Differentiation of survival outcomes by anatomic involvement and histology with the revised 2023 International Federation of Gynecology and Obstetrics staging system for endometrial cancer.

OBJECTIVES: The International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer underwent revision in 2023, incorporating histology, lymphovascular space invasion, and molecular classification. Herein, we compare overall survival (OS) outcomes by anatomic and histologic involvement for patients staged by the 2009 system versus 2023 system. METHODS: The National Cancer Database (NCDB) was queried for patients with newly-diagnosed uterine adenocarcinoma from 2004 to 2015, with follow-up data extending through 2020. Stage was determined by both the 2009 and 2023 FIGO staging systems. Kaplan-Meier estimators and Cox proportional hazards models were used for survival analysis. RESULTS: A total of 134,677 patients were analyzed. Per 2023 classification, patients with stage I disease decreased from 96,161 to 70,101 (-27.1%, p < 0.01), while stage II disease increased from 9295 to 36,294 (+390.5%, p < 0.01). Greatest OS change was observed for 2023 stage IA3 patients (low-risk, synchronous endometrial and ovarian tumors with a clonal relationship), whose 10-year OS was 73.4%, compared to 52.6% for 2009 stage IIIA disease. Ten-year OS for 2023 stage IIIB2 (pelvic peritoneal involvement), previously 2009 stage IVB, was 49.4%, compared to 18.7% for 2009 stage IVB patients. Akaike information criterion, Bayesian information criterion, and Harrel's concordance index were used to evaluate OS prognostication of each staging system across all stages, with likelihood ratio favoring the 2023 system (p = 0.020). CONCLUSIONS: With FIGO's 2023 endometrial cancer anatomic and histologic staging system, stage migration is greatest in early-stage disease. New staging groups may offer more precise prognostication. These changes may affect future management.

Image-guided preplanning workflow for high-dose-rate interstitial brachytherapy for gynecological malignancies.

PURPOSE: To demonstrate image-guided preplan workflows for high-dose-rate (HDR) brachytherapy for advanced gynecological malignancies. METHODS AND MATERIALS: Two different preplanning scenarios are presented: (1) CT- or MRI-based preplan with partial applicator in place; (2) Preplans generated from prior fractions. The first scenario can be applied to Syed-Neblett template-based implants or hybrid brachytherapy applicators, while the second scenario applies to hybrid applicators. Both scenarios use MRI or CT images acquired with the applicator in place to demonstrate tumor and applicator relative locations and therefore, provide the ability to show optimized suggested needle positions including the implant depths before the actual insertion. RESULTS: The preplanning techniques have demonstrated feasibility and shown five areas of potential improvement: (1) shorter procedure time, (2) decreased number of total needles inserted, (3) shorter physician tumor contour time, (4) shorter planning time, and (5) evaluation of appropriateness for brachytherapy. CONCLUSIONS: The use of image-guided brachytherapy preplanning improves clinical efficiency and is recommended for consideration for adaptation into clinical workflows for HDR interstitial and hybrid brachytherapy.

Gross Tumor and Intracranial Control Benefits with Fractionated Radiotherapy Compared with Stereotactic Radiosurgery for Patients with WHO Grade 2 Meningioma.

OBJECTIVE: Surgical resection is the mainstay of treatment for WHO grade 2 meningioma. Fractionated radiation therapy (RT) is frequently used after surgery, though many centers utilize stereotactic radiosurgery (SRS) for recurrence or progression. Herein, we report disease control outcomes from an institutional cohort with adjuvant fractionated RT versus salvage SRS. METHODS: We identified 32 patients from an institutional database with WHO grade 2 meningioma and residual/recurrent tumor treated with either SRS or fractionated RT. Patients were treated between 2007 and 2021 and had at least 1 year of follow-up. Kaplan-Meier estimators were used to determine gross tumor control (GTC) and intracranial control (IC). Univariate Cox proportional hazards models using biologically effective dose (BED) as a continuous parameter were used to assess for dose responses. RESULTS: With a median follow-up of 5.5 years, 13 patients (41%) received SRS to a recurrent or progressive nodule, 2 (6%) fractionated RT to a recurrent or progressive nodule, and 17 (53%) adjuvant fractionated RT following subtotal resection. Five-year GTC was higher with fractionated RT versus SRS (82% vs. 38%, P = 0.03). Five-year IC was also better with fractionated RT versus SRS (82% vs. 11%, P < 0.001). On univariate analysis, increasing BED10 was significantly associated with better GTC (P = 0.039); increasing BED3 was not (P = 0.82). CONCLUSIONS: In this patient cohort, GTC and IC were significantly higher in patients treated with adjuvant fractionated RT compared with salvage SRS. Increasing BED10 was associated with better GTC. Fractionated RT may provide a better therapeutic ratio than SRS for grade 2 meningiomas.

Outcomes of and treatment planning considerations for a hybrid technique delivering proton pencil-beam scanning radiation to women with metal-containing tissue expanders undergoing post-mastectomy radiation.

BACKGROUND: Following mastectomy, immediate breast reconstruction often involves the use of temporary tissue expanders (TEs). TEs contain metallic ports (MPs), which complicate proton pencil-beam scanning (PBS) planning. A technique was implemented for delivering PBS post-mastectomy radiation (PMRT) to patients with TEs and MPs. METHODS: A protocol utilizing a hybrid single- and multi-field optimization (SFO, MFO) technique was developed. Plans were robustly optimized using a Monte Carlo algorithm. A CTV_eval structure including chest wall (CW) and regional nodal (RNI) targets and excluding the TE was evaluated. Organ at risk (OAR) dosimetry and acute toxicities were analyzed. RESULTS: Twenty-nine women were treated with this technique. A 2-field SFO technique was used superior and inferior to the MP, with a 3 or 4-field MFO technique used at the level of the MP. Virtual blocks were utilized so that beams did not travel through the MP. A port-to-CW distance of 1 cm was required. Patients underwent daily image-guidance to ensure the port remained within a 0.5 cm internal planning volume (ITV). Median RT dose to CTV_eval was 50.4 Gy (45.0-50.4). Median 95% CTV_eval coverage was 99.5% (95-100). Optically stimulated luminescent dosimeter (OSLD) readings were available for 8 patients and correlated to the dose measurements in the treatment planning system (TPS); median OSLD ratio was 0.99 (range, 0.93-1.02). CONCLUSIONS: Delivering PMRT with PBS for women with metal-containing TEs using a hybrid SFO/MFO technique is feasible, reproducible, and achieves excellent dose distributions. Specialized planning and image-guidance techniques are required to safely utilize this treatment in the clinic.

Assessing the Need for Adjusted Organ-at-Risk Planning Goals for Patients Undergoing Adjuvant Radiation Therapy for Locally Advanced Breast Cancer with Proton Radiation.

PURPOSE: Locally advanced breast cancer requires surgical management via lumpectomy or mastectomy with or without systemic therapy followed by chest wall or breast (CW) and comprehensive nodal irradiation (CNI). Radiation (RT) dose constraints for the heart and ipsilateral lung have been developed based on photon RT. Proton therapy (PBT) can deliver significantly lower doses of RT to these organs-at-risk (OARs) and may warrant adjustments to OAR planning goals. METHODS AND MATERIALS: The RT plans of consecutive patients undergoing adjuvant CW-CNI RT with PBT within a single center were reviewed. A inital treatment volume, comprised of CW/intact breast + CNI (CTV_init) structure, including the CW and CNI but excluding any boost plans was analyzed. Frequency distributions were generated based on doses received by the heart, lungs, and esophagus for validated dosimetric parameters. Frequency distributions were generated and then stratified by laterality and compared using the Kruskal-Wallis H test. The 75th, 85th, and 95th percentiles for each dosimetric parameter were calculated, overall and by laterality. The 75th percentile (Q3), was used as a suggested primary goal, and the 95th percentile was used as a suggested secondary goal. RESULTS: One hundred and seventy-two plans were analyzed. Forty-nine plans were right-sided, 107 were left-sided, and 16 were bilateral. The overall Q3 of the mean and V25 of the heart were 1.5 Gy and 1.7%, respectively. The mean and V25 to the heart differed significantly by laterality. Pulmonary values were similar to current recommendations. For all lateralites, the median volume of the esophagus receiving 70% prescription dose was ≤1 cm3. CONCLUSIONS: We present the first dosimetric study providing complete OAR dose-volume histograms data for patients undergoing adjuvant pencil-beam scanning-PBT for locally advanced breast cancer, with detailed information on central tendencies, ranges and distributions of data. We have provided suggested planning goals and metrics for the lungs, heart, and esophagus; the latter 2 differing significantly from current Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) constraints and classical photon goals.

Pathologic complete response (pCR) rates and outcomes after neoadjuvant chemoradiotherapy with proton or photon radiation for adenocarcinomas of the esophagus and gastroesophageal junction.

BACKGROUND: Pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) is associated with improved survival in patients treated for esophageal cancer. While proton beam therapy (PBT) has been demonstrated to reduce toxicities with nCRT, no data comparing pCR rates between modalities exist to date. We investigated pCR rates in patients with distal esophageal/GEJ adenocarcinomas undergoing trimodality therapy with nCRT-PBT or photon-based nCRT with the hypothesis that pathologic responses with PBT would be at least as high as with photon therapy. METHODS: A single-institutional review of patients with distal esophageal adenocarcinoma treated with trimodality therapy from 2015-2018 using PBT was completed. PBT patients were matched 1:2 to patients treated with photons. Chi square and two-sample t-tests were utilized to compare characteristics, and the Kaplan Meier method was used to estimate oncologic endpoints. RESULTS: Eighteen consecutive PBT patients were identified and compared to 36 photon patients. All patients received concurrent chemotherapy; 98% with carboplatin/paclitaxel. Most patients were male (91%) and White (89%); median age was 62 years (range, 31-76 years). Median radiation dose in both cohorts was 50.4 Gy (range, 41.4-50.4 Gy); all courses were delivered in 1.8Gy fractions. Age, gender and race were well balanced. Patients treated with PBT had a significantly higher pre-treatment nodal stage (N) and AJCC 7th edition stage grouping (P=0.02, P=0.03). Despite this, tumoral and nodal clearance and pCR rates were equivalent between cohorts (P=0.66, P=0.11, P=0.63, respectively). Overall pCR and individual primary and nodal clearance rates, overall survival (OS), locoregional control (LRC), and distant metastatic control did not significantly differ between modalities (all P>0.05). Major perioperative events were balanced; however, there were 5 (14%) perioperative deaths in the photon cohort compared to 0 (0%) in the proton cohort (P=0.06). CONCLUSIONS: The use of PBT in trimodality therapy for distal esophageal adenocarcinoma yields pCR rates comparable to photon radiation and historical controls. Pathologic responses and oncologic outcomes in this study did not differ significantly between modalities despite PBT patients having higher AJCC stages and nodal disease burdens.

Assessing Outcomes of Patients Treated With Re-Irradiation Utilizing Proton Pencil-Beam Scanning for Primary or Recurrent Malignancies of the Esophagus and Gastroesophageal Junction.

INTRODUCTION: Re-irradiation (re-RT) for locoregionally recurrent esophageal and gastroesophageal junction (GEJ) cancer and de novo esophageal + GEJ cancer arising in-field after a course of prior radiation poses considerable treatment challenges given the sensitivity of surrounding organs at risk (OARs). Guidelines for treatment of this presentation are not well established. Pencil-beam scanning (PBS) proton therapy has the ability to decrease radiation dose to OARs relative to photon plans. We present the first published series to date of re-RT with PBS for esophageal + GEJ malignancies and hypothesize that re-RT with proton PBS will be feasible and improve the safety profile of re-RT for this cohort of patients. METHODS: Consecutive esophageal + GEJ cancers treated with PBS re-RT within a single institution were analyzed. Comparative volumetric-modulated arc therapy photon plans were generated. A total of 17 patients were included for analysis. RESULTS: At a median follow-up of 11.6 months, 1-year local control was 75.3% and overall survival was 68.9%. There were five (27.8%) grade 3 or higher late toxicities. When matched for clinical target volume coverage, proton PBS plans delivered significantly lower doses to the spinal cord, lungs, liver, and heart (all p < 0.05); five volumetric-modulated arc therapy plans would have been undeliverable on the basis of physician-specified OAR constraints. CONCLUSIONS: Re-RT for de novo or recurrent malignancies of the esophagus + GEJ, when delivered with PBS proton therapy, yields high rates of local control with acceptable acute and late toxicities in a high-risk population and decreased radiation dose to OARs relative to comparative photon plans. This is the largest series of proton re-RT for esophageal malignancies and the first that exclusively used PBS.

Quantification of Acute Skin Toxicities in Patients With Breast Cancer Undergoing Adjuvant Proton versus Photon Radiation Therapy: A Single Institutional Experience.

PURPOSE: Acute skin toxicity in the form of radiation dermatitis (RD) or skin hyperpigmentation (SH) is a common problem experienced by patients undergoing breast irradiation. Proton radiation has been thought to deliver higher doses to skin compared with photon radiation because of differences in the physical properties between photons and protons; however, limited literature exists directly comparing toxicity outcomes. METHODS AND MATERIALS: The highest recorded grades of acute RD and SH were analyzed in 86 patients undergoing adjuvant radiation therapy to the breast with or without regional lymph nodes after lumpectomy (breast-conserving surgery) or mastectomy with either proton pencil-beam scanning (n = 39) or photon (n = 47) radiation therapy within a single institution to analyze differences in severity of acute skin reactions. For 34 of 47 photon and 33 of 39 proton patients, a "skin" contour was retroactively created in our treatment planning systems, and multiple dosimetric parameters were calculated to quantify objective radiation doses received by skin. RESULTS: On χ2 analysis, the highest reported grade of RD was significantly higher in women undergoing proton radiation compared with photon radiation; grade ≥2 RD was present in 69.2% versus 29.8% of patients receiving proton and photon therapy, respectively (P = .002). Rates of grade 3 RD were 5.1% versus 4.3% for proton versus photon radiation, respectively (P = .848). Overall, there were no significant differences in rates of SH between modalities. There were no grade 4 to 5 toxicities in either cohort. CONCLUSIONS: In a comparison with patients receiving photon radiation, a significantly higher rate of grade ≥2 RD was observed in patients undergoing proton radiation, with very low rates of grade 3 toxicity in both groups. Rates of SH did not differ significantly between modalities. Women should be counseled regarding the possibility of increased grade 2 toxicities, although this might present a dosimetric advantage for physicians when treating patients in the postmastectomy setting or when skin was involved on presentation.

Use of Survivorship Care Plans and Analysis of Patient-Reported Outcomes in Multinational Patients With Lung Cancer.

PURPOSE: Lung cancer is the leading cause of cancer death and is a significant source of morbidity. Patient-reported outcomes (PROs) have been shown to be prognostic for survival. We have analyzed emerging patterns of longitudinal PROs collected in the development of survivorship care plans (SCPs). METHODS: OncoLife and the LIVESTRONG Care Plans are Internet-based programs designed to generate unique SCPs. We selected SCPs from patients identifying as survivors of primary lung cancer. Patient-reported demographics and treatment and toxicity data were examined. Effects were categorized by the physiologic system that they affected. RESULTS: Six hundred eighty-nine plans were created for users self-identifying as survivors of primary lung cancer. Average time from diagnosis to reporting was 1.68 years (range, 0 to 24 years). Most were white (85.9%), well educated (61.1% "some college" or higher), and lived in the United States (90.7%). Patients underwent chemotherapy (75.8%), radiotherapy (54.7%), and surgery (54.4%). Neurocognitive symptoms (eg, fatigue, cognitive changes) were the most common (48.8%), especially among those receiving chemotherapy, followed by musculoskeletal/dermatologic symptoms (14.1%) and thoracic symptoms (13.5%). Only 11.2% were initially offered an SCP. Of those offered SCPs, 54.5% were offered by their health care provider, and most often were at a non-university-based cancer center (66.2%). CONCLUSION: For patients with lung cancer worldwide, it is feasible to obtain PROs and to create SCPs through an Internet-based program. As patients with lung cancer achieve improved survival, further attention should be paid to PROs. Surprisingly, neurocognitive symptoms seem to be the most common issues and therefore the most important to address. Increased effort should be made to provide SCPs, particularly in urban and university cancer center settings.