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PURPOSE Application of linear-quadratic (LQ) model to large fractional dose treatments is inconsistent with observed cell survival curves having a straight portion at high doses. We have proposed a unified multi-activation (UMA) model to fit cell survival curves over the entire dose range that allows us to calculate EQD2 for hypofractionated SBRT, SRT, SRS, and HDRB. METHODS A unified formula of cell survival S=n/eDDo+n-1 using only the extrapolation number of n and the dose slope of Do was derived. Coefficient of determination, R2 , relative residuals, r, and relative experimental errors, e, normalized to survival fraction at each dose point, were calculated to quantify the goodness in modeling of a survival curve. Analytical solutions for α and β, the coefficients respectively describe the linear and quadratic parts of the survival curve, as well as the α/β ratio for the LQ model and EQD2 at any fractional doses were derived for tumor cells undertaking any fractionated radiation therapy. RESULTS Our proposed model fits survival curves of in-vivo and in-vitro tumor cells with R2 > 0.97 and r

Radiation-induced endothelial/vascular injury is a major complicating factor in radiotherapy and a leading cause of morbidity and mortality in nuclear or radiological catastrophes. Exposure of tissue to ionizing radiation (IR) leads to the release of oxygen radicals and proteases that result in loss of endothelial barrier function and leukocyte dysfunction leading to tissue injury and organ damage. Microvascular endothelial cells are particularly sensitive to IR and radiation-induced alterations in endothelial cell function are thought to be a critical factor in organ damage through endothelial cell activation, enhanced leukocyte-endothelial cell interactions, increased barrier permeability and initiation of apoptotic pathways. These radiation-induced inflammatory responses are important in early and late radiation pathologies in various organs. A better understanding of mechanisms of radiation-induced endothelium dysfunction is therefore vital, as radiobiological response of endothelium is of major importance for medical management and therapeutic development for radiation injuries. In this review, we summarize the current knowledge of cellular and molecular mechanisms of radiation-induced endothelium damage and their impact on early and late radiation injury. Furthermore, we review established and emerging in vivo and in vitro models that have been developed to study the mechanisms of radiation-induced endothelium damage and to design, develop and rapidly screen therapeutics for treatment of radiation-induced vascular damage. Currently there are no specific therapeutics available to protect against radiation-induced loss of endothelial barrier function, leukocyte dysfunction and resulting organ damage. Developing therapeutics to prevent endothelium dysfunction and normal tissue damage during radiotherapy can serve as the urgently needed medical countermeasures.

Radical cystectomy (RC) after neoadjuvant chemotherapy (NAC) is the gold standard for management of muscle-invasive bladder cancer (MIBC). Patients without residual tumor at the time of extirpative surgery (ypT0) have excellent prognosis. Distant metastases in this population are rare. We present a unique case of a patient with ypT0N0 urothelial carcinoma (UC) with rapid development of metastasis to the brain.

Objectives/hypothesis Although the multidisciplinary tumor board (MTB) is accepted as best practice for the management of head and neck squamous cell carcinoma (HNSCC), there is limited evidence showing its impact on survival. Our goal was to investigate the impact of an MTB following the hiring of a fellowship-trained head and neck surgeon and implementation of an MTB at our institution. We hypothesized that these changes would demonstrate an improvement in survival. Study design Retrospective chart review. Methods A review of HNSCC treated at our institution between October 2006 and May 2015 was performed. The cohort was divided into pre-MTB (October 2006-February 2011) and post-MTB (February 2011-May 2015) cohorts. Patient demographics, cancer stage, and treatment outcomes were reviewed. Univariate, multivariate, and survival analysis were performed. Results The study included 224 patients, 98 in the pre-MTB cohort and 126 in the post-MTB cohort. Of total patients, 139 (62%) were black and 91 (40%) were on Medicaid or uninsured. Average follow-up time was 2.8 years, and most cases were advanced stage (68%). On Kaplan-Meier evaluation, overall survival and disease-specific survival were significantly improved in the post-MTB cohort compared with the pre-MTB cohort, with a 5-year disease-specific survival of 52% vs. 75% (P = .003). A matched cohort analysis showed that the post-MTB cohort had significantly lower risk of death (hazard ratio: 0.48). Conclusions Our study demonstrates that treatment of HNSCC by a dedicated multidisciplinary team results in improved survival. Multidisciplinary care should be considered best practice in the care of HNSCC. Level of evidence 3b Laryngoscope, 130:946-950, 2020.

This formative research study describes the development and preliminary evaluation of a theory-guided, online multimedia psycho-educational program (PROGRESS) designed to facilitate adaptive coping among prostate cancer patients transitioning from treatment into long-term survivorship. Guided by the Cognitive-Social Health Information Processing Model (C-SHIP) and using health communications best practices, we conducted a two-phase, qualitative formative research study with early stage prostate cancer patients (n = 29) to inform the Web program development. Phase 1 included individual (n = 5) and group (n = 12) interviews to help determine intervention content and interface. Phase 2 employed iterative user/usability testing (n = 12) to finalize the intervention. Interview data were independently coded and collectively analyzed to achieve consensus. Survivors expressed interest in action-oriented content on (1) managing treatment side effects, (2) handling body image and comorbidities related to overweight/obesity, (3) coping with emotional and communication issues, (4) tips to reduce disruptions of daily living activities, and (5) health skills training tools. Patients also desired the use of realistic and diverse survivor images. Incorporation of an established theoretical framework, application of multimedia intervention development best practices, and an evidence-based approach to content and format resulted in a psycho-educational tool that comprehensively addresses survivors’ needs in a tailored fashion. The results suggest that an interactive Web-based multimedia program is useful for survivors if it covers the key topics of symptom control, emotional well-being, and coping skills training; this tool has the potential to be disseminated and implemented as an adjunct to routine clinical care.

Purpose The purpose of this case series is to describe the treatment and outcomes of a cohort of patients with inoperable early-stage endometrioid endometrial cancer with 3D image-guided high-dose-rate (HDR) intracavitary brachytherapy. Materials and Methods A review was performed of patients with early-stage endometrial cancer who underwent primary radiation treatment between 2010 and 2016. Staging and treatment planning were performed CT, pelvic ultrasound, and pelvic MRI. Gross tumor volume (GTV) was defined as the MRI or ultrasound demonstrated endometrial stripe width, with the entire uterine corpus, cervix, and proximal vagina representing the clinical target volume (CTV). Dosimetry calculations were performed in each fraction of HDR brachytherapy. RESULTS Eight patients received external beam radiation therapy followed by intracavitary HDR brachytherapy. Seven patients underwent intracavitary HDR brachytherapy alone. In all patients, mean cumulative dose to 90% (D90) of GTV was 95.99 Gy in equivalent dose in 2 Gy fractions (EQD2, α/β = 10). Mean cumulative D90 EQD2 to CTV was 51.64 Gy. Average follow-up was 29 months. Four patients died from concurrent disease(s) at an average of 2.83 years after completion of treatment. Except for 1 (6.6%) patient who recurred at 9 months following completion of treatment, all patients remained disease-free for the remainder of follow-up. Conclusions In patients who are poor surgical candidates and have early-stage endometrioid type endometrial carcinoma, image-guided HDR intracavitary brachytherapy carries minimal side effects and a high response rate.

Even in the posthuman genomic era, radiation therapy singularly continues to offer considerable hope to the patients with localized prostate cancer and the metastatic disease. The radiation therapy techniques and their combination with other emerging modalities have developed rapidly over the past two decades at an increasing pace. These newer treatment modalities, apart from their therapeutic benefits, have shown remarkable advantages such as shortening treatment durations, patient visits, saving medical resources, and reducing treatment costs. This chapter will attempt to highlight some of the novel modalities that are nearing clinical application. With the advent of improved patient stratification methods, advanced imaging modalities, adaptive radiation therapies, and expansion of new types of external beam irradiation, better understanding of molecular mechanisms of various radiation sensitization targets, promising genomic and metabolomic biomarkers, and critical findings derived from a wide-range of combinatorial treatment modality clinical trials involving systemic and surgical approaches, the future of radiation therapy treatment options for prostate cancer patients look bright.

Radiation therapy remains ideally suited for the curative treatment of localized prostate cancer and palliation of metastatic disease. New treatment techniques have been developed and the field has had rapid advances in technology. Brachytherapy (radioactive implants) has undergone changes with the increased use of high dose rate temporary implants. These have resulted in shorter treatment courses for favorable prostate cancer. Combined modality treatment with hormonal therapy has become standard for locally advanced definitive treatment. At the same time surgical and other techniques have also improved making the selection of the optimal management of localized prostate carcinoma difficult for patients and clinicians. There are no conclusive prospective randomized studies demonstrating significant differences in overall survival and freedom from biochemical relapse between surgery and radiation therapy. In this chapter, we provide an overview of radiation biology, different radiation treatment techniques, and the current standard of care for definitive and palliative radiation therapy in prostate cancer.

Oral mucositis is a common morbidity induced by radiation therapy and chemo-radiotherapy for head and neck malignancies. This often results in treatment delays, premature treatment cessation and increased cost. New treatments of oral mucositis are emerging but effective remedies remain limited. Between February 2007 and May 2008, 21 patients with head and neck malignancies were treated with a supersaturated calcium phosphate oral rinse (Caphosol) that was performed for 4-10 times daily, each consisting of two one-minute rinses. There were 21 matched patients who received supportive care without the oral rinse. All patients in the two groups were treated with intensity modulated radiation therapy (IMRT) for average prescription doses of 66 Gy in 33 fractions. The effects of this rinse vs. supportive care on mucositis, PEG tube requirements, hospitalization, xerostomia, analgesic requirements and weight was respectively evaluated. We have observed statistically significant decreases in the incidence of radiation induced oral mucositis (p=0.0002) with WHO grade 3 (38% vs. 52%) and 4 mucositis (0% vs. 19%), need for PEG tube placement (33% vs. 57%) and hospitalization (0% vs 19%). There was also a favorable impact on the incidence of grade 3 (29% vs. 43%) xerostomia in the treated patients but it was statistically insignificant (p=0.58). Incremental costs related to treatment of oral mucositis were reduced considerably. Our data suggest that use of a supersaturated calcium phosphate oral rinse is an effective treatment for mucositis in patients undergoing IMRT. It may also be helpful in the reduction of hospitalization and PEG tube requirements.

Given high rates of smoking among cancer patients, smoking cessation treatment is crucial; yet limited data exist to guide integration of such trials into the oncologic context. In order to determine the feasibility of conducting smoking cessation clinical trials with cancer patients, screening and baseline data from a large randomized placebo-controlled pharmacotherapy trial were analyzed. Descriptive statistics and regression analyses were used to compare enrollees to decliners, describe program enrollees, and assess correlates of confidence in quitting smoking. Out of 14,514 screened patients, 263 ( 30%) African Americans; participants had extensive smoking histories; many were highly nicotine dependent; and participants consumed about seven alcoholic beverages/week on average. Head and neck and breast cancer were the most common tumors. About 52 (25%) reported depressive symptoms. A higher level of confidence to quit smoking was related to lower depression and lower tumor stage. Integrating a smoking cessation clinical trial into the oncologic setting is challenging, yet feasible. Recruitment strategies are needed for patients with advanced disease and specific cancers. Once enrolled, addressing participant’s depressive symptoms is critical for promoting cessation.

Aims: We retrospectively compared results of surgery alone (SX) or radiotherapy alone (RT) for early stage tonsil and base of tongue cancers. Materials & methods: Outcomes for 386 SX and 362 RT patients from Surveillance, Epidemiology and End Results database were analyzed using propensity covariate adjusted and inverse probability weighting models. Results: With median follow-up of 71 months, unadjusted overall survival at 5 years was 66.1% for SX versus 50.2% for RT (p < 0.001). Unadjusted cancer-specific survival was 80.9% for SX versus 67.3% for RT (p < 0.001). In multivariate analysis, treatment modality maintained association with overall survival and cancer-specific survival. Inverse probability weighting-adjusted 5-year overall survival was 75.2% for SX versus 67.4% for RT (p = 0.002). Inverse probability weighting-adjusted cancer-specific survival was 86.0% for SX versus 77.4% for RT (p < 0.001). Conclusion: Explanations for higher survival for SX include comorbidities, superiority of surgery and underascertainment of postoperative radiation in Surveillance, Epidemiology and End Results.

BACKGROUND: Prolonged wound-discharge following total hip arthroplasty (THA) is associated with an increased risk of infection. However, the potential role of hypertension in prolonging the duration of wound healing in this population has not yet been investigated. The aim of the present study was to compare healing in this population that has not yet been investigated. The aim of the present study was to compare hypertensive and normotensive THA patients in terms of the length of time required to achieve a dry wound and the length of stay in the hospital. METHODS: One hundred and twenty primary THA patients were evaluated. Pre-operative clinical history and physical examination revealed that 29 were hypertensive and 91 were normotensive. The two groups were statistically matched using optimal propensity score matching. The outcomes of interest were the number of days until a dry wound was observed and the duration of hospital stay. RESULTS: The average systolic blood pressures were 150.1 mmHg and 120.3 mmHg for the hypertensive and normotensive groups, respectively. The mean number of days until the wound was dry was 3.79 for the hypertensive group and 2.03 for the normotensive group. Hypertensive patients required more days for their wounds to dry than normotensive patients (odds ratio = 1.65, p

Many cancer patients continue to smoke post diagnosis, yet there have been few smoking cessation trials for this population. Depression, which is prevalent among cancer patients, may be a barrier to cessation. This double-blind placebo-controlled trial randomized 246 cancer patients to 9 weeks of placebo or bupropion, stratifying by pre-treatment depression symptoms. In addition, all patients received transdermal nicotine and behavioral counseling. Primary outcomes were 7-day point-prevalence abstinence, biochemically confirmed, at the end of treatment (Week 12), and at 6 months post quit day (Week 27). Additional outcomes included: withdrawal, affect, quality of life, compliance, and side effects. There was no main effect of bupropion vs. placebo on abstinence (Odds Ratio [OR] = 1.36, 95% CI: 0.38–4.81, p = .64). Patients with depression symptoms reported significantly lower abstinence rates vs. patients without depression symptoms (OR = .14, 95% CI: 0.02–0.80, p = .03). Bupropion increased abstinence rates, vs. placebo, more for participants with depression vs. those without depression symptoms. For patients with depression symptoms, bupropion reduced withdrawal symptoms and improved quality of life vs. placebo. For patients with depression symptoms, bupropion increases abstinence rates, lowers withdrawal, and increases quality of life. However, abstinence rates among patients with depression symptoms were low vs. patients without depression symptoms, who exhibited similar abstinence rates when treated with bupropion or transdermal nicotine and counseling alone. These results can guide future smoking cessation intervention studies with cancer patients.

Ionizing radiation significantly alters the structure and function of microvasculature, which regulates delivery of oxygen to brain tissue. Previous experimental and modeling studies have shown that tissue oxygenation patterns are significantly different in irradiated normal tissue compared to age-matched controls, and the differences are apparent as early as 3 days postirradiation. However, oxygen delivery to irradiated tissue recovers within 6 months postirradiation. Changes in perfusion and oxygenation were studied in a bilaterally (both cerebral hemispheres) and unilaterally (only one hemisphere) irradiated mouse brain model at 6 and 24 h as well as 3, 7, 30, 60 and 120 days postirradiation. The results indicate that significant changes in the number of perfused vessels (as measured by fluorescent DiOC(7) staining) and anatomical vessels (as indicated by CD31 immunohistochemical staining) and tissue oxygenation (by immunohistochemical detection of a fluorescently conjugated monoclonal antibody to EF5) are most pronounced at 3 days postirradiation, while a degree of recovery is observed at later times. However, in the unilaterally irradiated animals, both irradiated and unirradiated (out-of-field) cerebral hemispheres showed similarly significant changes in oxygenation and/or perfusion compared to unirradiated controls. Anti-TNFA treatment inhibited radiation-induced local as well as abscopal effects in the brain tissue.

Purpose: To evaluate the treatment outcome and natural history of patients with the diagnosis of unilesional mycosis fungoides, treated according to a prospective radiotherapy protocol in our institution since July 1975. Methods and Materials: A total of 325 patients with the diagnosis of mycosis fungoides have been referred to the Department of Radiation Oncology at Allegheny University of Health Sciences from July 1975 through September 1996. Of these, 18 patients (5%) were classified as having unilesional mycosis fungoides and were irradiated with a curative intent using local electron fields. One patient received 22 Gy; 1 patient received 40 Gy, and the rest of the patients 30.6 Gy. Daily fractions ranged from 1.8 to 2.0 Gy. Treatments prior to radiation consisted of topical steroids and/or antifungal creams in the majority of patients, with temporary partial responses. One patient had received 2 years of topical mechlorethamine (HN2) and another patient had received topical carmustine solution (BCNU) without response prior to irradiation. Results: The responses were measured clinically; posttreatment skin biopsy was not performed routinely unless there was clinical evidence of disease persistence. Complete response rate was 100%; all treated lesions cleared completely within 4 to 8 weeks after the completion of radiation. With a median follow-up of 43 months (range 12 to 240 months), 2 relapses have occurred, 2 and 71 months after the completion of radiation. Both relapses were confined to the skin and were remote from the original site. Both relapses responded to topical application of HN2. There have been no recurrences in the irradiated field nor systemic dissemination. No long-term side effects were found related to treatment, and all the patients are currently alive and without evidence of disease. Actuarial relapse-free and overall survival at 10 years are, respectively, 86.2% and 100%. Conclusion: Unilesional mycosis fungoides has a long natural history, is possibly the earliest manifestation of a malignant process, and local treatments, including local radiotherapy, result in long-term disease-free intervals and, possibly, cure. Total skin electron beam radiotherapy is not indicated for this disease entity.

Objectives: Retrospective analysis of patients with recurrences at or closely adjacent to the site of prior lung stereotactic body radiation therapy (SBRT) who received repeat SBRT. Materials and Methods: Nine patients with non-small cell lung cancer (n = 8) or oligometastatic colonic adenocarcinoma (n = 1) were treated with image-guided lung SBRT to a median of 60 Gy (range, 30-60) in a median of 3 fractions (3-5). Patients developed in-field relapse (n = 3) or recurrence adjacent (≤3.5 cm away) to the previous tumor location (n = 6) and received 2 nd lung SBRT to a median of 60 Gy. Results: Median follow-up after 2 nd SBRT was 22 months (4-40). All completed prescribed course of repeat SBRT and acute toxicity was limited. There was no grade >3 late toxicity. 3 (33.3%) patients developed Grade 3 late reactions: 2 pulmonary and 1 chest wall pain. Late pulmonary toxicity included 2 (22.2%) patients with Grade 3 and 3 (33.3%) with Grade 2. One patient (11.1%) had late Grade 3 and 1 (11.1%) Grade 2 chest wall pain. 1 (11.1%) developed Grade 2 late brachial plexopathy. No myelopathy was observed. Two patients developed progression of tumors treated by 2 nd SBRT. Local recurrence free survival and overall survival was 75% and 68.6%, respectively at 2 years. Relative volume of ipsilateral lung receiving 5 Gy (V5) and V10 were lower for 2 nd SBRT. Conclusion: Repeat image-guided SBRT for patients with small peripheral recurrences was feasible and severe toxicity was not observed. Additional studies are needed to evaluate the safety and efficacy of lung reirradiation using 2 nd SBRT.

Objective To identify clinical predictive factors for visual outcome in a large series of patients who underwent plaque radiotherapy for uveal melanoma. Design Clinical factors, including patient data, tumor features, and radiation variables, were analyzed for their impact on visual acuity using Cox proportional hazards regression models. Participants Patients with uveal melanoma and initial visual acuity of 20/100 or better in the affected eye who were treated with plaque radiotherapy between July 1976 and June 1992. Main Outcome Measures Two end points were used to evaluate posttreatment visual acuity: (1) final visual acuity (good [20/20-20/100] vs poor [20/200 to no light perception]) and (2) loss of visual acuity (minimal [ Results Of 1300 consecutive patients with uveal melanoma treated by plaque radiotherapy, 1106 had a visual acuity of 20/100 or better at the time of treatment. In this group, poor visual acuity was found in 34% at 5 years and 68% at 10 years of follow-up. From multivariable analysis, clinical factors that best predicted poor visual acuity were increasing tumor thickness, proximity to foveola of less than 5 mm, notched plaque shape, tumor recurrence, patient age 60 years or older, subretinal fluid, cobalt isotope, anterior tumor margin posterior to equator, and worse initial visual acuity. Moderate loss of visual acuity of 5 Snellen lines or more was found in 33% at 5 years and 69% at 10 years of follow-up. From multivariable analysis, clinical factors that best predicted moderate visual acuity loss included increasing tumor thickness, worse initial visual acuity, notched plaque shape, tumor recurrence, proximity to foveola of less than 5 mm, patient age of 60 years or older, subretinal fluid, and diabetes mellitus or hypertension. When analyzing visual outcome with regard to tumor thickness, ultimate poor visual acuity of 20/200 or worse at 5 years was found in 24% with a small melanoma (≤3.0 mm), 30% with a medium melanoma (3.1-8.0 mm), and 64% with a large melanoma (>8.0 mm). When analyzing visual outcome with regard to tumor proximity to visually important structures, tumors less than 5 mm from the optic disc or foveola demonstrated poor visual acuity in 35% at 5 years, whereas those 5 mm or more from the optic disc and foveola showed poor visual acuity in 25% at 5 years. Conclusions Ultimate visual acuity after plaque radiotherapy for uveal melanoma depends on many factors, including patient age and general health, initial visual acuity, tumor location and size, subretinal fluid, radioactive isotope, and final tumor control. At 10 years' follow-up, 68% of patients demonstrate poor visual acuity. Visual acuity is most effectively preserved in eyes with small tumors outside a radius of 5 mm from the optic disc and foveola.

In summary, SRS and SBRT require a team-based approach, staffed by appropriately trained and credentialed specialists. SRS and SBRT training should become a required part of radiation oncology residency training and of Accreditation of Medical Physics Educational Programs accredited clinical medical physics training. SRS and SBRT require significant resources in personnel, specialized technology, and implementation time. A thorough feasibility analysis of resources required to achieve the clinical and technical goals must be performed and discussed with all personnel, including medical center administration. Because various disease sites may have different clinical and technical requirements, feasibility and planning discussions are needed prior to undertaking new disease sites. Treatment of SRS/SBRT patients should adhere to established national guidelines. Acceptance and commissioning protocols and tests must be developed to explore in detail every aspect of the individual and integrated systems with the goal of ensuring safe and effective operation. A comprehensive quality assurance program, encompassing all clinical, technical, and patient-specific treatment aspects, must be developed to ensure SRS and SBRT are performed in a safe and effective manner. Patient safety in radiation therapy is everyone's responsibility. Professional organizations, regulators, vendors, and end-users must demonstrate a clear commitment to working closely together to ensure the highest levels of safety and efficacy in stereotactic radiosurgery and stereotactic body radiation therapy.