NCCN Guidelines® Insights: Merkel Cell Carcinoma, Version 1.2024.

The NCCN Guidelines for Merkel Cell Carcinoma (MCC) provide recommendations for diagnostic workup, clinical stage, and treatment options for patients. The panel meets annually to discuss updates to the guidelines based on comments from expert review from panel members, institutional review, as well as submissions from within NCCN and external organizations. These NCCN Guidelines Insights focus on the introduction of a new page for locally advanced disease in the setting of clinical node negative status, entitled "Clinical N0 Disease, Locally Advanced MCC." This new algorithm page addresses locally advanced disease, and the panel clarifies the meaning behind the term "nonsurgical" by further defining locally advanced disease. In addition, the guideline includes the management of in-transit disease and updates to the systemic therapy options.

A review of the state of cervical cancer: updates from prevention to recurrent disease.

PURPOSE OF REVIEW: To summarize the recent updates in cervical cancer from prevention and early detection to the management of early stage and recurrent disease as well as future areas of exploration. RECENT FINDINGS: The importance of the human papilloma virus vaccine and screening continue to make an impact in reducing the global burden of cervical cancer. In early-stage, low risk disease, new studies have demonstrated the role of less radical surgery with similar disease related outcomes. Efforts to improve outcomes in locally advanced cervical cancer have been reported. The incorporation of adjuvant chemotherapy, novel agents and checkpoint inhibitors, with the latter impacting disease free survival. In advanced/recurrent disease, the role of immunotherapy continues to make an impact and, in addition to recurrent disease, has now moved to the frontline for patients with programmed cell death ligand 1 expression. Tisotumab vedotin, an antibody drug conjugate, and other novel agents continue to be studied in this setting. SUMMARY: In this review, we discuss prevention measures and the outcomes of recent trials in all stages of cervical cancer. As therapies continue to evolve, ongoing trials and new areas of exploration will continue to identify opportunities to improve survival in cervical cancer.

Basal Cell Skin Cancer, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.

Basal cell carcinoma (BCC) is the most common form of skin cancer in the United States. Due to the high frequency, BCC occurrences are not typically recorded, and annual rates of incidence can only be estimated. Current estimated rates are 2 million Americans affected annually, and this continues to rise. Exposure to radiation, from either sunlight or previous medical therapy, is a key player in BCC development. BCC is not as aggressive as other skin cancers because it is less likely to metastasize. However, surgery and radiation are prevalent treatment options, therefore disfigurement and limitation of function are significant considerations. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) outline an updated risk stratification and treatment options available for BCC.

Recent advances in gynecologic radiation oncology.

PURPOSE OF REVIEW: Radiation has long been a primary treatment modality in locally advanced gynecologic carcinomas and a tool for palliation of metastatic disease. Here we review advances in imaging and radiation technologies and the corresponding clinical evolution of the role for radiation oncology in the treatment of gynecologic malignancies. RECENT FINDINGS: Advances in MRI are impacting diagnosis, radiation target delineation, planning, treatment delivery, and response assessment. The combination of MRI and PET-computed tomography (PET-CT) has the potential to significantly change treatment recommendations as compared with a single imaging modality. Advances in radiation delivery including intensity modulated radiation therapy (IMRT) and stereotactic ablative radiotherapy (SABR) have expanded the role for radiation in the definitive treatment of high risk and oligometastatic ovarian cancer. Finally, global disparities in oncology resources has led to the development of resource stratified treatment guidelines for gynecologic malignancies. The use of ultrasound for brachytherapy planning may help improve access to this critical treatment modality. SUMMARY: As imaging and radiation technologies advance, the indications for radiation in the treatment of gynecologic malignancies continues to evolve. Here we review the changing landscape of radiation oncology in the multidisciplinary management of gynecologic cancers.

Recurrence patterns and associated factors of locoregional failure following neoadjuvant chemoradiation and surgery for esophageal cancer.

BACKGROUND: Despite neoadjuvant chemoradiation (nCRT) followed by esophagectomy for locally advanced esophageal cancer, locoregional recurrence (LRR) is common and factors associated with LRR have not been clearly identified. METHODS: Patients were identified from a single institution, prospectively maintained database (1996-2013). Patterns of recurrence were described and associated factors of LRR were analyzed using competing risks regression models. RESULTS: Of the 456 patients treated with nCRT and surgery, 167 patients developed recurrence. Locoregional and distant recurrences were observed in 69 (15.1%) and 140 (30.9%) patients, respectively. Time to recurrence (13.6 vs 10.4 months, P = 0.20) and median overall survival (29.3 vs 19.1 months, P = 0.12) were no different among the 27 patients (6%) who developed a solitary LRR compared to patients who developed distant recurrence. Univariable analysis identified lymphovascular invasion (HR 1.46, P = 0.07), lymph node ratio >0.5 (HR 2.16, P = 0.02), positive margin (HR 1.95, P = 0.05), lack of response to neoadjuvant therapy (HR 1.99, P < 0.01), clinical T stage (HR 2.62, P < 0.01) and final T3/4 stage (HR 2.06, P < 0.01) as factors significantly associated with LRR. Clinical T stage and response to neoadjuvant treatment were independently associated with LRR on multivariable analysis. CONCLUSIONS: Although aggressive tumor biology plays a significant role in LRR, optimizing neoadjuvant treatments to obtain a complete pathologic response may lead to improved locoregional control.

A genome-based model for adjusting radiotherapy dose (GARD): a retrospective, cohort-based study.

BACKGROUND: Despite its common use in cancer treatment, radiotherapy has not yet entered the era of precision medicine, and there have been no approaches to adjust dose based on biological differences between or within tumours. We aimed to assess whether a patient-specific molecular signature of radiation sensitivity could be used to identify the optimum radiotherapy dose. METHODS: We used the gene-expression-based radiation-sensitivity index and the linear quadratic model to derive the genomic-adjusted radiation dose (GARD). A high GARD value predicts for high therapeutic effect for radiotherapy; which we postulate would relate to clinical outcome. Using data from the prospective, observational Total Cancer Care (TCC) protocol, we calculated GARD for primary tumours from 20 disease sites treated using standard radiotherapy doses for each disease type. We also used multivariable Cox modelling to assess whether GARD was independently associated with clinical outcome in five clinical cohorts: Erasmus Breast Cancer Cohort (n=263); Karolinska Breast Cancer Cohort (n=77); Moffitt Lung Cancer Cohort (n=60); Moffitt Pancreas Cancer Cohort (n=40); and The Cancer Genome Atlas Glioblastoma Patient Cohort (n=98). FINDINGS: We calculated GARD for 8271 tissue samples from the TCC cohort. There was a wide range of GARD values (range 1·66-172·4) across the TCC cohort despite assignment of uniform radiotherapy doses within disease types. Median GARD values were lowest for gliomas and sarcomas and highest for cervical cancer and oropharyngeal head and neck cancer. There was a wide range of GARD values within tumour type groups. GARD independently predicted clinical outcome in breast cancer, lung cancer, glioblastoma, and pancreatic cancer. In the Erasmus Breast Cancer Cohort, 5-year distant-metastasis-free survival was longer in patients with high GARD values than in those with low GARD values (hazard ratio 2·11, 95% 1·13-3·94, p=0·018). INTERPRETATION: A GARD-based clinical model could allow the individualisation of radiotherapy dose to tumour radiosensitivity and could provide a framework to design genomically-guided clinical trials in radiation oncology. FUNDING: None.

Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma.

The role of external beam radiation therapy for primary liver malignancies has historically been limited due to the risk of radiation-induced liver disease. However, with the advent of stereotactic body radiotherapy (SBRT), we are able to dose escalate while safely sparing critical nearby structures. This review explores the evidence surrounding the use of SBRT for the treatment of primary liver malignancies. A review of the literature was performed. This article discusses the challenges, efficacy, and safety of SBRT for primary liver malignancies in order to conceptualize its role within a multidisciplinary framework. Prospective phase I and II trials show local control rates at 1 to 2 years ranging from 65% to 100%. Overall survival at 1 to 2 years ranged from 48% to 77%. Grade >3 toxicity ranged from 0% to 36%. Total radiotherapy doses ranged from 24 to 60 Gy delivered in 1 to 6 fractions. The SBRT offers a noninvasive therapy for patients with limited treatment options and should be considered in a multidisciplinary setting for the management of unresectable, locally advanced primary liver malignancies. Prospective randomized trials are warranted to determine the efficacy and safety of SBRT compared to and in combination with other treatment modalities.

Management of Oropharyngeal Cancer in the HPV Era.

BACKGROUND: Historically, oropharyngeal cancer (OPC) has been attributed to risk factors such as smoking and alcohol use. The increased incidence of OPC has been driven by human papillomavirus (HPV) infection. METHODS: A search of the literature involving HPV infection and OPC was performed, along with a search of ongoing clinical trials regarding HPV-positive OPC. RESULTS: This review summarizes the differences in epidemiology and prognosis of HPV-positive OPC compared with non-HPV-related OPC. It will also discuss use of de-escalating treatment to minimize toxicity while maintaining excellent outcomes. Disease management is also addressed, including prevention and follow-up recommendations for this cohort of patients. CONCLUSIONS: HPV-positive OPC is a distinct disease, and efforts should be made to personalize its management. Preventive measures and vaccinations, along with de-escalation of treatment, may help optimize outcomes in this population.

Percutaneous interstitial brachytherapy ablation for targeting oligometastatic gynecologic cancers.

INTRODUCTION: Treatment of recurrent oligometastatic gynecologic malignancy may involve targeted surgery, thermal ablation, or CT-guided high-dose-rate interstitial brachytherapy ablation (CT-HDR-IBTA). The purpose of this study was to describe the safety and efficacy of CT-HDR-IBTA for oligometastatic gynecologic malignancies. METHODS: With institutional review board approval (IRB) approval and compliance with the Health Insurance Portability and Accountability Act of 1996 (HIPAA) compliance, we searched our database to assemble a single-arm study cohort of all patients with oligometastatic gynecologic cancers who underwent CT-HDR-IBTA from 2012-2022 with follow-up. The electronic record was reviewed to determine relevant clinicopathological variables including patient demographics, prior treatments, clinical course, local control, and local and distant recurrence with follow-up imaging. RESULTS: The study cohort comprised 37 lesions in 34 patients treated with CT-HDR-IBTA for recurrent oligometastatic uterine (n = 17), cervix (n = 1), or ovarian cancer (n = 16) with an average lesion size of 2.5 cm with an average patient age of 61.4 years. Each lesion was treated with an average radiation dose of 23.8 Gy in 1.8 fractions and a median follow-up time of 24.0 months. The primary efficacy of CT HDR ITBA was 73% with a median progression-free survival of 8.0 months (95% CI 3.6-12.8 months) and with 58% of patients still alive at 43 months with median overall survival not reached. The rate of Grade 1 adverse events was 22% without any Grade 2, 3 or 4 events. CONCLUSIONS: CT HDR IBTA was safe and effective for treating oligometastatic gynecologic cancers in a heavily pretreated cohort.

A practical guide to hybrid interstitial/intracavitary brachytherapy for locally-advanced cervical cancer.

PURPOSE: In select cases of locally advanced cervical cancer, a hybrid brachytherapy (HBT) approach consisting of a combined intracavitary (IC)/insterstitial (IS) implant can yield improved target coverage and/or decreased organ at risk dose compared to IC techniques while limiting invasiveness compared to IS techniques. METHODS AND MATERIALS: The technique involves placement of transvaginal and/or perineal needles in addition to the tandem and ring/ovoids using either a specialized applicator or free-hand placement. Following applicator and needle placement, brachytherapy may then be planned using principles similar to IC or IS techniques. During treatment planning, it can be helpful to obtain both MRI and CT imaging, as plastic MRI-compatible needles do not show up well on MRI. RESULTS: In patients where acceptable target coverage cannot be achieved using IC alone or doses to nearby OAR are too high, HBT should be evaluated. HBT can improve both dose to target and OAR while sparing patients the morbidity of perineal template-based interstitial brachytherapy. Specific scenarios where HBT may be preferred include bulky residual primary tumor especially with poor response to EBRT, extension into the lateral parametrium, vaginal extension of tumor, and an asymmetric target. Use of HBT can typically permit extension of dose coverage by an additional 1-2 cm beyond what can be achieved with an IC alone technique. CONCLUSION: HBT allows for improved therapeutic ratio by improving target volume coverage and/or lowering doses to OARs. Brachytherapists should be trained on the practical aspects of administering HBT to be able to offer a less invasive and impactful treatment option when appropriate.

Analytical HDR prostate brachytherapy planning with automatic catheter and isotope selection.

BACKGROUND: High dose rate (HDR) brachytherapy is commonly used to treat prostate cancer. Existing HDR planning systems solve the dwell time problem for predetermined catheters and a single energy source. PURPOSE: Additional degrees of freedom can be obtained by relaxing the catheters' pre-designation and introducing more source types, and may have a dosimetric benefit, particularly in improving conformality to spare the urethra. This study presents a novel analytical approach to solving the corresponding HDR planning problem. METHODS: The catheter and dual-energy source selection problem was formulated as a constrained optimization problem with a non-convex group sparsity regularization. The optimization problem was solved using the fast-iterative shrinkage-thresholding algorithm (FISTA). Two isotopes were considered. The dose rates for the HDR 4140 Ytterbium (Yb-169) source and the Elekta Iridium (Ir-192) HDR Flexisource were modeled according to the TG-43U1 formalism and benchmarked accordingly. Twenty-two retrospective HDR prostate brachytherapy patients treated with Ir-192 were considered. An Ir-192 only (IRO), Yb-169 only (YBO), and dual-source (DS) plan with optimized catheter location was created for each patient with N catheters, where N is the number of catheters used in the clinically delivered plans. The DS plans jointly optimized Yb-169 and Ir-192 dwell times. All plans and the clinical plans were normalized to deliver a 15 Gy prescription (Rx) dose to 95% of the clinical treatment volume (CTV) and evaluated for the CTV D90%, V150%, and V200%, urethra D0.1cc and D1cc, bladder V75%, and rectum V75%. Dose-volume histograms (DVHs) were generated for each structure. RESULTS: The DS plans ubiquitously selected Ir-192 as the only treatment source. IRO outperformed YBO in organ at risk (OARs) OAR sparing, reducing the urethra D0.1cc and D1cc by 0.98% ( p = 2.22 ∗ 10 - 9 $p\ = \ 2.22*{10^{ - 9}}$ ) and 1.09% ( p = 1.22 ∗ 10 - 10 $p\ = \ 1.22*{10^{ - 10}}$ ) of the Rx dose, respectively, and reducing the bladder and rectum V75% by 0.09 ( p = 0.0023 $p\ = \ 0.0023$ ) and 0.13 cubic centimeters (cc) ( p = 0.033 $p\ = \ 0.033$ ), respectively. The YBO plans delivered a more homogenous dose to the CTV, with a smaller V150% and V200% by 3.20 ( p = 4.67 ∗ 10 - 10 $p\ = \ 4.67*{10^{ - 10}}$ ) and 1.91 cc ( p = 5.79 ∗ 10 - 10 $p\ = \ 5.79*{10^{ - 10}}$ ), respectively, and a lower CTV D90% by 0.49% ( p = 0.0056 $p\ = \ 0.0056$ ) of the prescription dose. The IRO plans reduce the urethral D1cc by 2.82% ( p = 1.38 ∗ 10 - 4 $p\ = \ 1.38*{10^{ - 4}}$ ) of the Rx dose compared to the clinical plans, at the cost of increased bladder and rectal V75% by 0.57 ( p = 0.0022 $p\ = \ 0.0022$ ) and 0.21 cc ( p = 0.019 $p\ = \ 0.019$ ), respectively, and increased CTV V150% by a mean of 1.46 cc ( p = 0.010 $p\ = \ 0.010$ ) and CTV D90% by an average of 1.40% of the Rx dose ( p = 8.80 ∗ 10 - 8 $p\ = \ 8.80*{10^{ - 8}}$ ). While these differences are statistically significant, the clinical differences between the plans are minimal. CONCLUSIONS: The proposed analytical HDR planning algorithm integrates catheter and isotope selection with dwell time optimization for varying clinical goals, including urethra sparing. The planning method can guide HDR implants and identify promising isotopes for specific HDR clinical goals, such as target conformality or OAR sparing.

The Current State of Departmental Diversity, Equity, and Inclusion Efforts Within US Academic Radiation Oncology Departments.

PURPOSE: Promoting a diverse workforce of health care professionals that delivers equitable patient care is an important goal in oncology, as in all of medicine. Although most medical schools have a diversity office and associated initiatives, little is known about radiation oncology (RO) department-level efforts to promote diversity, equity, and inclusion (DEI). We describe the current state of DEI leadership and initiatives in RO departments in the US to guide future policies and programs. METHODS AND MATERIALS: A total of 124 US RO departments affiliated with a medical school were contacted to identify departmental DEI leadership. Identified DEI leaders were asked to complete an anonymous survey assessing characteristics of their departmental DEI leadership, committee/organizational structure, activities, and perceived barriers to, and effect of, their work. Descriptive statistics are reported. RESULTS: Among 85 RO departments that responded (68.5% response rate), 48 (56.5%) reported having a departmental DEI leader. Thirty-four DEI leaders completed the survey (70.8%). Of those who answered each survey question, most DEI leaders were assistant or associate professors (n = 24, 82.8%), women (n = 19, 73.1%), and identified with at least one non-White race or Hispanic ethnicity (n = 15, 53.6%). Nineteen (57.6%) had an associated departmental DEI committee; with 10 of these starting in 2020 or later. Few DEI leaders had administrative support (38.2%), funding (29.4%), protected time (23.5%), or increased compensation for added duties Fifteen (50.0%) believed their DEI-focused efforts were considered for promotion. The most reported initiatives included offering programming/education, supporting students from backgrounds underrepresented in medicine, improving recruitment practices/hiring, and implementing pipeline/pathway projects. The perceived impact of DEI initiatives included an increased culture of respect (89.7%), improved health care disparity awareness (75.9%), and improved systemic/structural racism awareness (79.3%). CONCLUSIONS: Departmental DEI efforts are increasingly common within RO, however, the structure, resources, and recognition associated with DEI work are variable. Additional dedicated resources and recognition for these efforts will help ensure a culture of inclusive excellence for the RO workforce and patients.

Brachytherapy of the head and neck: An University of California Los Angeles guide to morbidity reduction.

The head and neck (H&N) region is among the most intricate and functional part of our anatomy. Major functional nerves and blood vessels with importance that affect the entire body emanate from the base of skull. Brachytherapy plays an important role as a single modality therapy in early cancer of the lip and oral cavity and a supplemental role in the pharynx or in advanced or recurrent disease. Morbidity in the H&N is intensely personal and disabling. Its avoidance is critical in determining the success or failure of a treatment program, and it is essential to preservation of quality of life. This article summarizes the current literature regarding morbidity related to H&N brachytherapy to aid patients and physicians to achieve optimal outcomes.

Provider-Level Variation in Treatment Planning of Radiation Oncology Procedures in the United States.

PURPOSE: Variation in the use of radiation oncology procedures and technologies is poorly characterized. We sought to identify associations between the treatment planning codes used to bill for radiotherapy procedures and the demographic characteristics of the radiation oncologists submitting them. METHODS: The Physician and Other Supplier Public Use File was linked to the Physician Compare database by using the physician National Provider Identifier for the year 2016. Analysis was stratified by practice setting, considering both the freestanding non-facility-based (NFB) setting and the facility-based (FB) setting. Multivariable logistic regression was used to determine provider characteristics (gender, practice rurality, and years since graduation) that predicted for the use of 3D-conformal RT (3DCRT) planning, intensity-modulated RT (IMRT) planning, and brachytherapy planning in the Medicare population. RESULTS: Three thousand twenty-nine physicians were linked for analysis. In both the FB and NFB settings together, male gender predicted for decreased likelihood of 3DCRT planning (OR, 0.70, 95% CI, 0.62 to 0.80, P < .001) and increased likelihood of IMRT planning (OR, 1.35, 95% CI, 1.19 to 1.54, P < .001). Brachytherapy planning was also more likely with increasing years since medical school graduation (OR, 1.03, 95% CI, 1.01 to 1.04, P < .001) in the combined FB and NFB settings. These significant associations persisted when examining the NFB and FB settings individually. In both settings overall, brachytherapy planning was more likely in male providers (OR, 1.75, 95% CI, 1.10 to 2.76, P = .02) and also more likely for providers practicing in metropolitan regions compared with those practicing in rural areas (OR, 3.01, 95% CI, 1.23 to 7.39, P = .02). CONCLUSION: Male gender predicts for utilization of IMRT planning, whereas female gender predicts for utilization of 3DCRT planning. Future research is warranted to better understand the role that provider gender and rurality play in the selection of radiation planning techniques for Medicare patients.

Socioeconomic and Racial Determinants of Brachytherapy Utilization for Cervical Cancer: Concerns for Widening Disparities.

PURPOSE: Cervical cancer (CC) disproportionately affects minorities who have higher incidence and mortality rates. Standard of care for locally advanced CC involves a multimodality approach including brachytherapy (BT), which independently improves oncologic outcomes. Here, we examine the impact of insurance status and race on BT utilization with the SEER database. MATERIALS AND METHODS: In total, 7,266 patients with stage I-IV CC diagnosed from 2007 to 2015 were included. BT utilization, overall survival (OS), and disease-specific survival (DSS) were compared. RESULTS: Overall, 3,832 (52.7%) received combined external beam radiation therapy (EBRT) + BT, whereas 3,434 (47.3%) received EBRT alone. On multivariate logistic regression analysis, increasing age (OR, 0.98; 95% CI, 0.98 to 0.99; P < .001); Medicaid (OR, 0.80; 95% CI, 0.72 to 0.88; P < .001), uninsured (OR, 0.67; 95% CI, 0.56 to 0.80; P < .001), and unknown versus private insurance (OR, 0.61; 95% CI, 0.43 to 0.86; P < .001); Black (OR, 0.68; 95% CI, 0.60 to 0.77; P < .001) and unknown versus White race (OR, 0.30; 95% CI, 0.13 to 0.77; P = .047); and American Joint Committee on Cancer stage II (OR, 1.07; 95% CI, 0.93 to 1.24; P = .36), stage III (OR, 0.82; 95% CI, 0.71 to 0.94; P = .006), stage IV (OR, 0.30; 95% CI, 0.23 to 0.40; P < .001), and unknown stage versus stage I (OR, 0.36; 95% CI, 0.28 to 0.45; P < .001) were associated with decreased BT utilization. When comparing racial survival differences, the 5-year OS was 44.2% versus 50.9% (P < .0001) and the 5-year DSS was 55.6% versus 60.5% (P < .0001) for Black and White patients, respectively. Importantly, the racial survival disparities resolved when examining patients who received combined EBRT + BT, with the 5-year OS of 57.3% versus58.5% (P = .24) and the 5-year DSS of 66.3% versus 66.6% (P = .53) for Black and White patients, respectively. CONCLUSION: This work demonstrates notable inequities in BT utilization for CC that particularly affects patients of lower insurance status and Black race, which translates into inferior oncologic outcomes. Importantly, the use of BT was able to overcome racial survival differences, thus highlighting its essential value.

High-Dose Rate Interstitial Spine Brachytherapy Using an Intraoperative Mobile Computed Tomography-Guided Surgical Navigation System.

BACKGROUND: Up to 15% of previously irradiated metastatic spine tumors will progress. Re-irradiation of these tumors poses a significant risk of exceeding the radiation tolerance to the spinal cord. High-dose rate (HDR) brachytherapy is a treatment alternative. OBJECTIVE: To develop a novel HDR spine brachytherapy technique using an intraoperative computed tomography-guided navigation (iCT navigation). METHODS: Patients with progressive metastatic spine tumors were included in the study. HDR brachytherapy catheters were placed under iCT navigation. CT-based planning with magnetic resonance imaging fusion was performed to ensure conformal dose delivery to the target while sparing normal tissue, including the spinal cord. Patients received single fraction radiation treatment. RESULTS: Five patients with thoracolumbar tumors were treated with HDR brachytherapy. Four patients previously received radiotherapy to the same spinal level. Preimplant plans demonstrated median clinical target volume (CTV) D90 of 116.5% (110.8%-147.7%), V100 of 95.7% (95.5%-99.6%), and Dmax of 8.08 Gy (7.65-9.8 Gy) to the spinal cord/cauda equina. Postimplant plans provided median CTV D90 of 113.8% (93.6%-120.1%), V100 of 95.9% (87%-99%), and Dmax of 9.48 Gy (6.5-10.3 Gy) to cord/cauda equina. Patients who presented with back pain (n = 3) noted symptomatic improvement at a median follow-up of 22 d after treatment. Four patients demonstrated local tumor control of spinal metastatic tumor at a median follow-up of 92 d after treatment. One patient demonstrated radiographic evidence of local tumor progression 2.7 mo after treatment. CONCLUSION: HDR spine brachytherapy with iCT navigation is a promising treatment alternative to induce local tumor control and reduce pain symptoms associated with metastatic spine disease.

Outcomes with multi-disciplinary management of central lung tumors with CT-guided percutaneous high dose rate brachyablation.

BACKGROUND: Centrally located lung tumors present treatment challenges given their proximity to mediastinal structures including the central airway, esophagus, major vessels, and heart. Therapeutic options can be limited for medically inoperable patients, particularly if they have received previous thoracic radiotherapy. High dose rate (HDR) brachyablation was developed to improve the therapeutic ratio for patients with central lung tumors. The purpose of this study is to report initial safety and efficacy outcomes with this treatment for central lung malignancies. METHODS: From September 2015 to August 2019, a total of 25 patients with 37 pulmonary tumors were treated with percutaneous HDR brachyablation. Treatment was delivered by a multi-disciplinary team of interventional radiologists, pulmonologists, and radiation oncologists. Twenty-three patients received a median dose of 21.5 Gy (range 15-27.5) in a single fraction, whereas two patients received median dose of 24.75 Gy (range 24-25.5) over 2-3 fractions. Tumor local control (LC) was evaluated by Response Evaluation Criteria in Solid Tumors v1.1. Treatment-related toxicities were graded by Common Terminology Criteria for Adverse Events v5.0, with adverse events less than 90 days defined as acute, and those occurring later were defined as late. LC, progression-free survival (PFS), and overall survival (OS) rates were estimated by the Kaplan-Meier method. RESULTS: Of 37 treated tumors, 88% were metastatic. Tumor location was central and ultra-central in 24.3% and 54.1%, respectively. Average tumor volume was 11.6 cm3 (SD 12.4, range 0.57-62.8). Median follow-up was 19 months (range 3-48). Two-year LC, PFS, and OS were 96.2%, 29.7%, and 65.5%, respectively. Thirteen of 39 (33.3%) catheter implantation procedures were associated with trace minor pneumothorax requiring no intervention, 1 (2.5%) procedure with minor radiographic pulmonary hemorrhage, and 4 (10.3%) with major pneumothorax requiring chest tube insertions. All procedural complications resolved within 24 h from treatment. Acute grade 1-2 toxicity was identified in 4 patients, whereas none developed late toxicity beyond 90 days of follow-up. CONCLUSION: Percutaneous HDR brachyablation is a safe and promising treatment option for centrally located primary and metastatic lung tumors. Future comparisons with stereotactic body radiotherapy and other ablative techniques are warranted to expand multi-disciplinary management options.

Clinical factors associated with the development of postoperative atrial fibrillation in esophageal cancer patients receiving multimodality therapy before surgery.

BACKGROUND: The incidence of esophageal cancer (EC) is increasing in the USA. Neoadjuvant therapy for locally advanced cancers followed by surgical resection is the standard of care. The most common post-esophagectomy cardiac complication is atrial fibrillation (AF). New-onset postoperative AF can require a prolonged hospital stay and may confer an overall poorer prognosis. In this study, we seek to identify clinical factors associated with postoperative AF. METHODS: Query of an IRB approved database of 1,039 esophagectomies at our institution revealed 677 patients with EC from 1999 to 2017 who underwent esophagectomy after neoadjuvant treatment. Age, treatment location (primary vs. other), gender, neoadjuvant radiation type [2D vs. 3D vs. intensity modulated radiation therapy (IMRT)], radiation dose, surgery type (transthoracic vs. transhiatal vs. three field), smoking history, coronary artery disease (CAD), chronic obstructive pulmonary disease (COPD), operative time, blood transfusions, fluid management, and length of stay (LOS) were analyzed in relationship to the development of AF. Statistical analysis was performed with SPSS 24. RESULTS: The mean age of the entire cohort was 64.3 (range, 28-86 years), with a Caucasian and male preponderance (White: 94.5%; male: 83.6%). Of the 677 patients, 14.9% (n=101) developed postoperative AF. Increasing age (P<0.001), increased radiation dose (P=0.034), operative time (P=0.001), and blood transfusions (P=0.027) were associated with AF. LOS was longer in patients with AF than those without AF (10.5 vs. 10.0 days, P=0.001). On multivariate analysis, increasing age (95% CI: 1.023-1.080, P<0.001) and radiation dose (95% CI: 1.000-1.001, P=0.034) remained significant. None of the other parameters assessed were associated with the development of AF. CONCLUSIONS: Increasing age and radiation dose were associated with the development of postoperative AF in this cohort. This study suggests that older patients or patients receiving higher radiation dose should be monitored more closely in the postoperative setting and potentially referred earlier preoperatively for cardio-oncology assessment. Future study is required to determine if modification of current radiation techniques and cardiac dose constraints in this patient population may be warranted.

Sanguinarine exhibits potent efficacy against cervical cancer cells through inhibiting the STAT3 pathway in vitro and in vivo.

BACKGROUND: Cervical cancer is the third most common malignancy among female cancer patients worldwide. Signal transducer and activator of transcription 3 (STAT3) is a transcription factor which regulates a variety of cancer cellular physiological activities including cervical cancer. Sanguinarine (SNG) is a natural plant-derived benzophenanthridine alkaloid that possesses antitumor activities in several cancer cells. However, its anticancer effect on human cervical cancer cells and the underlying mechanisms have not been fully defined. METHODS: In this study, the inhibitory effect of SNG on the proliferation and growth of HeLa cell was detected by MTT assay. Next, cell cycle and apoptosis of HeLa cells was analyzed using Annexin-V/PI double staining and flow cytometry. Then, we measured intracellular ROS generation induced by SNG in HeLa cells by DCFH-DA (10 µM) staining, and the expression level of p-STAT3 and STAT3 was detected by Western blot. Finally, in order to study the effect of SNG on tumor growth in vivo, athymic nude mice were used in the vivo experiments. RESULT: This study showed that SNG dose-dependently decreased the tumor cell proliferation and induced a marked increase in cell apoptosis in HeLa cells. Western blot analysis results revealed that SNG-induced antitumor effect might be mediated by STAT3 inhibition. SNG increased the expression of the proapoptotic protein Bax and reduced the expression of the antiapoptotic protein Bcl-2. We further found that SNG dose-dependently increased ROS level in Hela cells. Moreover, pretreatment with N-acetyl-l-cysteine, a scavenger of ROS, almost reversed the SNG-induced anticancer effect. In addition, SNG inhibited human cervical cancer xenograft growth without exhibiting toxicity in vivo. CONCLUSION: Our findings highlight STAT3 as a promising therapeutic target. We also demonstrate that SNG is a novel anticancer drug for the treatment of cervical cancer.