External beam management of stage I and II uterine cancer.

This review article highlights the treatment paradigms for early-stage endometrial cancer with a focus on the role of external beam radiation therapy. We aim for this review to serve as an introductory resource for gynecological oncologists, radiation oncologists, medical oncologists, and other practitioners to understand the treatments for this disease. The main treatment of endometrial cancer is surgical resection with total hysterectomy and bilateral salpingo-oophorectomy. The benefit of adjuvant radiation after surgery is primarily to prevent local recurrence. Patients with low risk of recurrence can be observed post-operatively. Vaginal cuff brachytherapy, which has been shown to be equally effective as pelvic radiation with fewer side effects, is typically recommended for high-intermediate risk patients (with characteristics such as lymphovascular space invasion, high grade, or significant myometrial invasion). In the adjuvant setting, pelvic radiation therapy is reserved for patients who have deeply invasive stage I grade 2 or 3 disease, stage II disease, and non-endometrioid histologies. In patients who are not medically operable, definitive treatment consists of brachytherapy±pelvic external beam radiation therapy. We have highlighted the main acute and long-term side effects of pelvic radiation as well as recommendations for symptom management and summarized promising evidence showing improved rates of toxicities with more conformal radiation techniques.

Executive summary of the American Radium Society appropriate use criteria for management of uterine clear cell and serous carcinomas.

BACKGROUND: Uterine clear cell and serous carcinomas have a high propensity for locoregional and distant spread, tend to be more advanced at presentation, and carry a higher risk of recurrence and death than endometrioid cancers. Limited prospective data exist to guide evidence-based management of these rare malignancies. OBJECTIVE: The American Radium Society sought to summarize evidence-based guidelines developed by a multidisciplinary expert panel that help to guide the management of uterine clear cell and serous carcinomas. METHODS: The American Radium Society Appropriate Use Criteria presented in this manuscript were developed by a multidisciplinary expert panel using an extensive analysis of current published literature from peer-reviewed journals. A well-established methodology (modified Delphi) was used to rate the appropriate use of diagnostic and therapeutic procedures for the management of uterine clear cell and serous carcinomas. RESULTS: The primary treatment for non-metastatic uterine clear cell and serous carcinomas is complete surgical staging, with total hysterectomy, salpingo-oophorectomy, omentectomy, and lymph node staging. Even in early-stage disease, patients with uterine clear cell and serous carcinomas have a worse prognosis than those with type I endometrial cancers, warranting consideration for adjuvant therapy regardless of the stage. Given the aggressive nature of these malignancies, and until further research determines the most appropriate adjuvant therapy, it may be reasonable to counsel patients about combined-modality treatment with systemic chemotherapy and radiotherapy. CONCLUSION: Patients diagnosed with uterine clear cell and serous carcinomas should undergo complete surgical staging. Multimodal adjuvant therapies should be considered in the treatment of both early-stage and advanced-stage disease. Further prospective studies or multi-institutional retrospective studies are warranted to determine optimal sequencing of therapy and appropriate management of patients based on their unique risk factors. Long-term surveillance is indicated due to the high risk of locoregional and distant recurrence.

Feasibility of function-guided lung treatment planning with parametric response mapping.

PURPOSE: Recent advancements in functional lung imaging have been developed to improve clinicians' knowledge of patient pulmonary condition prior to treatment. Ultimately, it may be possible to employ these functional imaging modalities to tailor radiation treatment plans to optimize patient outcome and mitigate pulmonary complications. Parametric response mapping (PRM) is a computed tomography (CT)-based functional lung imaging method that utilizes a voxel-wise image analysis technique to classify lung abnormality phenotypes, and has previously been shown to be effective at assessing lung complication risk in diagnostic applications. The purpose of this work was to demonstrate the implementation of PRM guidance in radiotherapy treatment planning. METHODS AND MATERIALS: A retrospective study was performed with 18 lung cancer patients to test the incorporation of PRM into a radiotherapy planning workflow. Paired inspiration/expiration pretreatment CT scans were acquired and PRM analysis was utilized to classify each voxel as normal, parenchymal disease, small airway disease, and emphysema. Density maps were generated for each PRM classification to contour high density regions of pulmonary abnormalities. Conventional volumetric-modulated arc therapy and PRM-guided treatment plans were designed for each patient. RESULTS: PRM guidance was successfully implemented into the treatment planning process. The inclusion of PRM priorities resulted in statistically significant (p < 0.05) improvements to the V20Gy within the PRM avoidance contours. On average, reductions of 5.4% in the V20Gy(%) were found. The PRM-guided treatment plans did not significantly increase the dose to the organs at risk or result in insufficient planning target volume coverage, but did increase plan complexity. CONCLUSIONS: PRM guidance was successfully implemented into a treatment planning workflow and shown to be effective for dose redistribution within the lung. This work has provided a framework for the potential clinical implementation of PRM-guided treatment planning.

Executive summary of the American Radium Society® Appropriate Use Criteria for management of uterine carcinosarcoma.

OBJECTIVE: Uterine carcinosarcomas (UCS) represent a rare but aggressive subset of endometrial cancers, comprising <5% of uterine malignancies. To date, limited prospective trials exist from which evidence-based management of this rare malignancy can be developed. METHODS: The American Radium Society Appropriate Use Criteria presented in this manuscript are evidence-based guidelines developed by a multidisciplinary expert panel for management of women with UCS. An extensive analysis of current medical literature from peer-reviewed journals was performed. A well-established methodology (modified Delphi) was used to rate the appropriate use of imaging and treatment procedures for the management of UCS. These guidelines are intended for the use of all practitioners who desire information about the management of UCS. RESULTS: The majority of patients with UCS will present with advanced extra uterine disease, with 10% presenting with metastatic disease. They have worse survival outcomes when compared to uterine high-grade endometrioid adenocarcinomas. The primary treatment for non-metastatic UCS is complete surgical staging with total hysterectomy, salpingo-oophorectomy and lymph node staging. Patients with UCS appear to benefit from adjuvant multimodality therapy to reduce the chance of tumor recurrence with the potential to improve overall survival. CONCLUSION: Women diagnosed with uterine UCS should undergo complete surgical staging. Adjuvant multimodality therapies should be considered in the treatment of both early- and advanced stage patients. Long-term surveillance is indicated as many of these women may recur. Prospective clinical studies of women with UCS are necessary for optimal management.

A utility approach to individualized optimal dose selection using biomarkers.

In many settings, including oncology, increasing the dose of treatment results in both increased efficacy and toxicity. With the increasing availability of validated biomarkers and prediction models, there is the potential for individualized dosing based on patient specific factors. We consider the setting where there is an existing dataset of patients treated with heterogenous doses and including binary efficacy and toxicity outcomes and patient factors such as clinical features and biomarkers. The goal is to analyze the data to estimate an optimal dose for each (future) patient based on their clinical features and biomarkers. We propose an optimal individualized dose finding rule by maximizing utility functions for individual patients while limiting the rate of toxicity. The utility is defined as a weighted combination of efficacy and toxicity probabilities. This approach maximizes overall efficacy at a prespecified constraint on overall toxicity. We model the binary efficacy and toxicity outcomes using logistic regression with dose, biomarkers and dose-biomarker interactions. To incorporate the large number of potential parameters, we use the LASSO method. We additionally constrain the dose effect to be non-negative for both efficacy and toxicity for all patients. Simulation studies show that the utility approach combined with any of the modeling methods can improve efficacy without increasing toxicity relative to fixed dosing. The proposed methods are illustrated using a dataset of patients with lung cancer treated with radiation therapy.

Isolation and Profiling of Circulating Tumor-Associated Exosomes Using Extracellular Vesicular Lipid-Protein Binding Affinity Based Microfluidic Device.

Extracellular vesicles (EVs) are emerging as a potential diagnostic test for cancer. Owing to the recent advances in microfluidics, on-chip EV isolation is showing promise with respect to improved recovery rates, smaller necessary sample volumes, and shorter processing times than ultracentrifugation. Immunoaffinity-based microfluidic EV isolation using anti-CD63 is widely used; however, anti-CD63 is not specific to cancer-EVs, and some cancers secrete EVs with low expression of CD63. Alternatively, phosphatidylserine (PS), usually expressed in the inner leaflet of the lipid bilayer of the cells, is shown to be expressed on the outer surface of cancer-associated EVs. A new exosome isolation microfluidic device (new ExoChip), conjugated with a PS-specific protein, to isolate cancer-associated exosomes from plasma, is presented. The device achieves 90% capture efficiency for cancer cell exosomes compared to 38% for healthy exosomes and isolates 35% more A549-derived exosomes than an anti-CD63-conjugated device. Immobilized exosomes are then easily released using Ca2+ chelation. The recovered exosomes from clinical samples are characterized by electron microscopy and western-blot analysis, revealing exosomal shapes and exosomal protein expressions. The new ExoChip facilitates the isolation of a specific subset of exosomes, allowing the exploration of the undiscovered roles of exosomes in cancer progression and metastasis.

Multiplex isolation and profiling of extracellular vesicles using a microfluidic DICE device.

Profiling of extracellular vesicles (EVs) is an emerging area in the field of liquid biopsies because of their innate significance in diseases and abundant information reflecting disease status. However, unbiased enrichment of EVs and thorough profiling of EVs is challenging. In this paper, we present a simple strategy to immobilize and analyze EVs for multiple markers on a single microfluidic device and perform differentiated immunostaining-based characterization of extracellular vesicles (DICE). This device, composed of four quadrants with a single inlet, captures biotinylated EVs efficiently and facilitates multiplexed immunostaining to profile their extracellular proteins, allowing for a multiplexed approach for non-invasive cancer diagnostics in the future. From controlled sample experiments using cancer cell line derived EVs and specific fluorescence staining with lipophilic dyes, we identified that the DICE device is capable of isolating biotinylated EVs with 84.4% immobilization efficiency. We extended our study to profile EVs of 9 clinical samples from non-small cell lung cancer (NSCLC) patients and healthy donors and found that the DICE device successfully facilitates immunofluorescent staining for both the NSCLC patients and the healthy control. This versatile and simple method to profile EVs could be extended to EVs of any biological origin, promoting discoveries of the role of EVs in disease diagnostics and monitoring.

A prediction model for early death in non-small cell lung cancer patients following curative-intent chemoradiotherapy.

BACKGROUND: Early death after a treatment can be seen as a therapeutic failure. Accurate prediction of patients at risk for early mortality is crucial to avoid unnecessary harm and reducing costs. The goal of our work is two-fold: first, to evaluate the performance of a previously published model for early death in our cohorts. Second, to develop a prognostic model for early death prediction following radiotherapy. MATERIAL AND METHODS: Patients with NSCLC treated with chemoradiotherapy or radiotherapy alone were included in this study. Four different cohorts from different countries were available for this work (N = 1540). The previous model used age, gender, performance status, tumor stage, income deprivation, no previous treatment given (yes/no) and body mass index to make predictions. A random forest model was developed by learning on the Maastro cohort (N = 698). The new model used performance status, age, gender, T and N stage, total tumor volume (cc), total tumor dose (Gy) and chemotherapy timing (none, sequential, concurrent) to make predictions. Death within 4 months of receiving the first radiotherapy fraction was used as the outcome. RESULTS: Early death rates ranged from 6 to 11% within the four cohorts. The previous model performed with AUC values ranging from 0.54 to 0.64 on the validation cohorts. Our newly developed model had improved AUC values ranging from 0.62 to 0.71 on the validation cohorts. CONCLUSIONS: Using advanced machine learning methods and informative variables, prognostic models for early mortality can be developed. Development of accurate prognostic tools for early mortality is important to inform patients about treatment options and optimize care.

Variation in care in concurrent chemotherapy administration during radiation for locally advanced cervical cancer.

BACKGROUND: To evaluate the usage of concurrent chemo-radiotherapy (C-CRT) for the treatment of locally advanced cervical cancer. METHODS: Patients with locally invasive cervical carcinoma diagnosed between January 1, 2004 and December 31, 2012 from the National Cancer Database (NCDB) were included. Outcomes for patients undergoing radiation therapy only, 'RT alone' group were compared to those receiving chemotherapy concurrent with radiation 'C-CRT group'. Trends in utilization of C-CRT and factors associated with the deviation from standard of care were explored. Lastly, the effect of hospital volume on utilization of C-CRT was investigated. RESULTS: A total of 18,164 patients undergoing definitive radiation therapy were available for analysis. Utilization of C-CRT increased from 72.4% in 2004 to 84.3% in 2012 (p-trend<0.001). After adjusting for patient, tumor, and treatment factors, a multivariable logistic regression model revealed increasing age, African-American race, Charlson-comorbidity index of ≥2, Medicaid insurance status, uninsured status, and Stage I disease were each independently associated with the lack of C-CRT. After adjusting for patient characteristics, low volume hospitals were noted to have overall significantly lower rates and greater variation in C-CRT administration. Patients in 'RT alone' group had an overall worse survival rate (adjusted-HR 1.47, 95%CI 1.4-1.56). CONCLUSION: Rates of C-CRT administration varied significantly across hospitals in the United States. Hospitals with a high case volume had higher rates and more consistent patterns of C-CRT administration. Furthermore, we identified independent factors, all of which represent noteworthy health disparities, associated with lower rates of C-CRT administration.

ACR Appropriateness Criteria® Adjuvant Management of Early-Stage Endometrial Cancer.

These consensus guidelines on adjuvant radiotherapy for early-stage endometrial cancer were developed from an expert panel convened by the American College of Radiology. The American College of Radiology Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method; and Grading of Recommendations Assessment, Development, and Evaluation, or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. After a review of the published literature, the panel voted on three variants to establish best practices for the utilization of imaging, radiotherapy, and chemotherapy after primary surgery for early-stage endometrial cancer.

ACR Appropriateness Criteria® Adjuvant Therapy in Vulvar Cancer.

These American College of Radiology consensus guidelines were formed from an expert panel on the appropriate use of adjuvant therapy in vulvar cancer after primary treatment with surgery. The American College of Radiology Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. The panel reviewed the pertinent literature in vulvar cancer and voted on three variants to establish appropriate use of imaging, adjuvant radiation, including dose, fields, and technique, as well as adjuvant chemotherapy. This report will aid clinicians in selecting appropriate patients for adjuvant treatment and will provide guidelines for the optimal delivery of adjuvant radiation therapy and chemotherapy.

Gender differences in time spent on parenting and domestic responsibilities by high-achieving young physician-researchers.

BACKGROUND: Female physician-researchers do not achieve career success at the same rate as men. Differences in nonprofessional responsibilities may partially explain this gap. OBJECTIVE: To investigate the division of domestic labor by gender in a motivated group of early-career physician-researchers. DESIGN: Nationwide postal survey between 2010 and 2011. SETTING: United States. PARTICIPANTS: Physician recipients of National Institutes of Health K08 or K23 awards between 2006 and 2009 with active academic affiliation at the time of the survey. MEASUREMENTS: Time spent on parenting and domestic tasks was determined through self-report. Among married or partnered respondents with children, a linear regression model of time spent on domestic activities was constructed considering age, gender, race, specialty, MD or MD/PhD status, age of youngest child, number of children, work hours, K award type, and spousal employment. RESULTS: A 74% response rate was achieved, and 1049 respondents were academic physicians. Women were more likely than men to have spouses or domestic partners who were employed full-time (85.6% [95% CI, 82.7% to 89.2%] vs. 44.9% [CI, 40.8% to 49.8%]). Among married or partnered respondents with children, after adjustment for work hours, spousal employment, and other factors, women spent 8.5 more hours per week on domestic activities. In the subgroup with spouses or domestic partners who were employed full-time, women were more likely to take time off during disruptions of usual child care arrangements than men (42.6% [CI, 36.6% to 49.0%] vs. 12.4% [CI, 5.4% to 19.5%]). LIMITATIONS: Analyses relied on self-reported data. The study design did not enable investigation of the relationship between domestic activities and professional success. CONCLUSION: In this sample of career-oriented professionals, gender differences in domestic activities existed among those with children. Most men's spouses or domestic partners were not employed full-time, which contrasted sharply with the experiences of women. PRIMARY FUNDING SOURCE: National Institutes of Health.

Clinical implementation of MR-guided vaginal cylinder brachytherapy.

We present an institutional experience on the clinical implementation of magnetic resonance (MR)-guided vaginal brachytherapy using commercially available solid applicator models. To test the fidelity of solid applicator models to digitize vaginal cylinder applicators, three datasets were evaluated. The first included 15 patients who were simulated with CT alone. Next, a water phantom was used to evaluate vaginal cylinders ranging from 20 to 35 mm in diameter with CT and MR. Finally, three patients undergoing HDR brachytherapy with vaginal cylinders that were simulated with both CT and MR were evaluated. In these assessments, the solid applicator models were aligned based on the outline of the applicators on the corresponding volumetric image, and deviations between the central source positions defined based on X-ray markers (on CT) and solid applicator models (on CT and MR), and the percent dose difference between select reference points were calculated. The mean central source deviation defined based on X-ray markers (on CT) and solid applicator models (on CT and MR) for the 15-patient cohort, the phantom, and the 3-patient cohort is 0.6 mm, 0.6 mm, and 1.2 mm, respectively. The average absolute percent dose difference for the bladder, rectum, prescription, and inferior reference points were 2.2%, 2.3%, 2.2%, and 2.4%, respectively, for the 15 patient cohort. For the phantom study, the average, absolute percent dose difference for the prescription and inferior reference points are 2.0% and 2.1% for the CT, 2.3% and 2.2% for the T1W, and 2.8% and 3.0% for the T2W images. For the three patient cohort, the average absolute percent dose difference for the bladder, rectum, prescription, and inferior reference points are 2.9%, 2.6%, 3.0%, and 4.2% for the CT, 6.5%, 1.6%, 2.5%, and 4.7% for the T1W, and 6.0%, 7.4%, 2.6, and 2.0% for the T2W images. Based on the current study, aligning the applicator model to MR images provides a practical, efficient approach to perform MR-based brachytherapy planning.

Primary peritoneal clear cell carcinoma treated with IMRT and interstitial HDR brachytherapy: a case report.

Primary peritoneal clear cell carcinoma (PP-CCC), which is a rare tumor with poor prognosis, is typically managed with surgery and/or chemotherapy. We present a unique treatment approach for a patient with a pelvic PP-CCC, consisting of postchemotherapy intensity-modulated radiation therapy (IMRT) followed by interstitial high-dose-rate (HDR) brachytherapy. A 54-year-old female with an inoperable pelvic-supravaginal 5.6 cm T3N0M0 PP-CCC tumor underwent treatment with 6 cycles of carboplatin and taxol chemotherapy. Postchemotherapy PET/CT scan revealed a residual 3.3 cm tumor. The patient underwent CT and MR planning simulation, and was treated with 50 Gy to the primary tumor and 45 Gy to the pelvis including the pelvic lymph nodes, using IMRT to spare bowel. Subsequently, the patient was treated with an interstitial HDR brachytherapy implant, planned using both CT and MR scans. A total dose of 15 Gy in 5 Gy fractions over two days was delivered with Ir-192 HDR brachytherapy. The total prescribed equivalent 2 Gy dose (EQD2) to the HDR planning target volume (PTV) from both the EBRT and HDR treatments ranged between 63 and 68.8 Gy2 due to differential dosing of the primary and pelvic targets. The patient tolerated radiotherapy well, except for mild diarrhea not requiring medication. There was no patient-reported acute toxicity one month following the radiotherapy course. At four months following adjuvant radiation therapy, the patient had near complete resolution of local tumor on PET/CT without any radiation-associated toxicity. However, the patient was noted to have metastatic disease outside of the radiation field, specifically lesions in the liver and bone. This case report illustrates the feasibility of the treatment of a pelvic PP-CCC with IMRT followed by interstitial HDR brachytherapy boost, which resulted in near complete local tumor response without significant morbidity.

Selective Personalized RadioImmunotherapy for Locally Advanced Non-Small-Cell Lung Cancer Trial (SPRINT).

PURPOSE: Standard therapy for locally advanced non-small-cell lung cancer (LA-NSCLC) is concurrent chemoradiotherapy followed by adjuvant durvalumab. For biomarker-selected patients with LA-NSCLC, we hypothesized that sequential pembrolizumab and risk-adapted radiotherapy, without chemotherapy, would be well-tolerated and effective. METHODS: Patients with stage III NSCLC or unresectable stage II NSCLC and an Eastern Cooperative Oncology Group performance status of 0-1 were eligible for this trial. Patients with a PD-L1 tumor proportion score (TPS) of ≥50% received three cycles of induction pembrolizumab (200 mg, once every 21 days), followed by a 20-fraction course of risk-adapted thoracic radiotherapy (55 Gy delivered to tumors or lymph nodes with metabolic volume exceeding 20 cc, 48 Gy delivered to smaller lesions), followed by consolidation pembrolizumab to complete a 1-year treatment course. The primary study end point was 1-year progression-free survival (PFS). Secondary end points included response rates after induction pembrolizumab, overall survival (OS), and adverse events. RESULTS: Twenty-five patients with a PD-L1 TPS of ≥50% were enrolled. The median age was 71, most patients (88%) had stage IIIA or IIIB disease, and the median PD-L1 TPS was 75%. Two patients developed disease progression during induction pembrolizumab, and two patients discontinued pembrolizumab after one infusion because of immune-related adverse events. Using RECIST criteria, 12 patients (48%) exhibited a partial or complete response after induction pembrolizumab. Twenty-four patients (96%) received definitive thoracic radiotherapy. The 1-year PFS rate is 76%, satisfying our efficacy objective. One- and 2-year OS rates are 92% and 76%, respectively. The most common grade 3 adverse events were colitis (n = 2, 8%) and esophagitis (n = 2, 8%), and no higher-grade treatment-related adverse events have occurred. CONCLUSION: Pembrolizumab and risk-adapted radiotherapy, without chemotherapy, are a promising treatment approach for patients with LA-NSCLC with a PD-L1 TPS of ≥50%.

Circulating tumor cells reveal early predictors of disease progression in patients with stage III NSCLC undergoing chemoradiation and immunotherapy.

Circulating tumor cells (CTCs) are early signs of metastasis and can be used to monitor disease progression well before radiological detection by imaging. Using an ultrasensitive graphene oxide microfluidic chip nanotechnology built with graphene oxide sheets, we were able to demonstrate that CTCs can be specifically isolated and molecularly characterized to predict future progression in patients with stage III non-small cell lung cancer (NSCLC). We analyzed CTCs from 26 patients at six time points throughout the treatment course of chemoradiation followed by immune checkpoint inhibitor immunotherapy. We observed that CTCs decreased significantly during treatment, where a larger decrease in CTCs predicted a significantly longer progression-free survival time. Durvalumab-treated patients who have future progression were observed to have sustained higher programmed death ligand 1+ CTCs compared to stable patients. Gene expression profiling revealed phenotypically aggressive CTCs during chemoradiation. By using emerging innovative bioengineering approaches, we successfully show that CTCs are potential biomarkers to monitor and predict patient outcomes in patients with stage III NSCLC.

Predictors of Early Hospice or Death in Patients With Inoperable Lung Cancer Treated With Curative Intent.

INTRODUCTION: Treatment for inoperable stage II to III non-small cell lung cancer (NSCLC) involves chemo-radiotherapy (CRT). However, some patients transition to hospice or die early during their treatment course. We present a model to prognosticate early poor outcomes in NSCLC patients treated with curative-intent CRT. METHODS AND MATERIALS: Across a statewide consortium, data was prospectively collected on stage II to III NSCLC patients who received CRT between 2012 and 2019. Early poor outcomes included hospice enrollment or death within 3 months of completing CRT. Logistic regression models were used to assess predictors in prognostic models. LASSO regression with multiple imputation were used to build a final multivariate model, accounting for missing covariates. RESULTS: Of the 2267 included patients, 128 experienced early poor outcomes. Mean age was 71 years and 59% received concurrent chemotherapy. The best predictive model, created parsimoniously from statistically significant univariate predictors, included age, ECOG, planning target volume (PTV), mean heart dose, pretreatment lack of energy, and cough. The estimated area under the ROC curve for this multivariable model was 0.71, with a negative predictive value of 95%, specificity of 97%, positive predictive value of 23%, and sensitivity of 16% at a predicted risk threshold of 20%. CONCLUSIONS: This multivariate model identified a combination of clinical variables and patient reported factors that may identify individuals with inoperable NSCLC undergoing curative intent chemo-radiotherapy who are at higher risk for early poor outcomes.

Factors associated with acute esophagitis during radiation therapy for lung cancer.

INTRODUCTION: Limiting acute esophagitis remains a clinical challenge during the treatment of locally advanced non-small cell lung cancer (NSCLC). METHODS: Demographic, dosimetric, and acute toxicity data were prospectively collected for patients undergoing definitive radiation therapy +/- chemotherapy for stage II-III NSCLC from 2012 to 2022 across a statewide consortium. Logistic regression models were used to characterize the risk of grade 2 + and 3 + esophagitis as a function of dosimetric and clinical covariates. Multivariate regression models were fitted to predict the 50 % risk of grade 2 esophagitis and 3 % risk of grade 3 esophagitis. RESULTS: Of 1760 patients, 84.2 % had stage III disease and 85.3 % received concurrent chemotherapy. 79.2 % of patients had an ECOG performance status ≤ 1. Overall rates of acute grade 2 + and 3 + esophagitis were 48.4 % and 2.2 %, respectively. On multivariate analyses, performance status, mean esophageal dose (MED) and minimum dose to the 2 cc of esophagus receiving the highest dose (D2cc) were significantly associated with grade 2 + and 3 + esophagitis. Concurrent chemotherapy was associated with grade 2 + but not grade 3 + esophagitis. For all patients, MED of 29 Gy and D2cc of 61 Gy corresponded to a 3 % risk of acute grade 3 + esophagitis. For patients receiving chemotherapy, MED of 22 Gy and D2cc of 50 Gy corresponded to a 50 % risk of acute grade 2 + esophagitis. CONCLUSIONS: Performance status, concurrent chemotherapy, MED and D2cc are associated with acute esophagitis during definitive treatment of NSCLC. Models that quantitatively account for these factors can be useful in individualizing radiation plans.

Clinical review of physical activity and functional considerations in head and neck cancer patients.

Patients facing head and neck cancer treatment are profoundly vulnerable to physiologic and functional disability. Exercise and nutrition have been shown to have many benefits in cancer patients, but much of this work has been performed in groups of breast, colon, and prostate cancer patients. Limited data exists regarding the role of exercise and nutrition in the management of head and neck cancer patients given their unique set of challenges relating to the cancer as well as its treatment. In this paper, we review the existing literature about general or recreational physical exercise as well as nutrition in this patient population as it pertains to lean muscle body composition, functional well-being, and overall quality of life.

Pelvic Recovery After Endometrial Cancer Treatment: Patient-Reported Outcomes and MRI Findings.

RATIONALE AND OBJECTIVES: Most women with endometrial cancer (EC) have an excellent prognosis and may be cured. However, treatment-related pelvic functional impacts may affect long-term quality of life. To better understand these concerns, we explored correlations between patient-reported outcomes and pelvic magnetic resonance imaging (MRI) features in women treated for EC. MATERIALS AND METHODS: Women with histologic diagnosis of EC were consented preoperatively and completed the validated Female Sexual Function Index (FSFI) and Pelvic Floor Dysfunction Index (PFDI) questionnaires at preoperative, 6-week, and 6-month follow-up visits. Pelvic MRIs with dynamic pelvic floor sequences were performed at 6 weeks and 6 months. RESULTS: A total of 33 women participated in this prospective pilot study. Only 53.7% had been asked about sexual function by providers while 92.4% thought they should have been. Sexual function became more important to women over time. Baseline FSFI was low, declined at 6 weeks, and climbed above baseline at 6 months. Hyperintense vaginal wall signal on T2-weighted images (10.9 vs. 4.8, p = .002) and intact Kegel function (9.8 vs. 4.8, p = .03) were associated with higher FSFI. PFDI scores trended toward improved pelvic floor function over time. Pelvic adhesions on MRI were associated with better pelvic floor function (23.0 vs. 54.9, p = .003). Urethral hypermobility (48.4 vs. 21.7, p = .01), cystocele (65.6 vs. 24.8, p < .0001), and rectocele (58.8 vs. 18.8, p < .0001) predicted worse pelvic floor function. CONCLUSION: Use of pelvic MRI to quantify anatomic and tissue changes may facilitate risk stratification and response assessment for pelvic floor and sexual dysfunction. Patients articulated the need for attention to these outcomes during EC treatment.