Personalized survivorship care: Routine breast cancer risk assessment in the gynecologic oncology clinic.

INTRODUCTION: Gynecologic and breast cancers share several risk factors. Breast cancer risk assessment tools can identify those at elevated risk and allow for enhanced breast surveillance and chemoprevention, however such tools are underutilized. We aim to evaluate the use of routine breast cancer risk assessment in a gynecologic oncology clinic. METHODS: A patient-facing web-based tool was used to collect personal and family history and run four validated breast cancer risk assessment models (Tyrer-Cuzick (TC), Gail, BRCAPRO, and Claus) in a gynecologic oncology clinic. We evaluated completion of the tools and identification of patients at elevated risk for breast cancer using the four validated models. RESULTS: A total of 99 patients were included in this analysis. The BRCAPRO model had the highest completion rate (84.8%), followed by the TC model (74.7%), Gail model (74.7%), and the Claus model (52.1%). The TC model identified 21.6% of patients completing the model as having ≥20% lifetime risk of breast cancer, compared to 6.8% by the Gail model, and 0% for both the BRCAPRO and Claus models. The Gail model identified 52.5% of patients as having ≥1.67% 5-year risk of breast cancer. Among patients identified as high-risk for breast cancer and eligible for screening, 9/9 (100%) were referred to a high-risk breast clinic. CONCLUSION: Among patients that completed the TC breast cancer risk assessment in a gynecologic oncology clinic, approximately 1 in 5 were identified to be at significantly elevated lifetime risk for breast cancer. The gynecologic oncologist's office might offer a convenient and feasible setting to incorporate this risk assessment into routine patient care, as gynecologic oncologists often have long-term patient relationships and participate in survivorship care.

Genomic Characterization and Clinical Outcomes of Patients with Peritoneal Metastases from the AACR GENIE Biopharma Collaborative Colorectal Cancer Registry.

Peritoneal metastases (PM) are common in metastatic colorectal cancer (mCRC). We aimed to characterize patients with mCRC and PM from a clinical and molecular perspective using the American Association of Cancer Research Genomics Evidence Neoplasia Information Exchange (GENIE) Biopharma Collaborative (BPC) registry. Patients' tumor samples underwent targeted next-generation sequencing. Clinical characteristics and treatment outcomes were collected retrospectively. Overall survival (OS) from advanced disease and progression-free survival (PFS) from start of cancer-directed drug regimen were estimated and adjusted for the left truncation bias. A total of 1,281 patients were analyzed, 244 (19%) had PM at time of advanced disease. PM were associated with female sex [OR: 1.67; 95% confidence interval (CI): 1.11-2.54; P = 0.014] and higher histologic grade (OR: 1.72; 95% CI: 1.08-2.71; P = 0.022), while rectal primary tumors were less frequent in patients with PM (OR: 0.51; 95% CI: 0.29-0.88; P < 0.001). APC occurred less frequently in patients with PM (N = 151, 64% vs. N = 788, 79%) while MED12 alterations occurred more frequently in patients with PM (N = 20, 10% vs. N = 32, 4%); differences in MED12 were not significant when restricting to oncogenic and likely oncogenic variants according to OncoKB. Patients with PM had worse OS (HR: 1.45; 95% CI: 1.16-1.81) after adjustment for independently significant clinical and genomic predictors. PFS from initiation of first-line treatment did not differ by presence of PM. In conclusion, PM were more frequent in females and right-sided primary tumors. Differences in frequencies of MED12 and APC alterations were identified between patients with and without PM. PM were associated with shorter OS but not with PFS from first-line treatment. SIGNIFICANCE: Utilizing the GENIE BPC registry, this study found that PM in patients with colorectal cancer occur more frequently in females and right-sided primary tumors and are associated with worse OS. In addition, we found a lower frequency of APC alterations and a higher frequency in MED12 alterations in patients with PM.

Rate of pachymeningeal failure following adjuvant WBRT vs SRS in patients with brain metastases.

Background: Stereotactic radiosurgery (SRS) has supplanted whole brain radiotherapy (WBRT) as standard-of-care adjuvant treatment following surgery for brain metastasis (BrM). Concomitant with the adoption of adjuvant SRS, a new pattern of failure termed "Pachymeningeal failure" (PMF) has emerged. Methods: We reviewed a prospective registry of 264 BrM patients; 145 and 119 were treated adjuvantly with WBRT and SRS, respectively. The Cox proportional hazards model was used to identify variables correlating to outcomes. Outcomes were calculated using the cumulative incidence (CI) method. Univariate (UVA) and multivariate analyses (MVA) were done to identify factors associated with PMF. Results: CI of PMF was 2 % and 18 % at 12 months, and 2 % and 23 % at 24 months for WRBT and SRS, respectively (p < 0.001). The CI of classic leptomeningeal disease (LMD) was 3 % and 4 % at 12 months, and 6 % and 6 % at 24 months for WBRT and SRS, respectively (P = 0.67). On UVA, adjuvant SRS [HR 9.75 (3.43-27.68) (P < 0.001)]; preoperative dural contact (PDC) [HR 6.78 (1.64-28.10) (P = 0.008)]; GPA score [HR 1.64 (1.11-2.42) (P = 0.012)]; and lung EGFR/ALK status [HR 3.11 (1.02-9.45) (P = 0.045)]; were associated with PMF risk. On MVA, adjuvant SRS [HR 8.15 (2.69-24.7) (P < 0.001)]; and PDC [HR 6.28 (1.51-26.1) (P = 0.012)] remained associated with PMF. Conclusions: Preoperative dural contact and adjuvant SRS instead of adjuvant WBRT were associated with an increased risk of PMF. Strategies to improve pachymeningeal radiation coverage to sterilize at risk pachymeninges should be investigated.

Recommended first-line management of asymptomatic brain metastases from EGFR mutant and ALK positive non-small cell lung cancer varies significantly according to specialty: an international survey of clinical practice.

Background: The role for radiotherapy or surgery in the upfront management of brain metastases (BrM) in epidermal growth factor receptor mutant (EGFRm) or anaplastic lymphoma kinase translocation positive (ALK+) non-small cell lung cancer (NSCLC) is uncertain because of a lack of prospective evidence supporting tyrosine kinase inhibitor (TKI) monotherapy. Further understanding of practice heterogeneity is necessary to guide collaborative efforts in establishing guideline recommendations. Methods: We conducted an international survey among medical (MO), clinical (CO), and radiation oncologists (RO), as well as neurosurgeons (NS), of treatment recommendations for asymptomatic BrM (in non-eloquent regions) EGFRm or ALK+ NSCLC patients according to specific clinical scenarios. We grouped and compared treatment recommendations according to specialty. Responses were summarized using counts and percentages and analyzed using the Fisher exact test. Results: A total of 449 surveys were included in the final analysis: 48 CO, 85 MO, 60 NS, and 256 RO. MO and CO were significantly more likely than RO and NS to recommend first-line TKI monotherapy, regardless of the number and/or size of asymptomatic BrM (in non-eloquent regions). Radiotherapy in addition to TKI as first-line management was preferred by all specialties for patients with ≥4 BrM. NS recommended surgical resection more often than other specialties for BrM measuring >2 cm. Conclusions: Recommendations for the management of BrM from EGFRm or ALK+ NSCLC vary significantly according to oncology sub-specialties. Development of multidisciplinary guidelines and further research on establishing optimal treatment strategies is warranted.

Programmed Cell Death Protein 1 Inhibitors and MET Targeted Therapies in NSCLC With MET Exon 14 Skipping Mutations: Efficacy and Toxicity as Sequential Therapies.

Introduction: NSCLC with MET exon 14 skipping mutation (METex14) is associated with poor outcomes. Integration of novel targeted therapies is challenging because of barriers in testing and drug access. We, therefore, sought to characterize the treatment patterns, outcomes, and emerging issues of treatment sequencing in patients with METex14-mutant NSCLC. Methods: We reviewed all NSCLC cases with METex14 alterations between 2014 and 2020 across four Canadian cancer centers. Demographics, disease characteristics, systemic therapy, overall response rates (ORRs), survival, and toxicity were summarized. Results: Among 64 patients with METex14-mutant NSCLC, the median overall survival was 23.1 months: 127.0 months in stage 1, 27.3 months in resected stage 2 and 3, and 16.6 months in unresectable stage 3 or 4 disease, respectively. In patients with advanced disease, 22% were too unwell for systemic treatment. MET tyrosine kinase inhibitors (TKIs) were administered to 28 patients with an ORR of 33%, median progression-free survival of 2.7 months, and 3.8 months for selective TKIs. Programmed cell death protein-1 (PD-1) inhibitors were given to 25 patients-the ORR was 44% and progression-free survival was 10.6 months. No responses were seen with subsequent MET TKIs after initial TKI treatment. Grade 3 or higher toxicities occurred in 64% of patients who received MET TKI after PD-1 inhibitors versus 8% in those who did not receive PD-1 inhibitors. Conclusions: Many patients with advanced METex14 NSCLC were too unwell to receive treatment. PD-1 inhibitors seem effective as an initial treatment, although greater toxicity was seen with subsequent MET TKIs. Thus, timely testing for METex14 skipping and initial therapy are imperative to improving patient survival.

Clinical Outcomes of Patients with Metastatic Breast Cancer Treated with Hypo-Fractionated Liver Radiotherapy.

PURPOSE: To retrospectively review the clinical outcomes of patients with metastatic breast cancer (MBCa) following liver directed ablative intent radiotherapy (RT). METHODS: Demographics, disease and treatment characteristics of patients with MBCa who received liver metastasis (LM) directed ablative RT between 2004-2020 were analysed. The primary outcome was local control (LC), secondary outcomes included overall survival (OS) and progression-free survival (PFS) analyzed by univariate (UVA) and multi-variable analysis (MVA). RESULTS: Thirty MBCa patients with 50 LM treated with 5-10 fraction RT were identified. Median follow-up was 14.6 (range 0.9-156.2) months. Class of metastatic disease was described as induced (12 patients, 40%), repeat (15 patients, 50%) and de novo (three patients, 10%). Median size of treated LM was 3.1 cm (range 1-8.8 cm) and median biologically effective dose delivered was 122 (Q1-Q3; 98-174) Gy3. One-year LC rate was 100%. One year and two-year survival was 89% and 63%, respectively, with size of treated LM predictive of OS (HR 1.35, p = 0.023) on UVA. Patients with induced OMD had a significantly higher rate of progression (HR 4.77, p = 0.01) on UVA, trending to significance on MVA (HR 3.23, p = 0.051). CONCLUSIONS: Hypo-fractionated ablative liver RT in patients with MBCa provides safe, tolerable treatment with excellent LC.

Hypofractionation Adoption in Prostate Cancer Radiotherapy: Results of an International Survey.

PURPOSE: Hypofractionation is noninferior to conventional fractionation in the treatment of localized prostate cancer. Using results from the European Society of Radiation Oncology's (ESTRO) Global Impact of Radiotherapy in Oncology (GIRO) initiative survey on hypofractionation, this study identifies rates of adoption, facilitating factors, and barriers to adoption of hypofractionation in prostate cancer across World Bank income groups. MATERIALS AND METHODS: The ESTRO-GIRO initiative administered an international, anonymous, electronic survey to radiation oncologists from 2018 to 2019. Physician demographics, clinical practice characteristics, and hypofractionation regimen use (if any) for several prostate cancer scenarios were collected. Responders were asked about specific justifications and barriers to adopting hypofractionation, and responses were stratified by World Bank income group. Multivariate logistic regression models were used to analyze variables associated with hypofractionation preference. RESULTS: A total of 1,157 physician responses were included. Most respondents (60%) were from high-income countries (HICs). In the curative setting, hypofractionation was most often preferred in low- and intermediate-risk prostate cancers, with 52% and 47% of respondents reporting hypofractionation use in ≥50% of patients, respectively. These rates drop to 35% and 20% in high-risk prostate cancer and where pelvic irradiation is indicated. Most respondents (89%) preferred hypofractionation in the palliative setting. Overall, respondents from upper-middle-income countries and lower-middle- and low-income countries were significantly less likely to prefer hypofractionation than those from HICs (P < .001). The most frequently cited justification and barrier were availability of published evidence and fear of worse late toxicity, respectively. CONCLUSION: Hypofractionation preference varies by indication and World Bank income group, with greater acceptance among providers in HICs for all indications. These results provide a basis for targeted interventions to increase provider acceptance of this treatment modality.

University campus breastfeeding, knowledge, and perceptions of support: An exploratory study.

Breastfeeding is often considered principally a biological issue but success is impacted by the socio-ecological environment of the lactating parent. Identifying current attitudes towards breastfeeding is essential in the effort toward normalizing breastfeeding in communities, including university campuses. The study explored campus community knowledge, awareness, and attitudes about breastfeeding, including available resources and applicable laws on two university campuses in the southern United States. This cross-sectional, self-reporting study utilized the Iowa Infant Feeding Attitude Scale and an adaptation of the Breastfeeding Behavior Questionnaire to survey a convenience sample. Results revealed decreased awareness of protective laws, availability of private lactation space, and insufficient public appreciation of breastfeeding's unique advantages to both lactating parent and infant as barriers to breastfeeding. These findings will help develop additional breastfeeding strategies to improve university campus community breastfeeding initiatives.

Hypofractionation in Breast Cancer Radiotherapy Across World Bank Income Groups: Results of an International Survey.

PURPOSE: Hypofractionated breast radiotherapy has been found to be equivalent to conventional fractionation in many clinical trials. Using data from the European Society for Radiotherapy and Oncology Global Impact of Radiotherapy in Oncology survey, we identified preferences for hypofractionation in breast cancer across World Bank income groups and the perceived facilitators and barriers to its use. MATERIALS AND METHODS: An international, electronic survey was administered to radiation oncologists from 2018 to 2019. Demographics, practice characteristics, preferred hypofractionation regimen for specific breast cancer scenarios, and facilitators and barriers to hypofractionation were reported and stratified by World Bank income groups. Variables associated with hypofractionation were assessed using multivariate logistic regression models. RESULTS: One thousand four hundred thirty-four physicians responded: 890 (62%) from high-income countries (HICs), 361 (25%) from upper-middle-income countries (UMICs), 183 (13%) from low- and lower-middle-income countries (LLMICs). Hypofractionation was preferred most frequently in node-negative disease after breast-conserving surgery, with the strongest preference reported in HICs (78% from HICs, 54% from UMICs, and 51% from LLMICs, P < .001). Hypofractionation for node-positive disease postmastectomy was more frequently preferred in LLMICs (28% from HICs, 15% from UMICs, and 35% from LLMICs, P < .001). Curative doses of 2.1 to < 2.5 Gy in 15-16 fractions were most frequently reported, with limited preference for ultra-hypofractionation, but significant variability in palliative dosing. In adjusted analyses, UMICs were significantly less likely than LLMICs to prefer hypofractionation across all curative clinical scenarios, whereas respondents with > 1 million population catchments and with intensity-modulated radiotherapy were more likely to prefer hypofractionation. The most frequently cited facilitators and barriers were published evidence and fear of late toxicity, respectively. CONCLUSION: Preference for hypofractionation varied for curative indications, with greater acceptance in earlier-stage disease in HICs and in later-stage disease in LLMICs. Targeted educational interventions and greater inclusivity in radiation oncology clinical trials may support greater uptake.

Validation of a miniaturized handheld arterial pressure monitor for guiding full and partial REBOA use during resuscitation.

PURPOSE: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a well-validated method for the control of noncompressible truncal hemorrhage. In lower resource or battlefield settings, the need for arterial line setup and monitoring is problematic and potentially prohibitive. We sought to evaluate the accuracy and precision of a miniaturized portable device (Centurion COMPASS®) versus standard arterial pressure monitoring using standard ER-REBOA and partial REBOA (pREBOA) as a high-fidelity and space-/time-conserving alternative. METHODS: A total of 40 swine underwent a four-phase validation/precision study (each phase using five ER-REBOAs and five pREBOAs). Phases I/II evaluated accuracy with full and pREBOA in uninjured animals. Phases III/IV duplicated the previous phases but in a severe hemorrhagic shock model. Carotid and femoral pressures were monitored with both intra-arterial pressure systems and the COMPASS® device. The vascular flow was measured by aortic flow probes. Correlation and Bland-Altman analysis were performed. RESULTS: There was a strong correlation in accuracy testing of proximal and distal COMPASS® devices compared to standard intra-arterial pressure monitoring (r = 0.94, 0.8; p < 0.005) as well as during precision testing (r = 0.98, 0.89 p < 0.005) in the uninjured phases. Similar accuracy and reliability were demonstrated in hemorrhagic shock, with a strong correlation for the proximal and distal COMPASS® devices (r = 0.98, 0.97; p < 0.005), as well as during precision testing (r = 0.99, 0.95; p < 0.005) in both full and pREBOA scenarios. Bland-Altman analysis showed extremely low bias between the COMPASS® and arterial line for both proximal (bias = 1.9) and distal (bias = 0.8) pressure measurements. CONCLUSION: The COMPASS® provides accurate and precise pressure measurements during standard and partial REBOA in both uninjured and shock conditions. This device may help extend and enhance capability in any low-resource/battlefield settings, or even eliminate the need for standard intra-arterial invasive pressure monitoring and external setup.

Evolving management of early stage pancreatic adenocarcinoma in older patients.

BACKGROUND: Due to the aging population, the number of older patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) will continue to rise. STUDY DESIGN: Utilizing the NCDB from 2010 to 2016, patients with early stage, clinically node negative PDAC who were ≥70 years old and had a Whipple were identified. Multivariable logistic regressions were used to determine independent factors for R0 resection and NAT. Cox-proportional-hazards regression analyses examined for the impact of NAT on the risk of death. RESULTS: Of 5086 patients, 51.7% received upfront surgery + adjuvant therapy (UFS + AT), followed by 29.9% UFS only, and the remainder NAT. NAT significantly improved OS compared to a combined cohort of those that had UFS ± AT. NAT retained its independent survival benefit when compared to only patients that had UFS + AT. CONCLUSION: For older patients diagnosed with early stage PDAC, NAT was associated with improved R0 resection rates and a significant survival benefit when compared to the current standard of care.

Mitochondrial Aconitase ACO2 Links Iron Homeostasis with Tumorigenicity in Non-Small Cell Lung Cancer.

The ability of a patient tumor to engraft an immunodeficient mouse is the strongest known independent indicator of poor prognosis in early-stage non-small cell lung cancer (NSCLC). Analysis of primary NSCLC proteomes revealed low-level expression of mitochondrial aconitase (ACO2) in the more aggressive, engrafting tumors. Knockdown of ACO2 protein expression transformed immortalized lung epithelial cells, whereas upregulation of ACO2 in transformed NSCLC cells inhibited cell proliferation in vitro and tumor growth in vivo. High level ACO2 increased iron response element binding protein 1 (IRP1) and the intracellular labile iron pool. Impaired cellular proliferation associated with high level ACO2 was reversed by treatment of cells with an iron chelator, whereas increased cell proliferation associated with low level ACO2 was suppressed by treatment of cells with iron. Expression of CDGSH iron-sulfur (FeS) domain-containing protein 1 [CISD1; also known as mitoNEET (mNT)] was modulated by ACO2 expression level and inhibition of mNT by RNA interference or by treatment of cells with pioglitazone also increased iron and cell death. Hence, ACO2 is identified as a regulator of iron homeostasis and mNT is implicated as a target in aggressive NSCLC. IMPLICATIONS: FeS cluster-associated proteins including ACO2, mNT (encoded by CISD1), and IRP1 (encoded by ACO1) are part of an "ACO2-Iron Axis" that regulates iron homeostasis and is a determinant of a particularly aggressive subset of NSCLC.

The Impact of Parent and Family Caregiver Roles Among Canadian Radiation Oncologists.

PURPOSE: Working parents, and a rising number of adults delivering care for aging relatives, experience numerous challenges in their personal, family, professional, and financial lives owing to multiple responsibilities. This study describes the experiences of Canadian radiation oncologist (RO) parents and family caregivers, reporting challenges that may exist in providing family care with clinical and academic work commitments. METHODS AND MATERIALS: Canadian ROs, via RO heads of departments in cancer centers across Canada, and physician members of the Canadian Association of Radiation Oncology were invited to participate in an anonymous online survey between November 2021 and January 2022. The survey focused on demographics, experiences of pregnancy and leave, parenting and adult caregiving responsibilities, and self-care. RESULTS: A total of 103 staff ROs (38%) completed the survey and 78 (75.7%) identified as having a parental (76 [89.7%]) and/or other family caregiver (8 [10.3%]) role; 41% were female and 59% were male, with no difference between genders in the number of children (median, 2; interquartile range, 1-3; P = .17). More female respondents took parental leave for their first child compared with male respondents (mean, 29 vs 6 weeks; P < .001). Of male respondents who started caring for their first child during residency, 27% took parental leave, compared with 77% who started caring for their first child as a staff member (P = .003). The majority of respondents described "always/usually" having collegial support for each pregnancy and parental leave. Both genders described parental responsibilities as negatively affecting attendance at conferences (male, 65%; female, 77%; P = .31) and early or late work-related meetings (male, 76%; female, 79%; P = 1.0). More female respondents described parental responsibilities as negatively affecting their career (50% vs 29%; P = .085). Of female respondents, 52% (vs 26% of male respondents; P = .044) identified a physician mentor or positive role model around parenting issues. CONCLUSIONS: Parental and other family caregiving responsibilities are not gender unique in Canadian ROs, but competing work and family roles may affect genders differently.

Evaluating Healthcare Professionals' Knowledge, Attitudes, Practices and Education Interest in LGBTQ2 + Cancer Care.

The lesbian, gay, bisexual, transgender, queer/questioning and two-spirited, plus (LGBTQ2 +) community experiences cancer-related health disparities and inequities. Our objective was to assess LGBTQ2 + knowledge, attitudes, practices and education interest of healthcare professionals (HCPs), identify opportunities to improve care and inform the development of an HCP education curriculum. This was a mixed methods quality improvement study conducted within a tertiary academic cancer centre. An email was sent to all gynaecologic oncology disease site staff (n = 92) with a secure link to an online survey. We measured respondents' sociodemographic characteristics and LGBTQ2 + knowledge, attitudes, practice behaviours and education interest. Open comments explored HCP experiences and reservations caring for LGBTQ2 + patients and suggestions to improve care. Seventy-five out of ninety-two (82%) HCPs completed the survey, with 7% identifying as LGBTQ2 + . HCPs reported feeling less comfortable (88% vs. 80%, p = 0.031) and knowledgeable (44% vs. 27%, p < 0.001) caring for transgender patients compared to LGBQ2 + patients. Most (76%) were unaware whether LGBTQ2 + -specific patient educational materials existed within their institution. Almost all (92% strongly agreed/agreed) were interested in receiving LGBTQ2 + -specific education. Two themes emerged from analysis of open comments: (i) HCPs are concerned of offending LGBTQ2 + individuals because of their lack of knowledge and (ii) HCPs desire LGBTQ2 + -specific health training, specifically in asking pronouns and caring for transgender patients. HCPs report competency gaps in caring for LGBTQ2 + patients with cancer but desire education. In response, we recommend institutions develop an educational curriculum for HCPs improve communication and inclusivity in cancer care.

Optimizing Drug Response Study Design in Patient-Derived Tumor Xenografts.

Patient-derived tumor xenograft (PDX) models were used to evaluate the effectiveness of preclinical anticancer agents. A design using 1 mouse per patient per drug (1 × 1 × 1) was considered practical for large-scale drug efficacy studies. We evaluated modifiable parameters that could increase the statistical power of this design based on our consolidated PDX experiments. Real studies were used as a reference to investigate the relationship between statistical power with treatment effect size, inter-mouse variation, and tumor measurement frequencies. Our results showed that large effect sizes could be detected at a significance level of .2 or .05 under a 1 × 1 × 1 design. We found that the minimum number of mice required to achieve 80% power at an alpha level of .05 under all situations explored was 21 mice per group for a small effect size and 5 mice per group for a medium effect size.

3'-Deoxy-3'-(18F) Fluorothymidine Positron Emission Tomography/Computed Tomography in Non-small Cell Lung Cancer Treated With Stereotactic Body Radiation Therapy: A Pilot Study.

Purpose: The primary objective was to compare 3'-deoxy-3'-(18F) fluorothymidine (FLT) positron emission tomography (PET)/computed tomography (CT) uptake in 3 cohorts of stereotactic body radiation therapy (SBRT) patients: (1) pre-SBRT, (2) stable post-SBRT lung fibrosis, and (3) suspicious or proven local recurrence post-SBRT. The secondary objectives were to optimize FLT-PET imaging by comparing FLT uptake in respiratory-gated (4-dimensional) versus nongated (3-dimensional) FLT-PET scans. Methods: Patients with early-stage non-small cell lung cancer planned or treated with SBRT at the institution with radiographic findings of fibrosis or recurrence were eligible for the study. All patients underwent imaging with FLT-PET/CT before SBRT in cohort 1 and at fibrosis or recurrence in cohort 2 and 3, respectively. The planned sample size was 20 patients in each cohort, with 60 patients total. FLT-PET standardized uptake value (SUV) variables including SUVmax, SUVmean, SUVpeak, SUV50, and SUV95 were compared among the 3 cohorts using the Kruskal-Wallis test. The correlation of respiratory-gated and nongated FLT-PET SUV variables was performed using the Spearman correlation coefficient. Results: Forty-one patients were recruited for the study (20 in cohort 1, 16 in cohort 2, and 5 in cohort 3) between 2015 and 2019. The majority received a diagnosis of stage I lung cancer (86%), and the most common prescription was 48 Gy in 4 fractions (59%). Respiratory-gated FLT-PET was performed in 35 patients. The FLT SUV variables were well correlated between respiratory-gated and nongated scans (r = 0.8-1.0). The SUVpeak, SUVmean, and SUVmax were significantly lower in the fibrosis cohort compared with the recurrence and pretreatment cohorts. The SUV50 and SUV95 values in the recurrence cohort were statistically similar to the pretreatment cohort. Conclusions: FLT-PET/CT may be helpful in differentiating SBRT-related fibrosis from recurrence. Nongated FLT-PET/CT with reporting of SUVmax and SUV95 values is recommended.

Treatment Utilization and Outcomes for Locally Advanced Rectal Cancer in Older Patients.

Importance: The number of older patients (80 years and older) diagnosed with locally advanced rectal cancer (LARC) is expected to increase. Although current guidelines recommend neoadjuvant chemoradiation therapy (NACRT) followed by resection, little is known about management and outcomes in this older population. Objective: To assess the trends in management of older patients diagnosed with LARC who had a surgical resection. Design, Setting, and Participants: Patients 80 years and older who had a surgical resection for LARC were identified in the 2004-2016 National Cancer Database. Patients were grouped based on therapy sequence: (1) surgery followed by adjuvant therapy (AT), ie, chemotherapy or radiation; (2) surgery alone; or (3) NACRT followed by surgical resection. Data were analyzed in May 2021. Exposures: NACRT followed by surgery, and surgery with or without AT. Main Outcomes and Measures: Overall survival (OS) was assessed using Kaplan-Meier analyses with inverse probability of treatment weighting (IPTW) and Cox proportional hazards regression were performed to examine the association of NACRT with the risk of death. Results: Of 3868 patients with LARC who underwent surgical resection, 2042 (52.8%) were male, and the mean (SD) age was 83.4 (3.0) years. A total of 2273 (58.8%) received NACRT followed by surgical resection. Factors independently associated with NACRT were more recent diagnosis, age 80 to 85 years (vs 86 years and older), fewer comorbidities, larger tumors, and node-positive disease. The Kaplan-Meier analyses with IPTW showed that 3-year and 5-year OS for NACRT (3-year: 68.9%; 95% CI, 67.0-70.8; 5-year: 51.1%; 95% CI, 49.0-53.4) vs surgery with AT (3-year: 64.4%; 95% CI, 59.0-70.2; 5-year: 43.0%; 95% CI, 37.4-49.5) vs surgery alone (3-year: 55.8%; 95% CI, 52.0-60.0; 5-year: 34.7%; 95% CI, 30.8-39.0) was significantly different (P < .001). After adjusting for confounders, patients who received NACRT were more likely to undergo an R0 resection (adjusted odds ratio, 2.16; 95% CI, 1.62-2.88), which independently improved OS (P < .001). Moreover, receipt of NACRT was independently associated with a 25% decreased risk of death (adjusted hazard ratio, 0.75; 95% CI, 0.69-0.82) compared with alternative treatment sequences. Conclusions and Relevance: Approximately 40% of older patients with LARC did not receive the current standard of care. In this cohort, NACRT was associated with a higher likelihood of an R0 resection and improved OS. Clinicians should advocate for receipt of NACRT in older patients with LARC.

Predicting Regional Lymph Node Recurrence in the Modern Age of Tumor-Positive Sentinel Node Melanoma: The Role of the First Postoperative Ultrasound.

BACKGROUND: The Multicenter Selective Lymphadenectomy Trial II (MSLT-II) led to a change in the management of tumor-positive sentinel lymph nodes (SLNs) from completion node dissection (CLND) to nodal observation. This study aimed to evaluate prognostic factors for predicting sentinel node basin recurrence (SNBR) using data from MSLT-II trial participants. METHODS: In MSLT-II, 1076 patients were treated with observation. Patients were included in the current study if they had undergone a post-sentinel node basin ultrasound (PSNB-US) within 4 months after surgery. The study excluded patients with positive SLN by reverse transcription-polymerase chain reaction (RT-PCR) or incomplete SLN pathologic data. Primary tumor, patient, PSNB-US, and SLN characteristics were evaluated. Multivariable regression analyses were performed to determine independent prognostic factors associated with SNBR. RESULTS: The study enrolled 737 patients: 193 (26.2%) patients with SNBR and 73 (9.9%) patients with first abnormal US. The patients with an abnormal first US were more likely to experience SNBR (23.8 vs. 5.0%). In the multivariable analyses, increased risk of SNBR was associated with male gender (adjusted hazard ratio [aHR], 1.38; 95% confidence interval [CI], 1.00-1.9; p = 0.049), increasing Breslow thickness (aHR, 1.10; 95% CI, 1.01-1.2; p = 0.038), presence of ulceration (aHR, 1.93; 95% CI, 1.42-2.6; p < 0.001), sentinel node tumor burden greater than 1 mm (aHR, 1.91; 95% CI, 1.10-3.3; p = 0.022), lymphovascular invasion (aHR, 1.53; 95% CI, 1.00-2.3; p = 0.048), and presence of abnormal PSNB-US (aHR, 4.29; 95% CI, 3.02-6.1; p < 0.001). CONCLUSIONS: The first postoperative US together with clinical and pathologic factors may play an important role in predicting SNBR.