Analysis of COVID-19 pandemic in USA, using Topological Weighted Centroid.

The first case of COVID-19 in USA was reported on January 20, 2020. The number of COVID-19 confirmed cases and death has increased since the first reported case and the outbreak has appeared in all states. This paper analyzes disease outbreak using Topological Weighted Centroid (TWC), which is a data driven intelligent geographical dynamical system that models disease spread in space and time. In this analysis the COVID-19 cases in USA on March 26, 2020 as provided by Johns Hopkins University is used. The COVID-19 outbreak is mapped by the TWC method. We were able to predict and capture some features of the pandemic spread using the early data. Although we have used the geographical distance from the latitude and longitude coordinates, our results indicate that one of the main paths of diseases spread are arguably airline routes. In this analysis, we used a large set of data. A modified version of TWC, is named TWC-Windowing to elaborate the effect of data from all places.

Left-sided breast cancer irradiation using rotational and fixed-field radiotherapy.

The 3-dimensional conformal radiotherapy (3DCRT) technique is the standard for breast cancer radiotherapy. During treatment planning, not only the coverage of the planning target volume (PTV) but also the minimization of the dose to critical structures, such as the lung, heart, and contralateral breast tissue, need to be considered. Because of the complexity and variations of patient anatomy, more advanced radiotherapy techniques are sometimes desired to better meet the planning goals. In this study, we evaluated external-beam radiation treatment techniques for left breast cancer using various delivery platforms: fixed-field including TomoDirect (TD), static intensity-modulated radiotherapy (sIMRT), and rotational radiotherapy including Elekta volumetric-modulated arc therapy (VMAT) and tomotherapy helical (TH). A total of 10 patients with left-sided breast cancer who did or did not have positive lymph nodes and were previously treated with 3DCRT/sIMRT to the entire breast were selected, their treatment was planned with Monaco VMAT, TD, and TH. Dosimetric parameters including PTV coverage, organ-at-risk (OAR) sparing, dose-volume histograms, and target minimum/maximum/mean doses were evaluated. It is found that for plans providing comparable PTV coverage, the Elekta VMAT plans were generally more inhomogeneous than the TH and TD plans. For the cases with regional node involvement, the average mean doses administered to the heart were 9.2 (± 5.2) and 8.8 (± 3.0)Gy in the VMAT and TH plans compared with 11.9 (± 6.4) and 11.8 (± 9.2)Gy for the 3DCRT and TD plans, respectively, with slightly higher doses given to the contralateral lung or breast or both. On average, the total monitor units for VMAT plans are 11.6% of those TH plans. Our studies have shown that VMAT and TH plans offer certain dosimetric advantages over fixed-field IMRT plans for advanced breast cancer requiring regional nodal treatment. However, for early-stage breast cancer fixed-field radiotherapy is potentially more beneficial in terms of OAR sparing.

Respiration induced heart motion and indications of gated delivery for left-sided breast irradiation.

PURPOSE: To investigate respiration-induced heart motion for left-sided breast irradiation using a four-dimensional computed tomography (4DCT) technique and to determine novel indications to assess heart motion and identify breast patients who may benefit from a gated treatment. METHODS AND MATERIALS: Images of 4DCT acquired during free breathing for 20 left-sided breast cancer patients, who underwent whole breast irradiation with or without regional nodal irradiation, were analyzed retrospectively. Dose distributions were reconstructed in the phases of 0%, 20%, and 50%. The intrafractional heart displacement was measured in three selected transverse CT slices using D(LAD) (the distance from left ascending aorta to a fixed line [connecting middle point of sternum and the body] drawn on each slice) and maximum heart depth (MHD, the distance of the forefront of the heart to the line). Linear regression analysis was used to correlate these indices with mean heart dose and heart dose volume at different breathing phases. RESULTS: Respiration-induced heart displacement resulted in observable variations in dose delivered to the heart. During a normal free-breathing cycle, heart-induced motion D(LAD) and MHD changed up to 9 and 11 mm respectively, resulting in up to 38% and 39% increases of mean doses and V(25.2) for the heart. MHD and D(LAD) were positively correlated with mean heart dose and heart dose volume. Respiratory-adapted gated treatment may better spare heart and ipsilateral-lung compared with the conventional non-gated plan in a subset of patients with large D(LAD) or MHD variations. CONCLUSION: Proposed indices offer novel assessment of heart displacement based on 4DCT images. MHD and D(LAD) can be used independently or jointly as selection criteria for respiratory gating procedure before treatment planning. Patients with great intrafractional MHD variations or tumor(s) close to the diaphragm may particularly benefit from the gated treatment.

Esophageal cancer patients undergoing external beam radiation after placement of self-expandable metal stents: is there a risk of radiation dose enhancement?

BACKGROUND: Self-expandable metal stents (SEMSs) are used for palliation of malignant dysphagia. It is not known whether dose adjustments are required when there is a stent in the radiation field. OBJECTIVE: To measure the effects of esophageal stents of various designs and materials on radiation dose to the tissue adjacent to the stent in the radiation field to determine whether there should be any dose adjustment. DESIGN: Simulated clinical protocol. SETTING: Linear accelerator radiation treatment center. PATIENTS: Solid Water phantoms were used to mimic the tissue environment of the human esophagus as well as stents of various designs and materials and controls. INTERVENTIONS: Radiation beams composed of photons (x-rays) delivered in split dosing with energies of 6, 10, and 15 million volts. MAIN OUTCOME MEASUREMENTS: Film and image-based evidence of dose enhancement; Monte Carlo calculations. RESULTS: Dose enhancement from single beams was seen only on the anterior surface, particularly in the stainless steel Z-stent (3.5%-7.8%) and the nonmetal Polyflex stent (5.5%-8.8%); less dose enhancement was seen on the anterior surface of the Alimaxx and Ultraflex nitinol stents (2%-2.5%). A negligible dose effect was seen on the posterior wall of all the stents tested. Monte Carlo calculation results were roughly similar to actual dosimeter measurements. LIMITATIONS: Simulated clinical protocol. CONCLUSIONS: This tissue-mimicking model reveals that radiation dose enhancement is a function of stent design and material, and the dose reduction is unnecessary as long as multiple fields are used.

Improved survival in patients with early stage low-grade follicular lymphoma treated with radiation: a Surveillance, Epidemiology, and End Results database analysis.

BACKGROUND: External beam radiation therapy (RT) is the standard treatment for stage I-II, grade 1-2 follicular lymphoma. Because of an indolent natural history, some advocate alternative management strategies, including watchful waiting for this disease. The relative improvement in outcomes for patients treated with and without RT has never been tested in randomized trials. METHODS: The Surveillance, Epidemiology, and End Results database was queried for adult patients with stage I-II, grade 1-2 follicular lymphoma diagnosed from 1973 to 2004. Retrievable patient data included age, sex, race, stage, extranodal disease, and treatment with RT within the first year after diagnosis. Actuarial overall survival (OS) and disease-specific survival (DSS) were analyzed. RESULTS: A total of 6568 patients were identified. DSS at 5, 10, 15, and 20 years in the RT group was 90%, 79%, 68%, and 63% versus 81%, 66%, 57%, and 51% in the no RT group (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.55-0.68; P<.0001). OS at 5, 10, 15, and 20 years in the RT group was 81%, 62%, 45%, and 35% versus 71%, 48%, 34%, and 23% in patients not receiving RT (HR, 0.68; 95% CI, 0.63-0.73; P<.0001). On multivariate analysis, upfront RT remained independently associated with improved DSS (P<.0001, Cox HR, 0.65; 95% CI, 0.57-0.72) and OS (P<.0001; Cox HR, 0.73; 95% CI, 0.67-0.79). Lymphoma was the most common cause of death (52%). Only 34% of patients received upfront RT. CONCLUSIONS: Upfront RT was associated with improved DSS and OS compared with alternate management approaches, a benefit that persisted over time. This benefit suggests that watchful waiting with administration of salvage therapies on progression/relapse do not compensate for inadequate initial definitive treatment. Although it is the standard of care for this disease, RT for early stage low-grade follicular lymphoma is greatly underused in the US population; increased use of upfront RT could prevent thousands of deaths from lymphoma in these patients.

Cardiac mortality in patients with stage I and II diffuse large B-cell lymphoma treated with and without radiation: a surveillance, epidemiology, and end-results analysis.

PURPOSE: Standard therapy for stage I and II diffuse large B-cell lymphoma consists of combined modality therapy with anthracycline-based chemotherapy, anti-CD20 antibody, and radiation therapy (RT). Curative approaches without RT typically utilize more intensive and/or protracted chemotherapy schedules. Anthracycline-based chemotherapy regimens are associated with a dose-dependent risk of left ventricular systolic dysfunction. We hypothesize that patients treated without RT, i.e., those who are treated with greater total chemotherapy cycles and hence cumulative anthracycline exposure, are at increased risk of cardiac mortality. METHODS AND MATERIALS: The rate of cardiac-specific mortality (CSM) was analyzed in patients with stage I and II diffuse large B-cell lymphoma diagnosed between 1988 and 2004 by querying the National Cancer Institute Surveillance, Epidemiology, and End-Results database. Analyzable data included gender, age, race, stage, presence of extranodal disease, and RT administration. RESULTS: A total of 15,454 patients met selection criteria; 6,021 (39%) patients received RT. The median follow-up was 36 months (range, 6-180 months). The median age was 64 years. The actuarial incidence rates of CSM at 5, 10, and 15 years were 4.3%, 9.0%, and 13.8%, respectively, in patients treated with RT vs. 5.9%, 10.8% and 16.1%, respectively, in patients treated without RT (p < 0.0001; hazard ratio, 1.35; 95% confidence interval [CI]: 1.16-1.56). The increase in cardiac deaths for patients treated without RT persisted throughout the follow-up period. On multivariate analysis, treatment without RT remained independently associated with an increased risk of CSM (Cox hazard ratio, 1.32; 95% CI: 1.13-1.54; p = 0.0005). CONCLUSIONS: Increased anthracycline exposure in patients treated only with chemotherapy regimens may result in an increase in cardiac deaths, detectable only through analysis of large sample sizes. Confirmatory evaluation through meta-analysis of randomized data and design of large prospective trials is warranted.

Supine craniospinal irradiation setup with two spine fields.

Craniospinal irradiation is an integral part of treatment for a number of cancers. Typically, patients are positioned prone, which allows visualization of field matches. However, a supine position allows better airway access for patients requiring anesthesia, and is more comfortable for patients. One potential difficulty with supine positioning occurs when the patient is tall and requires matching 2 spine fields. We describe a technique to match the spine fields using light fields on the bottom of the treatment table, and verified the approach on a phantom. The accuracy of the technique is demonstrated for the first 4 patients, with the majority of field gaps and overlaps below our clinical tolerance of 2 mm.

Toxicity assessment of pelvic intensity-modulated radiotherapy with hypofractionated simultaneous integrated boost to prostate for intermediate- and high-risk prostate cancer.

PURPOSE: To evaluate the toxicity of pelvic intensity-modulated radiotherapy (IMRT) with hypofractionated simultaneous integrated boost (SIB) to the prostate for patients with intermediate- to high-risk prostate cancer. METHODS AND MATERIALS: A retrospective toxicity analysis was performed in 30 consecutive patients treated definitively with pelvic SIB-IMRT, all of whom also received androgen suppression. The IMRT plans were designed to deliver 70 Gy in 28 fractions (2.5 Gy/fraction) to the prostate while simultaneously delivering 50.4 Gy in 28 fractions (1.8 Gy/fraction) to the pelvic lymph nodes. The National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, was used to score toxicity. RESULTS: The most common acute Grade 2 events were cystitis (36.7%) and urinary frequency/urgency (26.7%). At a median follow-up of 24 months, late toxicity exceeding Grade 2 in severity was uncommon, with two Grade 3 events and one Grade 4 event. Grade 2 or greater acute bowel toxicity was associated with signficantly greater bowel volume receiving > or =25 Gy (p = .04); Grade 2 or greater late bowel toxicity was associated with a higher bowel maximal dose (p = .04) and volume receiving > or =50 Gy (p = .02). Acute or late bladder and rectal toxicity did not correlate with any of the dosimetric parameters examined. CONCLUSION: Pelvic IMRT with SIB to the prostate was well tolerated in this series, with low rates of Grade 3 or greater acute and late toxicity. SIB-IMRT combines pelvic radiotherapy and hypofractionation to the primary site and offers an accelerated approach to treating intermediate- to high-risk disease. Additional follow-up is necessary to fully define the long-term toxicity after hypofractionated, whole pelvic treatment combined with androgen suppression.

Dosimetric comparison between 3DCRT and IMRT using different multileaf collimators in the treatment of brain tumors.

We investigated the differences between 3-dimensional conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT), and the impact of collimator leaf-width on IMRT plans for the treatment of nonspherical brain tumors. Eight patients treated by 3DCRT with Novalis were selected. We developed 3 IMRT plans with different multileaf collimators (Novalis m3, Varian MLC-120, and Varian MLC-80) with the same treatment margins, number of beams, and gantry positions as in the 3DCRT treatment plans. Treatment planning utilized the BrainLAB treatment planning system. For each patient, the dose constraints and optimization parameters remained identical for all plans. The heterogeneity index, the percentage target coverage, critical structures, and normal tissue volumes receiving 50% of the prescription dose were calculated to compare the dosimetric difference. Equivalent uniform dose (EUD) and tumor control probability (TCP) were also introduced to evaluate the radiobiological effect for different plans. We found that IMRT significantly improved the target dose homogeneity compared to the 3DCRT. However, IMRT showed the same radiobiological effect as 3DCRT. For the brain tumors adjacent to (or partially overlapping with) critical structures, IMRT dramatically spared the volume of the critical structures to be irradiated. In IMRT plans, the smaller collimator leaf width could reduce the volume of critical structures irradiated to the 50% level for those partially overlapping with the brain tumors. For relatively large and spherical brain tumors, the smaller collimator leaf widths give no significant benefit.

Outcomes and effect of radiotherapy in patients with stage I or II diffuse large B-cell lymphoma: a surveillance, epidemiology, and end results analysis.

PURPOSE: To assess disease-specific survival (DSS), overall survival (OS), and the effect of radiotherapy (RT) in patients with localized diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: The Surveillance, Epidemiology, and End Results database was queried for all patients diagnosed with Stage I, IE, II, or IIE DLBCL between 1988 and 2004. The analyzable data included gender, age, race, stage, presence of extranodal disease, and RT administration. Patients who had died or were lost to follow-up within 6 months of diagnosis were excluded. RESULTS: A total of 13,420 patients met the search criteria. Of these, 5,547 (41%) had received RT and 7,873 (59%) had not. RT was associated with a significant DSS (hazard ratio, 0.82, p <0.0001) and OS benefit that persisted during the 15 years of follow-up. Elderly patients, defined either as those >60 or >70 years old, had significantly improved DSS and OS associated with RT. On multivariate analysis, RT was significantly associated with increased DSS and OS. The 5-year DSS outcomes were highly variable among patient subsets, defined by age, stage, and extranodal disease (range for RT-treated patients, 70% for Stage II, age >60 years to 87% for Stage I, age

Visual sensations during megavoltage radiotherapy to the orbit attributable to Cherenkov radiation.

During megavoltage photon and electron beam radiotherapy treatment involving the eye, patients commonly report visual sensations; "nerve stimulation" is the conventional explanation. We propose that the phenomenon can be attributed to Cherenkov radiation inside the eye. The threshold electron energy for Cherenkov radiation in water is 260 keV. The human retina is able to perceive approximately 5-14 visible photons in 0.001 s. A single 500 keV electron traversing 1 mm of water will induce nearly 15 Cherenkov visible range photons. We propose that a portal image involving the eye will produce sufficient Cherenkov radiation to be detected by the retina.

An optimization model and solution for radiation shielding design of radiotherapy treatment vaults.

In radiation shielding design, one is usually faced with a set of conflicting goals that are navigated by an experienced physicist. If one has abundant space, the task is simplified because concrete is relatively inexpensive and will provide adequate shielding for high energy photons and neutrons, when applicable. However, if space is constrained (which is usually the case), the design becomes more difficult since one will likely have to employ combinations of steel, lead, and concrete, or other new materials--each with different properties and costs. Very experienced shielding designers can draw upon previous plans, but they do not know if their design is optimal in any sense. We have constructed a linear program that minimizes the cost of the shielding materials and minimizes the dose at the protection point or the shielding thickness subject to space constraints and to Federal or State regulations regarding the allowable exposure to individuals adjacent to the radiotherapy vault. In spite of what appears to be a simple model, the solution may require iterations of the optimization to arrive at the optimal solution.

Evaluation of breast sentinel lymph node coverage by standard radiation therapy fields.

BACKGROUND: Biopsy of the breast sentinel lymph node (SLN) is now a standard staging procedure for early-stage invasive breast cancer. The anatomic location of the breast SLN and its relationship to standard radiation fields has not been described. METHODS AND MATERIALS: A retrospective review of radiotherapy treatment planning data sets was performed in patients with breast cancer who had undergone SLN biopsy, and those with a surgical clip at the SLN biopsy site were identified. The location of the clip was evaluated relative to vertebral body level on an anterior-posterior digitally reconstructed radiograph, treated whole-breast tangential radiation fields, and standard axillary fields in 106 data sets meeting these criteria. RESULTS: The breast SLN varied in vertebral body level position, ranging from T2 to T7 but most commonly opposite T4. The SLN clip was located below the base of the clavicle in 90%, and hence would be excluded from standard axillary radiotherapy fields where the inferior border is placed at this level. The clip was within the irradiated whole-breast tangent fields in 78%, beneath the superior-posterior corner multileaf collimators in 12%, and outside the tangent field borders in 10%. CONCLUSIONS: Standard axillary fields do not encompass the lymph nodes at highest risk of containing tumor in breast cancer patients. Elimination of the superior-posterior corner MLCs from the tangent field design would result in inclusion of the breast SLN in 90% of patients treated with standard whole-breast irradiation.

The dosimetric effect of inhomogeneity correction in dynamic conformal arc stereotactic body radiation therapy for lung tumors.

For patients treated with lung stereotactic body radiation therapy (SBRT) using dynamic conformal arcs, the influence of inhomogeneity correction (IC) on normal tissue and tumor dosimetry was studied. For the same numbers of monitor units, the planning target volume equivalent uniform doses calculated without path-length IC were lower than those calculated with IC (mean difference 18%, range 1-34%; p < 0.0001). Normal lung dose differences were of the same magnitude in opposite direction. In reports of SBRT, it will be helpful to maintain clear communication about the type of IC used to avoid future uncertainties about true normal tissue tolerance and tumor dose-response relationships.

New radiation therapy techniques for the treatment of head and neck cancer.

This article reviews the most recent technology used in the treatment of head and neck cancer. It discusses brachytherapy, new ways to mix radionuclides for enhanced radiobiologic effects, and different fractionation schemes that have grown in clinical importance. Intensity-modulated radiotherapy has become a mainstay in head and neck cancer treatment, and the authors discuss several popular and emerging approaches. Patient immobilization and imaging are also discussed.

Clinical application of intensity-modulated radiotherapy for locally advanced cervical cancer.

Intensity-modulated radiotherapy (IMRT) offers technical advantages over conventional external beam radiotherapy (CXRT) that might prove clinically advantageous in the management of gynecologic malignancies. Especially in the case of locally advanced cervical cancer, IMRT provides an opportunity to improve the therapeutic ratio by allowing a selective combination of normal tissue dose reduction and/or concomitant integrated boost dose to the tumor. The clinical and biologic rationale for IMRT in this setting is presented here, and pertinent technical considerations such as the delineation of relevant clinical and planning target volumes are discussed. The capacity for IMRT-mediated normal tissue sparing is illustrated by example and review of the literature. Furthermore, for a small cohort of patients with locally advanced or recurrent cervical cancer treated with concomitant integrated boost IMRT and concurrent chemotherapy, preliminary clinical observations of toxicity and tumor response are presented. Concomitant integrated boost IMRT appears clinically tolerable and efficacious in this setting, and formal clinical investigation is warranted as a means of exploiting the fraction-size dependence of radiosensitizers in common clinical use.

Technical considerations in the application of intensity-modulated radiotherapy as a concomitant integrated boost for locally-advanced cervix cancer.

The technical aspects of IMRT applied to cervix cancer are discussed in this paper, as well as issues related to tumor delineation, target volume definitions, inverse planning, and IMRT delivery. A theoretical example illustrating how IMRT can accurately mimic dose distributions obtained using conventional planning plus HDR brachytherapy is also shown. The notion of clinical optimization parameters is introduced to account for the radiation delivery variables, which affect the overall treatment time. This is especially relevant to the possible introduction of intrafractional movement and resulting inaccuracy, as well as facility efficiency.