (i.e., physical functional outcomes, cognitive functional outcomes, and frailty), given the known associations between chemotherapy and biologic mechanisms that affect aging-related physiologic processes. A search was conducted across electronic databases, including PubMed, Scopus, and Web of Science, for manuscripts published between August 2018 and July 2023. Eligible studies: 1) included physical function, cognitive function, and/or frailty as outcomes; 2) included cancer survivors (as either the whole sample or a subgroup); 3) reported on physical or cognitive functional outcomes and/or frailty related to chemotherapy treatment (as either the whole sample or a subgroup); and 4) were observational in study design. The search yielded 989 potentially relevant articles, of which 65 met the eligibility criteria. Of the 65 studies, 49 were longitudinal, and 16 were cross-sectional; 30 studies (46%) focused on breast cancer, 20 studies (31%) focused on the age group 60 + years, and 17 (26%) focused on childhood cancer survivors. With regards to outcomes, 82% of 23 studies reporting on physical function showed reduced physical function, 74% of 39 studies reporting on cognitive functional outcomes found reduced cognitive function, and 80% of 15 studies reporting on frailty found increasing frailty among cancer survivors treated with chemotherapy over time and/or compared to individuals not treated with chemotherapy. Fourteen studies (22%) evaluated biologic mechanisms and their relationship to aging-related outcomes. Inflammation was consistently associated with worsening physical and cognitive functional outcomes and epigenetic age increases. Further, DNA damage was consistently associated with worse aging-related outcomes. Chemotherapy is associated with reduced physical function, reduced cognitive function, and an increase in frailty in cancer survivors; these associations were demonstrated in longitudinal and cross-sectional studies. Inflammation and epigenetic age acceleration are associated with worse physical and cognitive function; prospective observational studies with multiple time points are needed to confirm these findings. This scoping review highlights the need for interventions to prevent declines in physical and cognitive function in cancer survivors who have received chemotherapy.

Developing national cancer survivorship standards to inform quality of care in the United States using a consensus approach.

To develop United States (US) standards for survivorship care that informs (1) essential health system policy and process components and (2) evaluation of the quality of survivorship care. The National Cancer Institute and the Department of Veterans Affairs led a review to identify indicators of quality cancer survivorship care in the domains of health system policy, process, and evaluation/assessment. A series of three virtual consensus meetings with survivorship care and research experts and advocates was conducted to rate the importance of the indicators and refine the top indicators. The final set of standards was developed, including ten indicators in each domain. Prioritized items were survivor-focused, including processes to both assess and manage physical, psychological, and social issues, and evaluation of patient outcomes and experiences. Specific indicators focused on developing a business model for sustaining survivorship care and collecting relevant business metrics (e.g., healthcare utilization, downstream revenue) to show value of survivorship care to health systems. The National Standards for Cancer Survivorship Care can be used by health systems to guide development of new survivorship care programs or services or to assess alignment and enhance services in existing survivorship programs. Given the variety of settings providing care to survivors, it is necessary for health systems to adapt these standards based on factors including age-specific needs, cancer types, treatments received, and health system resources. With over 18 million cancer survivors in the United States, many of whom experience varied symptoms and unmet needs, it is essential for health systems to have a comprehensive strategy to provide ongoing care. The US National Standards for Survivorship Care should serve as a blueprint for what survivors and their families can anticipate after a cancer diagnosis to address their needs.

Acupuncture for Chronic Radiation-Induced Xerostomia in Head and Neck Cancer

Patients with head and neck cancer who undergo radiotherapy can develop chronic radiation-induced xerostomia. Prior acupuncture studies were single center and rated as having high risk of bias, making it difficult to know the benefits of acupuncture for treating radiation-induced xerostomia. To compare true acupuncture (TA), sham acupuncture (SA), and standard oral hygiene (SOH) for treating radiation-induced xerostomia. A randomized, blinded, 3-arm, placebo-controlled trial was conducted between July 29, 2013, and June 9, 2021. Data analysis was performed from March 9, 2022, through May 17, 2023. Patients reporting grade 2 or 3 radiation-induced xerostomia 12 months or more postradiotherapy for head and neck cancer were recruited from community-based cancer centers across the US that were part of the Wake Forest National Cancer Institute Community Oncology Research Program Research Base. Participants had received bilateral radiotherapy with no history of xerostomia. Participants received SOH and were randomized to TA, SA, or SOH only. Participants in the TA and SA cohorts were treated 2 times per week for 4 weeks. Those experiencing a minor response received another 4 weeks of treatment. Patient-reported outcomes for xerostomia (Xerostomia Questionnaire, primary outcome) and quality of life (Functional Assessment of Cancer Therapy-General) were collected at baseline, 4 (primary time point), 8, 12, and 26 weeks. All analyses were intention to treat. A total of 258 patients (201 men [77.9%]; mean [SD] age, 65.0 [9.16] years), participated from 33 sites across 13 states. Overall, 86 patients were assigned to each study arm. Mean (SD) years from diagnosis was 4.21 (3.74) years, 67.1% (n = 173) had stage IV disease. At week 4, Xerostomia Questionnaire scores revealed significant between-group differences, with lower Xerostomia Questionnaire scores with TA vs SOH (TA: 50.6; SOH: 57.3; difference, -6.67; 95% CI, -11.08 to -2.27; P = .003), and differences between TA and SA (TA: 50.6; SA: 55.0; difference, -4.41; 95% CI, -8.62 to -0.19; P = .04) yet did not reach statistical significance after adjustment for multiple comparisons. There was no significant difference between SA and SOH. Group differences in Functional Assessment of Cancer Therapy-General scores revealed statistically significant group differences at week 4, with higher scores with TA vs SOH (TA: 101.6; SOH: 97.7; difference, 3.91; 95% CI, 1.43-6.38; P = .002) and at week 12, with higher scores with TA vs SA (TA: 102.1; SA: 98.4; difference, 3.64; 95% CI, 1.10-6.18; P = .005) and TA vs SOH (TA: 102.1; SOH: 97.4; difference, 4.61; 95% CI, 1.99-7.23; P = .001). The findings of this trial suggest that TA was more effective in treating chronic radiation-induced xerostomia 1 or more years after the end of radiotherapy than SA or SOH. ClinicalTrials.gov Identifier: NCT02589938.

Explainable machine learning approach for cancer prediction through binarilization of RNA sequencing data.

In recent years, researchers have proven the effectiveness and speediness of machine learning-based cancer diagnosis models. However, it is difficult to explain the results generated by machine learning models, especially ones that utilized complex high-dimensional data like RNA sequencing data. In this study, we propose the binarilization technique as a novel way to treat RNA sequencing data and used it to construct explainable cancer prediction models. We tested our proposed data processing technique on five different models, namely neural network, random forest, xgboost, support vector machine, and decision tree, using four cancer datasets collected from the National Cancer Institute Genomic Data Commons. Since our datasets are imbalanced, we evaluated the performance of all models using metrics designed for imbalance performance like geometric mean, Matthews correlation coefficient, F-Measure, and area under the receiver operating characteristic curve. Our approach showed comparative performance while relying on less features. Additionally, we demonstrated that data binarilization offers higher explainability by revealing how each feature affects the prediction. These results demonstrate the potential of data binarilization technique in improving the performance and explainability of RNA sequencing based cancer prediction models.