Stability and reproducibility comparisons between deep inspiration breath-hold techniques for left-sided breast cancer patients: A prospective study.

PURPOSE: Deep inspiration breath-hold (DIBH) is crucial in reducing the lung and cardiac dose for treatment of left-sided breast cancer. We compared the stability and reproducibility of two DIBH techniques: Active Breathing Coordinator (ABC) and VisionRT (VRT). MATERIALS AND METHODS: We examined intra- and inter-fraction positional variation of the left lung. Eight left-sided breast cancer patients were monitored with electronic portal imaging during breath-hold (BH) at every fraction. For each patient, half of the fractions were treated using ABC and the other half with VRT, with an equal amount starting with either ABC or VRT. The lung in each portal image was delineated, and the variation of its area was evaluated. Intrafraction stability was evaluated as the mean coefficient of variation (CV) of the lung area for the supraclavicular (SCV) and left lateral (LLat) field over the course of treatment. Reproducibility was the CV for the first image of each fraction. Daily session time and total imaging monitor units (MU) used in patient positioning were recorded. RESULTS: The mean intrafraction stability across all patients for the LLat field was 1.3 ± 0.7% and 1.5 ± 0.9% for VRT and ABC, respectively. Similarly, this was 1.5 ± 0.7% and 1.6 ± 0.8% for VRT and ABC, respectively, for the SCV field. The mean interfraction reproducibility for the LLat field was 11.0 ± 3.4% and 14.9 ± 6.0% for VRT and ABC, respectively. Similarly, this was 13.0 ± 2.5% and 14.8 ± 9% for VRT and ABC, respectively, for the SCV. No difference was observed in the number of verification images required for either technique. CONCLUSIONS: The stability and reproducibility were found to be comparable between ABC and VRT. ABC can have larger interfractional variation with less feedback to the treating therapist compared to VRT as shown in the increase in geometric misses at the matchline.

Correlating Quantitative Para-Aortic Lymph Node Computed Tomography Parameters With Fluorodeoxyglucose Positron Emission Tomography for Cervical Cancer Staging: Possible Solution for Resource Constrained Countries.

OBJECTIVE: The aim of the study was to determine the most accurate quantitative morphological parameters on computed tomography (CT) that correlate with fluorodeoxyglucose (FDG)-avid para-aortic nodes (PANs) in patients with cervical cancer. METHODS: A single-institution retrospective evaluation was performed of women with cervical cancer who underwent pretreatment positron emission tomography (PET)/CT and radiotherapy therapy planning CT between 2009 and 2020. A node-by-node correlation between pretreatment CT and PET/CT was performed for the reference standard of FDG avidity for short- and long-axis diameters, volume, and long-/short-axis ratio (L/S). The FDG-avid PANs were defined as PET-positive and non-FDG-avid PANs from patients without PET-determined PAN metastasis were defined as PET negative. Area under the receiver operator curve was calculated to access diagnostic accuracy of the different quantitative parameters. RESULTS: A total of 94 women (mean age ± standard deviation, 52 ± 13 years) with cervical cancer were included. Forty-seven patients had PET-positive PANs (181 PET-positive PANs) and 47 patients had no PET-positive PANs (141 PET-negative PANs). The area under the receiver operator curve for volume (0.945) was greater ( P < 0.001) than that of short axis (0.895), long axis (0.885), and L/S (0.583). At a specificity set point of 0.90 (127/141 PANs), the cutoff for volume was 0.443 cm 3 or greater (0.85 sensitivity [154/181 PANs]; 95% confidence interval, 0.83-0.93) and for short-axis diameter was 5.9 mm or greater (0.75 sensitivity [135/181 PANs]; 95% confidence interval, 0.68-0.81). CONCLUSIONS: Para-aortic lymph node volume demonstrated that improved node-by-node correlation between CT and PET/CT compared with short-axis diameter, long-axis diameter, and L/S and is an alternative to improve detection of PAN suspicious of metastatic diseases in locations without access to PET/CT.

Advances in management of locally advanced cervical cancer.

Globally, cervical cancer has the fourth highest cancer incidence and mortality in women. Cervical cancer is unique because it has effective prevention, screening, and treatment options. This review discusses the current cervical cancer advances with a focus on locally advanced cervical cancer. Topics discussed include diagnostic imaging principles, surgical management with adjuvant therapy and definitive concurrent chemoradiotherapy. Emphasis is given on current advances and future research directions in radiation therapy (RT) with an emphasis on three-dimensional brachytherapy, intensity-modulated RT, image-guided RT, proton RT and hyperthermia.

Multimodality Imaging of Uterine Cervical Malignancies.

OBJECTIVE. In this article, we provide an updated review on the role of imaging in initial staging, treatment monitoring, and follow-up of cervical cancer with a focus on the role of MRI and FDG PET/CT. In addition, the 2018 International Federation of Gynecology and Obstetrics staging system and its implication on management of cervical cancer are explored. CONCLUSION. Imaging plays a major role in treatment planning and as a prognostic indicator in patients with cervical cancer. MRI and PET/CT have complementary roles: MRI is essential for the local staging of the primary tumor, and PET/CT is the most useful modality for detecting regional nodal and distant metastases.

Value of Intratumoral Metabolic Heterogeneity and Quantitative 18F-FDG PET/CT Parameters in Predicting Prognosis for Patients With Cervical Cancer.

OBJECTIVE. The purpose of this study is to evaluate the prognostic value of quantitative metabolic parameters from pretreatment PET/CT scans of patients with squamous cell cervical cancer. MATERIALS AND METHODS. This retrospective study included 120 patients with biopsy-proven squamous cell carcinoma of the cervix who underwent FDG PET/CT for initial tumor staging. The primary tumor maximum standardized uptake value (SUVmax) and mean standardized uptake value (SUVmean), tumor glycolytic activity, metabolic tumor volume (MTV), and metabolic intratumoral heterogeneity index (calculated as the AUC for the cumulative standardized uptake value [SUV]-volume histogram [CSH] index) were obtained. Information on patient demographic characteristics and tumor staging were collected. Median follow-up was 27.5 months. Overall survival (OS) and progression-free survival (PFS) were calculated using a multivariate Cox proportional hazards regression model and log-rank (Mantel-Cox) test to generate Kaplan-Meier survival plots. RESULTS. The mean (± SD) age of the patients was 54.4 ± 13.1 years. Twenty-two patients had stage I disease; 58, stage II; 23, stage III; and 17, stage IV. Thirty-three patients died, 82 were living, and five were lost to follow-up and were censored; 29 patients had disease progression. The median survival was 74.9 months (95% CI, 63.6-86.9 months). A higher MTV was significantly associated with reduced OS in multivariate analysis (hazard ratio, 1.085; 95% CI, 1.036-1.136; p = 0.0005). A higher AUC-CSH index (denoting lower tumor heterogeneity) was significantly associated with increased OS (hazard ratio, 0.662; 95% CI, 0.448-0.979; p = 0.04) and PFS (hazard ratio, 0.683; 95% CI, 0.471-0.991; p = 0.045) in multivariate analysis. Kaplan-Meier survival analysis using the median value for MTV (61 mL) significantly predicted OS (p = 0.0009). CONCLUSION. Tumor heterogeneity on pretreatment PET/CT is associated with OS and PFS in patients with cervical cancer. MTV is significantly associated with OS.

Novel hyaluronan formulation for preventing acute skin reactions in breast during radiotherapy: a randomized clinical trial.

PURPOSE: We conducted a randomized, double-blind, vehicle-controlled clinical trial to investigate the use of a new proprietary hyaluronan (HA) formulation for the prevention of acute skin toxicity in breast cancer patients undergoing radiotherapy (RT). METHODS: Thirty women with breast cancer undergoing whole breast RT were enrolled. Each patient was randomly assigned to HA formulation (study cream, S) on the medial or lateral half of the irradiated breast and the control cream (placebo, P) on the other half. The primary endpoint was physician's evaluation of skin symptoms at week 5 during RT and week 2 post-RT. We also collected patients' independent assessment of skin after RT, patient's product preference, and an independent physician panel assessment of skin reactions based on photographs. RESULTS: Twenty-eight patients were evaluable. On physician's evaluation, there was no significant difference in radiation dermatitis between S and P and no overall preference to either cream at week 5 during or week 2 post-RT. More patients preferred S in evaluating skin appearance and skin reactions, but this did not reach statistical significance. Univariate analysis showed that physicians had an overall preference to the S cream at week 2 post-RT in patients with larger breasts. On the independent panel assessment, 3 reviewers saw no significant difference in radiation toxicity, whereas one reviewer reported better skin outcome with S cream at week 5. CONCLUSIONS: We found a nonstatistically significant patient preference but overall no significant radioprotective effects for this HA formulation compared with placebo except in patients with larger breasts. TRIAL REGISTRATION: The study was registered at www.clinicaltrials.gov (NCT02165605).

Role of Locoregional Treatment in Vulvar Cancer With Pelvic Lymph Node Metastases: Time to Reconsider FIGO Staging?

BACKGROUND: Vulvar cancer with pelvic nodal involvement is considered metastatic (M1) disease per AJCC staging. The role of definitive therapy and its resulting impact on survival have not been defined. PATIENTS AND METHODS: Patients with pelvic lymph node-positive vulvar cancer diagnosed in 2009 through 2015 were evaluated from the National Cancer Database. Patients with known distant metastatic disease were excluded. Logistic regression was used to evaluate use of surgery and radiation therapy (RT). Overall survival (OS) was evaluated with log-rank test and Cox proportional hazards modeling (multivariate analysis [MVA]). A 2-month conditional landmark analysis was performed. RESULTS: A total of 1,304 women met the inclusion criteria. Median follow-up was 38 months for survivors. Chemotherapy, RT, and surgery were used in 54%, 74%, and 62% of patients, respectively. Surgery was associated with prolonged OS (hazard ratio [HR], 0.58; P<.001) but had multiple significant differences in baseline characteristics compared with nonsurgical patients. In patients managed nonsurgically, RT was associated with prolonged OS (HR, 0.66; P=.019) in MVA. In patients undergoing surgery, RT was associated with better OS (3-year OS, 55% vs 48%; P=.033). Factors predicting use of RT were identified. MVA revealed that RT was associated with prolonged OS (HR, 0.75; P=.004). CONCLUSIONS: In this cohort of women with vulvar cancer and positive pelvic lymph nodes, use of RT was associated with prolonged survival in those who did not undergo surgery. Surgery followed by adjuvant RT was associated with prolonged survival compared with surgery alone.

Long-term Benefit of Tumor Volume-Directed Involved Field Radiation Therapy in the Management of Recurrent Ovarian Cancer.

OBJECTIVES: This study aimed to report on long-term effectiveness of involved field radiation therapy (IFRT) in the salvage of localized recurrent ovarian cancer (ROC). METHODS: A retrospective analysis of 27 patients with a diagnosis of epithelial ovarian cancer who received tumor volume-directed IFRT for localized extraperitoneal recurrences (either as consolidation after cytoreductive surgery (CRS) or as attempted salvage if unresectable) forms the basis of this report. All patients were heavily pretreated with multiple chemotherapy regimens. Involved field radiation therapy was primarily with external beam (median dose, 50.4 Gy). Local recurrence-free survival (LRFS) was defined as freedom from in-field recurrences and was considered as a measure of effectiveness of radiotherapy. Statistical analyses evaluated association between disease-free survival, overall survival, LRFS, and various prognostic factors. Comparison was also made with a similar but unmatched cohort with localized recurrences salvaged by additional chemotherapy instead of local therapies (NIFRT group). RESULTS: Of 27 patients, 17 had optimal CRS before RT. The actuarial survival at 5 and 10 years (in parenthesis) from date of radiation were LRFS (70% and 60%), overall survival (30% and 19%), and disease-free survival (33% and 20%). None of the NIFRT patients survived beyond 5 years from initiation of salvage chemotherapy. CONCLUSIONS: Long-term follow-up in this selected series confirmed the benefit of IFRT (±CRS) in localized ROC. Chemotherapy salvage in a similar NIFRT group was not equivalent, suggesting a role for locoregional therapies in selected patients with ROC.

Recurrence patterns and survival endpoints in women with stage II uterine endometrioid carcinoma: a multi-institution study.

OBJECTIVE: There is paucity of data in regard to prognostic factors and outcome of women with 2009 FIGO stage II disease. The objective of this study was to investigate prognostic factors, recurrence patterns and survival endpoints in this group of patients. METHODS: Data from four academic institutions were analyzed. 130 women were identified with 2009 FIGO stage II. All patients underwent hysterectomy, oophorectomy and lymph node evaluation with or without pelvic and paraaortic lymph node dissections and peritoneal cytology. The Kaplan-Meier approach and Cox regression analysis were used to estimate recurrence-free (RFS), disease-specific (DSS) and overall survival (OS). RESULTS: Median follow-up was 44months. 120 patients (92%) underwent simple hysterectomy, 78% had lymph node dissection and 95% had peritoneal cytology examination. 99 patients (76%) received adjuvant radiation treatment (RT). 5-year RFS, DSS and OS were 77%, 90%, and 72%, respectively. On multivariate analysis of RFS, adjuvant RT, the presence of lymphovascular space invasion (LVSI) and high tumor grades were significant predictors. For DSS, LVSI and high tumor grades were significant predictors while older age and high tumor grade were the only predictors of OS. CONCLUSIONS: In this multi-institutional study, disease-specific survival for women with FIGO stage II uterine endometrioid carcinoma is excellent. High tumor grade, lymphovascular space invasion, adjuvant radiation treatment and old age are important prognostic factors. There was no significant difference in the outcome between patients who received vaginal cuff brachytherapy compared to those who received pelvic external beam radiation treatment.

Para-aortic nodal metastases in cervical cancer: a blind spot in the International Federation of Gynecology and Obstetrics staging system: current diagnosis and management.

In cervical cancer, para-aortic nodal (PALN) metastases at presentation is a strong indicator of poor prognosis. Despite this, International Federation of Gynecology and Obstetrics staging system does not require evaluation of lymph node involvement and does not incorporate clinically detected PALN into the staging system. In the USA, despite screening, a significant number of women still present at an advanced stage often with nodal metastases. While the presence of PALN metastases often indicates occult systemic disease, it is possible with modern therapies to provide long-term control of disease in a percentage of patients. We review the epidemiology, diagnosis and treatment of PALN metastases in cervical cancer outlining advances in modern imaging and combined modality therapies (surgery, chemotherapy and radiation therapy).

Magnetic Resonance Spectroscopy for Cervical Cancer: Review and Potential Prognostic Applications.

This review article investigates the utilization of MRS in the setting of cervical cancer. A variety of different techniques have been used in this space including single-voxel techniques such as point-resolved spectroscopy (PRESS) and stimulated echo acquisition mode spectroscopy (STEAM). Furthermore, the experimental parameters for these acquisitions including field strength, repetition times (TR), and echo times (TE) vary greatly. This study critically examines eleven MRS studies that focus on cervical cancer. Out of the eleven studies, ten studies utilized PRESS acquisition, while the remaining study used STEAM acquisition. These studies generally showed that the choline signal is altered in cervical cancer (4/11 studies), the lipid signal is generally increased in cervical cancer or the lipid distribution is changed (5/11 studies), and that diffusion-weighted imaging (DWI) can quantitatively detect lower apparent diffusion coefficient (ADC) values in cervical cancer (2/11 studies). Two studies also investigated the role of MRS for monitoring treatment response and demonstrated mixed results regarding choline signal, and one of these studies showed increased lipid signal for non-responders. There are several new MRS technologies that have yet to be implemented for cervical cancer including advanced spectroscopic imaging and artificial intelligence, and those technologies are also discussed in the article.

Predicting treatment plan approval probability for high-dose-rate brachytherapy of cervical cancer using adversarial deep learning.

Objective.Predicting the probability of having the plan approved by the physician is important for automatic treatment planning. Driven by the mathematical foundation of deep learning that can use a deep neural network to represent functions accurately and flexibly, we developed a deep-learning framework that learns the probability of plan approval for cervical cancer high-dose-rate brachytherapy (HDRBT).Approach.The system consisted of a dose prediction network (DPN) and a plan-approval probability network (PPN). DPN predicts organs at risk (OAR)D2ccand CTVD90%of the current fraction from the patient's current anatomy and prescription dose of HDRBT. PPN outputs the probability of a given plan being acceptable to the physician based on the patients anatomy and the total dose combining HDRBT and external beam radiotherapy sessions. Training of the networks was achieved by first training them separately for a good initialization, and then jointly via an adversarial process. We collected approved treatment plans of 248 treatment fractions from 63 patients. Among them, 216 plans from 54 patients were employed in a four-fold cross validation study, and the remaining 32 plans from other 9 patients were saved for independent testing.Main results.DPN predicted equivalent dose of 2 Gy for bladder, rectum, sigmoidD2ccand CTVD90%with a relative error of 11.51% ± 6.92%, 8.23% ± 5.75%, 7.12% ± 6.00%, and 10.16% ± 10.42%, respectively. In a task that differentiates clinically approved plans and disapproved plans generated by perturbing doses in ground truth approved plans by 20%, PPN achieved accuracy, sensitivity, specificity, and area under the curve 0.70, 0.74, 0.65, and 0.74.Significance.We demonstrated the feasibility of developing a novel deep-learning framework that predicts a probability of plan approval for HDRBT of cervical cancer, which is an essential component in automatic treatment planning.

Optimizing Online Adaptation Timing in the Treatment of Locally Advanced Cervical Cancer.

PURPOSE: Online adaptive radiation therapy (ART) has emerged as a new treatment modality for cervical cancer. Daily online adapting improves target coverage and organ-at-risk (OAR) sparing compared with traditional image guided radiation therapy (IGRT); however, the required resources may not be feasible in a busy clinical setting. Less frequent adapting may still benefit cervical cancer patients due to large volume changes of the uterocervix of the treatment course. In this study, the dosimetry from different online adapt-on-demand schedules was compared. MATERIALS AND METHODS: A retrospective cohort of 10 patients with cervical cancer treated with 260 fractions of definitive daily online ART was included. Plans with different adaptation schedules were simulated with adaptations weekly, every other week, once during treatment, and no adaptations (IGRT). These plans were applied to the synthetic computed tomography (CT) images and contours generated during the patient's delivered daily adaptive workflow. The dosimetry of the weekly replan, every-other-week replan, once replan, and IGRT plans were compared using a paired t test. RESULTS: Compared with traditional IGRT plans, weekly and every-other-week ART plans had similar clinical target volume (CTV) coverage, but statistically significant improved sparing of OARs. Weekly and every-other-week ART had reduced bowel bag V40 by 1.57% and 1.41%, bladder V40 by 3.82% and 1.64%, rectum V40 by 8.49% and 7.50%, and bone marrow Dmean by 0.81% and 0.61%, respectively. Plans with a single adaptation had statistically significantly worse target coverage, and moderate improvements in OAR sparing. Of the 18-dose metrics evaluated, improvements were seen in 15 for weekly ART, 14 for every-other-week ART, and 10 for single ART plans compared with IGRT. When every-other-week ART was compared with weekly ART, both plans had similar CTV coverage and OAR sparing with only small improvements in bone marrow dosimetry with weekly ART. CONCLUSIONS: This retrospective work compares different adapt-on-demand treatment schedules using data collected from patients treated with daily online adaptive radiation therapy. Results suggest weekly or every-other-week online ART is beneficial for reduced OAR dose compared with IGRT by exploiting the gradual changes in the uterocervix target volume.

Definitive radiation for advanced cervix cancer is not associated with vaginal shortening-a prospective vaginal length and dose correlation.

PURPOSE: Prospectively measure change in vaginal length after definitive chemoradiation (C-EBRT) with Intracavitary Brachytherapy (ICBT) for locally advanced cervix cancer (LACC) and correlate with vaginal dose (VD). MATERIALS AND METHODS: Twenty one female patients with LACC receiving C-EBRT and ICBT underwent serial vaginal length (VL) measurements. An initial measurement was made at the time of the first ICBT procedure and subsequently at 3 month intervals up to 1 year post radiation. The vagina was contoured as a 3-dimensional structure for each brachytherapy plan. The difference in VL before and at least 6 months after the last fraction of brachytherapy was considered as an indicator of toxicity. RESULTS: The mean initial VL was 8.7 cm (6.5-12) with median value of 8.5 cm. The mean VL after 6 months was 8.6 cm (6.5-12) and VL change was not found to be statistically significant. The median values (interquartile ranges) for vaginal D0.1cc, D1cc, and D2cc were 129.2 Gy (99.6-252.2), 96.9 Gy (84.2-114.9), and 89.6 Gy (82.4-102.2), respectively. No significant correlation was found between vaginal length change and the dosimetric parameters calculated for all patients. CONCLUSION: Definitive C-EBRT and ICBT did not significantly impact VL in this prospective cohort probably related to acceptable doses per ICRU constraints. Estimate of vaginal stenosis and sexual function was not performed in this cohort which is a limitation of this study and which we hope to study prospectively going forward.

The accuracy of artificial intelligence deformed nodal structures in cervical online cone-beam-based adaptive radiotherapy.

Background and Purpose: Online cone-beam-based adaptive radiotherapy (ART) adjusts for anatomical changes during external beam radiotherapy. However, limited cone-beam image quality complicates nodal contouring. Despite this challenge, artificial-intelligence guided deformation (AID) can auto-generate nodal contours. Our study investigated the optimal use of such contours in cervical online cone-beam-based ART. Materials and Methods: From 136 adaptive fractions across 21 cervical cancer patients with nodal disease, we extracted 649 clinically-delivered and AID clinical target volume (CTV) lymph node boost structures. We assessed geometric alignment between AID and clinical CTVs via dice similarity coefficient, and 95% Hausdorff distance, and geometric coverage of clinical CTVs by AID planning target volumes by false positive dice. Coverage of clinical CTVs by AID contour-based plans was evaluated using D100, D95, V100%, and V95%. Results: Between AID and clinical CTVs, the median dice similarity coefficient was 0.66 and the median 95 % Hausdorff distance was 4.0 mm. The median false positive dice of clinical CTV coverage by AID planning target volumes was 0. The median D100 was 1.00, the median D95 was 1.01, the median V100% was 1.00, and the median V95% was 1.00. Increased nodal volume, fraction number, and daily adaptation were associated with reduced clinical CTV coverage by AID-based plans. Conclusion: In one of the first reports on pelvic nodal ART, AID-based plans could adequately cover nodal targets. However, physician review is required due to performance variation. Greater attention is needed for larger, daily-adapted nodes further into treatment.

Stereotactic Ablative Radiotherapy for Gynecological Oligometastatic and Oligoprogessive Tumors.

Importance: The role of stereotactic ablative radiotherapy (SABR) for gynecologic malignant tumors has yet to be clearly defined despite recent clinical uptake. Objective: To evaluate the outcomes of SABR in patients with oligometastatic and oligoprogressive gynecologic cancers. Design, Setting, and Participants: In this retrospective pooled analysis, patients with oligometastatic and oligoprogressive gynecologic cancers receiving SABR at 5 institutions from Canada and the US were studied. Data were collected from January 2011 to December 2020, and data were analyzed from January to December 2023. Exposure: Stereotactic ablative radiotherapy. Main Outcomes and Measures: Cumulative incidence of local and distant recurrence, chemotherapy-free survival (CFS), and overall survival (OS) probabilities after SABR were calculated using Kaplan-Meier methods. Univariable and multivariable analysis was conducted using Cox regression methods. Results: A total of 215 patients with 320 lesions meeting criteria were included in the analysis; the median (range) age at primary diagnosis was 59 (23-86) years. The median (range) follow-up from SABR was 18.5 (0.1-124.5) months. The primary site included the endometrium (n = 107), ovary (n = 64), cervix (n = 30), and vulva or vagina (n = 14). Local cumulative incidence of recurrence was 13.7% (95% CI, 9.4-18.9) and 18.5% (95% CI, 13.2-24.5) at 1 and 5 years, respectively. Distant cumulative incidence of recurrence was 48.5% (95% CI, 41.4-55.1) and 73.1% (95% CI, 66.0-79.0) at 1 and 5 years, respectively. OS was 75.7% (95% CI, 69.2-81.1) and 33.1% (95% CI, 25.3-41.1) at 1 and 5 years, respectively. The median CFS was 21.7 months (95% CI, 15.4-29.9). On multivariable analysis, local recurrence was significantly associated with nodal metastasis, lesion size, biologically effective dose, treatment indication, institution, and primary disease type. Distant progression-free survival was associated with nodal targets and lesion size. OS and CFS were significantly associated with lesion size. Conclusions and Relevance: In this study, SABR appeared to have excellent local control with minimal toxic effects in this large patient group, and certain patients may achieve durable distant control and OS as well. It may be possible to delay time to chemotherapy in select patient subtypes and therefore reduce associated toxic effects. Prospective multicenter trials will be critical to establish which characteristics procure the greatest benefit from SABR use and to define the ideal time to implement SABR with other oncologic treatments.

Prognostic Effect of Mismatch Repair Status in Early-Stage Endometrial Cancer Treated With Adjuvant Radiation: A Multi-institutional Analysis.

PURPOSE: The aim of this work was to report the effect of mismatch repair (MMR) status on outcomes of patients with stage I-II endometrioid endometrial adenocarcinoma (EEC) who receive adjuvant radiation therapy. METHODS AND MATERIALS: This is a multi-institutional retrospective cohort study across 11 institutions in North America. Patients with known MMR status and stage I-II EEC status postsurgical staging were included. Overall survival (OS) and recurrence-free survival (RFS) rates were estimated via the Kaplan-Meier method. Univariable and multivariable analyses were performed via Cox proportional hazard models for RFS and OS. Statistical analyses were conducted using SPSS version 27. RESULTS: In total, 744 patients with a median age at diagnosis of 65 years (IQR, 58-71) were included. Most patients were White (69.4%) and had Federation of Obstetrics and Gynecology 2009 stage I (84%) and Federation of Obstetrics and Gynecology grade 1 to 2 (73%). MMR deficiency was reported in 234 patients (31.5%), whereas 510 patients (68.5%) had preserved MMR. External beam radiation therapy with or without vaginal brachytherapy was delivered to 186 patients (25%), whereas 558 patients (75%) received vaginal brachytherapy alone. At a median follow-up of 43.5 months, the estimated crude OS and RFS rates for the entire cohort were 92.5% and 84%, respectively. MMR status was significantly correlated with RFS. RFS was inferior for MMR deficiency compared with preserved MMR (74.3% vs 88.6%, P < .001). However, no difference in OS was seen (90.8% vs 93.2%, P = .5). On multivariable analysis, MMR deficiency status was associated with worse RFS (hazard ratio, 1.86; P = .001) but not OS. CONCLUSIONS: MMR status was independently associated with RFS but not OS in patients with early-stage EEC who were treated with adjuvant radiation therapy. These findings suggest that differential approaches to surveillance and/or treatment based on MMR status could be warranted.

Childhood adversity increases vulnerability for behavioral symptoms and immune dysregulation in women with breast cancer.

Women respond differentially to the stress-associated with breast cancer diagnosis and treatment, with some women experiencing more intense and/or sustained behavioral symptoms and immune dysregulation than others. Childhood adversity has been identified to produce long-term dysregulation of stress response systems, increasing reactivity to stressors encountered during adulthood. This study determined whether childhood adversity increased vulnerability for more intense and sustained behavioral symptoms (fatigue, perceived stress, and depressive symptoms), poorer quality of life, and greater immune dysregulation in women (N=40) with breast cancer. Evaluation was after breast surgery and through early survivorship. Hierarchical linear modeling was used to examine intra-individual and inter-individual differences with respect to initial status and to the pattern of change (i.e. trajectory) of outcomes. At initial assessment, women exposed to childhood emotional neglect/abuse had greater perceived stress, fatigue, depressive symptoms and poorer quality of life, as well as lower natural killer cell activity (NKCA). Although these outcomes improved over time, women with greater childhood emotional neglect/abuse exhibited worse outcomes through early survivorship. No effect was observed on the pattern of change for these outcomes. In contrast, childhood physical neglect predicted sustained trajectories of greater perceived stress, worse quality of life, and elevated plasma IL-6; with no effect observed at initial assessment. Thus, childhood adversity leaves an enduring imprint, increasing vulnerability for behavioral symptoms, poor quality of life, and elevations in IL-6 in women with breast cancer. Further, childhood adversity predisposes to lower NKCA at a critical time when this immune-effector mechanism is most effective at halting nascent tumor seeding.

The New Kid on the Block: Online Adaptive Radiotherapy in the Treatment of Gynecologic Cancers.

Online adaptive radiation is a new and exciting modality of treatment for gynecologic cancers. Traditional radiation treatments deliver the same radiation plan to cancers with large margins. Improvements in imaging, technology, and artificial intelligence have made it possible to account for changes between treatments and improve the delivery of radiation. These advances can potentially lead to significant benefits in tumor coverage and normal tissue sparing. Gynecologic cancers can uniquely benefit from this technology due to the significant changes in bladder, bowel, and rectum between treatments as well as the changes in tumors commonly seen between treatments. Preliminary studies have shown that online adaptive radiation can maintain coverage of the tumor while sparing nearby organs. Given these potential benefits, numerous clinical trials are ongoing to investigate the clinical benefits of online adaptive radiotherapy. Despite the benefits, implementation of online adaptive radiotherapy requires significant clinical resources. Additionally, the timing and workflow for online adaptive radiotherapy is being optimized. In this review, we discuss the history and evolution of radiation techniques, the logistics and implementation of online adaptive radiation, and the potential benefits of online adaptive radiotherapy for gynecologic cancers.

Airway Edema after Keloid Resection and Superficial Radiation: Unexpected Event in an Unusual Location.

Postoperative radiation therapy has been shown to significantly reduce recurrence rates of keloids after surgical excision. Adverse effects of radiation therapy in this setting are generally minimal because the radiation utilized quickly dissipates below the skin, and the radiation effects on the internal organs are usually negligible. This case report describes a patient who underwent excision of a wide anterior neck keloid and received postoperative external beam radiation therapy of the incision. She presented with extensive upper airway edema, dyspnea, and dysphagia requiring readmission and steroids. Re-evaluation of the radiation protocol revealed an inadvertent intersection of the multiple abutting radiation fields at the supraglottic region, resulting in tripling of the dose in the area, and likely leading to her complication. She did well with conservative management with IV steroids, and did not require intubation. She has had no long-term sequelae and no recurrence at 6 months postoperative.