Radiation-based Treatment Research Articles

LI-RADS radiation-based treatment response algorithm for HCC: what to know and how to use it.

Locoregional treatments (LRT) continue to advance for hepatocellular carcinoma (HCC). Selective internal radiation therapy (SIRT) or transarterial radioembolization (TARE) with radioactive 90 Yttrium (Y90) microspheres is currently widely accepted, and external beam and stereotactic body radiation (EBRT/SBRT) are increasingly used as LRT1-5. Assessment of treatment response after these radiation-based therapies can be challenging, given that the adjacent liver also undergoes treatment related changes, inflammatory changes occur, and there is a variable time for response to develop. In 2017, the liver imaging reporting and data system (LI-RADS) workgroup initially developed a single algorithm for the imaging assessment of treatment response encompassing all types of locoregional therapies, the LI-RADS treatment response (LR-TR) algorithm. Recognizing that response and imaging patterns differ between radiation and non-radiation based therapies, the LR-TR working group recently updated the algorithm to reflect the unique characteristics of tumor response for therapies involving radiation. This article aims to elucidate the changes in the new version of the LI-RADS TR, with a guide for algorithm utilization and illustration of expected and unexpected findings post liver directed therapies for HCC.

Performance evaluation of an inorganic optical fibre dosimeter for use in external beam radiotherapy with pulsed beams

Objective. Optical fibre dosimeters (OFDs) offer great promise for real-timein vivodose measurement in radiation-based treatment modalities such as radiotherapy and brachytherapy. This is attributed to their many useful qualities such as high spatial resolution and sensitivity. However, there are several requirements that an optical fibre dosimeter must meet to be acceptable for dose measurement in a specified treatment modality. In this work, the dosimetric performance of a novel optical fibre dosimeter for use in external beam radiotherapy is presented.Approach. The dosimeter was characterised for photon beam energies between 6-15 MV using a Varian TrueBeam Linac at dose rates between 100-2400 MU/min and assessed based on its repeatability, dose dependence, dose rate dependence, energy dependence and dose-per-pulse dependence.Main Results. The results demonstrated excellent short-term repeatability of 0.3%, good linearity in response (R2>0.9997), and minor dose rate dependence between 0.53%-2.49% for all beam qualities investigated. As the scintillator of the OFD is non-water equivalent, Monte-Carlo-TOPAS simulations were used to calculate the absorbed dose energy dependence. A dose-per-pulse dependence was also investigated and compared with dosimetry measurements made with an ionisation chamber and simulated from the treatment planning system. An over-response of 20%was found at the lowest investigated dose-per-pulse, and an under-response of 34%was found at the highest investigated dose-per-pulse. This is believed to be due to an intrinsic energy dependence making this type of OFD unsuitable for external beam radiotherapy dosimetry.Significance. The OFD evaluated in this work was primarily designed for high-dose-rate brachytherapy whereas this study includes the first measurements made in external beam radiotherapy and highlights the challenges of transferability of the dosimeter to a different radiation source.

Leveraging tardigrade proteins Dsup and CAHS D for enhanced neural protection in neurosurgery and neuroscience.

Tardigrades are microscopic organisms known for their remarkable resilience to extreme environmental conditions, including radiation and desiccation. Two key proteins, Dsup (Damage suppressor protein) and CAHS D (Cytoplasmic Abundant Heat Soluble protein D), play crucial roles in this resilience. Dsup protects DNA from radiation-induced damage, while CAHS D stabilizes cellular structures during desiccation by interacting with, but not retaining, water. These unique mechanisms have significant potential applications in neurosurgery and neuroscience. Dsup could inspire the development of protective agents for neural tissues during radiation-based treatments, minimizing collateral damage and improving patient outcomes. Meanwhile, CAHS D's stabilization properties could lead to new neuroprotective strategies, safeguarding brain cells under stress. Together, these tardigrade proteins offer innovative solutions for enhancing neural protection, opening new avenues for treating neurological conditions and improving the safety and efficacy of neurosurgical procedures.

Tunable X-ray-induced luminescence in lanthanide-doped LaPO4 nanoparticles

X-ray luminescent nanoparticles have gained significant attention as promising tools for implementing multimodal imaging and radiation-based treatments in theragnostics. The intricate comprehension of their properties and the underlying mechanisms driving the conversion of X-rays into light is critical for their success in various applications. LaPO4 nanoparticles doped with various individual luminescence centers, gadolinium (Gd3+), europium (Eu3+), dysprosium (Dy3+), and terbium (Tb3+), were produced via co-precipitation and investigated for their behavior upon X-ray excitation using energies of up to 225 kV. These materials evidenced a radioluminescent response dependent on the dopant concentrations, with emission lines from 300 to 700 nm, providing insights into the luminescence quenching effect in these structures. The luminescent characteristics of the nanoparticles were studied under continuous irradiation, evidencing the materials’ ability to withstand high absorbed doses and preserve their properties. Furthermore, the influence of dopant concentrations on crystallite size and the dependence of luminescence on thermal treatments was investigated. The assessment of nanoparticle stability in aqueous suspension was evaluated over a broad pH range, revealing a tendency of the LaPO4 surface to selectively interact with electropositive species. This insight enhances our comprehension of the colloidal stability of the material, positioning it for extended applications and in vitro evaluations, along with further surface functionalization.

Radiation combined with ultrasound and microbubbles: A potential novel strategy for cancer treatment

Cancer is one of the leading causes of death worldwide. Several emerging technologies are helping to battle cancer. Cancer therapies have been effective at killing cancer cells, but a large portion of patients still die to this disease every year. As such, more aggressive treatments of primary cancers are employed and have been shown to be capable of saving a greater number of lives. Recent research advances the field of cancer therapy by employing the use of physical methods to alter tumor biology. It uses microbubbles to enhance radiation effect by damaging tumor vasculature followed by tumor cell death. The technique can specifically target tumor volumes by conforming ultrasound fields capable of microbubbles stimulation and localizing it to avoid vascular damage in surrounding tissues. Thus, this new application of ultrasound-stimulated microbubbles (USMB) can be utilized as a novel approach to cancer therapy by inducing vascular disruption resulting in tumor cell death. Using USMB alongside radiation has showed to augment the anti-vascular effect of radiation, resulting in enhanced tumor response. Recent work with nanobubbles has shown vascular permeation into intracellular space, extending the use of this new treatment method to potentially further improve the therapeutic effect of the ultrasound-based therapy. The significant enhancement of localized tumor cell kill means that radiation-based treatments can be made more potent with lower doses of radiation. This technique can manifest a greater impact on radiation oncology practice by increasing treatment effectiveness significantly while reducing normal tissue toxicity. This review article summarizes the past and recent advances in USMB enhancement of radiation treatments. The review mainly focuses on preclinical findings but also highlights some clinical findings that use USMB as a therapeutic modality in cancer therapy.

Very delayed CSF leak in patients after craniotomy for resection of skull base tumors

ObjectiveCerebrospinal fluid (CSF) leak is a potentially dangerous neurosurgical complication. Delayed CSF leak has already been described after trauma, radiation therapy and endonasal transsphenoidal surgery for Sella turcica pathologies. Still, very few reported cases describe delayed CSF leak after craniotomy for tumors. We present our experience with patients showing delayed CSF leak after skull base tumor resection. MethodsData for all tumors resected from the skull base region from January 2004 to December 2018 was retrieved from the surgeon’s prospective database and supplemented with a retrospective file review. Patients who presented CSF leak within the first 12 months after surgery and those with a history of trauma or radiation-based treatment to the skull base region were excluded from the study. Epidemiology, clinical presentation, previous surgical approach, pathology, interval between craniotomy and CSF leak and proposed treatment were analyzed. ResultsOverall, more than two thousand patients underwent surgery for resection of skull base tumors during the study period. Six patients (two male, four female; mean age 57.5 years, range 30–80) presented with delayed CSF leak, including five (83%) who presented with bacterial meningitis. After skull base tumor resection, CSF leak developed in a mean of 72 months (range 12–132). Three patients underwent retrosigmoid craniotomy, two for resection of cerebellopontine angle epidermoid cyst and one for resection of a petro tentorial meningioma; one had trans petrosal retrolabyrinthine craniotomy for resection of a petroclival epidermoid cyst; one had far lateral craniotomy for resection of a foramen magnum meningioma; and one had pterional craniotomy for resection of a cavernous sinus meningioma. All patients underwent surgical re-exploration and repair. CSF leak was managed with mastoid obliteration in five patients and skull base reconstruction with fat graft in one. ConclusionRecognition of very delayed CSF leak as a potential complication after resection of skull base tumors may be useful tool in long-term patient management. In our experience, these patients usually present with bacterial meningitis. Surgical options should be considered as a definitive treatment.

Meningiomas and Somatostatin Analogs: A Systematic Scoping Review on Current Insights and Future Perspectives.

Meningioma is the most frequent brain tumor, and the incidence is ever-increasing. Though often benign and slow growth, recurrence rates are substantial and today's surgical and radiation-based treatment are not without complications. No drugs specific for meningiomas are hitherto approved and patients with inoperable or recurrent meningioma are left with few treatment options. Somatostatin receptors are previously detected in meningiomas and may inhibit growth when stimulated by somatostatin. Hence, somatostatin analogs could provide a targeted drug therapy. The aim of this study was to compile the current insights of somatostatin analogs for patients with meningioma. This paper adheres to the PRISMA extension for Scoping Reviews. A systematic search was conducted in the search databases PubMed, Embase via Ovid, and Web of Science. Seventeen papers adhered to the inclusion and exclusion criteria, and critical appraisal was conducted. The overall quality of evidence is low, as none of the studies were randomized or controlled. Various efficacy of somatostatin analogs is reported, and adverse effects are sparse. Due to the beneficial effects reported by some studies, somatostatin analogs may offer a novel last-option treatment for severely ill-patients. Nonetheless, only a controlled study, preferably a randomized clinical trial, could clarify the efficacy of somatostatin analogs.

ASO Visual Abstract: Distinct Failure Patterns in Hypopharyngeal Cancer Patients Receiving Surgery-Based Versus Radiation-Based Treatment.

ASO Visual Abstract: Distinct Failure Patterns in Hypopharyngeal Cancer Patients Receiving Surgery-Based Versus Radiation-Based Treatment.

Distinct Failure Patterns in Hypopharyngeal Cancer Patients Receiving Surgery-Based Versus Radiation-Based Treatment

BackgroundTo cure advanced hypopharyngeal squamous cell carcinoma (HPSCC), primary operation followed by adjuvant (chemo-)radiotherapy (OP-CRT) or definitive chemoradiation (CCRT) are the two primary options. This study aimed to compare the failure patterns and long-term survival outcomes of HPSCC patients treated with these two strategies.Patients and MethodsFrom 2007 to 2015, 198 pathologically confirmed HPSCC patients receiving either OP-CRT or CCRT were retrospectively reviewed. Failure patterns and survival outcomes stratified by the 7th American Joint Committee on Cancer staging system and treatment modalities were compared.ResultsOne hundred and eighty-nine patients (95.4%) were stage III/IV and 62 patients (31.3%) received OP-CRT. Median follow-up duration was 4.9 years. Compared with CCRT, OP-CRT provided better 3-year local relapse-free survival for T3 (93 vs 48%, p < 0.0001), T4a (88 vs 37%, p = 0.0005) and better 3-year regional relapse-free survival for N2b+2c (93 vs 60%, p < 0.0001). Of note, for stage IVA subjects, OP-CRT provided better 3-year loco-regional relapse-free survival (85 vs 37%, p < 0.0001), marginal poor 3-year distant metastasis-free survival (62 vs 79%, p = 0.06), but comparable 3-year OS (52 vs 44%, p = 0.37) and 5-year OS (44 vs 31%, p = 0.15) compared with CCRT.ConclusionsFor patients with advanced HPSCC, although OP-CRT and CCRT provided similar overall survival, failure patterns were distinct. OP-CRT provided better loco-regional control but was more likely to encounter distant metastases than CCRT. The detailed analysis of failure patterns will pave the way to improve this devastating disease.

Understanding the Radiobiological Mechanisms Induced by 177Lu-DOTATATE in Comparison to External Beam Radiation Therapy.

Radionuclide Therapy (RNT) with 177Lu-DOTATATE targeting somatostatin receptors (SSTRs) in neuroendocrine tumours (NET) has been successfully used in routine clinical practice, mainly leading to stable disease. Radiobiology holds promise for RNT improvement but is often extrapolated from external beam radiation therapy (EBRT) studies despite differences in these two radiation-based treatment modalities. In a panel of six human cancer cell lines expressing SSTRs, common radiobiological endpoints (i.e., cell survival, cell cycle, cell death, oxidative stress and DNA damage) were evaluated over time in 177Lu-DOTATATE- and EBRT-treated cells, as well as the radiosensitizing potential of poly (ADP-ribose) polymerase inhibition (PARPi). Our study showed that common radiobiological mechanisms were induced by both 177Lu-DOTATATE and EBRT, but to a different extent and/or with variable kinetics, including in the DNA damage response. A higher radiosensitizing potential of PARPi was observed for EBRT compared to 177Lu-DOTATATE. Our data reinforce the need for dedicated RNT radiobiology studies, in order to derive its maximum therapeutic benefit.

Modulation of Secondary Cancer Risks from Radiation Exposure by Sex, Age and Gonadal Hormone Status: Progress, Opportunities and Challenges

Available data on cancer secondary to ionizing radiation consistently show an excess (2-fold amount) of radiation-attributable solid tumors in women relative to men. This excess risk varies by organ and age, with the largest sex differences (6- to more than 10-fold) found in female thyroid and breasts exposed between birth until menopause (~50 years old) relative to age-matched males. Studies in humans and animals also show large changes in cell proliferation rates, radiotracer accumulation and target density in female reproductive organs, breast, thyroid and brain in conjunction with physiological changes in gonadal hormones during the menstrual cycle, puberty, lactation and menopause. These sex differences and hormonal effects present challenges as well as opportunities to personalize radiation-based treatment and diagnostic paradigms so as to optimize the risk/benefit ratios in radiation-based cancer therapy and diagnosis. Specifically, Targeted Radionuclide Therapy (TRT) is a fast-expanding cancer treatment modality utilizing radiopharmaceuticals with high avidity to specific molecular tumor markers, many of which are influenced by sex and gonadal hormone status. However, past and present dosimetry studies of TRT agents do not stratify results by sex and hormonal environment. We conclude that cancer management using ionizing radiation should be personalized and informed by the patient sex, age and hormonal status.

Higher Radiation Dose to the Immune Cells Correlates with Worse Tumor Control and Overall Survival in Patients with Stage III NSCLC: A Secondary Analysis of RTOG0617.

Simple SummaryEmerging evidence indicates that the immune system plays an important role in controlling tumors during radiotherapy, and radiation-induced immune toxicity such as lymphopenia is associated with poor survival. However, the immune system is not considered as a critical organ at risk in radiotherapy partially because the radiation dose to the immune system is difficult to compute. In this study, we developed a model to compute the radiation dose to the circulating blood, which contains the majority of active immune cells. We then validated this model by examining the correlations of the blood dose with treatment outcome for patients enrolled in the NRG/RTOG0617 phase III clinical trial. We demonstrated that the blood dose was significantly and independently associated with overall survival and local progression-free survival. This result suggests that radiation dose to circulating immune cells is critical for tumor control, and decreasing the dose to the immune system has the potential to improve survival.Background: We hypothesized that the Effective radiation Dose to the Immune Cells (EDIC) in circulating blood is a significant factor for the treatment outcome in patients with locally advanced non-small-cell lung cancer (NSCLC). Methods: This is a secondary study of a phase III trial, NRG/RTOG 0617, in patients with stage III NSCLC treated with radiation-based treatment. The EDIC was computed as equivalent uniform dose to the entire blood based on radiation doses to all blood-containing organs, with consideration of blood flow and fractionation effect. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS) and local progression-free survival (LPFS). The EDIC–survival relationship was analyzed with consideration of clinical significant factors. Results: A total of 456 patients were eligible. The median EDIC values were 5.6 Gy (range, 2.1–12.2 Gy) and 6.3 Gy (2.1–11.6 Gy) for the low- and high-dose groups, respectively. The EDIC was significantly associated with OS (hazard ratio [HR] = 1.12, p = 0.005) and LPFS (HR = 1.09, p = 0.02) but PFS (HR = 1.05, p = 0.17) after adjustment for tumor dose, gross tumor volume and other factors. OS decreased with an increasing EDIC in a non-linear pattern: the two-year OS decreased first with a slope of 8%/Gy when the EDIC < 6 Gy, remained relatively unchanged when the EDIC was 6–8 Gy, and followed by a further reduction with a slope of 12%/Gy when the EDIC > 8 Gy. Conclusions: The EDIC is a significant independent risk factor for poor OS and LPFS in RTOG 0617 patients with stage III NSCLC, suggesting that radiation dose to circulating immune cells is critical for tumor control. Organ at risk for the immune system should be considered during RT plan.

HDR Brachytherapy and SBRT as Bridging Therapy to Liver Transplantation in HCC Patients: A Single-Center Experience.

BackgroundIn the treatment of patients with HCC awaiting liver transplantation (LT), local ablative treatments (LAT) are available either for downstaging or as bridging treatment. We present our clinical experience with both available radiation-based techniques, brachytherapy (BT), and stereotactic body radiotherapy (SBRT).MethodsAll patients diagnosed with HCC and who were treated with BT or SBRT at our institution between 2011 and 2018 were retrospectively reviewed. The current analysis included all patients who subsequently underwent LT.ResultsA total of 14 patients (male=9; female=5) were evaluated. Seven underwent BT for bridging before LT, and seven were treated with SBRT. BT was performed with a prescribed dose of 1 × 15 Gy, while SBRT was applied with 37 Gy (65%-iso) in three fractions in six patients, and one patient was treated with 54 Gy (100%-iso) in nine fractions. The treatment was generally well tolerated. One case of grade 3 bleeding was reported after BT, and one case of liver failure occurred following SBRT. All patients underwent LT after a median time interval of 152 days (range 47–311) after BT and 202 days (range 44–775) following SBRT. In eight cases, no viable tumor was found in the explanted liver, while four liver specimens showed vital tumor. The median follow-up after SBRT was 41 months and 17 months following BT. Overall, no hepatic HCC recurrence occurred following LT.ConclusionBoth SBRT and BT are feasible and well tolerated as bridging to LT when applied with caution in patients with impaired liver function. Radiation-based treatments can close the gap for patients not suitable for other locally ablative treatment options.

Acupuncture for radiation-induced toxicity in head and neck squamous cell carcinoma: a systematic review based on PICO criteria

PurposeIn head and neck squamous cell carcinoma (HNSCC), the potential mitigating effect of complementary medicine interventions such as acupuncture for radiation-induced toxicity is unknown. This study aimed to assess the impact of acupuncture on the incidence and degree of severity of common radiation-induced side effects.MethodsIn accordance with pre-specified PICO criteria, a systematic review was performed. Two electronic databases (Medline and Embase) were searched over a 10-year time frame (01/01/10 to 30/09/20). Patients undergoing a curatively intended, radiation-based treatment for histologically confirmed squamous cell carcinoma of the nasopharynx, oropharynx, larynx, hypopharynx and oral cavity represented the target population of our study. Accurate information on the acupuncture methodology was reported. All included articles were evaluated to identify any potential source of biasResultsFive papers were included in our qualitative analysis, for a total of 633 subjects. Compliance to per-protocol defined schedule of acupuncture sessions was high, ranging from 82 to 95.9%. Most patients (70.6%) were randomly allocated to receive acupuncture for its potential preventive effect on xerostomia. The large heterogeneity in study settings and clinical outcomes prevented from performing a cumulative quantitative analysis, thus no definitive recommendations can be provided.ConclusionsAlthough shown to be feasible and safe, no firm evidence currently supports the use of acupuncture for the routine management of radiation-induced toxicity in HNSCC.

The Effectiveness of Surgery-Based Treatment in Advanced Oropharyngeal Cancers

Background and Objectives Oropharyngeal cancers (OPCs) can be staged down to a lower stage with p16 positivity and de-escalated therapy has been the common practice. The aim of this study is to evaluate the survival outcomes based on various clinical factors in advanced OPC patients. Subjects and Method A total of 58 OPC patients in the stage IVA based on the American Joint Committee on Cancer 7th edition were treated with primary surgery or primary chemoradiation therapy from 2010 to 2016. A survival analysis was carried out using the Kaplan- Meier method, log-rank test, and Cox proportional hazards model. Results The median follow-up was 39.5 months. Thirty-eight and 20 patients received surgery- based and radiation therapy (RT)-based treatments, respectively. Clinical T-stage and treatment method were significant risk factors for 5-year disease-free survival (DFS) rate, and the treatment method was the only significant risk factor for overall-survival (OS) rate. 5-year DFS rate in the surgery-based treatment and RT-based treatment was 76.1% and 36.0% (p=0.001). On multivariate analysis, the surgery-based treatment group was associated with a significantly reduced hazard of death [the hazard ratio (HR) for the radiation-based treatment was 6.565 compared to the surgery-based treatment, p=0.002]. 5-year OS rate in the surgery-based treatment and RT-based treatment was 91.1% and 53.4% (p=0.003), respectively. On the multivariate analysis, the surgery-based treatment group was associated with a significantly reduced hazard of death (the HR for the radiation-based treatment was 7.544 compared to the surgerybased treatment, p=0.012). Conclusion The primary surgery-based treatment for advanced OPC showed a better survival outcome than the primary radiation-based treatment, irrespective of p16 positivity.

Esomeprazole enhances the effect of ionizing radiation to improve tumor control.

The resistance of cancer cells to radiation-based treatment is a major clinical challenge confounding standard of care in cancer. This problem is particularly notable in many solid tumors where cancer cells are only partially responsive to radiation therapy. Combination of radiation with radiosensitizers is able to enhance tumor cell killing. However, currently available radiosensitizers are associated with significant normal tissue toxicity. Accordingly, there is an unmet need to develop safer and more effective radiosensitizers to improve tumor control. Here, we evaluated the radiosensitizing effect of the FDA-approved drug esomeprazole in normal and radioresistant human head and neck squamous cell carcinoma (HNSCC) cells in vitro, and in a mouse model of HNSCC. For the in vitro studies, we used cancer cell colony formation (clonogenicity) assay to compare cancer cell growth in the absence or presence of esomeprazole. To determine mechanism(s) of action, we assessed cell proliferation and profiled cell cycle regulatory proteins. In addition, we performed reverse phase protein array (RPPA) study to understand the global effect of esomeprazole on over 200 cancer-related proteins. For the in vivo study, we engrafted HNSCC in a mouse model and compared tumor growth in animals treated with radiation, esomeprazole, and combination of radiation with esomeprazole. We found that esomeprazole inhibits tumor growth and dose-dependently enhances the cell killing effect of ionizing radiation in wildtype and p53-mutant radioresistant cancer cells. Mechanistic studies demonstrate that esomeprazole arrests cancer cells in the G1 phase of the cell cycle through upregulation of p21 protein and inhibition of cyclin-dependent kinases (Cdks) type 1 (Cdk1) and type 2 (Cdk2). In vivo data showed greater tumor control in animals treated with combination of radiation and esomeprazole compared to either treatment alone, and that this was associated with inhibition of cell proliferation in vivo. In addition, combination of esomeprazole with radiation significantly impaired repair following radiation-induced DNA damage. Our studies indicate that esomeprazole sensitizes cancer cells to ionizing radiation, and is associated with upregulation of p21 to arrest cells in the G1 phase of the cell cycle. Our findings have significant therapeutic implications for the repurposing of esomeprazole as a radiosensitizer in HNSCC and other solid tumors.

Dysphagia, trismus and speech impairment following radiation-based treatment for advanced stage oropharyngeal carcinoma: a one-year prospective evaluation.

The objective was to assess swallowing, mouth opening and speech function during the first year after radiation-based treatment (RT(+)) after introduction of a dedicated preventive rehabilitation program for stage III-IV oropharyngeal carcinoma (OPC). Swallowing, mouth opening and speech function were collected before and at six- and twelve-month follow-up after RT(+) for OPC as part of ongoing prospective assessments by speech-language pathologists . Objective and patient-perceived function deteriorated until 6months and improved until 12months after treatment, but did not return to baseline levels with 25%, 20% and 58% of the patients with objective dysphagia, trismus and speech problems, respectively. Feeding tube dependency and pneumonia prevalence was low. Despite successful implementation, a substantial proportion of patients still experience functional limitations after RT(+) for OPC, suggesting room for improvement of the current rehabilitation program. Pretreatment sarcopenia seems associated with worse functional outcomes and might be a relevant new target for rehabilitation strategies.

Costs Associated With Imaging Surveillance After Treatment for Head and Neck Cancer

The National Comprehensive Cancer Network recommends imaging within 6 months after treatment for head and neck cancer (HNC). Further imaging is recommended only if the patient has symptoms or abnormal findings on physical examination. However, in many instances, asymptomatic patients continue to have imaging evaluations. To assess practice patterns in surveillance imaging in patients with HNC and evaluate the costs associated with these imaging practices. This single-institution retrospective economic evaluation study screened 435 patients to identify patients newly diagnosed with head and neck mucosal and salivary gland malignant tumors between January 1, 2010, and December 31, 2016. Data analyses were performed from October 25, 2018, to November 24, 2020. Imaging practice patterns. Number and costs of imaging studies during the surveillance period for all patients, patients who remained disease free, and patients who developed recurrence. A total of 136 patients (mean [SD] age at diagnosis, 62 [14] years; 84 [61.8%] male; 106 [77.9%] White) with HNC were included in the study. The oropharynx was the most common subsite (64 [47.1%]), most HNCs were stage IVA (62 [45.6%]), and most patients received definitive radiation-based treatment (71 [52.2%]). During the median surveillance period of 3.2 years (range, 0.3-6.8 years), a mean (SD) of 14 (10) imaging studies were performed for all patients, with a mean (SD) total cost of $36 800 ($24 500). In patients who remained disease free, a mean (SD) of 13 (10) imaging studies were performed during the surveillance period, with a mean (SD) total cost of $35 000 ($21 700). Patients who lacked symptoms had a mean (SD) of 4 (3) studies performed per year, resulting in a mean cost of $9600 ($5900) per year. Patients who developed recurrence had more studies per year of follow-up (mean difference, 5.0; 95% CI, 3.4-6.6) and higher associated mean costs (mean difference, $10 600; 95% CI, $6100-$15 000) than patients who remained disease free. In this economic evaluation study, many patients treated for HNCs received imaging studies beyond what is recommended by National Comprehensive Cancer Network guidelines. These findings suggest that the cost burden of imaging in the asymptomatic patient needs to be considered against the value obtained from routine imaging in this current health care environment.

Swallowing dysfunction following radiation to the rat mylohyoid muscle is associated with sensory neuron injury

Radiation based treatments for oropharyngeal and hypopharyngeal cancers result in impairments in swallowing mobility, but the mechanisms behind the dysfunction are not clear. The purpose of this study was to determine if we could establish an animal model of radiation-induced dysphagia in which mechanisms could be examined. We hypothesized that (1) radiation focused at the depth of the mylohyoid muscle would alter normal bolus transport and bolus size; and (2) that radiation to the mylohyoid muscle will induce an injury/stress-like response in trigeminal sensory neurons whose input might modulate swallow. Rats were exposed to 48 or 56 Gy of radiation to the mylohyoid given 8 Gy in 6 or 7 fractions. Swallowing function was evaluated by videofluoroscopy 2- and 4-weeks following treatment. Neuronal injury/stress was analyzed in trigeminal ganglion by assessing ATF3 and GAP-43 mRNA at 2-, 4- and 8-weeks post. Irradiated rats exhibited decreases in bolus movement through the pharynx and alterations in bolus clearance. Additionally, ATF3 and GAP-43 mRNAs were upregulated in trigeminal ganglion in irradiated rats, suggesting that radiation to mylohyoid muscle induced an injury/stress response in neurons with cell bodies that are remote from the irradiated tissue. These results suggest that radiation-induced dysphagia can be assessed in the rat, and that radiation induces injury/stress-like responses in sensory neurons.

Abstract PS1-42: Locoregional treatment in de novo metastatic breast cancer: An overview of the current evidence

Abstract Background: Patients presenting with de novo metastatic breast cancer (dnMBC) is considered incurable but treatable. Despite the advances in systemic therapies, the role of locoregional treatment (LRT, primary tumor surgery and/or radiotherapy) for dnMBC remains controversial. Aim: To review and discuss the present evidence of surgery- and radiation-based treatment strategies for dnMBC. Settings and design: A systematic review and meta-analysis of the literature were carried out. Methods: We did a systematic review and meta-analysis of observational studies and randomised controlled trials (RCTs) published from database inception to Feb 28, 2020, which reported on survival outcomes of LRT in patients with dnMBC. Studies were identified by searches in PubMed, MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and by hand searching of previous publications. The review and meta-analysis were conducted to assess the effect of LRT on overall survival (OS). Robustness of pooled estimates from random-effects models was considered with sensitivity analyses, meta-regression, and subgroup analyses. All statistical analyses were performed with Stata 16.0. Findings: Data on 714 patients in 3 RCTs and 173476 patients in 39 observational studies were included. In total 174190 patients, 76711 patients (44.04 %) underwent LRT ± systemic therapy, and 97479 patients (55.96 %) received systemic therapy alone (STA). Observational data showed LRT significantly improved overall survival (HR=0.63; 95%CI, 0.57 to 0.69, P&amp;lt;0.001, I2=96.3%). The subgroup analysis found a favorable impact on survival in both patients undergoing surgery plus radiotherapy and surgery. However, the pooled outcomes of prospective trials suggested a 19.0% reduction in mortality which was not statistically significant (HR=0.81; 95% CI, 0.57 to 1.14, P=0.06, I2=64.4%). Interpretation: Due to the paucity of RCTs exploring LRT in patients with dnMBC, this was a meta-analysis which included retrospective and prospective data; both sets provide a complete picture of the effect. However, withstanding for retrospective bias, separate analyses was conducted to specifically examine the prospective trials. Findings from observational studies and RCTs associated with LRT and OS in these patients were inconsistent. Given the retrospective nature of observational studies, its results cannot be used as level I evidence to support LRT in patients with dnMBC. As level I evidence, prospective data suggest that the relationship between the LRT and survival benefit in these patients could not be causal. Although these trials have been criticized due to systemic therapy protocols which differ from standard modern treatments, they continue to provide important data. Ongoing well-designed prospective studies, including ECOG 2108 trial, are awaiting mature data. Conclusions: Based on the results of current level I evidence, LRT should not be part of routine clinical practice in patients with dnMBC but might be performed in specific patients. Key words: Locoregional treatment; De novo metastatic breast cancer; Systematic review; Meta-analysis Citation Format: Ren Chongxi. Locoregional treatment in de novo metastatic breast cancer: An overview of the current evidence [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-42.