Precision Population Cancer Medicine in Cancer of the Uterine Cervix: A Potential Roadmap to Eradicate Cervical Cancer.

With the success of the Human Genome Project, the era of genomic medicine (GM) was born. Later on, as GM made progress, there was a feeling of exhilaration that GM could help resolve many disease processes. It also led to the conviction that personalized medicine was possible, and a relatively synonymous word, precision medicine (PM), was coined. However, the influence of environmental factors and social determinants of diseases was only partially given their due importance in the definition of PM, although more recently, this has been recognized. With the rapid advances in GM, big data, data mining, wearable devices for health monitoring, telemedicine, etc., PM can be more easily extended to population-level health care in disease management, prevention, early screening, and so on.and the term precision population medicine (PPM) more aptly describes it. PPM's potential in cancer care was posited earlier,and the current authors planned a series of cancer disease-specific follow-up articles. These papers are mainly aimed at helping emerging students in health sciences (medicine, pharmacy, nursing, dentistry, public health, population health), healthcare management (health-focused business administration, nonprofit administration, public institutional administration, etc.), and policy-making (e.g., political science), although not exclusively. This first disease-specific report focuses on the cancer of the uterine cervix (CC). It describes how recent breakthroughs can be leveraged as force multipliers to improve outcomes in CC - by improving early detection, better screening for CC, potential GM-based interventions during the stage of persistent Human papillomavirus (HPV) infection and treatment interventions - especially among the disadvantaged and resource-scarce populations. This work is a tiny step in our attempts to improve outcomes in CC and ultimately eradicate CC from the face of the earth.

Eye Plaque Brachytherapy for Choroidal Malignant Melanoma: A Case Report on the Use of Innovative Technology to Expand Access, Improve Practice, and Enhance Outcomes.

Our institute established an eye plaque interstitial brachytherapy (EPIBT) program in 2007 using the Collaborative Ocular Melanoma Study (COMS) eye plaque. In this case report, we demonstrated an eye plaque treatment planned and executed using Eye Physics Plaque (Los Alamitos, CA) for a 72-year-old male patient with an extra-large tumor with a maximum width of 18.6 mm and height of 13.7 mm. The use of a customized eye plaque, manufactured through three-dimensional (3D) printing, has empowered us to plan and administer treatment for this patient with uveal melanoma. Without this option, enucleation, an option declined by the patient, or proton beam therapy (PBT), which the patient was unwilling to pursue in another state, would have been the alternative course of action. We were able to use more than one activity of the I-125 seeds, which enabled us to shape and reduce the dose to normal surrounding structures at risk within the orbit and in the vicinity of the orbital cavity. Using the dose evaluation tools available with the modern treatment planning system, we reduced the prescription dose from 85 to 70 Gy, with D90 of 140 Gy, thereby providing effective treatment and limiting risk organ doses. In summary, we were able to dose-deescalate without compromising the chances of controlling retinal/scleral tumors. The patient is doing well from a recent follow-up visit 12 months after the eye plaque brachytherapy treatment. The tumor was 4.80 mm high, 1/3 of the original height, and vision is back to 20/60, demonstrating a successful treatment.

A gradient mapping guided explainable deep neural network for extracapsular extension identification in 3D head and neck cancer computed tomography images.

BACKGROUND: Diagnosis and treatment management for head and neck squamous cell carcinoma (HNSCC) is guided by routine diagnostic head and neck computed tomography (CT) scans to identify tumor and lymph node features. The extracapsular extension (ECE) is a strong predictor of patients' survival outcomes with HNSCC. It is essential to detect the occurrence of ECE as it changes staging and treatment planning for patients. Current clinical ECE detection relies on visual identification and pathologic confirmation conducted by clinicians. However, manual annotation of the lymph node region is a required data preprocessing step in most of the current machine learning-based ECE diagnosis studies. PURPOSE: In this paper, we propose a Gradient Mapping Guided Explainable Network (GMGENet) framework to perform ECE identification automatically without requiring annotated lymph node region information. METHODS: The gradient-weighted class activation mapping (Grad-CAM) technique is applied to guide the deep learning algorithm to focus on the regions that are highly related to ECE. The proposed framework includes an extractor and a classifier. In a joint training process, informative volumes of interest (VOIs) are extracted by the extractor without labeled lymph node region information, and the classifier learns the pattern to classify the extracted VOIs into ECE positive and negative. RESULTS: In evaluation, the proposed methods are well-trained and tested using cross-validation. GMGENet achieved test accuracy and area under the curve (AUC) of 92.2% and 89.3%, respectively. GMGENetV2 achieved 90.3% accuracy and 91.7% AUC in the test. The results were compared with different existing models and further confirmed and explained by generating ECE probability heatmaps via a Grad-CAM technique. The presence or absence of ECE has been analyzed and correlated with ground truth histopathological findings. CONCLUSIONS: The proposed deep network can learn meaningful patterns to identify ECE without providing lymph node contours. The introduced ECE heatmaps will contribute to the clinical implementations of the proposed model and reveal unknown features to radiologists. The outcome of this study is expected to promote the implementation of explainable artificial intelligence-assiste ECE detection.

Model development of dose and volume predictors for esophagitis induced during chemoradiotherapy for lung cancer as a step towards radiobiological treatment planning.

BACKGROUND: Currently, radiation therapy treatment planning system intends biological optimization that relies heavily upon plan metrics from tumor control probability (TCP) and normal tissue complication probability (NTCP) modeling. Implementation and expansion of TCP and NTCP models with alternative data is an important step towards reliable radiobiological treatment planning. In this retrospective single institution study, the treatment charts of 139 lung cancer patients treated with chemo-radiotherapy were reviewed and correlated dosimetric predictors with the incidence of esophagitis and established NTCP model of esophagitis grade 1 and 2 for lung cancer patients. METHODS: Esophagus is an organ at risk (OAR) in lung cancer radiotherapy (RT). Esophagitis is a common toxicity induced by RT. In this study, dose volume parameters Vx (Vx: percentage esophageal volume receiving ≥ x Gy) and mean esophagus dose (MED) as quantitative dose-volume metrics, the esophagitis grade 1 and 2 as endpoints, were reviewed and derived from the treatment planning system and the electronic medical record system. Statistical analysis of binary logistic regression and probit were performed to have correlated the probability of grade 1 and 2 esophagitis to MED and Vx. IBM SPSS software version 24 at 5% significant level (α = 0.05) was used in the statistical analysis. RESULTS: The probabilities of incidence of grade 1 and 2 esophagitis proportionally increased with increasing the values of Vx and MED. V20, V30, V40, V50 and MED are statistically significant good dosimetric predictors of esophagitis grade 1. 50% incidence probability (TD50) of MED for grade 1 and 2 esophagitis were determined. Lyman Kutcher Burman model parameters, such as, n, m and TD50, were fitted and compared with other published findings. Furthermore, the sigmoid shaped dose responding curve between probability of esophagitis grade 1 and MED were generated respecting to races, gender, age and smoking status. CONCLUSIONS: V20, V30, V40 and V50 were added onto Quantitative Analysis of Normal Tissue Effects in the clinic, or QUANTEC group's dose constrains of V35, V50, V70 and MED. Our findings may be useful as both validation of 3-Dimensional planning era models and also additional clinical guidelines in treatment planning and plan evaluation using radiobiology optimization.

An Overview of the Use of Precision Population Medicine in Cancer Care: First of a Series.

Advances in science and technology in the past century and a half have helped improve disease management, prevention, and early diagnosis and better health maintenance. These have led to a longer life expectancy in most developed and middle-income countries. However, resource- and infrastructure-scarce countries and populations have not enjoyed these benefits. Furthermore, in every society, including in developed nations, the lag time from new advances, either in the laboratory or from clinical trials, to using those findings in day-to-day medical practice often takes many years and sometimes close to or longer than a decade. A similar trend is seen in the application of "precision medicine" (PM) in terms of improving population health (PH). One of the reasons for such lack of application of precision medicine in population health is the misunderstanding of equating precision medicine with genomic medicine (GM) as if they are the same. Precision medicine needs to be recognized as encompassing genomic medicine in addition to other new developments such as big data analytics, electronic health records (EHR), telemedicine, and information communication technology. By leveraging these new developments together and applying well-tested epidemiological concepts, it can be posited that population/public health can be improved. In this paper, we take cancer as an example of the benefits of recognizing the potential of precision medicine in applying it to population/public health. Breast cancer and cervical cancer are taken as examples to demonstrate these hypotheses. There exists significant evidence already to show the importance of recognizing "precision population medicine" (PPM) in improving cancer outcomes not only in individual patients but also for its applications in early detection and cancer screening (especially in high-risk populations) and achieving those goals in a more cost-efficient manner that can reach resource- and infrastructure-scarce societies and populations. This is the first report of a series that will focus on individual cancer sites in the future.

The Influence of Patient and System Factors on the Radiotherapy Treatment Time in the Treatment of Non-metastatic Cervical Cancer Patients in a Rural and Resource-Lean State's Safety-Net Hospital: Benefits of Strategic Planning.

Objective To decrease radiotherapy treatment time (RTT), measured from the day of initiation of radiotherapy to the day of its completion, specific strategies were initiated in early 2020 in the only academic safety-net medical center in a rural, resource-lean state. The factors that can succeed and those that need further improvements were analyzed in this initial assessment phase of our efforts to shorten the RTT. Methods This is an analysis of 28 cervix cancer patients treated with magnetic resonance imaging (MRI)-guided brachytherapy (February 2020-November 2021). The relationship between independent and dependent variable were analyzed by simple linear regression, and p-values ≤ 0.05 were considered statistically significant. SPSS software version 28.0 (IBM, Armonk, NY, USA) was used for statistical analysis. Results Two RTT groups (≤ 60 (32.1%) vs. > 60 days {67.9%}) with median RTT of 68 days (range, 51 to 106 days) were analyzed. Caucasians represented 66.7% of the RTT ≤ 60 days group. Four 'issues' were identified that increased the RTT: non-compliance, learning curve (early days of implementation of MRI-guided brachytherapy in the department), stage IV comorbidities, and with more than one issue mentioned; 77.8% with no issues had ≤ 60 days RTT vs. 26.3% for the > 60 days group. The breakdown of the no-issues factor by calendar year showed the RTT of ≤ 60 days was achieved higher in 2021 (85.7% vs. 20.0%; p=0.023) compared to 2020. For this entire cohort, the RTT of ≤ 60 days was achieved higher in 2021 (50.0% vs. 8.3%; p=0.019) compared to 2020. Data also showed improvement in RTT of ≤ 60 days for every sequential six months. 'Non-compliance' and 'learning curve' were the most important factors among patients having the longest RTTs. Conclusion The RTT can be further decreased. As a result of this preliminary analysis of the our strategic planning approach of 'circular' "See it," "Own it," "Solve it," and "Do it" and go back to the first step again, we plan to implement the following strategies in the immediate future to shorten the RTTs further and, in turn, improve our overall outcomes (local/regional control, disease-free survival, and overall survival): (a) Interdigitate MRI-guided brachytherapy during external beam radiotherapy (EBRT); patients who can not get the interdigitated brachytherapy procedures performed during the course of EBRT for any reason will receive two brachytherapy procedures per week; (c) attempt to add a cervix cancer care navigator to our staff to help patients having social issues, thus leading to compliance problems; (d) finally, in a year or two after these new strategic implementations, the RTT data will be reanalyzed.

Real World and Public Health Perspectives of Intraoperative Radiotherapy in Early-Stage Breast Cancer: A Multidisciplinary Analysis Beyond the Statistical Facts.

Breast conservation therapy (BCT) (usually a lumpectomy plus radiotherapy (RT)) has become a standard alternative to radical mastectomy in early-stage breast cancers with equal, if not higher, survival rates. The established standard of the RT component of the BCT had been about six weeks of Monday through Friday external beam RT to the whole breast (WBRT). Recent clinical trials have shown that partial breast radiation therapy (PBRT) to the region surrounding the lumpectomy cavity with shorter courses can result in equal local control, survival, and slightly improved cosmetic outcomes. Intraoperative RT (IORT) wherein RT is administered at the time of operation for BCT to the lumpectomy cavity as a single-fraction RT is also considered PBRT. The advantage of IORT is that weeks of RT are avoided. However, the role of IORT as part of BCT has been controversial. The extreme views go from "I will not recommend to anyone" to "I can recommend to all early-stage favorable patients." These divergent views are due to difficulty in interpreting the clinical trial results. There are two modalities of delivering IORT, namely, the use of low-energy 50 kV beams or electron beams. There are several retrospective, prospective, and two randomized clinical trials comparing IORT versus WBRT. Yet, the opinions are divided. In this paper, we try to bring clarity and consensus from a highly broad-based multidisciplinary team approach. The multidisciplinary team included breast surgeons, radiation oncologists, medical physicists, biostatisticians, public health experts, nurse practitioners, and medical oncologists. We show that there is a need to more carefully interpret and differentiate the data based on electron versus low-dose X-ray modalities; the randomized study results have to be extremely carefully dissected from biostatistical points of view; the importance of the involvement of patients and families in the decision making in a very transparent and informed manner needs to be emphasized; and the compromise some women may be willing to accept between 2-4% potential increase in local recurrence (as interpreted by some of the investigators in IORT randomized studies) versus mastectomy. We conclude that, ultimately, the choice should be that of women with detailed facts of the pros and cons of all options being presented to them from the angle of patient/family-focused care. Although the guidelines of various professional societies can be helpful, they are only guidelines. The participation of women in IORT clinical trials is still needed, and as genome-based and omics-based fine-tuning of prognostic fingerprints evolve, the current guidelines need to be revisited. Finally, the use of IORT can help rural, socioeconomically, and infrastructure-deprived populations and geographic regions as the convenience of single-fraction RT and the possibility of breast preservation are likely to encourage more women to choose BCT than mastectomy. This option can also likely lead to more women choosing to get screened for breast cancer, thus enabling the diagnosis of breast cancer at an earlier stage and improving the survival outcomes.

Preoperative Prediction and Identification of Extracapsular Extension in Head and Neck Cancer Patients: Progress and Potential.

Background This study aimed to demonstrate both the potential and development progress in the identification of extracapsular nodal extension in head and neck cancer patients prior to surgery. Methodology A deep learning model has been developed utilizing multilayer gradient mapping-guided explainable network architecture involving a volume extractor. In addition, the gradient-weighted class activation mapping approach has been appropriated to generate a heatmap of anatomic regions indicating why the algorithm predicted extension or not. Results The prediction model shows excellent performance on the testing dataset with high values of accuracy, the area under the curve, sensitivity, and specificity of 0.926, 0.945, 0.924, and 0.930, respectively. The heatmap results show potential usefulness for some select patients but indicate the need for further training as the results may be misleading for other patients. Conclusions This work demonstrates continued progress in the identification of extracapsular nodal extension in diagnostic computed tomography prior to surgery. Continued progress stands to see the obvious potential realized where not only can unnecessary multimodality therapy be avoided but necessary therapy can be guided on a patient-specific level with information that currently is not available until postoperative pathology is complete.

Patients and Families' Participation in Multidisciplinary Tumor Conferences Improves Patient and Family-Focused Cancer Care: Lessons Learned From a Debate on the Role of Radiation Therapy in Primary Mediastinal Non-Hodgkin Lymphoma.

Incorporation of patients' preferences often leads to improved outcomes when included in the multidisciplinary tumor conference/board (MTC). However, patients' wishes are not included or considered in the MTC decision-making. We need better strategies and approaches for patient-inclusive, shared decision-making. When finding ourselves at a crossroads regarding the next step in a patient's treatment, we saw a unique opportunity for an MTC with the patient and her husband in attendance. The results of a full literature review regarding the role of consolidative radiation therapy (RT) in a patient with primary (thymic) B-cell lymphoma after completion of chemotherapy and fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT) scan with a Deauville score of 4 were presented in a creative, engaging debate-style forum with visual aids. The patient and her husband were able to follow the discussion and, in the end, a consensus recommendation, heavily focused on the patient's preferences, was offered and adopted, which ultimately resulted in the avoidance of excess treatment and likely improved her long-term quality of life outcome. These collaborative and innovative interactions benefit not only our patients but enrich our lives too as healthcare providers and strengthen us as a cancer care team in terms of understanding diversity in decision-making processes.

The Emerging Boon of Information and Communication Technology in Multidisciplinary Cancer Care: A Force Multiplier With a Human Touch.

Cancer care (CC) is incredibly complex and requires the coordination of multiple disciplines for optimal outcomes. Historically, this has been accomplished with multidisciplinary tumor boards (MDTBs), but the benefits, while perhaps intuitive, have not always been demonstrated with sufficient research robustness and validity. We hypothesize that this difficulty in demonstrating the benefit of MDTBs may be related to a delay in decision-making and operationalizing those decisions. The history and value of MDTBs are presented as well as their weaknesses and limited demonstration of improved outcomes. A major weakness highlighted by the challenges of MDTBs is the concept of total package time (TPT) (rather, the inability to keep it as short as possible); any significant delays in CC for any discipline may have a deleterious impact on any given patient's care outcome. Drawing on our own experience with utilizing information and communication technology (ICT) during an effort to apply accountability theory to improve specifically radiation therapy package time (RTPT), we argue that similar principles will be applicable in the improvement of not only the TPT which relies on multiple disciplines, but other factors of CC as well, such as coordination. Experience with improvement in RTPT is discussed and the underlying theory is demonstrated as a sound methodology to apply beyond RTPT to TPT involving coordination of multiple disciplines and stands to lead to the full realization of the benefits of the multidisciplinary approach. The complexity of cancer means that real solutions to optimal outcomes are also, by nature, complex, but here simple accountability theory is demonstrated that may unlock the next phase of multidisciplinary coordination. In this work, we argue that the benefits of the MDTB format can be fully realized with the addition of ICT, a technological breakthrough in the past two decades, while not forgetting about continued human factors.

Strategic Reduction of Package Time in Head and Neck Cancer.

Purpose: Total package time, or the time from diagnosis to completion of definitive treatment, has been associated with outcomes for a variety of tumor sites, but especially to head and neck (HN) cancer. Patients with HN cancer often undergo a complex diagnosis and treatment process involving multiple disciplines both within and outside of oncology. This complexity can lead to longer package times, and each involved discipline has the responsibility to maintain an efficient and effective process. Strategic intervention to improve package time must involve not only new technology or tools, but also "soft" components such as accountability, motivation, and leadership. This combination is necessary to truly optimize radiation therapy for HN cancer, leading to shorter total package times for these patients. Methods and Materials: Two interventions were strategically executed to improve radiation therapy workflow: upgrade of the treatment planning system and implementation of an automated patient management and accountability system. The radiation therapy-related timelines of 112 patients with HN cancer treated over 2 years were reviewed, and the average time differences were compared between the patient populations before and after the strategic interventions. Results: Purely upgrading the treatment planning system did not show significant improvements, but when combined with the patient management system, significant improvement in radiation-related package time can be noted for every time point. The overall reduction of radiation-related package time was statistically significant at 22.85 days (P = .002). Conclusions: On face value, the patient management system could be credited as responsible for the improvement, but on qualitative analysis, it is noted that the new system is only a tool that can be ignored or underused. Owing to the addition of important "soft" components such as accountability, motivation, and leadership, the patient management system was optimized and implemented in such a manner as to have the desired effect.

Parkinson's Syndrome After Cranial Radiotherapy: A Case Report.

Parkinson's syndrome is a group of signs and symptoms where the core issue is bradykinesia and could be a manifestation of idiopathic parkinsonism (Parkinson's disease, PD), secondary parkinsonism, or parkinsonism due to neurodegenerative disease. PD is the most common cause of Parkinson's syndrome, accounting for approximately 80% of cases. The secondary causes of Parkinson's syndrome include tumors, trauma, hydrocephalus, chemotherapy, medications including amphotericin B, metoclopramide, and radiation treatment. Parkinsonian symptoms secondary to radiation treatment are rarely reported in the literature and are usually not alleviated by carbidopa-levodopa. This report describes a 64-year-old man diagnosed with low-grade astrocytoma of the midbrain who developed unilateral parkinsonian symptoms one year after chemoradiation treatment. This case report also sheds further light on the details of reported cases and the treatment options through an extensive literature review. Clinicians need to be aware of patients developing this rare complication following radiation treatment.

Educating the Colleagues: Radiation Basics for Obstetrics and Gynecology Residents.

Exposure to radiation oncology (RO) is limited among medical students, excluding those who wish to pursue a radiation oncology career. Consequently, RO knowledge in gynecological malignancies may differ among obstetricians and gynecologists (OB&G), depending on their experience and training level. Establishing a program to educate OB&G residents about basic radiation oncology principles may improve patients' coordination and treatment with gynecological malignancies. At our institution, radiation oncology residents conducted a 2-part training session for OB&G colleagues, which included a lecture and hands-on training. Educational sessions targeting OB&G residents are needed to enhance knowledge about radiation treatments and improve patient care.

Changing Role of PET/CT in Cancer Care With a Focus on Radiotherapy.

Positron emission tomography (PET) integrated with computed tomography (CT) has brought revolutionary changes in improving cancer care (CC) for patients. These include improved detection of previously unrecognizable disease, ability to identify oligometastatic status enabling more aggressive treatment strategies when the disease burden is lower, its use in better defining treatment targets in radiotherapy (RT), ability to monitor treatment responses early and thus improve the ability for early interventions of non-responding tumors, and as a prognosticating tool as well as outcome predicting tool. PET/CT has enabled the emergence of new concepts such as radiobiotherapy (RBT), radioimmunotherapy, theranostics, and pharmaco-radiotherapy. This is a rapidly evolving field, and this primer is to help summarize the current status and to give an impetus to developing new ideas, clinical trials, and CC outcome improvements.

Stage Migration in Cervical Cancer Using the FIGO 2018 Staging System: A Retrospective Survival Analysis Using a Single-Institution Patient Cohort.

Introduction The International Federation of Gynecology and Obstetrics (FIGO) changed the staging system for cervical cancer in 2018 and formally allowed cross-sectional imaging for staging purposes. Stage IB is now divided into three substages based on tumor size (IB1 < 2 cm, IB2 2-4 cm and IB3 > 4 cm). The presence of lymph nodes in the pelvis or para-aortic region will upstage the patient to stage IIIC. The purpose of this study was to evaluate the extent of stage migration using the FIGO 2018 staging system for cervical cancer and validate the new staging system by assessing the survival outcomes. Methods An Institutional Review Board-approved and Health Insurance Portability and Accountability Act-compliant retrospective analysis was performed on 158 patients from the cervical cancer database at the University of Mississippi Medical Center, USA. Patients had been treated between January 2010 and December 2018, and they were all staged according to the FIGO 2009 staging system previously. We collected data regarding tumor size, lymph node presence, and extent of metastatic disease in the pretreatment CT, positron emission tomography (PET), or MRI scans and restaged the patients using the FIGO 2018 system. The extent of stage migration was evaluated using the new staging system. We analyzed the three-year overall survival (OS) using both FIGO 2009 and 2018 staging systems for validation purposes. Kaplan-Meier analyses were performed using SPSS version 24. Results Fifty-nine percent of the patients were upstaged when they were restaged using the FIGO 2018 staging system. In the current 2018 staging system, Stage IB3 accounted for 4%, and Stage IIIC accounted for 48% of the patient cohort, while other stages accounted for the rest. The median overall survival of the entire cohort was 20.5 months. There was a change in the survival curves using FIGO 2018 stages compared to those of FIGO 2009. There was a numerical improvement in three-year OS in stages IB and III among the two staging systems; however, it was not statistically significant. Interestingly, the three-year overall survival of Stage IIIC patients was better when compared to Stages III A& B combined (61% vs. 25%, p=0.017). Conclusion The increased availability of cross-sectional imaging across the world has led to recent changes in the FIGO staging system for cervical cancer, which allowed imaging in staging. We identified a significant stage migration in our patient cohort with the FIGO 2018 staging system, but no difference in the three-year overall survival was observed. Local tumor extent may be a worse prognostic indicator than nodal metastasis among stage III patients.

Single Institution Experience of Stereotactic Body Radiation Therapy in Non-small Cell Lung Cancer: Comparison of Two Dose Regimes and a Perspective on Ideal Dose Regimens.

Introduction Stereotactic body radiation therapy (SBRT) is an effective treatment for early-stage non-small cell lung cancer (NSCLC) patients who are either medically inoperable or who decline surgery. SBRT improves tumor control and overall survival (OS) in medically inoperable, early-stage, NSCLC patients. In this study, we investigated the effectiveness of two different SBRT doses commonly used and present our institutional experience. Purpose To determine the clinical outcomes between two treatment regiments (50 Gray [Gy] vs. 55 Gy in five fractions) among Stage I NSCLC patients treated with SBRT at a state academic medical center. Methods We performed a retrospective analysis of 114 patients with Stage I (T1-2 N0 M0) NSCLC treated at a state academic medical center between October 2009 and April 2019. Survival analyses with treatment regimens of 50 Gy and 55 Gy in five fractions were conducted to detect any improvement in outcomes associated with the higher dose. The primary endpoints of this study included OS, local control (LC), and disease-free survival (DFS). Log-rank test and the Kaplan-Meier method were used to analyze the survival curves of the two treatment doses. The SPSS v.24.0 (IBM Corp., Armonk, NY, USA) was used for statistical analyses. Results The 114 early-stage NSCLC patients (median age, 68 years; range 12 to 87 years) had a median follow-up of 25 months (range two to 86 months). The number of males (n = 72; 63.2 %) exceeded the number of females (n = 42; 36.8 %). The majority of patients in this study were Caucasians (n = 68; 59.6 %) and 46 patients were African Americans (40.4 %). Two-thirds of the patients (n = 76; 66.7 %) were treated with 50 Gy in five fractions, and 38 patients (33.3 %) with 55 Gy in five fractions. The one-, two-, and three-year OS and DFS rates were improved in the patients treated with 55 Gy [OS, 81.7 % vs. 72.8 %; 81.7 % vs. 58.9 %; 81.7 % vs. 46.7 % (p = 0.049)], [DFS, 69.7 % vs. 69.7 %; 61.9 % vs. 55.7 %; 61.9 % vs. 52.0 % (p = 0.842)], compared to those treated with 50 Gy. Adenocarcinoma was the most common histology in both groups (51.3 % and 68.4 %). Failure rates were elevated for the 50 Gy regimen [39 (34.2 %) vs. 12 (8.5 %)]. Three year control rates were (66.3 % vs. 96.6 %; p = 0.002) local control; (63.3 % vs. 94.4 %; p = 0.000) regional control; and (65.7 % vs. 97.1 %; p = 0.000) distant control, compared to those treated with 55 Gy. Conclusion Early-stage NSCLC patients treated with SBRT 55 Gy in five fractions did better in terms of local control, overall survival, and disease-free survival rates compared to the 50 Gy in five fractions group.

Initial Institutional Experience with 18F-Fluciclovine PET-CT in Biochemical Recurrence of Prostate Cancer.

OBJECTIVES: 18F-fluciclovine (fluciclovine) is an amino acid analog approved by the Food and Drug Administration for use as a radiotracer in positron emission tomography (PET) in men with biochemical recurrence of suspected prostate cancer. The purpose of this study was to investigate the initial institutional experience with 18F-fluciclovine in the evaluation of prostate cancer with biochemical recurrence. METHODS: This study was a retrospective review of 135 patients who underwent 18F-fluciclovine PET-computed tomography (PET-CT) at a single institution from August 2018 through January 2020. Prognostic information, including prostate-specific level antigen (PSA) at the time of diagnosis, initial risk, initial Gleason score, and initial stage, was reviewed as well as the PSA level at the time of the scan. The images were reviewed by two radiologists with fellowship training in nuclear medicine and additional training to interpret the fluciclovine studies. A minority of studies were reviewed by a third fellowship-trained radiologist under the guidance of the two nuclear medicine-trained radiologists. In cases with abnormal radiopharmaceutical uptake in lymph nodes, the short-axis dimension of the lymph node or largest lymph node with abnormal uptake was noted. If CT or bone scan was performed within 4 months of the 18F-fluciclovine PET-CT, findings on the alternate imaging were compared with the results of the 18F-fluciclovine PET-CT. RESULTS: Our institutional positivity rate was 75.6%, with 64 (67.4%) patients with metastatic disease and 71 (52.6%) patients with local recurrence detected by fluciclovine. As expected, the rate of positive examinations increased with increasing PSA values measured at the time of imaging (P < 0.001). Of the 54 patients with nodal disease, 35 had nonpathologically enlarged lymph nodes measuring <1 cm in maximum short-axis dimension. In more than half of the patients in this study, with conventional imaging, fluciclovine either discovered otherwise undetectable metastatic disease or suggested the presence of local recurrence. CONCLUSIONS: Our single-institution experience with 18F-fluciclovine PET-CT has the largest number of patients to date in the literature and demonstrates the ability of fluciclovine to help guide clinical management in the detection of early recurrent disease.

Predictors of Extracapsular Extension in Patients With Squamous Cell Carcinoma of the Head and Neck and Outcome Analysis.

Introduction Extracapsular extension (ECE) in the lymph nodes for patients with head and neck cancer has been found to be a poor prognostic factor in multiple studies. The purpose of the study is to evaluate the predictive factors for ECE on computer tomography (CT) imaging for patients undergoing surgery and to analyze outcomes. Methods We conducted an Institutional Review Board-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant retrospective review of 82 patients with biopsy-proven squamous cell carcinomas of the head and neck who underwent definitive surgery without neoadjuvant chemotherapy or radiation therapy. CT scans were evaluated for the level of involvement, size, and presence or absence of central necrosis. Extracapsular extension in lymph nodes on the postoperative pathology was correlated with the central necrosis in the lymph nodes appreciated on the CT neck with contrast. Survival estimates were evaluated using the Kaplan-Meier test. Results ECE on postoperative pathology was seen in 74.07% of patients who had evidence of central necrosis in lymph nodes on preoperative CT neck compared to 46.43% without CT necrosis (p=0.013). The incidence of ECE is higher in poorly differentiated tumors and also nodal stages >N2c at presentation. Patents with ECE had inferior disease-free and overall survival (OS). Conclusions Our results reveal that patients with necrosis on CT and with moderately to poorly differentiated tumors have a high incidence of extracapsular extension. There was no difference in local control (LC) between the groups of patients, but the OS was inferior in patients with ECE. Predicting extracapsular extension upfront helps to formulate the appropriate treatment. We propose to study additional chemotherapy to improve outcomes in patients with positive extracapsular extension.

MRI-Directed Brachytherapy for Cancer of the Uterine Cervix: A Case Report, Review, and Perspective on the Importance of Widespread Use of This Technological Advance in the United States.

Cervical cancer remains a major health challenge in the United States (US), especially among the low socioeconomic and African American populations. The demographics of Mississippi constitute a relatively high percentage of this high-risk population. External beam radiation therapy (EBRT) combined with concurrent chemotherapy and followed by brachytherapy is the gold standard of treatment for stage IB3 through IVA cervical cancer. Arguably, brachytherapy is the most important component of this treatment process. Patterns of Care studies (PCS) and other more recent studies have shown that brachytherapy cannot be omitted or replaced by conventional or image-guided EBRT. The last decade has witnessed the expanding use of image-guided brachytherapy (IGBT). Studies have established the superiority of IGBT over point-based brachytherapy. MRI is associated with superior soft tissue definition compared with CT and is emerging as the new standard of care. The Gynaecological Groupe Européen de Curiethérapie and the European Society for Radiotherapy and Oncology [(GYN) GEC-ESTRO] have recommended that the dose be prescribed to the high-risk clinical target volume (HR-CTV). This volume includes residual tumor present at the time of brachytherapy, the cervix, and any gray areas seen on the scan. The (GYN) GEC-ESTRO has shown that a dose of >8500 cGy delivered in <50 days results in an approximate 10% increase in pelvic control (PC), disease-specific survival, and overall survival (OS) compared to historical controls. The normal tissue toxicity is comparable or better than historical controls as well. This dose, while maintaining normal tissue constraints, may only be achievable with a hybrid intracavitary/interstitial (IC/IS) needle device guided by MRI-based targeting.  The University of Mississippi Medical Center (UMMC) has initiated an MRI-based cervical brachytherapy program and has treated 18 patients to date; our experience confirms the above findings. In this report, we propose that MRI guidance is necessary and a hybrid IC/IS needle device is required to achieve adequate dose coverages.