How deep is too deep? Assessing myometrial invasion as a predictor of distant recurrence in stage I endometrioid endometrial cancer.

OBJECTIVES: The goal of this study was to evaluate the depth of myometrial invasion as a predictor of distant recurrence in patients with node-negative stage IB endometrioid endometrial cancer. METHODS: A retrospective multicenter study, including surgically staged endometrial cancer patients at Mayo Clinic, Rochester (MN, USA) between January 1999 and December 2017, and Fondazione Policlinico Universitario A. Gemelli (Rome, Italy) between March 2002 and March 2017, was conducted. Patients without lymph node assessment were excluded. The follow-up was restricted to the first 5 years following surgery. Recurrence-free survival was estimated using the Kaplan-Meier method. Cox proportional hazards models were fit to evaluate the association of clinical and pathologic characteristics with the risk of recurrence. RESULTS: Of 386 patients, the mean (SD) depth of myometrial invasion was 70.4 (13.2)%. We identified 51 recurrences (14 isolated vaginal, 37 non-vaginal); the median follow-up of the remaining patients was 4.5 (IQR 2.3-7.0) years. At univariate analysis, the risk of non-vaginal recurrence increased by 64% (95% CI 1.28 to 2.12) for every 10-unit increase in the depth of myometrial invasion. International Federation of Gynecology and Obstetrics (FIGO) grade and myometrial invasion were independent predictors of non-vaginal recurrence. The 5-year non-vaginal recurrence-free survival was 95.2% (95% CI 92.0% to 98.6%), 84.0% (95% CI 76.6% to 92.1%), and 67.1% (95% CI 54.2% to 83.0%) for subsets of patients with myometrial invasion <71% (n=207), myometrial invasion ≥71% and grade 1-2 (n=132), and myometrial invasion ≥71% and grade 3 (n=47), respectively. A total of 256 (66.3%) patients received either vaginal brachytherapy only or no adjuvant therapy. Patients who received adjuvant chemotherapy, regardless of receipt of external beam radiotherapy or vaginal brachytherapy, had an approximately 70% lower risk of any recurrence (HR adjusted for age, grade, myometrial invasion 0.31, 95% CI 0.12 to 0.85) and of non-vaginal recurrence (adjusted HR 0.32, 95% CI 0.10 to 0.99). CONCLUSION: The invasion of the outer third of the myometrium and histologic grade were found to be independent predictors of distant recurrence among patients with endometrioid, node-negative stage IB endometrial cancer. Future studies should investigate if systemic adjuvant therapy for patients with myometrial invasion of the outer third would improve outcomes.

Integration of Telemedicine Consultation Into a Tertiary Radiation Oncology Department: Predictors of Use, Treatment Yield, and Effects on Patient Population.

PURPOSE: The COVID-19 pandemic led to rapid expansion of telemedicine. The implications of telemedicine have not been rigorously studied in radiation oncology, a procedural specialty. This study aimed to evaluate the characteristics of in-person patients (IPPs) and virtual patients (VPs) who presented to a large cancer center before and during the pandemic and to understand variables affecting likelihood of receiving radiotherapy (yield) at our institution. METHODS: A total of 17,915 patients presenting for new consultation between 2019 and 2021 were included, stratified by prepandemic and pandemic periods starting March 24, 2020. Telemedicine visits included video and telephone calls. Area deprivation indices (ADIs) were also compared. RESULTS: The overall population was 56% male and 93% White with mean age of 63 years. During the pandemic, VPs accounted for 21% of visits, were on average younger than their in-person (IP) counterparts (63.3 years IP v 62.4 VP), and lived further away from clinic (215 miles IP v 402 VP). Among treated VPs, living closer to clinic was associated with higher yield (odds ratio [OR], 0.95; P < .001). This was also seen among IPPs who received treatment (OR, 0.96; P < .001); however, the average distance from clinic was significantly lower for IPPs than VPs (205 miles IP v 349 VP). Specialized radiotherapy (proton and brachytherapy) was used more in VPs. IPPs had higher ADI than VPs. Among VPs, those treated had higher ADI (P < .001). CONCLUSION: Patient characteristics and yield were significantly different between IPPs and VPs. Telemedicine increased reach to patients further away from clinic, including from rural or health care-deprived areas, allowing access to specialized radiation oncology care. Telemedicine has the potential to increase the reach of other technical and procedural specialties.

Patient Education Practices and Preferences of Radiation Oncologists and Interprofessional Radiation Therapy Care Teams: A Mixed-Methods Study Exploring Strategies for Effective Patient Education Delivery.

PURPOSE: Patients' understanding of radiation therapy (RT) and data regarding optimal approaches to patient education (PE) within radiation oncology (RO) are limited. We aimed to evaluate PE practices of radiation oncologists and interprofessional RT care team members to inform recommendations for delivering inclusive and accessible PE. METHODS AND MATERIALS: An anonymous survey was administered to all Radiation Oncology Education Collaborative Study Group members (10/5/22-11/23/22). Respondent demographics, individual practices/preferences, and institutional practices were collected. Qualitative items explored strategies, challenges, and desired resources for PE. Descriptive statistics summarized survey responses. The Fisher exact test compared PE practices by respondent role and PE timing. Thematic analysis was used for qualitative responses. RESULTS: One hundred thirteen Radiation Oncology Education Collaborative Study Group members completed the survey (28.2% response rate); RO attendings comprised 68.1% of respondents. Most practiced in an academic setting (85.8%) in North America (80.5%). Institution-specific materials were the most common PE resource used by radiation oncologists (67.6%). Almost half (40.2%) reported that their PE practices differed based on clinical encounter type, with paper handouts commonly used for in-person and multimedia for telehealth visits. Only 57.7% reported access to non-English PE materials. PE practices among radiation oncologists differed according to RT clinical workflow timing (consultation versus simulation versus first RT, respectively): one-on-one teaching: 88.5% versus 49.4% versus 56.3%, P < .01, and paper handouts: 69.0% versus 28.7% versus 16.1%, P < .01. Identified challenges for PE delivery included limited time, administrative barriers to the development or implementation of new materials or practices, and a lack of customized resources for tailored PE. Effective strategies for PE included utilization of visual diagrams, multimedia, and innovative education techniques to personalize PE delivery/resources for a diverse patient population, as well as fostering interprofessional collaboration to reinforce educational content. CONCLUSIONS: Radiation oncologists and interprofessional RO team members engage in PE, with most using institution-specific materials often available only in English. PE practices differ according to clinical encounter type and RT workflow timing. Increased adoption of multimedia materials and partnerships with patients to tailor PE resources are needed to foster high-quality, patient-centered PE delivery.

Postmastectomy Intensity Modulated Proton Therapy: 5-Year Oncologic and Patient-Reported Outcomes.

PURPOSE: To report oncologic, physician-assessed, and patient-reported outcomes (PROs) for a group of women homogeneously treated with modern, skin-sparing multifield optimized pencil-beam scanning proton (intensity modulated proton therapy [IMPT]) postmastectomy radiation therapy (PMRT). METHODS AND MATERIALS: We reviewed consecutive patients who received unilateral, curative-intent, conventionally fractionated IMPT PMRT between 2015 and 2019. Strict constraints were applied to limit the dose to the skin and other organs at risk. Five-year oncologic outcomes were analyzed. Patient-reported outcomes were evaluated as part of a prospective registry at baseline, completion of PMRT, and 3 and 12 months after PMRT. RESULTS: A total of 127 patients were included. One hundred nine (86%) received chemotherapy, among whom 82 (65%) received neoadjuvant chemotherapy. The median follow-up was 4.1 years. Five-year locoregional control was 98.4% (95% CI, 93.6-99.6), and overall survival was 87.9% (95% CI, 78.7-96.5). Acute grade 2 and 3 dermatitis was seen in 45% and 4% of patients, respectively. Three patients (2%) experienced acute grade 3 infection, all of whom had breast reconstruction. Three late grade 3 adverse events occurred: morphea (n = 1), infection (n = 1), and seroma (n = 1). There were no cardiac or pulmonary adverse events. Among the 73 patients at risk for PMRT-associated reconstruction complications, 7 (10%) experienced reconstruction failure. Ninety-five patients (75%) enrolled in the prospective PRO registry. The only metrics to increase by >1 point were skin color (mean change: 5) and itchiness (2) at treatment completion and tightness/pulling/stretching (2) and skin color (2) at 12 months. There was no significant change in the following PROs: bleeding/leaking fluid, blistering, telangiectasia, lifting, arm extension, or bending/straightening the arm. CONCLUSIONS: With strict dose constraints to skin and organs at risk, postmastectomy IMPT was associated with excellent oncologic outcomes and PROs. Rates of skin, chest wall, and reconstruction complications compared favorably to previous proton and photon series. Postmastectomy IMPT warrants further investigation in a multi-institutional setting with careful attention to planning techniques.

R0 Resection in Recurrent Gynecologic Malignancy: Pelvic Exenteration and Beyond.

OPINION STATEMENT: Pelvic exenteration is a radical surgery, but oftentimes, it is the last curative option for patients with recurrent gynecologic malignancies who have exhausted more conservative therapies. Mortality and morbidity outcomes have improved over time, but there are still significant peri-operative risks. Considerations before pursing pelvic exenteration must include the likelihood of oncologic cure and patients' fitness to undergo such a procedure, particularly given the high rate of surgical morbidity. Pelvic sidewall tumors have been a traditional contraindication for pelvic exenteration due to the difficulty in obtaining negative margins, but the use of laterally extended endopelvic resection and intra-operative radiation therapy allows for more radical resection of recurrent disease. We believe that these procedures to achieve R0 resection can expand the use of curative-intent surgery in recurrent gynecologic cancer, but require the surgical expertise of colleagues in orthopedic and vascular surgery and collaboration with plastic surgery for complex reconstruction and optimization of post-operative healing. Surgery of recurrent gynecologic cancer including pelvic exenteration, requires careful patient selection, pre-operative medical optimization and prehabilitation, and thorough counseling to optimize outcomes, both oncologic and peri-operative. We believe the creation of a well-developed team, including surgical teams and supportive care services, can lead to the best patient outcomes and improved professional satisfaction amongst providers.

Outcomes of Proton Beam Therapy Compared With Intensity-Modulated Radiation Therapy for Uterine Cancer.

Purpose: To compare Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in patients with endometrial cancer receiving adjuvant pelvic radiation therapy with proton beam therapy (PT) versus intensity-modulated radiation therapy (IMRT). Materials and Methods: Patients with uterine cancer treated with curative intent who received either adjuvant PT or IMRT between 2014 and 2020 were identified. Patients were enrolled into a prospective registry using a gynecologic-specific subset of PRO-CTCAE designed to assess symptom impact on daily living. Questions included gastrointestinal (GI) symptoms of diarrhea, flatulence, bowel incontinence, and constipation in addition to other pertinent gynecologic, urinary, and other general symptoms. Symptom-based questions were on a 0- to 4-point scale, with grade 3+ symptoms occurring frequently or almost always. Patient-reported toxicity was analyzed at baseline, end of treatment (EOT), and at 3, 6, 9, and 12 months after treatment. Unequal variance t tests were used to determine if treatment type was a significant factor in baseline-adjusted PRO-CTCAE. Results: Sixty-seven patients met inclusion criteria. Twenty-two received PT and 45 patients received IMRT. Brachytherapy boost was delivered in 73% of patients. Median external beam dose was 45 Gy for both PT and IMRT (range, 45-58.8 Gy). When comparing PRO-CTCAE, PT was associated with less diarrhea at EOT (P = .01) and at 12 months (P = .24) than IMRT. Loss of bowel control at 12 months was more common in patients receiving IMRT (P = .15). Any patient reporting grade 3+ GI toxicity was noted more frequently with IMRT (31% versus 9%, P = .09). Discussion: Adjuvant PT is a promising treatment for patients with uterine cancer and may reduce patient-reported GI toxicity as compared with IMRT.

Intensity Modulated Proton Therapy for Bilateral Breast or Chest Wall and Comprehensive Nodal Irradiation for Synchronous Bilateral Breast Cancer: Initial Clinical Experience and Dosimetric Comparison.

Purpose: Synchronous bilateral breast cancer (SBBC) poses distinct challenges for radiation therapy planning. We report our proton therapy experience in treating patients with SBBC. We also provide a dosimetric comparison of intensity modulated proton therapy (IMPT) versus photon therapy. Methods and Materials: Patients with SBBC who received IMPT at our institution were retrospectively analyzed. The clinical target volume (CTV) included the breast or chest wall and comprehensive regional lymph nodes, including axilla, supraclavicular fossa, and the internal mammary chain. Intensity modulated proton therapy and volumetric modulated arc therapy (VMAT) plans were generated with the goal that 90% of the CTV would recieve at least 90% of the prescription dose (D90>=90%). Comparisons between modalities were made using the Wilcoxon signed rank test. Physician-reported acute toxic effects and photography were collected at baseline, end of treatment, and each follow-up visit. Results: Between 2015 and 2018, 11 patients with SBBC were treated with IMPT. The prescription was 50 Gy in 25 fractions. The median CTV D90 was 99.9% for IMPT and 97.6% for VMAT (P = .001). The mean heart dose was 0.7 Gy versus 7.2 Gy (P = .001), the total lung mean dose was 7.8 Gy versus 17.3 Gy (P = .001), and the total lung volume recieving 20 Gy was 13.0% versus 27.4% (P = .001). The most common acute toxic effects were dermatitis (mostly grade 1-2 with 1 case of grade 3) and grade 1 to 2 fatigue. The most common toxic effects at the last-follow up (median, 32 months) were grade 1 skin hyperpigmentation, superficial fibrosis, and extremity lymphedema. No nondermatologic or nonfatigue adverse events of grade >1 were recorded. Conclusions: Bilateral breast and/or chest wall and comprehensive nodal IMPT is technically feasible and associated with low rates of severe acute toxic effects. Treatment with IMPT offered improved target coverage and normal-tissue sparing compared with photon therapy. Long-term follow-up is ongoing to assess efficacy and toxic effects.

Intensity modulated radiotherapy for anal canal squamous cell carcinoma: A 16-year single institution experience.

INTRODUCTION: To report long-term efficacy and adverse events (AEs) associated with intensity modulated radiotherapy (IMRT) for patients with anal canal squamous cell carcinoma (ASCC). MATERIALS AND METHODS: This was a retrospective review of patients with ASCC who received curative-intent IMRT and concurrent chemotherapy (98%) between 2003 and 2019. Overall survival (OS), colostomy-free survival (CFS), and progression-free survival (PFS) were estimated using the Kaplan-Meier method. The cumulative incidence of local recurrence (LR), locoregional recurrence (LRR), and distant metastasis (DM) were reported. Acute and late AEs were recorded per National Cancer Institute Common Terminology Criteria for AEs. RESULTS: 127 patients were included. The median patient age was 63 years (interquartile range [IQR] 55-69) and 79% of patients were female. 33% of patients had T3-4 disease and 68% had clinically involved pelvic or inguinal lymph nodes (LNs).The median patient follow-up was 47 months (IQR: 28-89 months). The estimated 4-year OS, CFS, and PFS were 81% (95% confidence interval [CI]: 73%-89%), 77% (95% CI: 68%-86%), and 78% (95% CI: 70%-86%), respectively. The 4-year cumulative incidences of LR, LRR, and DM were 3% (95% CI: 1%-9%), 9% (95% CI: 5%-17%), and 10% (95% CI: 6%-18%), respectively. Overall treatment duration greater than 39 days was associated with an increased risk of LRR (Hazard Ratio [HR]: 5.2, 95% CI: 1.4-19.5, p = 0.015). The most common grade 3+ acute AEs included hematologic (31%), gastrointestinal (GI) (17%), dermatologic (16%), and pain (15%). Grade 3+ late AEs included: GI (3%), genitourinary (GU) (2%), and pain (1%). Current smokers were more likely to experience grade 3+ acute dermatologic toxicity compared to former or never smokers (34% vs. 7%, p < 0.001). CONCLUSIONS: IMRT was associated with favorable toxicity rates and long-term efficacy. These data support the continued utilization of IMRT as the preferred treatment technique for patients with ASCC.

Patterns of inguinal lymph node metastases in anal canal cancer and recommendations for elective clinical target volume (CTV) delineation.

PURPOSE: Optimal clinical target volume (CTV) for inguinal lymph node irradiation in anal cancer remains uncertain. This study documents the location of radiographically involved inguinal lymph nodes and proposes guidelines for CTV delineation. MATERIALS AND METHODS: Patients with anal canal squamous cell carcinoma with inguinal lymph node metastases were identified. Criteria for lymph node involvement included: >15 mm short axis or suspicious morphology on CT or MRI, increased avidity on 18-FDG-PET, or positive biopsy. Distances from center of involved nodes to femoral vessels and inferior pubic symphysis were measured. RESULTS: Forty patients with 79 inguinal lymph nodes were included. Relative to right femoral vessels, nodes were located: 12:00 (n = 6); 1:00 (n = 28); 2:00 (n = 35), 3:00 (n = 5); 4:00 (n = 1); 10:00 (n = 1); 11:00 (n = 3). No nodes were identified lateral or posterior to vessels. Published AGITG guidelines covered 68% of nodes anteriorly and 85% medially. Margins from nearest femoral vessel to cover 95% of nodes were 30 mm anteriorly and 26 mm medially. Inferior margin to cover 95% of nodes was 14 mm below inferior pubic symphysis. Proposed borders include cranial, where external iliac vessels leave bony pelvis; caudal, 14 mm below inferior pubic symphysis; posterior, posterior border of femoral vessels; lateral, lateral border of femoral vessels; anterior, 30 mm margin on femoral vessels and medial, 26 mm margin on femoral vessels, including radiographically suspicious nodes. CONCLUSIONS: Published guidelines for inguinal CTV in anal cancer may result in inadequate coverage of high risk areas. Updated guidelines based on this study ensure coverage of at-risk areas.

Utilizing clinical pathways and web-based conferences to improve quality of care in a large integrated network using breast cancer radiation therapy as the model.

BACKGROUND: Clinical pathways outline criteria for dose homogeneity and critical organ dosimetry. Based upon an internal audit showing suboptimal compliance with dosimetric parameters in whole breast irradiation (WBI), we conducted a mandatory web-based teaching conference for the network. This study reports the impact of this initiative on subsequent treatment plans. METHODS: Radiation treatment plans were collected for the 10 most recent patients receiving WBI at 16 institutions within the UPMC Hillman Cancer Center network. Subsequently, a web-based conference was conducted to educate staff physicians, physicists, and dosimetrists with goals for dose homogeneity and critical organ dosimetry. Six months post-conference, another 10 plans were collected from each site and compared to pre-conference plans for deviations from dosimetric criteria. RESULTS: Dose homogeneity significantly improved after the conference with breast V105% decreasing from 15.6% to 11.2% (p = 0.004) and breast V110% decreasing from 1.3% to 0.04% (p = 0.008). A higher percentage of cases were compliant with dosimetric criteria, with breast V105% > 20% decreasing from 22.5% to 7.5% of cases (p = 0.0002) and breast V110% > 0% decreasing from 13.8% to 4.4% of cases (p = 0.003). CONCLUSIONS: Implementation of a web-based teaching conference helped improve adherence to clinical pathway dosimetric guidelines for WBI. In radiation oncology networks, this may be an effective model to ensure quality in routine practice and can be extrapolated to other disease sites.

Implanted spacer approaches for pelvic radiation therapy.

INTRODUCTION: Recent clinical advances in radiation therapy have aimed to improve the therapeutic ratio through shortening the treatment duration through increasing the biologically effective dose (either through dose escalation or hypofractionation). However, despite using advanced techniques such as intensity modulated radiation therapy (IMRT) and image-guidance methods, dose escalation can be limited by its resultant gastrointestinal toxicity. In an effort to reduce rectal toxicity, biodegradable spacer materials and implantable balloons have been injected into the prostate-rectal space to increase the separation between the rectum and prostate thereby reducing rectal irradiation. AREAS COVERED: The purpose of this review is to describe the commercially available rectal spacers in pelvic radiation therapy, including prostate cancer and gynecologic malignancies, and to discuss the application, dosimetric effects, and reported clinical outcomes to date. Expert commentary: Several groups have reported significantly reduced rectal doses and decreased rectal toxicity with prostate-rectal spacers, and additional evidence continues to emerge to support this promising approach.