Risk of secondary malignancies in ovarian cancer survivors: 52,680 patients analyzed with over 40 years of follow-up.

OBJECTIVE: Survivors of ovarian cancer are at risk of developing a secondary malignancy (SM). We sought to evaluate the risk of developing SM, stratified by treatment modality. METHODS: Standardized incidence ratios (SIR, observed-to-expected [O/E] ratio) were assessed in 52,680 patients diagnosed with ovarian cancer between 1975 and 2016 in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. RESULTS: Of the 52,680 patients, 3366 patients (6.4%) developed SM, which was more than the endemic rate (O/E 1.13; p < .05). Patients who received any radiation (RT) had an increased risk of overall SM compared to those who didn't (O/E 1.42 vs 1.11; p < .05), and specifically, in the bladder (O/E 2.81). Patients who received any chemotherapy (CT) had an increased risk of leukemia (O/E 3.06), and a similar risk of overall SM compared to those not treated with CT (O/E 1.11 vs 1.14; p < .05). The excess risk of developing a solid tumor SM was greatest at latencies of 10-20 years. Patients younger than 50 had the highest risk of developing SM. Non-White patients had a higher risk of SM compared to White patients. CONCLUSIONS: This is the largest study to examine the risk of SM in patients with ovarian cancer and has the longest follow-up. Risk of SM was increased after ovarian cancer and varied with treatment modality, race, latency, and age. These results may help inform SM screening protocols for women diagnosed with ovarian cancer.

Trial of restarting and tolerating metformin (TreatMet).

This randomized, double-blind, placebo-controlled, n-of-1 crossover study assessed whether metformin's side effects are reproducible in patients with a history of metformin intolerance. Participants completed up to four cycles of 2 weeks of metformin exposure and 2 weeks of placebo exposure. Participants completed surveys based on the Gastrointestinal Symptom Rating Scale and the Treatment Satisfaction Questionnaire for Medication. The primary hypotheses were that treatment satisfaction would be equal for placebo and metformin and that more than 30% of the study enrollees would be able to adhere to a higher dose of metformin 6 months after participation. Thirteen patients (all women, mean age 52.4 years) enrolled, three of whom were lost to follow-up or were non-adherent to study protocol. Metformin was associated with significantly lower global treatment satisfaction scores compared with placebo (39.58 vs. 53.75, P < .05 ) but participants could not distinguish metformin from placebo and did not report higher rates of gastrointestinal side effects on metformin. Two out of 10 participants adhered to a higher dose of metformin after trial completion. Metformin appears to have barriers to use beyond its classic gastrointestinal side effects.

The impact of food order on postprandial glycaemic excursions in prediabetes.

Data suggest that nutrient order during a meal significantly impacts postprandial glucose and insulin excursions in type 2 diabetes, while its effects in prediabetes have not been reported. Fifteen participants with prediabetes consumed the same meal on 3 days in random order: carbohydrate first, followed 10 minutes later by protein and vegetables (CF); protein and vegetables first, followed 10 minutes later by carbohydrate (PVF); or vegetables first followed by protein and carbohydrate (VF). Blood was sampled for glucose and insulin measurements at 0, 30, 60, 90, 120, 150 and 180 minutes. Incremental glucose peaks were similarly attenuated by >40% in the PVF and VF meal conditions compared with CF. The incremental area under the curve for glucose was 38.8% lower following the PVF meal order, compared with CF, and postprandial insulin excursions were significantly lower in the VF meal condition compared with CF. The CF meal pattern showed marked glycaemic variability whereas glucose levels were stable in the PVF and VF meal conditions. Food order presents a novel, simple behavioural strategy to reduce glycaemic excursions in prediabetes.

Nationwide changes in radiation oncology travel and location of care before and during the COVID-19 pandemic.

PURPOSE: Patients with cancer are particularly vulnerable to coronavirus disease (COVID). Transportation barriers made travel to obtain medical care more difficult during the pandemic. Whether these factors led to changes in the distance traveled for radiotherapy and the coordinated location of radiation treatment is unknown. MATERIALS AND METHODS: We analyzed patients across 60 cancer sites in the National Cancer Database from 2018 to 2020. Demographic and clinical variables were analyzed for changes in distance traveled for radiotherapy. We designated the facilities in the 99th percentile or above in terms of the proportion of patients who traveled more than 200 miles as "destination facilities." We defined "coordinated care" as undergoing radiotherapy at the same facility where the cancer was diagnosed. RESULTS: We evaluated 1,151,954 patients. There was a greater than 1% decrease in the proportion of patients treated in the Mid-Atlantic States. Mean distance traveled from place of residence to radiation treatment decreased from 28.6 to 25.9 miles, and the proportion traveling greater than 50 miles decreased from 7.7% to 7.1%. At "destination facilities," the proportion traveling more than 200 miles decreased from 29.3% in 2018 to 24% in 2020. In comparison, at the other hospitals, the proportion traveling more than 200 miles decreased from 1.07% to 0.97%. In 2020, residing in a rural area resulted in a lower odds of having coordinated care (multivariable odds ratio = 0.89; 95% confidence interval, 0.83-0.95). CONCLUSION: The first year of the COVID pandemic measurably impacted the location of U.S. radiation therapy treatment.

Dosimetric Evaluation of Organs at Risk From SAVE Protocol.

PURPOSE: The objective of this work was to evaluate dosimetric characteristics to organs at risk (OARs) from short-course adjuvant vaginal cuff brachytherapy (VCB) in early endometrial cancer compared with standard of care (SOC) in a multi-institutional prospective randomized trial. METHODS AND MATERIALS: SAVE (Short Course Adjuvant Vaginal Brachytherapy in Early Endometrial Cancer Compared to Standard of Care) is a prospective, phase 3, multisite randomized trial in which 108 patients requiring VCB were randomized to an experimental short-course arm (11 Gy × 2 fractions [fx] to surface) and SOC arm. Those randomized to the SOC arm were subdivided into treatment groups based on treating physician discretion as follows: 7 Gy × 3 fx to 5 mm, 5 to 5.5 Gy × 4 fx to 5 mm, and 6 Gy × 5 fx to surface. To evaluate doses to OARs of each SAVE cohort, the rectum, bladder, sigmoid, small bowel, and urethra were contoured on planning computed tomography, and doses to OARs were compared by treatment arm. Absolute doses for each OAR and from each fractionation scheme were converted to 2 Gy equivalent dose (EQD23). Each SOC arm was compared with the experimental arm separately using 1-way analysis of variance, followed by pairwise comparisons using Tukey's honestly significant difference test. RESULTS: The experimental arm had significantly lower doses for rectum, bladder, sigmoid, and urethra compared with the 7 Gy × 3 and 5 to 5.5 Gy × 4 fractionation schemes; however, the experimental arm did not differ from the 6 Gy × 5 fractionation scheme. For small bowel doses, none of the SOC fractionation schemes were statistically different than the experimental. The highest EQD23 doses to the examined OARs were observed to come from the most common dose fractionation scheme of 7 Gy × 3 fx. With a short median follow-up of 1 year, there have been no isolated vaginal recurrences. CONCLUSIONS: Experimental short-course VCB of 11 Gy × 2 fx to the surface provides a comparable biologically effective dose to SOC courses. Experimental short-course VCB was found to reduce or be comparable to D2cc and D0.1cc EQD23 doses to rectum, bladder, sigmoid, small bowel, and urethra critical structures. This may translate into a comparable or lower rate of acute and late adverse effects.

A Randomized Controlled Pilot Study of the Food Order Behavioral Intervention in Prediabetes.

(1) Background: Prior research in individuals with overweight/obesity and prediabetes or type 2 diabetes has shown that the ingestion of protein-rich food and non-starchy vegetables before concentrated carbohydrates (a carbohydrate-last food order) led to lower postprandial glucose excursions over 180 min, compared to eating the same foods in the reverse order. To expand upon this research, we sought to examine the feasibility and impact of carbohydrate-last food order behavioral intervention on glucose tolerance (GT), HbA1c, weight, and nutrient intake in adults with prediabetes in the real world over a 16-week span. (2) Methods: A total of 45 adults with overweight/obesity and prediabetes were randomized to receive 4-monthly standard nutritional counseling (C) or standard nutritional counseling plus carbohydrate-last food order counseling (FO) sessions (NCT# NCT03896360). (3) Results: The FO group decreased in body weight (-3.6 ± 5.7 lbs, p = 0.017), and trended toward lower HbA1c (-0.1 ± 0.2, p = 0.054). The C group weight trended lower (-2.6 ± 6.8 lbs, p = 0.102) without altering HbA1c (-0.03 ± 0.3, p = 0.605). GT was unchanged in both groups after 16 weeks. Changes in weight, HbA1c, and GT were similar between groups. Sensitivity analysis of pre-COVID participants showed significant weight loss in the FO group (-5.9 ± 5.3 lbs, p = 0.003) but not in C group (-1.0 ± 6.8 lbs, p = 0.608). After 16 weeks, the C group significantly reduced its daily intake of calories, fat, protein, and grains whereas the FO group increased its daily intake of vegetables and protein. There were 17 (94%) FO participants that reported high intervention adherence and 13 (72%) reported it was easy to eat protein/vegetables before carbohydrates. (4) Conclusions: A carbohydrate-last food order is a feasible behavioral strategy in individuals with prediabetes that improves diet quality, notably increasing protein and vegetable intake.

Medical weight management protects against weight gain during the COVID-19 pandemic.

Background: American adults have gained weight during the COVID-19 pandemic. Little is known about how patients who are medically managed for overweight and obesity, including patients who are prescribed antiobesity pharmacotherapy, have fared. Objective: To assess the COVID-19 pandemic's effect on weight, food choices, and health behaviors in patients receiving medical treatment for overweight or obesity. Methods: Adult patients treated at an urban academic weight management center between 1 May 2019 and 1 May 2020 were electronically surveyed between 23 February and 23 March 2021. The survey assessed changes in weight, eating, behaviors, and the use of antiobesity medications (AOMs) following issuance of social distancing/stay-at-home policies in March 2020. Results: In 970 respondents, median percent weight change for those taking AOMs was -0.459% [interquartile range -5.46%-(+3.73%)] compared to +2.33% [IQR -1.92%-(+6.52%)] for those not taking AOMs (p < 0.001). More participants achieved ≥5% weight loss if they were taking AOMs compared to those who were not (26.7% vs. 15.8%, p = 0.004), and weight gain ≥5% was also lower in those taking AOMs (19.8% vs. 30.3%, p = 0.004). Patients with pre-pandemic BMI ≥30 kg/m2 taking AOMs experienced the greatest weight reduction, and there was greater weight loss associated with increased physical activity. Conclusions and Relevance: Medical weight management protected against weight gain during this period of the COVID-19 pandemic. Increased physical activity, decreased alcohol intake, and use of AOMs were factors that contributed to this protective effect.

Carbohydrate-last meal pattern lowers postprandial glucose and insulin excursions in type 2 diabetes.

BACKGROUND: There are limited data regarding the timing of carbohydrate ingestion during a meal and postprandial glucose regulation. METHODS: Sixteen subjects with type 2 diabetes mellitus (T2DM) consumed the same meal on 3 days in random order: carbohydrate first, followed 10 min later by protein and vegetables; protein and vegetables first, followed 10 min later by carbohydrate; or all components together. Blood was sampled for glucose, insulin, glucagon-like peptide-1 (GLP-1), and glucagon measurements at baseline (just before meal ingestion) and subsequently at 30 min intervals up to 180 min. RESULTS: The incremental areas under the curve for glucose (iAUC0-180) and incremental glucose peaks were 53% and 54% lower, respectively, when carbohydrate was consumed last compared with carbohydrate consumed first (3124.7±501.2 vs 6703.5±904.6 mg/dL×180min, p<0.001; 34.7±4.1 vs 75.0±6.5 mg/dL, p<0.001) and 44% and 40% lower, respectively, compared with the all components together condition (3124.7±501.2 vs 5587.1±828.7 mg/dL×180min, p=0.003; 34.7±4.1 vs 58.2±5.9 mg/dL, p<0.001). Postprandial insulin excursions were lower (iAUC0-180: 7354.1±897.3 vs 9769.7±1002.1 µU/mL×min, p=0.003) and GLP-1 excursions higher (iAUC0-180: 3487.56±327.7 vs 2519.11±494.8 pg/mL×min, p=0.019) following the carbohydrate-last meal order compared with carbohydrate first. CONCLUSION: The carbohydrate-last meal pattern may be an effective behavioral strategy to improve postprandial glycemia.