Gross tumor and intracranial control benefits with fractionated radiotherapy compared to 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 employed following 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 radiation to a recurrent or progressive nodule, and 17 (53%) adjuvant fractionated radiation following subtotal resection. 5-year GTC was higher with fractionated RT versus SRS (82% vs. 38%, p=0.03). 5-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 to salvage SRS. Increasing BED10 was associated with better GTC. Fractionated RT may provide a better therapeutic ratio than SRS for grade 2 meningiomas.

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.

Patterns of failure after radiosurgery for WHO grade 1 or imaging defined meningiomas: Long-term outcomes and implications for management.

BACKGROUND: We analyzed long-term control and patterns of failure in patients with World Health Organization Grade 1 meningiomas treated with definitive or postoperative stereotactic radiosurgery at the authors' affiliated institution. METHODS: 96 patients were treated between 2004 and 2019 with definitive (n = 57) or postoperative (n = 39) stereotactic radiosurgery. Of the postoperative patients, 17 were treated adjuvantly following subtotal resection and 22 were treated as salvage at time of progression. Patients were treated to the gross tumor alone without margin or coverage of the dural tail to a median dose of 15 Gy. Median follow up was 7.4 years (inter-quartile range 4.8-11.3). Local control, marginal control, regional control, and progression-free survival were analyzed. RESULTS: Local control at 5 and 10 years was 97 % and 95 %. PFS at 5 and 10 years was 94 % and 90 % with no failures reported after 6 years. Definitive and postoperative local control were similar at 5 (95 % [82-99 %] vs. 100 %) and 10 years (92 % [82-99 %] vs. 100 %). Patients treated with postoperative SRS did not have an increased marginal failure rate (p = 0.83) and only 2/39 (5 %) experienced recurrence elsewhere in the cavity. CONCLUSIONS: Stereotactic radiosurgery targeting the gross tumor alone provides excellent local control and progression free survival in patients treated definitively and postoperatively. As in the definitive setting, patients treated postoperatively can be treated to gross tumor alone without need for additional margin or dural tail coverage.

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.

Trends in use of radiation therapy, chemotherapy, and combination chemoradiotherapy in advanced uterine cancer before, during, and after GOG 258.

OBJECTIVE: To explore the use of Gynecologic Oncology Group 258 (GOG 258) study regimens before, during, and after the study. METHODS: Patients aged 18 years or older with endometrial cancer between 2004-2019 were identified in the National Cancer Database. Inclusion criteria were stage III or IVA of any histology and stage I-IVA clear cell or serous histologies with positive washings that received adjuvant therapy. Adjuvant therapy use was examined in the pre-GOG 258 era (before 2009), during GOG 258 enrollment and maturation (2010-2017), and after results presentation in 2017 (2018-2019). Two-sided Cochran-Armitage tests, Wilcoxen rank sum tests, and χ2 tests were used for continuous and categorical variables. Multi-variable logistic regression assessed factors associated with the receipt of chemoradiotherapy compared with chemotherapy only or radiation therapy only. RESULTS: From 2004 to 2019, 41 408 high-risk endometrial cancer patients received adjuvant therapy (12% radiation therapy, 38% chemotherapy, 50% chemoradiotherapy). Chemoradiotherapy increased over the GOG 258 study period (40% before study opening, 54% during enrollment, and 59% after results). Serous (OR 0.6, 95% CI 0.6 to 0.7) and clear cell histology (0.7, 0.6 to 0.8), higher grade (0.8, 0.7 to 0.9), and lymph node positivity (0.8, 0.7 to 0.9) were negatively associated with receipt of chemoradiotherapy compared with single-modality treatment. Non-Hispanic Black ethnicity (0.8, 0.8 to 0.9) and residing ≥50 miles from the treatment facility (0.8, 0.7 to 0.9) were also negatively associated with chemoradiotherapy. Private insurance (1.2, 1.0 to 1.4) and treatment at community hospitals (1.2, 1.2 to 1.3) were positively associated with chemoradiotherapy. CONCLUSION: Despite the lack of benefit in the GOG 258 experimental arm, chemoradiotherapy use increased during study enrollment and after results publication.

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.

Long-term outcomes of a prospective randomized trial of 131Cs/125I permanent prostate brachytherapy.

PURPOSE: Iodine-125 (125I) is the most commonly used isotope for prostate brachytherapy (BT). Cesium-131 (131Cs) has a higher dose rate and shorter dose delivery time resulting in decreased duration of acute urinary morbidity. Long-term data suggest excellent oncologic outcomes; it is not known how outcomes compare. A prospective randomized trial comparing the two isotopes was initiated. MATERIALS AND METHODS: Patients with low- or intermediate-risk disease were treated with a BT in a single outpatient facility. Prescription dose was 144 Gy for 125I and 115 Gy for 131Cs. Androgen deprivation or supplemental EBRT was not allowed. The primary study objective was comparison of the mean EPIC Urinary Domain Score. Secondary objective was biochemical relapse-free survival (BRFS) comparison. Time-to-event for all outcomes of interest was measured from implant date. RESULTS: One hundred forty men were enrolled; 81.4% were low-risk and 18.6% were intermediate-risk. The median followup was 97 months. Urinary and sexual health-related quality of life did not differ between isotopes at any recorded time point. At 2 months after implantation, bowel health-related quality of life was worse with 125I; however, this difference was lost at subsequent time points. The 9-year BRFS was 87.2% and 84.0% for the 125I and 131Cs group, respectively (p = 0.897). There was no statistically significant difference in BRFS based on initial T stage, PSA, or Gleason score. CONCLUSIONS: Short- and long-term urinary, sexual, and bowel quality of life, as well as long-term biochemical control were comparable between 125I and 131Cs. This report therefore supports the continued use of 131Cs as an effective and comparable alternative isotope.

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.

Multiple Computed Tomography Robust Optimization to Account for Random Anatomic Density Variations During Intensity Modulated Proton Therapy.

PURPOSE: To propose a method of optimizing intensity modulated proton therapy (IMPT) plans robust against dosimetric degradation caused by random anatomic variations during treatment. METHODS AND MATERIALS: Fifteen patients with prostate cancer treated with IMPT to the pelvic targets were nonrandomly selected. On the repeated quality assurance computed tomography (QACTs) for some patients, bowel density changes were observed and caused dose degradation because the treated plans were not robustly optimized (non-RO). To mitigate this effect, we developed a robust planning method based on 3 CT images, including the native planning CT and its 2 copies, with the bowel structures being assigned to air and tissue, respectively. The RO settings included 5 mm setup uncertainty and 3.5% range uncertainty on 3 CTs. This method is called pseudomultiple-CT RO (pMCT-RO). Plans were also generated using RO on the native CT only, with the same setup and range uncertainties. This method is referred to as single-CT RO (SCT-RO). Doses on the QACTs and the nominal planning CT were compared for the 3 planning methods. RESULTS: All 3 plan methods provided sufficient clinical target volumes D95% and V95% on the QACTs. For pMCT-RO plans, the normal tissue Dmax on QACTs of all patients was at maximum 109.1%, compared with 144.4% and 116.9% for non-RO and SCT-RO plans, respectively. On the nominal plans, the rectum and bladder doses were similar among all 3 plans; however, the volume of normal tissue (excluding the rectum and bladder) receiving the prescription dose or higher is substantially reduced in either pMCT-RO plans or SCT-RO plans, compared with the non-RO plans. CONCLUSIONS: We developed a robust optimization method to further mitigate undesired dose heterogeneity caused by random anatomic changes in pelvic IMPT treatment. This method does not require additional patient CT scans. The pMCT-RO planning method has been implemented clinically since 2017 in our center.

Spatially Fractionated Radiotherapy (GRID) Prior to Standard Neoadjuvant Conventionally Fractionated Radiotherapy for Bulky, High-Risk Soft Tissue and Osteosarcomas: Feasibility, Safety, and Promising Pathologic Response Rates.

Spatially fractionated radiotherapy (GRID) has been utilized primarily in the palliative and definitive treatment of bulky tumors. Delivered in the modern era primarily with megavoltage photon therapy, this technique offers the promise of safe dose escalation with potential immunogenic, bystander and microvasculature effects that can augment a conventionally fractionated course of radiotherapy. At the University of Maryland, an institutional standard has arisen to incorporate a single fraction of GRID radiation in large (>8 cm), high-risk soft tissue and osteosarcomas prior to a standard fractionated course. Herein, we report on the excellent pathologic responses and apparent safety of this regimen in 26 consecutive patients.

The Impact of Radiation Energy on Dose Homogeneity and Organ Dose in the Göttingen Minipig Total-Body Irradiation Model.

Animal models of total-body irradiation (TBI) are used to elucidate normal tissue damage and evaluate the efficacy of medical countermeasures (MCM). The accuracy of these TBI models depends on the reproducibility of the radiation dose-response relationship for lethality, which in turn is highly dependent on robust radiation physics and dosimetry. However, the precise levels of radiation each organ absorbs can change dramatically when different photon beam qualities are used, due to the interplay between their penetration and the natural variation of animal sizes and geometries. In this study, we evaluate the effect of varying the radiation energy, namely cobalt-60 (Co-60); of similar penetration to a 4-MV polyenergetic beam), 6 MV and 15 MV, in the absorbed dose delivered by TBI to individual organs of eight Göttingen minipigs of varying weights (10.3-24.1 kg) and dimensions (17.5-25 cm width). The main organs, i.e. heart, lungs, esophagus, stomach, bowels, liver, kidneys and bladder, were contoured by an experienced radiation oncologist, and the volumetric radiation dose distribution was calculated using a commercial treatment planning system commissioned and validated for Co-60, 6-MV and 15-MV teletherapy units. The dose is normalized to the intended prescription at midline in the abdomen. For each animal and each energy, the body and organ dose volume histograms (DVHs) were computed. The results show that more penetrating photon energies produce dose distributions that are systematically and consistently more homogeneous and more uniform, both within individual organs and between different organs, across all animals. Thoracic organs (lungs, heart) received higher dose than prescribed while pelvic organs (bowel, bladder) received less dose than prescribed, due to smaller and wider separations, respectively. While these trends were slightly more pronounced in the smallest animals (10.3 kg, 19 cm abdominal width) and largest animals (>20 kg, ∼25 cm abdominal width), they were observed in all animals, including those in the 9-15 kg range typically used in MCM models. Some organs received an average absorbed dose representing <80% of prescribed dose when Co-60 was used, whereas all organs received average doses of >87% and >93% when 6 and 15 MV were used, respectively. Similarly, average dose to the thoracic organs reached as high as 125% of the intended dose with Co-60, compared to 115% for 15 MV. These results indicate that Co-60 consistently produces less uniform dose distributions in the Göttingen minipig compared to 6 and 15 MV. Moreover, heterogeneity of dose distributions for Co-60 is accentuated by anatomical and geometrical variations across various animals, leading to different absorbed dose delivered to organs for different animals. This difference in absorbed radiation organ doses, likely caused by the lower penetration of Co-60 and 6 MV compared to 15 MV, could potentially lead to different biological outcomes. While the link between the dose distribution and variation of biological outcome in the Göttingen minipig has never been explicitly studied, more pronounced dose heterogeneity within and between organs treated with Co-60 teletherapy units represents an additional confounding factor which can be easily mitigated by using a more penetrating energy.

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.

Perceptions and Patterns in Academic Publishing: A Survey of United States Residents in Radiation Oncology.

PURPOSE: We aimed to assess perceptions of, and training regarding, the publishing process among US radiation oncology (RO) residents, focusing on awareness and understanding of criteria for selecting appropriate and legitimate peer-reviewed journals for academic publishing. The growing challenge of predatory publication in the broader scientific realm and its relevancy to resident training is also briefly discussed. METHODS AND MATERIALS: A survey was opened to residents of all Accreditation Council for Graduate Medical Education-accredited RO programs in the United States, focusing on 3 categories: (1) demographics; (2) submission, peer review, and publication of academic research; and (3) subjective ranking of factors for choosing an appropriate publisher/journal. Results were stratified by level of training and number of publications. RESULTS: Overall, 150 of 690 residents (19.8%) responded, with a 98% (147 of 150) completion rate. Twenty of 150 residents (13.3%) reported formal training in manuscript preparation and choosing academic journals. Only 3.4% of residents reported departmental guidelines regarding publication in "predatory" journals; 57.7% were unsure. The 3 most important factors influencing publisher and journal choice were impact factor (ranked first for 59.0%), whether a journal is found in a major index (ranked first for 18.0%), and association with a reputable organization (ranked first for 17.0%). Importance of impact factor increased with number of publications (50% with 0 publications, 48.3% with 1-5, 63.9% with 5-10, 76.2% with 10-15, and 70.6% with >15). Cost considerations influenced journal choice at least once for 79 (52.7%) residents. CONCLUSIONS: Impact factor was the most important consideration for residents when choosing an appropriate publisher, with increased emphasis with increasing number of publications. A minority had formal training in choosing appropriate academic journals and knowing how to identify so-called predatory journals or were aware if their department has proscriptions regarding publication in such journals. Additional emphasis on formal training for RO residents in manuscript preparation and choosing academic journals is warranted.

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.

Early Detection of Recurrence in Patients With Locally Advanced Non-Small-Cell Lung Cancer via Circulating Tumor Cell Analysis.

BACKGROUND: Assays to identify circulating tumor cells (CTCs) might allow for noninvasive and sequential monitoring of lung cancer. We investigated whether serial CTC analysis could complement conventional imaging for detecting recurrences after treatment in patients with locally advanced non-small-cell lung cancer (LA-NSCLC). PATIENTS AND METHODS: Patients with LA-NSCLC (stage II-III) who definitively received concurrent chemoradiation were prospectively enrolled, with CTCs from peripheral blood samples identified using an adenoviral probe that detects elevated telomerase activity present in nearly all lung cancer cells. A "detectable" CTC level was defined as 1.3 green flourescent protein-positive cells per milliliter of collected blood. Samples were obtained before, during (at weeks 2, 4, and 6), and after treatment (post-radiation therapy [RT]; at months 1, 3, 6, 12, 18, and 24). RESULTS: Forty-eight patients were enrolled. At a median follow-up of 10.9 months, 22 (46%) patients had disease recurrence at a median time of 7.6 months post-RT (range, 1.3-32.0 months). Of the 20 of 22 patients for whom post-RT samples were obtained, 15 (75%) had an increase in CTC counts post-RT. In 10 of these 15 patients, CTCs were undetectable on initial post-RT draw but were then detected again before radiographic detection of recurrence, with a median lead time of 6.2 months and mean lead time of 6.1 months (range, 0.1-12.0 months) between CTC count increase and radiographic evidence of recurrence. One patient with an early recurrence (4.7 months) had persistently elevated detectable CTC levels during and after treatment. CONCLUSION: These results indicate that longitudinal CTC monitoring in patients with LA-NSCLC treated with chemoradiation is feasible, and that detectable CTC levels in many patients meaningfully precede radiologic evidence of disease recurrence.

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.