Technical note: A comparison of in-house 3D-printed and commercially available patient-specific skin collimators for use with electron beam therapy.

PURPOSE: Skin collimation is a useful tool in electron beam therapy (EBT) to decrease the penumbra at the field edge and minimize dose to nearby superficial organs at risk (OARs), but manually fabricating these collimation devices in the clinic to conform to the patient's anatomy can be a difficult and time intensive process. This work compares two types of patient-specific skin collimation (in-house 3D printed and vendor-provided machined brass) using clinically relevant metrics. METHODS: Attenuation measurements were performed to determine the thickness of each material needed to adequately shield both 6 and 9 MeV electron beams. Relative and absolute dose planes at various depths were measured using radiochromic film to compare the surface dose, flatness, and penumbra of the different skin collimation materials. RESULTS: Clinically acceptable thicknesses of each material were determined for both 6 and 9 MeV electron beams. Field width, flatness, and penumbra results between the two systems were very similar and significantly improved compared to measurements performed with no surface collimation. CONCLUSION: Both skin collimation methods investigated in this work generate sharp penumbras at the field edge and can minimize dose to superficial OARs compared to treatment fields with no surface collimation. The benefits of skin collimation are greatest for lower energy electron beams, and the benefits decrease as the measurement depth increases. Using bolus with skin collimation is recommended to avoid surface dose enhancement seen with collimators placed on the skin surface. Ultimately, the appropriate choice of material will depend on the desire to create these devices in-house or outsource the fabrication to a vendor.

Disease Control after Radiotherapy for Adult Craniopharyngioma: Clinical Outcomes from a Large Single-Institution Series.

PURPOSE: To report disease control and treatment-related side effects among adult patients with craniopharyngioma treated with radiotherapy. METHODS: We performed a single-institution review of adult patients (> 21 years old) with craniopharyngioma treated with radiotherapy either definitively or postoperatively for gross residual disease. We report disease control, survival, and radiotherapy-related side effects. RESULTS: A total of 49 adult patients with craniopharyngioma were included, 27 of whom were treated at initial presentation and 22 for recurrent disease following initial surgery and observation. Overall, 77% received radiotherapy postoperatively (either after primary surgery or surgery for recurrence). With a median clinical and radiographic follow-up of 4.2 (range, 0.4-21.6) years and 3.0 (range, 0-21.5) years, the 5- and 10-year local control rates were 100 and 94%, respectively. The 5- and 10-year overall survival rates were 80 and 66%, respectively. Eleven percent of patients experienced grade 2 vision deterioration and 18% suffered grade 2 endocrinopathies following radiotherapy. CONCLUSIONS: Radiotherapy provides excellent disease control with acceptable toxicity among adult patients with craniopharyngioma. These data support the use of fractionated radiotherapy in adult patients with recurrent or gross residual disease after surgery. For inoperable patients or those with moderate or high surgical risk to neurologic and/or vascular structures, we advocate for limited surgical resection and postoperative radiotherapy to balance optimal tumor control with tumor- and treatment-related morbidity.

The incidence of brainstem toxicity following high-dose conformal proton therapy for adult skull-base malignancies.

BACKGROUND: Dose escalation for skull-based malignancies often presents risks to critical adjacent neural structures, including the brainstem. We report the incidence of brainstem toxicity following fractionated high-dose conformal proton therapy and associated dosimetric parameters. MATERIAL AND METHODS: We performed a single-institution review of patients with skull-base chordoma or chondrosarcoma who were treated with proton therapy between February 2007 and January 2020 on a prospective outcomes-tracking protocol. The primary endpoint was grade ≥2 brainstem toxicity. No patients received concurrent chemotherapy, and brainstem toxicity was censored for analysis if it coincided with local disease progression. RESULTS: We analyzed 163 patients who received a minimum of 45 GyRBE to 0.03 cm3 of the brainstem. Patients were treated to a median total dose of 73.8 (range 64.5-74.4) GyRBE at 1.8 GyRBE per fraction with 17 patients undergoing twice-daily treatment at 1.2 GyRBE per fraction. With a median follow-up of 4 years, the 5-year cumulative incidence of grade ≥2 brainstem injury was 1.3% (95% CI 0.25-4.3%). There was one grade 2, one grade 3, and no grade 4 or 5 events, with all patients recovering function with medical management. CONCLUSION: In delivering curative-intent radiotherapy for skull-base chordoma and chondrosarcoma in adults, small volumes of the brainstem can safely receive at least 64 GyRBE with minimal risk of serious brainstem injury.

Proton therapy for adult medulloblastoma: Acute toxicity and disease control outcomes.

PURPOSE: We report disease control, survival outcomes, and treatment-related toxicity among adult medulloblastoma patients who received proton craniospinal irradiation (CSI) as part of multimodality therapy. METHODS: We reviewed 20 adults with medulloblastoma (≥ 22 years old) who received postoperative proton CSI ± chemotherapy between 2008 and 2020. Patient, disease, and treatment details and prospectively obtained patient-reported acute CSI toxicities were collected. Acute hematologic data were analyzed. RESULTS: Median age at diagnosis was 27 years; 45% of patients had high-risk disease; 75% received chemotherapy, most (65%) after CSI. Eight (40%) patients received concurrent vincristine with radiotherapy. Median CSI dose was 36GyE with a median tumor bed boost of 54GyE. Median duration of radiotherapy was 44 days. No acute ≥ grade 3 gastrointestinal or hematologic toxicities attributable to CSI occurred. Grade 2 nausea and vomiting affected 25% and 5% of patients, respectively, while 36% developed acute grade 2 hematologic toxicity (36% grade 2 leukopenia and 7% grade 2 neutropenia). Those receiving concurrent chemotherapy with CSI had a 38% rate of grade 2 hematologic toxicity compared to 33% among those not receiving concurrent chemotherapy. Among patients receiving adjuvant chemotherapy (n = 13), 100% completed ≥ 4 cycles and 85% completed all planned cycles. With a median follow-up of 3.1 years, 4-year actuarial local control, disease-free survival, and overall survival rates were 90%, 90%, and 95%, respectively. CONCLUSIONS: Proton CSI in adult medulloblastoma patients is very well tolerated and shows promising disease control and survival outcomes. These data support the standard use of proton CSI for adult medulloblastoma.

The Role of Radiation Therapy for Symptomatic Desmoid Tumors.

OPINION STATEMENT: Desmoid tumors have a variable clinical course that ranges from indolence or spontaneous regression to an aggressive pattern marked by local invasion. Up to half may remain stable or regress; watchful waiting is the preferred approach in the initial management of desmoid tumors. Symptomatic or progressive tumors or those that may affect adjacent critical structures require surgery, radiotherapy, or systemic therapy. Although radiotherapy effectively controls desmoid tumors in most cases, concerns regarding late toxicity exist. Definitive radiotherapy for macroscopic disease is indicated when a non-morbid complete surgical resection cannot be accomplished and provides similar control rates to surgery plus radiotherapy but avoids toxicity from combined-modality treatment (surgery and radiotherapy). Adjuvant radiotherapy can be considered for microscopically involved margins, particularly for recurrent cases or when a future recurrence may be challenging to treat. Large size, extremity site, and younger age are poor prognostic factors after radiotherapy. In the extremity, radiotherapy may have superior outcomes to surgery. Younger patients, especially children, are challenging to manage as they are at particular risk for late toxicity due to the number of potential years at risk. For patients under 20 years old, for whom a non-morbid complete resection is not possible, we recommend systemic therapy as the first line of treatment. Although the long-term efficacy of systemic therapy is unproven, this strategy allows additional time for growth and development prior to radiotherapy. In younger patients and those with axial desmoid tumors adjacent to critical organs, consideration should be given to using proton therapy as the dosimetric advantages may mitigate some of the toxicity associated with conventional radiotherapy.

LSD2/KDM1B and its cofactor NPAC/GLYR1 endow a structural and molecular model for regulation of H3K4 demethylation.

Dynamic regulation of histone methylation represents a fundamental epigenetic mechanism underlying eukaryotic gene regulation, yet little is known about how the catalytic activities of histone demethylases are regulated. Here, we identify and characterize NPAC/GLYR1 as an LSD2/KDM1b-specific cofactor that stimulates H3K4me1 and H3K4me2 demethylation. We determine the crystal structures of LSD2 alone and LSD2 in complex with the NPAC linker region in the absence or presence of histone H3 peptide, at resolutions of 2.9, 2.0, and 2.25 Å, respectively. These crystal structures and further biochemical characterization define a dodecapeptide of NPAC (residues 214-225) as the minimal functional unit for its cofactor activity and provide structural determinants and a molecular mechanism underlying the intrinsic cofactor activity of NPAC in stimulating LSD2-catalyzed H3K4 demethylation. Thus, these findings establish a model for how a cofactor directly regulates histone demethylation and will have a significant impact on our understanding of catalytic-activity-based epigenetic regulation.

Clinical outcomes following proton therapy for adult craniopharyngioma: a single-institution cohort study.

BACKGROUND: Craniopharyngioma is a benign tumor that commonly develops within the suprasellar region. The tumor and treatment can have debilitating consequences for pediatric and adult patients, including vision loss and pituitary/hypothalamic dysfunction. Most craniopharyngioma series focus on treatment of the pediatric population. We evaluated the outcomes of all adult craniopharyngioma patients treated at our institution using proton therapy to report outcomes for disease control, treatment-related toxicity, and tumor response. METHODS: We analyzed 14 adult patients (≥ 22 years old). All patients had gross disease at the time of radiotherapy. Five were treated for de novo disease and 9 for recurrent disease. Patients received double-scattered conformal proton therapy to a mean dose of 54 GyRBE in 1.8 GyRBE/fraction (range 52.2-54 GyRBE). Weekly magnetic resonance imaging (MRI) helped to evaluate tumor changes during radiotherapy. RESULTS: With median clinical and radiographic follow-up of 29 and 26 months, respectively, the 3-year local control and overall survival rates were both 100%. There were no grade 3 or greater acute or late radiotherapy-related side effects. There was no radiotherapy-related vision loss or optic neuropathy. No patients required intervention or treatment replanning due to tumor changes during radiotherapy. Two patients experienced transient cyst expansion at their first post-radiotherapy MRI. Both patients were followed closely clinically and radiographically and had subsequent dramatic tumor/cyst regression, requiring no interventions. CONCLUSIONS: Our data support the safety and efficacy of proton therapy in the treatment of adult craniopharyngioma as part of primary or salvage treatment. We recommend early consideration of radiotherapy. This trial was registered at www.clinicaltrials.gov as #NCT03224767.

Proton therapy for skull-base chondrosarcoma, a single-institution outcomes study.

BACKGROUND: We sought to evaluate the effectiveness of definitive or adjuvant external-beam proton therapy on local control and survival in patients with skull-base chondrosarcoma. METHODS: We reviewed the medical records of 43 patients with a median age of 49 years (range, 23-80 years) treated with double-scattered 3D conformal proton therapy for skull-base chondrosarcomas between January 2007 and February 2016. Proton therapy-related toxicities were scored using CTCAE v4.0. RESULTS: The median radiotherapy dose was 73.8 Gy(RBE) (range, 64.5-74.4 Gy[RBE]). Thirty-six (84%) and 7 (16%) patients underwent surgical resection or biopsy alone. Tumor grade distribution included: grade 1, 19 (44%) patients; grade 2, 22 (51%); and grade 3, 2 (5%). Forty patients had gross disease at the time of radiotherapy and 7 patients were treated for locally recurrent disease following surgery. The median follow-up was 3.7 years (range, 0.7-10.1 years). There were no acute grade 3 toxicities related to RT. At 4 years following RT, actuarial rates of overall survival, cause-specific survival, local control, and RT-related grade 3 toxicity-free survival were 95%, 100%, 89%, and 95%. CONCLUSION: High-dose, double-scattered 3D conformal proton therapy alone or following surgical resection for skull-base chondrosarcoma is an effective treatment with a high rate of local control with no acute grade 3 radiation-related toxicity. Further follow-up of this cohort is necessary to better characterize long-term disease control and late toxicities.

A comprehensive dosimetric study of Monte Carlo and pencil-beam algorithms on intensity-modulated proton therapy for breast cancer.

PB algorithms are commonly used for proton therapy. Previously reported limitations of the PB algorithm for proton therapy are mainly focused on high-density gradients and small-field dosimetry, the effect of PB algorithms on intensity-modulated proton therapy (IMPT) for breast cancer has yet to be illuminated. In this study, we examined 20 patients with breast cancer and systematically investigated the dosimetric impact of MC and PB algorithms on IMPT. Four plans were generated for each patient: (a) a PB plan that optimized and computed the final dose using a PB algorithm; (b) a MC-recomputed plan that recomputed the final dose of the PB plan using a MC algorithm; (c) a MC-renormalized plan that renormalized the MC-recomputed plan to restore the target coverage; and (d) a MC-optimized plan that optimized and computed the final dose using a MC algorithm. The DVH on CTVs and on organ-at-risks (OARs) from each plan were studied. The Mann-Whitney U-test was used for testing the differences between any two types of plans. We found that PB algorithms significantly overestimated the target dose in breast IMPT plans. The median value of the CTV D99% , D95% , and Dmean dropped by 3.7%, 3.4%, and 2.1%, respectively, of the prescription dose in the MC-recomputed plans compared with the PB plans. The magnitude of the target dose overestimation by the PB algorithm was higher for the breast CTV than for the chest wall CTV. In the MC-renormalized plans, the target dose coverage was comparable with the original PB plans, but renormalization led to a significant increase in target hot spots as well as skin dose. The MC-optimized plans led to sufficient target dose coverage, acceptable target hot spots, and good sparing of skin and other OARs. Utilizing the MC algorithm for both plan optimization and final dose computation in breast IMPT treatment planning is therefore desirable.

Human LSD2/KDM1b/AOF1 regulates gene transcription by modulating intragenic H3K4me2 methylation.

Dynamic histone H3K4 methylation is an important epigenetic component of transcriptional regulation. However, most of our current understanding of this histone mark is confined to the regulation of transcriptional initiation. We now show that human LSD2/KDM1b/AOF1, the human homolog of LSD1, is an H3K4me1/2 demethylase that specifically regulates histone H3K4 methylation within intragenic regions of its target genes. Genome-wide mapping reveals that LSD2 associates predominantly with the gene bodies of actively transcribed genes, but is markedly absent from promoters. Depletion of endogenous LSD2 results in an increase of H3K4me2 as well as a decrease of H3K9me2 at LSD2-binding sites and a consequent dysregulation of target gene transcription. Furthermore, characterization of the LSD2 complex reveals that LSD2 forms active complexes with euchromatic histone methyltransferases G9a and NSD3 as well as cellular factors involved in transcription elongation. These data provide a possible molecular mechanism linking LSD2 to transcriptional regulation after initiation.

Prompt Pain Relief From Bone Metastases: The Virtual Simulation Program.

Purpose: Rapid pain relief for patients with bone metastases can be a challenge due to the lengthy and complex radiation therapy workflow. The purpose of this study was to evaluate the time (in days) between initial radiation oncology consultation and start of palliative radiation treatment after implementing an alternative virtual simulation palliative workflow. Methods and Materials: Patients meeting strict criteria were selected for virtual simulation, which included only those with painful bone metastases who were recommended palliative radiation therapy using standard anterior-posterior/posterior-anterior or opposed lateral fields. A recent (within 30 days) diagnostic computed tomography (CT) scan clearly visualizing the target volume was required for treatment planning. For comparison, a reference group of 40 consecutive patients with bone metastases who underwent in-person CT simulation before virtual simulation implementation was reviewed. Results: Forty-five patients were treated for painful bone metastases as part of the virtual simulation program from May 2021 to October 2022. Regarding travel distance, 23 patients lived locally (<50 miles from the treatment center) and 22 patients were distant (≥50 miles from the treatment center). Average time from consultation to treatment for all patients undergoing virtual simulation was 3.7 days, compared with 7.5 days for patients undergoing in-person CT simulation (3.8 days sooner, on average; P ≤ .001). Before full implementation of the virtual simulation program, 5 eligible patients participated in a virtual simulation pilot from April 2021 to May 2021, in which each patient was contoured and planned on both a pre-existing diagnostic CT scan and a standard CT simulation scan. For virtual simulation-based plans, the average V90, V95, and V99 were 99.99%, 99.87%, and 96.70%. No significant planning target volume (PTV) coverage difference was found on subsequent in-person CT simulation scans. Conclusions: The virtual simulation program decreased the time from consultation to start of treatment by more than 50% for patients recommended palliative radiation therapy for painful bone metastases. This benefit was most significant for outpatients traveling ≥50 miles for treatment. Virtual simulation-based planning can be considered for patients anxious to proceed with radiation therapy quickly or in underserved settings with limited transportation options to regional treatment centers.

The histone H3K4 demethylase SMCX links REST target genes to X-linked mental retardation.

Gene transcription is critically influenced by chromatin structure and the modification status of histone tails. Methylation of lysine residues in histone tails is dynamically regulated by the opposing activities of histone methyltransferases and histone demethylases. Here we show that JARID1C/SMCX, a JmjC-domain-containing protein implicated in X-linked mental retardation and epilepsy, possesses H3K4 tri-demethylase activity and functions as a transcriptional repressor. An SMCX complex isolated from HeLa cells contains additional chromatin modifiers (the histone deacetylases HDAC1 and HDAC2, and the histone H3K9 methyltransferase G9a) and the transcriptional repressor REST, suggesting a direct role for SMCX in chromatin dynamics and REST-mediated repression. Chromatin immunoprecipitation reveals that SMCX and REST co-occupy the neuron-restrictive silencing elements in the promoters of a subset of REST target genes. RNA-interference-mediated depletion of SMCX derepresses several of these targets and simultaneously increases H3K4 trimethylation at the sodium channel type 2A (SCN2A) and synapsin I (SYN1) promoters. We propose that loss of SMCX activity impairs REST-mediated neuronal gene regulation, thereby contributing to SMCX-associated X-linked mental retardation.

Future Perspective: Carbon Ion Radiotherapy for Head and Neck and Skull Base Malignancies.

Head and neck and base of skull malignancies are challenging for surgical and radiotherapy treatment due to the density of sensitive tissues. Carbon ion radiotherapy (CIRT) is a form of heavy particle therapy that uses accelerated carbon ions to treat malignancies that may be radioresistant or in challenging anatomic locations. CIRT has an increased biological effectiveness (ie, increased cell killing) at the end of the range of the carbon beam (ie, within the target tissue) but not in the entrance dose. This increased biological effectiveness can overcome the effects of radioresistant tumors, tissue hypoxia, and the need for radiotherapy fractionation.

Targeting KRAS in pancreatic adenocarcinoma: Progress in demystifying the holy grail.

Pancreatic cancer (PC) remains one of the most challenging diseases, with a very poor 5-year overall survival of around 11.5%. Kirsten rat sarcoma virus (KRAS) mutation is seen in 90%-95% of PC patients and plays an important role in cancer cell proliferation, differentiation, metabolism, and survival, making it an essential mutation for targeted therapy. Despite extensive efforts in studying this oncogene, there has been little success in finding a drug to target this pathway, labelling it for decades as "undruggable". In this article we summarize some of the efforts made to target the KRAS pathway in PC, discuss the challenges, and shed light on promising clinical trials.

Proton Therapy With Concurrent Chemotherapy for Thoracic Esophageal Cancer: Toxicity, Disease Control, and Survival Outcomes.

Purpose: When treating esophageal cancer with radiation therapy, it is critical to limit the dose to surrounding structures, such as the lung and/or heart, as much as possible. Proton radiation therapy allows a reduced radiation dose to both the heart and lungs, potentially reducing the risk of cardiopulmonary toxicity. Here, we report disease control, survival, and toxicity outcomes among patients with esophageal cancer treated with proton radiation therapy and concurrent chemotherapy (chemoradiation therapy; CRT) with or without surgery. Materials and Methods: We enrolled 17 patients with thoracic esophageal carcinoma on a prospective registry between 2010 and 2021. Patients received proton therapy to a median dose of 50.4-GyRBE (range, 50.4-64.8) in 1.8-Gy fractions.Acute and late toxicities were graded per the Common Terminology Criteria for Adverse Events, version 4.0 (US National Cancer Institute, Bethesda, Maryland). In addition, disease control, patterns of failure, and survival outcomes were collected. Results: Nine patients received preoperative CRT, and 8 received definitive CRT. Overall, 88% of patients had adenocarcinoma, and 12% had squamous cell carcinoma. With a median follow-up of 2.1 years (range, 0.5-9.4), the 3-year local progression-free, disease-free, and overall survival rates were 85%, 66%, and 55%, respectively. Two patients (1 with adenocarcinoma and 1 with squamous cell carcinoma) recurred at the primary site after refusing surgery after a complete clinical response to CRT. The most common acute nonhematologic and hematologic toxicities, respectively, were grades 1 to 3 esophagitis and grades 1 to 4 leukopenia, both affecting 82% of patients. No acute cardiopulmonary toxicities were observed in the absence of surgical resection. Reagarding surgical complications, 3 postoperative cardiopulmonary complications occurred as follows: 1 grade 1 pleural effusion, 1 grade 3 pleural effusion, and 1 grade 2 anastomotic leak. Two severe late CRT toxicities occurred: 1 grade 5 tracheoesophageal fistula and 1 grade 3 esophageal stenosis requiring a feeding tube. Conclusion: Proton radiation therapy is a safe, effective treatment for esophageal cancer with increasing evidence supporting its role in reducing cardiopulmonary toxicity.

Carbon Ion Radiotherapy: An Evidence-Based Review and Summary Recommendations of Clinical Outcomes for Skull-Base Chordomas and Chondrosarcomas.

Skull-base chordoma and chondrosarcoma are rare radioresistant tumors treated with surgical resection and/or radiotherapy. Because of the established dosimetric and biological benefits of heavy particle therapy, we performed a systematic and evidence-based review of the clinical outcomes of patients with skull-base chordoma and chondrosarcoma treated with carbon ion radiotherapy (CIRT). A literature review was performed using a MEDLINE search of all articles to date. We identified 227 studies as appropriate for review, and 24 were ultimately included. The published data illustrate that CIRT provides benchmark disease control outcomes for skull-base chordoma and chondrosarcoma, respectively, with acceptable toxicity. CIRT is an advanced treatment technique that may provide not only dosimetric benefits over conventional photon therapy but also biologic intensification to overcome mechanisms of radioresistance. Ongoing research is needed to define the magnitude of benefit, patient selection, and cost-effectiveness of CIRT compared to other forms of radiotherapy.

Dose-escalated proton therapy with elective nodal irradiation and concomitant chemotherapy for unresectable, borderline resectable, or medically inoperable pancreatic cancer: a phase II trial.

Background: To report outcomes of a phase II single-institution trial of dose-escalated proton radiotherapy with elective nodal irradiation (ENI) and concomitant chemotherapy for patients with unresectable, borderline resectable, or medically inoperable pancreatic adenocarcinoma. Methods: Patients received 40.5 GyRBE in 18 fractions to the gross disease and elective nodal volumes followed by 22.5 GyRBE as a 10-fraction boost to the gross disease for a cumulative dose of 63 GyRBE over 28 fractions. Oral capecitabine (1,000 mg taken orally twice daily) was given on radiation treatment days. The primary objective of this study was to improve the proportion surviving to at least 1 year from the historical rate of 50% to 75%. Secondary objectives included assessing gastrointestinal (GI) toxicity and weight loss during treatment, and evaluating the safety of subsequent surgical resection. This single-institution study was closed to accrual early after the opening of the multicenter PAN009-18 trial by the Proton Collaborative Group (PCG), which follows a similar protocol. Results: At enrollment, 10 (67%) patients had unresectable disease, 3 (20%) had borderline-resectable disease, and 2 (13%) refused surgery. All 15 patients successfully completed radiation therapy as prescribed. With regard to toxicity, a single patient experienced grade 3 nausea requiring cessation of capecitabine, which ultimately resolved by treatment completion. The median percentage weight loss during treatment was -3.0% (range, -9.6% to +12.0%). Two (13%) initially borderline patients ultimately underwent R0 resection: their total operating room times were 267 and 410 minutes, and blood loss was 700 and 400 mL, respectively. Neither patient experienced intraoperative or postoperative complications. Both were discharged on postoperative day 6. The median follow-up was 0.93 years (range, 0.21 to 2.14 years). The 1-year overall survival (OS) rate was 47%. Three enrolled patients are currently alive: 2 with no evidence of disease and 1 with stable disease. Conclusions: The primary objective of 1-year OS of 75% was not reached. Proton therapy was well-tolerated. Patients undergoing surgery did not experience operative or perioperative complications, suggesting that patients with borderline resectable or even resectable disease may benefit from neoadjuvant proton therapy. The PCG will test this premise as patients accrue to the multicenter PAN009-18 trial. Trial Registration: NCT02598349.

Patterns-of-care disparities among uninsured versus insured patients with anorectal carcinoma referred for radiotherapy at an Urban Safety-Net Hospital.

Background: To compare patterns-of-care and clinical outcomes among uninsured versus insured patients (IPs) with anorectal malignancies referred for radiotherapy at an urban safety-net hospital. This topic is important because uninsured patients (UPs) in the US often have limited access to health care, which can result in worse health outcomes. Methods: We reviewed the medical records of 59 patients with biopsy-proven, non-metastatic anal and rectal cancers who received curative-intent primary or neoadjuvant/adjuvant radiotherapy between May 2002 and August 2012. Data regarding patient and disease characteristics, weight loss, insurance status at symptom onset, date of first therapeutic intervention, and survival status at last follow-up, were collected and analyzed. Results: The percentage of IPs presenting with T4 tumors was 7% versus 40% among the uninsured (P=0.005). The median interval between first symptom onset and diagnosis date was 89 (range, 0-1,428) days for IPs and 221 (range, 0-1,576) days for UPs (P=0.01). The median interval between first symptom onset and treatment initiation was 172 (range, 9-1,498) days for IPs and 302 (range, 35-1,624 days) days for UPs (P=0.01). The 5-year overall survival rate was 59% for the entire cohort, 62% for the insured patients, and 55% for the uninsured patients (P=0.76). Conclusions: Differences in health insurance status demonstrated various disparities in patterns-of-care, including significant delay in diagnosis, more advanced-stage disease at presentation, and treatment initiation delays among UPs. Nevertheless, overall survival at 5 years was not statistically significant between the insured and the uninsured.