The Clinical Utility of a 7-Gene Biosignature on Radiation Therapy Decision Making in Patients with Ductal Carcinoma In Situ Following Breast-Conserving Surgery: An Updated Analysis of the DCISionRT® PREDICT Study.

BACKGROUND: Breast-conserving surgery (BCS) followed by adjuvant radiotherapy (RT) is a standard treatment for ductal carcinoma in situ (DCIS). A low-risk patient subset that does not benefit from RT has not yet been clearly identified. The DCISionRT test provides a clinically validated decision score (DS), which is prognostic of 10-year in-breast recurrence rates (invasive and non-invasive) and is also predictive of RT benefit. This analysis presents final outcomes from the PREDICT prospective registry trial aiming to determine how often the DCISionRT test changes radiation treatment recommendations. METHODS: Overall, 2496 patients were enrolled from February 2018 to January 2022 at 63 academic and community practice sites and received DCISionRT as part of their care plan. Treating physicians reported their treatment recommendations pre- and post-test as well as the patient's preference. The primary endpoint was to identify the percentage of patients where testing led to a change in RT recommendation. The impact of the test on RT treatment recommendation was physician specialty, treatment settings, individual clinical/pathological features and RTOG 9804 like criteria. Multivariate logisitc regression analysis was used to estimate the odds ratio (ORs) for factors associated with the post-test RT recommendations. RESULTS: RT recommendation changed 38% of women, resulting in a 20% decrease in the overall recommendation of RT (p < 0.001). Of those women initially recommended no RT (n = 583), 31% were recommended RT post-test. The recommendation for RT post-test increased with increasing DS, from 29% to 66% to 91% for DS <2, DS 2-4, and DS >4, respectively. On multivariable analysis, DS had the strongest influence on final RT recommendation (odds ratio 22.2, 95% confidence interval 16.3-30.7), which was eightfold greater than clinicopathologic features. Furthermore, there was an overall change in the recommendation to receive RT in 42% of those patients meeting RTOG 9804-like low-risk criteria. CONCLUSIONS: The test results provided information that changes treatment recommendations both for and against RT use in large population of women with DCIS treated in a variety of clinical settings. Overall, clinicians changed their recommendations to include or omit RT for 38% of women based on the test results. Based on published clinical validations and the results from current study, DCISionRT may aid in preventing the over- and undertreatment of clinicopathological 'low-risk' and 'high-risk' DCIS patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03448926 ( https://clinicaltrials.gov/study/NCT03448926 ).

Qualitative Study of Patients' and Caregivers' Perceptions and Information Preferences About Hospice.

OBJECTIVE: The goal of this study is to assess perceptions about hospice among patients with metastatic cancer and their caregivers (i.e., family and/or friends). DESIGN AND SETTING: We conducted semi-structured interviews with 16 adult patients with a prognosis ≤12 months and 7 of their caregivers. The interviews focused on perceptions, knowledge, and information preferences about hospice. Two raters coded interviews independently (κ > 0.85). We used a framework approach for data analysis. RESULTS: Participants showed variable gaps in understanding about hospice, including who would benefit from hospice care and the extent of services provided. They all perceived that hospice involves a psychological transition to accepting imminent death and often referred to hospice from a relatively cognitive distance, using hypothetical scenarios of others for whom hospice would be more relevant. Participants' attitudes about hospice reflected their concerns about suffering, loss of dignity, and death, as well as their perceived understanding of hospice services. These attitudes along with the psychological barriers to projecting a need for hospice and lack of knowledge were all perceived as important barriers to hospice utilization. All participants felt they needed more information about hospice, yet they were mixed regarding the optimal timing of this information. CONCLUSIONS: Study participants had misunderstandings about hospice and perceived end-of-life (EOL) concerns such as fear of suffering, loss of dignity, and death, as well as lack of knowledge as the main barriers to hospice utilization. Interventions are needed to educate patients and their families about hospice and to address their EOL concerns.

Clinical and treatment factors associated with vaginal stenosis after definitive chemoradiation for anal canal cancer.

PURPOSE: We sought to evaluate the incidence of vaginal stenosis (VS) and identify clinical and treatment factors that predict for VS in female patients with anal cancer treated with definitive chemoradiation. METHODS AND MATERIALS: The cohort included 95 consecutive women receiving definitive chemoradiation between 2003 and 2012. All but 1 received intensity modulated radiation therapy; median primary tumor dose 50.4 Gy (range, 41.4-60). A modified National Cancer Institute Common Terminology Criteria for Adverse Events version 4 was used to score VS based on the medical record description of dyspareunia, pain with dilator use, vaginal dryness, or difficult pelvic examination. Ordered logistic regression was performed to assess VS predictors. RESULTS: Median age was 60.4 years (range, 19-97). With median follow-up of 2.5 years, 70 women (74%) had adequate information to assess VS. Of these, VS grade distribution was 21.4% grade 0, 14.3% grade 1, 27.1% grade 2, and 37.1% grade 3. By multivariable ordered logistic regression, younger age (P = .02), higher tumor dose (P = .06), and earlier treatment year (P = .04) were associated with higher grade of VS. CONCLUSIONS: VS is a common late complication in women treated definitively with chemoradiation for anal canal cancer. Younger age, higher tumor dose, and earlier year of treatment were associated with a higher grade of stenosis. Prospective investigation into patient reported outcomes is warranted, including sexual function and VS prevention strategies to better understand its effect on long-term survivorship.

Complications of pelvic radiation in patients treated for gynecologic malignancies.

Radiation therapy is a critical treatment modality in the management of patients with gynecologic tumors. New highly conformal external-beam and brachytherapy techniques have led to important reductions in recurrence and patient morbidity and mortality. However, patients who receive pelvic radiation for gynecologic malignancies may experience a unique constellation of toxicity because of the anatomic locations, combination with concurrent chemotherapy and/or surgery, as well as potential surgical interventions. Although side effects are often categorized into acute versus late toxicities, several late toxicities represent continuation and evolution of the same pathologic process. Comorbidities and radiation dose can significantly increase the risk of morbidity. Current understanding of the incidence of various morbidities in patients treated with current radiation techniques for gynecologic malignancies, the impact of chemotherapy and surgery, treatment options for those effects, and future areas of research are highlighted.

Dosimetric consequences of interobserver variability in delineating the organs at risk in gynecologic interstitial brachytherapy.

PURPOSE: To investigate the dosimetric variability associated with interobserver organ-at-risk delineation differences on computed tomography in patients undergoing gynecologic interstitial brachytherapy. METHODS AND MATERIALS: The rectum, bladder, and sigmoid of 14 patients treated with gynecologic interstitial brachytherapy were retrospectively contoured by 13 physicians. Geometric variability was calculated using κ statistics, conformity index (CIgen), and coefficient of variation (CV) of volumes contoured across physicians. Dosimetric variability of the single-fraction D0.1cc and D2cc was assessed through CV across physicians, and the standard deviation of the total EQD2 (equivalent dose in 2 Gy per fraction) brachytherapy dose (SD(TOT)) was calculated. RESULTS: The population mean ± 1 standard deviation of κ, CIgen, and volume CV were, respectively: 0.77 ± 0.06, 0.70 ± 0.08, and 20% ± 6% for bladder; 0.74 ± 06, 0.67 ± 0.08, and 20% ± 5% for rectum; and 0.33 ± 0.20, 0.26 ± 0.17, and 82% ± 42% for sigmoid. Dosimetric variability was as follows: for bladder, CV = 31% ± 19% (SD(TOT) = 72 ± 64 Gy) for D0.1cc and CV = 16% ± 10% (SD(TOT) = 9 ± 6 Gy) for D2cc; for rectum, CV = 11% ± 5% (SD(TOT) = 16 ± 17 Gy) for D0.1cc and CV = 7% ± 2% (SD(TOT) = 4 ± 3 Gy) for D2cc; for sigmoid, CV = 39% ± 28% (SD(TOT) = 12 ± 18 Gy) for D0.1cc and CV = 34% ± 19% (SD(TOT) = 4 ± 4 Gy) for D2cc. CONCLUSIONS: Delineation of bladder and rectum by 13 physicians demonstrated substantial geometric agreement and resulted in good dosimetric agreement for all dose-volume histogram parameters except bladder D0.1cc. Small delineation differences in high-dose regions by the posterior bladder wall may explain these results. The delineation of sigmoid showed fair geometric agreement. The higher dosimetric variability for sigmoid compared with rectum and bladder did not correlate with higher variability in the total brachytherapy dose but rather may be due to the sigmoid being positioned in low-dose regions in the cases analyzed in this study.

Quality of life (QOL) in women treated for gynecologic malignancies with radiation therapy: a literature review of patient-reported outcomes.

OBJECTIVE: To summarize the literature on quality of life for patients treated with definitive radiation for gynecologic cancers, with a specific focus on patient reported outcomes. METHODS: A literature review was performed to summarize studies about patient-reported outcomes and quality of life in women with gynecologic malignancies who were treated with definitive radiation therapy. Summaries are by disease site, including endometrial, cervical and vulvar cancers. RESULTS: Over 20 different survey instruments have been used to describe patient-reported outcomes for women treated with radiation for gynecologic cancer. Regardless of disease site, all patients describe a degree of compromise in physical and social functioning, as well as sexual dysfunction. Specific symptoms which are most bothersome for patients vary by disease site, such as bowel concerns predominating for endometrial cancer patients, while body image is more concerning for cervical cancer patients. CONCLUSIONS: Several quality of life concerns exist for women treated with radiation therapy for gynecologic malignancies. Significant overlap exists in the QOL issues affecting these patients. Whether to combine or separate surveys by diagnosis, treatment type, age, or time point should be explored further. Assessing patients' psychological, emotional, and physical concerns helps to understand long-term adjustment, enabling incorporation of these domains into future trials that will ultimately improve patient well-being.

Prior-cancer diagnosis in men with nonmetastatic prostate cancer and the risk of prostate-cancer-specific and all-cause mortality.

Purpose. We evaluated the impact a prior cancer diagnosis had on the risk of prostate-cancer-specific mortality (PCSM) and all-cause mortality (ACM) in men with PC. Methods. Using the SEER data registry, 166,104 men (median age: 66) diagnosed with PC between 2004 and 2007 comprised the study cohort. Competing risks and Cox regression were used to evaluate whether a prior cancer diagnosis impacted the risk of PCSM and ACM adjusting for known prognostic factors PSA level, age at and year of diagnosis, race, and whether PC treatment was curative, noncurative, or active surveillance (AS)/watchful waiting (WW). Results. At a median followup of 2.75 years, 12,453 men died: 3,809 (30.6%) from PC. Men with a prior cancer were followed longer, had GS 8 to 10 PC more often, and underwent WW/AS more frequently (P < 0.001). Despite these differences that should increase the risk of PCSM, the adjusted risk of PCSM was significantly decreased (AHR: 0.66 (95% CI: (0.45, 0.97); P = 0.033), while the risk of ACM was increased (AHR: 2.92 (95% CI: 2.64, 3.23); P < 0.001) in men with a prior cancer suggesting that competing risks accounted for the reduction in the risk of PCSM. Conclusion. An assessment of the impact that a prior cancer has on life expectancy is needed at the time of PC diagnosis to determine whether curative treatment for unfavorable-risk PC versus AS is appropriate.

Long-term adjustment of survivors of ovarian cancer treated for advanced-stage disease.

This study described the long-term adjustment of 42 ovarian cancer survivors diagnosed with advanced-stage disease with no evidence of recurrence, a mean of 6.1 years postdiagnosis. 64% of survivors' mental health was at or above the norm of medical outpatients (Mental Health Inventory-17). No patients reported post-traumatic stress disorder at a diagnosable level (Post-Traumatic Stress Disorder (PTSD) Checklist-Civilian). The majority of survivors (> or = 75%) reported a positive impact of cancer on their lives (Impact of Cancer Scale) and excellent social support (Medical Outcomes Study Social Support Survey). However, a subset of survivors reported needing more help than was received regarding emotional problems (28.9%).

Comparison of the quality of life of early and advanced stage ovarian cancer survivors.

OBJECTIVE: The objective of this study was to compare the long-term adjustment and QOL of early and advanced stage ovarian cancer survivors (OCS). METHODS: Early and advanced OCS >3 years from diagnosis with no evidence of recurrent cancer were interviewed. The following surveys were administered: EORTC QLQ-C30 (overall QOL) and QLQ-OV28 (ovarian specific issues), MHI-17 (anxiety, depression and global well-being), CALGB sexual functioning, FACT Fatigue, Beck's Hopelessness Scale, Fear of Recurrence (FOR), PCL-C post-traumatic stress disorder (PTSD), Unmet Needs, FACT-Spirituality (FACT-Sp), complementary therapy (CAM use), and MOS Social Support Survey (MOS). The results of the surveys were compared between the early and advanced stage groups. RESULTS: 42 advanced and 58 early stage patients were interviewed. The majority of survivors scored above the medical outpatient norm for emotional status (71% of early stage and 64% of advanced stage survivors). Overall QOL, fatigue, hopelessness, spirituality, social support, degree to which unmet needs were met and use of complementary therapy, did not differ between the two groups. No advanced stage OCS had diagnosable PTSD scores, while 6.9% of early stage survivors had scores indicative of PTSD. Decreased sexual interest attributed to cancer and anxiety when getting CA-125 testing were of concern for both groups. OCS used on average 5 CAM to improve their QOL. CONCLUSION: Regardless of staging, OCS experience similarly overall positive QOL and adjustment, though PTSD, sexual problems and fear of recurrence are still important for some survivors.