Utility of TTMV-HPV DNA in resolving indeterminate findings during oropharyngeal cancer surveillance.

OBJECTIVES: Clinical and imaging examinations frequently have indeterminate results during cancer surveillance, which can lead to overtreatment and cause psychological and financial harm to the patient. This study addresses the critical need to enhance diagnostic precision and decision-making in the management of HPV-associated oropharyngeal cancer. This study evaluated the utility of tumor tissue-modified viral (TTMV)-HPV DNA to resolve indeterminate disease status following definitive treatment for HPV-associated oropharyngeal cancer. MATERIALS AND METHODS: In this retrospective cohort, patients treated for HPV-associated oropharyngeal cancer at eight U.S. institutions and who received one or more TTMV-HPV DNA tests during post-treatment surveillance between February 2020 and January 2022 were included. RESULTS: Among 543 patients, 210 patients (38.7%; 210/543) experienced one or more clinically indeterminate findings (CIFs) during surveillance, with 503 CIFs recorded. Of those patients with an "indeterminate" disease status at a point during surveillance, 79 were associated with contemporaneous TTMV-HPV DNA testing. TTMV-HPV DNA testing demonstrated high accuracy (97.5%; 77/79) in correctly determining recurrence status. Patients whose disease status was "indeterminate" at the time of a positive TTMV-HPV DNA test were clinically confirmed to recur faster than those whose disease status was "no evidence of disease." Only 3% of patients (17/543) experienced indeterminate TTMV-HPV DNA tests during surveillance. Discordance between TTMV-HPV DNA tests and clinical results was minimal, with only 0.6% (3/543) of patients showing positive tests without recurrence. CONCLUSION: Our findings support the utility of circulating TTMV-HPV DNA in resolving indeterminate disease status and informing the subsequent clinical course.

Tubarial gland sparing with intensity modulated radiation therapy for oropharyngeal cancers: A pilot study of dosimetric feasibility.

BACKGROUND: Tubarial glands are a new organ at risk for head and neck cancer radiation therapy (RT). We aimed to study the feasibility of sparing them using intensity-modulated radiation therapy (IMRT). METHODS: Tubarial glands were delineated for 17 patients with oropharyngeal carcinoma receiving definitive RT, and treatment plans were re-optimized to spare dose to the tubarial glands while maintaining target coverage. A paired t test was performed to compare the mean dose of tubarial glands and target coverage. RESULTS: The difference in mean doses was 4.9 and 7.0 Gy for the ipsilateral and contralateral tubarial glands, respectively (p < 0.01). The mean dose to tubarial gland was ≤39 Gy in 35% versus 47% (ipsilateral) and 70% versus 100% (contralateral) in clinical and re-optimized plans, respectively. Re-optimized ipsilateral tubarial gland mean ≤39 Gy was achieved more commonly in patients with base of tongue versus tonsil primaries (86% vs. 20%, p = 0.02). CONCLUSION: This pilot study demonstrates the dosimetric feasibility of tubarial gland sparing with IMRT. Dosimetric constraints need to be determined with larger studies.

Interdisciplinary Collaboration in Head and Neck Cancer Care: Optimizing Oral Health Management for Patients Undergoing Radiation Therapy.

Radiation therapy (RT) plays a crucial role in the treatment of head and neck cancers (HNCs). This paper emphasizes the importance of effective communication and collaboration between radiation oncologists and dental specialists in the HNC care pathway. It also provides an overview of the role of RT in HNC treatment and illustrates the interdisciplinary collaboration between these teams to optimize patient care, expedite treatment, and prevent post-treatment oral complications. The methods utilized include a thorough analysis of existing research articles, case reports, and clinical guidelines, with terms such as 'dental management', 'oral oncology', 'head and neck cancer', and 'radiotherapy' included for this review. The findings underscore the significance of the early involvement of dental specialists in the treatment planning phase to assess and prepare patients for RT, including strategies such as prophylactic tooth extraction to mitigate potential oral complications. Furthermore, post-treatment oral health follow-up and management by dental specialists are crucial in minimizing the incidence and severity of RT-induced oral sequelae. In conclusion, these proactive measures help minimize dental and oral complications before, during, and after treatment.

Dose-Escalated Preoperative Proton Therapy for Retroperitoneal Sarcomas: Initial Outcomes of a New Treatment Paradigm.

Purpose: Retroperitoneal sarcomas (RPS) have varied treatment practices with regard to the use of radiation therapy (RT). Preoperative RT ∼50 Gy is commonly used, but the Surgery With or Without Radiation Therapy in Untreated Nonmetastatic Retroperitoneal Sarcoma (STRASS-1) randomized trial demonstrated no improvement in abdominal recurrence-free survival with preoperative RT. Dose escalation has been proposed to improve the efficacy of preoperative RT. We analyzed RPS treated with preoperative intensity modulated proton therapy (IMPT) to an escalated dose of 63 Gy at a single institution. Methods and Materials: Patients who received preoperative RT with IMPT with RPS between January 2015 and October 2021 were reviewed. IMPT 63 Gy in 28 fractions to the clinical target volume high-risk and 50.4 Gy in 28 fractions to clinical target volume low-risk was used. Patient baseline characteristics, RT dose parameters, toxicities, margin status, and recurrence patterns were recorded. Local control was computed by Fine-Gray analysis and overall survival by Kaplan-Meier analysis. Results: Sixteen patients met the study criteria (n = 16): 12 primary and 4 isolated local recurrences. Median age was 62 years (IQR, 43.5-66 years) and 62.5% were male; 10 were liposarcoma. The median maximum tumor diameter was 19.9 cm (IQR, 12-24 cm). With a median follow-up of 18 months (IQR, 11.5-37 months), the estimated 3-year freedom from local failure rate was 68.2% (95% CI, 41.7%-94.7%); 3-year overall survival (OS) rate was 68.8% (95% CI, 41.9%-95.8%). No Radiation Therapy Oncology Group grade ≥3 acute or late toxicities were noted. Conclusions: In our RPS cohort, preoperative dose-escalated RT to 63 Gy demonstrated comparable local control without G3 acute toxicities. Given the high local recurrence rates of RPS, this approach warrants further study to validate these results and identify patients most likely to benefit from therapy.

Head and Neck Squamous Cell Carcinoma of Unknown Primary: A Diagnostic Work-Up.

The current work-up of the primary tumor site of a head and neck squamous cell carcinoma of unknown primary is not standardized and results in several time-consuming procedures that delay treatment initiation. This article seeks to consolidate contemporary strategies used to identify the primary tumor site of an unknown primary head and neck squamous cell carcinoma and offer recommendations based on current literature review.

Negative Predictive Value of Circulating Tumor Tissue Modified Viral (TTMV)-HPV DNA for HPV-driven Oropharyngeal Cancer Surveillance.

PURPOSE: Human papillomavirus (HPV) is causally linked to oropharyngeal squamous cell carcinoma (OPSCC). Consensus guidelines recommend clinical exams and imaging in decreasing frequency as part of posttreatment surveillance for recurrence. Plasma tumor tissue modified viral (TTMV)-HPV DNA testing has emerged as a biomarker which can inform disease status during surveillance. EXPERIMENTAL DESIGN: This retrospective observational cohort study involved 543 patients who completed curative-intent therapy for HPV-associated OPSCC between February 2020 and January 2022 at eight U.S. cancer care institutions. We determined the negative predictive value (NPV) of TTMV-HPV DNA for recurrence when matched to physician-reported clinical outcome data (median follow-up time: 27.9 months; range: 4.5-154). RESULTS: The cohort included mostly men with a median age of 61 who had locoregionally advanced disease. HPV status was determined by p16 positivity in 87% of patients, with a positive HPV PCR/ISH among 55%; while pretreatment TTMV-HPV DNA status was unknown for most (79%) patients. Patients had a mean of 2.6 tests and almost half had three or more TTMV-HPV DNA results during surveillance. The per-test and per-patient sensitivity of the assay was 92.5% [95% confidence interval (CI): 87.5-97.5] and 87.3% (95% CI: 79.1-95.5), respectively. The NPV for the assay was 99.4% (95% CI: 98.9-99.8) and 98.4% (95% CI: 97.3-99.5), respectively. CONCLUSIONS: TTMV-HPV DNA surveillance testing yields few false negative results and few missed recurrences. These data could inform decisions on when to pursue reimaging following first disease restaging and could inform future surveillance practice. Additional study of how pretreatment TTMV-HPV DNA status impacts sensitivity for recurrence is needed.

Implementation of superficial radiation therapy (SRT) using SRT-100 Vision™ for non-melanoma skin cancer in a Radiation Oncology clinic.

PURPOSE: This article describes our experience in implementation of superficial radiation therapy (SRT) using SRT-100 Vision™ for non-melanoma skin cancer. METHODS: Following the American Association of Physicists in Medicine Task Group-61 protocol, absolute output (absorbed dose to water at surface (cGy/min)) was measured for three energies (50, 70, and 100 kV) and for six applicators (1.5-5.0 cm in diameter). Percent depth dose (PDD) and profiles were also measured. Timer testing and ultrasound testing were performed. A treatment time calculation worksheet was created. Quality assurance (QA) of SRT-100 Vision was implemented. After treatment workflow for our clinic was developed, end-to-end (E2E) testing was performed using a Rando phantom. Considerations for treatment using SRT-100 Vision were made. RESULTS: Absolute output (cGy/min) decreases as energy increases and applicator size decreases. Due to scatter from the applicator, PDD at depths ≤5 mm does not follow conventional trends but PDD at depths ≥15 mm increases with increasing applicator size. Profiles for the 5 cm applicator do not have strong dependence on depth except profiles at 5 mm for 50 kV. Timer/end errors are negligible for all three energies. Ultrasound images confirm allowed field of view and depth as well as no image artifacts and spatial integrity. Daily, monthly and annual QA of SRT-100 Vision implemented in our clinic is listed in a table format. E2E testing results (<1%) demonstrate the functionality and performance of our treatment workflow. Our considerations for SRT treatment include patient, applicator size and energy selections, patient setup, and shields. CONCLUSIONS: This article is expected to serve as guidance for Radiation Oncology and/or Dermatology clinics aspiring to initiate an SRT program in their clinics.

Multi-Institutional Outcomes of Stereotactic Magnetic Resonance Image Guided Adaptive Radiation Therapy With a Median Biologically Effective Dose of 100 Gy10 for Non-bone Oligometastases.

Purpose: Randomized data show a survival benefit of stereotactic ablative body radiation therapy in selected patients with oligometastases (OM). Stereotactic magnetic resonance guided adaptive radiation therapy (SMART) may facilitate the delivery of ablative dose for OM lesions, especially those adjacent to historically dose-limiting organs at risk, where conventional approaches preclude ablative dosing. Methods and Materials: The RSSearch Registry was queried for OM patients (1-5 metastatic lesions) treated with SMART. Freedom from local progression (FFLP), freedom from distant progression (FFDP), progression-free survival (PFS), and overall survival (LS) were estimated using the Kaplan-Meier method. FFLP was evaluated using RECIST 1.1 criteria. Toxicity was evaluated using Common Terminology Criteria for Adverse Events version 4 criteria. Results: Ninety-six patients with 108 OM lesions were treated on a 0.35 T MR Linac at 2 institutions between 2018 and 2020. SMART was delivered to mostly abdominal or pelvic lymph nodes (48.1%), lung (18.5%), liver and intrahepatic bile ducts (16.7%), and adrenal gland (11.1%). The median prescribed radiation therapy dose was 48.5 Gy (range, 30-60 Gy) in 5 fractions (range, 3-15). The median biologically effective dose corrected using an alpha/beta value of 10 was 100 Gy10 (range, 48-180). No acute or late grade 3+ toxicities were observed with median 10 months (range, 3-25) follow-up. Estimated 1-year FFLP, FFDP, PFS, and OS were 92.3%, 41.1%, 39.3%, and 89.6%, respectively. Median FFDP and PFS were 8.9 months (95% confidence interval, 5.2-12.6 months) and 7.6 months (95% confidence interval, 4.5-10.6 months), respectively. Conclusions: To our knowledge, this represents the largest analysis of SMART using ablative dosing for non-bone OM. A median prescribed biologically effective dose of 100 Gy10 resulted in excellent early FFLP and no significant toxicity, likely facilitated by continuous intrafraction MR visualization, breath hold delivery, and online adaptive replanning. Additional prospective evaluation of dose-escalated SMART for OM is warranted.

Implementation Strategies to Increase Clinical Trial Enrollment in a Community-Academic Partnership and Impact on Hispanic Representation: An Interrupted Time Series Analysis.

PURPOSE: Community-academic partnerships have the potential to improve access to clinical trials for under-represented minority patients who more often receive cancer treatment in community settings. In 2017, the Memorial Sloan Kettering (MSK) Cancer Center began opening investigator-initiated clinical trials in radiation oncology in targeted community-based partner sites with a high potential to improve diverse population accrual. This study evaluates the effectiveness of a set of implementation strategies for increasing overall community-based enrollment and the resulting proportional enrollment of Hispanic patients on trials on the basis of availability in community-based partner sites. METHODS: An interrupted time series analysis evaluating implementation strategies was conducted from April 2018 to September 2021. Descriptive analysis ofHispanic enrollment on investigator-initiated randomized therapeutic radiation trials open at community-based sites was compared with those open only at themain academic center. RESULTS: Overall, 84 patients were enrolled in clinical trials in the MSK Alliance, of which 48 (56%) identified as Hispanic. The quarterly patient enrollment pre- vs postimplementation increased from 1.39 (95% CI, -3.67 to 6.46) to 9.42 (95% CI, 2.05 to 16.78; P5 .017). In the investigator-initiated randomized therapeutic radiation trials open in the MSK Alliance, Hispanic representation was 11.5% and 35.9% in twometastatic trials and 14.2% in a proton versus photon trial. Inmatched trials open only at the main academic center, Hispanic representation was 5.6%, 6.0%, and 4.0%, respectively. CONCLUSION: A combination of practice-level and physician-level strategies implemented at community-based partner sites was associated with increased clinical trial enrollment, which translated to improved Hispanic representation. This supports the role Q:2 of strategic community-academic partnerships in addressing disparities in clinical trial enrollment.

Submandibular gland transfer for the prevention of radiation-induced xerostomia in oropharyngeal cancer: Dosimetric impact in the intensity modulated radiotherapy era.

BACKGROUND: Submandibular gland (SMG) transfer decreased radiation-associated xerostomia in the 2/3-dimensional radiotherapy era. We evaluated the dosimetric implications of SMG transfer on modern intensity modulated radiotherapy (IMRT) plans. METHODS: Eighteen oropharynx cancer patients underwent SMG transfer followed by IMRT; reoptimized plans using the baseline SMG location were generated. Mean salivary gland, oral cavity, and larynx doses were compared between clinical plans and reoptimized plans. RESULTS: No statistically significant difference in mean SMG dose (27.53 Gy vs. 29.61 Gy) or total salivary gland dose (26.12 Gy vs. 26.41 Gy) was observed with or without SMG transfer (all p > 0.05). Mean oral cavity and larynx doses were not statistically different. Neither tumor site, target volume crossing midline, stage, nor salivary gland volumes were associated with mean doses. CONCLUSIONS: Salivary gland doses were similar with or without SMG transfer. IMRT likely decreases the benefit of SMG transfer on the risk of radiation-associated xerostomia.

Initial clinical experience with magnetic resonance-guided radiotherapy in pediatric patients: Lessons learned from a single institution with proton therapy.

Purpose/Objectives: Magnetic resonance-guided radiotherapy (MRgRT) is increasingly used in a variety of adult cancers. To date, published experience regarding the use of MRgRT in pediatric patients is limited to two case reports. We report on the use of MRgRT for pediatric patients at our institution during a four-year period and describe important considerations in the selection and application of this technology in children. Materials/Methods: All patients treated with MRgRT since inception at our institution between 4/2018 and 4/2022 were retrospectively reviewed. We also evaluated all pediatric patients treated at our institution during the same period who received either imaging or treatment using our magnetic resonance-guided linear accelerator (MR Linac). We summarize four clinical cases where MRgRT was selected for treatment in our clinic, including disease outcomes and toxicities and describe our experience using the MR Linac for imaging before and during treatment for image fusion and tumor assessments. Results: Between 4/2018 and 4/2022, 535 patients received MRgRT at our center, including 405 (75.7%) with stereotactic ablative radiotherapy (SABR). During this period, 347 distinct radiotherapy courses were delivered to pediatric patients, including 217 (62.5%) with proton therapy. Four pediatric patients received MRgRT. One received SABR for lung metastasis with daily adaptive replanning and a second was treated for liver metastasis using a non-adaptive workflow. Two patients received fractionated MRgRT for an ALK-rearranged non-small cell lung cancer and neuroblastoma. No Grade 2 or higher toxicities were observed or reported during MRgRT or subsequent follow-up. Twelve patients underwent MR imaging without contrast during treatment for brain tumors to assess for tumor/cystic changes. Two patients treated with other modalities underwent MR simulation for target volume delineation and organ at risk sparing due to anatomic changes during treatment or unexpected delays in obtaining diagnostic MR appointments. Conclusions: In four pediatric patients treated with MRgRT, treatment was well tolerated with no severe acute effects. At our center, most pediatric patients are treated with proton therapy, but the cases selected for MRgRT demonstrated significant organ at risk sparing compared to alternative modalities. In particular, MRgRT may provide advantages for thoracic/abdominal/pelvic targets using gated delivery and adaptive replanning, but selected patients treated with fractionated radiotherapy may also benefit MRgRT through superior organ at risk sparing.

Interobserver reliability in describing radiographic lung changes after stereotactic body radiation therapy.

PURPOSE: Radiographic lung changes after stereotactic body radiation therapy (SBRT) vary widely between patients. Standardized descriptions of acute (≤6 months after treatment) and late (>6 months after treatment) benign lung changes have been proposed but the reliable application of these classification systems has not been demonstrated. Herein, we examine the interobserver reliability of classifying acute and late lung changes after SBRT. METHODS AND MATERIALS: A total of 280 follow-up computed tomography scans at 3, 6, and 12 months post-treatment were analyzed in 100 patients undergoing thoracic SBRT. Standardized descriptions of acute lung changes (3- and 6-month scans) include diffuse consolidation, patchy consolidation and ground glass opacity (GGO), diffuse GGO, patchy GGO, and no change. Late lung change classifications (12-month scans) include modified conventional pattern, mass-like pattern, scar-like pattern, and no change. Five physicians scored the images independently in a blinded fashion. Fleiss' kappa scores quantified the interobserver agreement. RESULTS: The Kappa scores were 0.30 at 3 months, 0.20 at 6 months, and 0.25 at 12 months. The proportion of patients in each category at 3 and 6 months was as follows: Diffuse consolidation 11% and 21%; patchy consolidation and GGO 15% and 28%; diffuse GGO 10% and 11%; patchy GGO 15% and 15%; and no change 49% and 25%, respectively. The percentage of patients in each category at 12 months was as follows: Modified conventional 46%; mass-like 16%; scar-like 26%; and no change 12%. Uniform scoring between the observers occurred in 26, 8, and 14 cases at 3, 6, and 12 months, respectively. CONCLUSIONS: Interobserver reliability scores indicate a fair agreement to classify radiographic lung changes after SBRT. Qualitative descriptions are insufficient to categorize these findings because most patient scans do not fit clearly into a single classification. Categorization at 6 months may be the most difficult because late and acute lung changes can arise at that time.

Diabetes mellitus and radiation induced lung injury after thoracic stereotactic body radiotherapy.

BACKGROUND: Radiographic radiation induced lung injury (RILI) is frequently observed after stereotactic body radiotherapy (SBRT). Models of radiographic change can identify patient risk factors that predict clinical toxicity. We examined the association between radiographic lung changes and lung tissue dose-density response over time with clinical risk factors for RILI, such as diabetes. METHODS: 424 baseline and follow up CT scans at 3, 6, and 12 months post-treatment were analyzed in 116 patients (27 with diabetes) undergoing thoracic SBRT. Volumes of dense/hazy regions and lung parenchyma dose-density response curves were evaluated with respect to follow up time, diabetes, and other factors. RESULTS: Dense and hazy tissue regions were larger in the diabetic population, with the effect most pronounced at 3 months. Similarly, dose-density response curves showed greater density change versus dose in the diabetic group (all p < 0.05). Diabetes, time, the interaction of diabetes and time, smoking status, African American race, baseline lung density, and tumor location were significantly associated with radiographic changes on mixed effect analyses. PTV size, pulmonary function, and medication exposure did not significantly impact RILI. Clinical grade 1-2 pneumonitis was more prevalent in diabetic patients (p = 0.02). However, radiographic change did not correlate with clinical pneumonitis. CONCLUSIONS: The presence of diabetes and other clinical factors is associated with increased volume and density of radiographic RILI after lung SBRT, most prominently early after treatment. This is the first report demonstrating the increased severity of RILI after SBRT in diabetic patients. Increased caution treating diabetic patients may be warranted.

Cardiac radiation dose distribution, cardiac events and mortality in early-stage lung cancer treated with stereotactic body radiation therapy (SBRT).

BACKGROUND: The impact of radiation dose to the heart in early-stage lung cancer patients treated with definitive stereotactic body radiation therapy (SBRT) is not well known. We, therefore, analyzed whether higher radiation dose to the heart would lead to an increase in cardiac toxicity and overall mortality. METHODS: Seventy-four patients with 75 tumors treated definitively with SBRT for early-stage non-small cell lung cancer (NSCLC) and two cases of limited-stage small cell lung cancer (SCLC) with an average follow-up of 35 months (range, 1-130 months) were retrospectively analyzed. The whole heart and cardiac substructures including atria, ventricles, heart valves, atrioventricular (AV) node and four major coronary artery branches were contoured using commercial treatment planning software. For each structure, multiple dose-volume parameters were recorded. The relation between radiation doses to the heart, tumor location, and preexisting medical conditions with the development of cardiac events and mortality was assessed. RESULTS: Overall, there was large variability in dose to cardiac substructures: mean heart dose (MHD) averaged 1.90 Gy (range, 0.04-11.00 Gy) equivalent 2 Gy dose (EQD2) and average max dose to the left anterior descending artery (LAD) was 5.67 Gy (range, 0.04-48.60 Gy) EQD2. Patients with tumor location in the upper lobes received higher cardiac radiation dose compared to other lobes (P<0.0001). There was no difference in MHD between central and peripheral tumor locations. The distance between heart and tumor was negatively associated with MHD (r=-0.61, P<0.0001). Eighteen patients developed cardiac complications including the need for defibrillator placement, arrhythmia development and worsening heart failure. Preexisting cardiac disease was associated with an increased number of cardiac events after radiotherapy (P=0.039). However, neither radiation dose to the whole heart or the cardiac substructures, nor comorbidities such as diabetes, hypercholesterolemia, hypertension or COPD were associated with the number of cardiac events or overall mortality. CONCLUSIONS: Radiation doses to the heart and its substructures show large variability. Cardiac events occurred more frequently in patients with a history of heart problems. At present, the effect of radiation dose on cardiac toxicity is unclear in patients undergoing SBRT for early-stage lung cancer. Longer follow-up and a larger cohort are needed to assess for late cardiac sequelae.

Local Radiotherapy Intensification for Locally Advanced Non-small-cell Lung Cancer - A Call to Arms.

Chemoradiotherapy, the standard of care for locally advanced non-small-cell lung cancer (NSCLC), often fails to eradicate all known disease. Despite advances in chemotherapeutic regimens, locally advanced NSCLC remains a difficult disease to treat, and locoregional failure remains common. Improved radiographic detection can identify patients at significant risk of locoregional failure after definitive treatment, and newer methods of escalating locoregional treatment may allow for improvements in locoregional control with acceptable toxicity. This review addresses critical issues in escalating local therapy, focusing on using serial positron emission tomography-computed tomography to select high-risk patients and employing stereotactic radiotherapy to intensify treatment. We further propose a clinical trial concept that incorporates the review's findings.

Reducing rectal injury in men receiving prostate cancer radiation therapy: current perspectives.

Dose escalation is now the standard of care for the treatment of prostate cancer with radiation therapy. However, the rectum tends to be the dose-limiting structure when treating prostate cancer, given its close proximity. Early and late toxicities can occur when the rectum receives large doses of radiation therapy. New technologies allow for prevention of these toxicities. In this review, we examine the evidence that supports various dose constraints employed to prevent these rectal injuries from occurring. We also examine the use of intensity-modulated radiation therapy and how this compares to older radiation therapy techniques that allow for further sparing of the rectum during a radiation therapy course. We then review the literature on endorectal balloons and the effects of their daily use throughout a radiation therapy course. Tissue spacers are now being investigated in greater detail; these devices are injected into the rectoprostatic fascia to physically increase the distance between the prostate and the anterior rectal wall. Last, we review the use of systemic drugs, specifically statin medications and antihypertensives, as well as their impact on rectal toxicity.

Current Status of Targeted Radioprotection and Radiation Injury Mitigation and Treatment Agents: A Critical Review of the Literature.

As more cancer patients survive their disease, concerns about radiation therapy-induced side effects have increased. The concept of radioprotection and radiation injury mitigation and treatment offers the possibility to enhance the therapeutic ratio of radiation therapy by limiting radiation therapy-induced normal tissue injury without compromising its antitumor effect. Advances in the understanding of the underlying mechanisms of radiation toxicity have stimulated radiation oncologists to target these pathways across different organ systems. These generalized radiation injury mechanisms include production of free radicals such as superoxides, activation of inflammatory pathways, and vascular endothelial dysfunction leading to tissue hypoxia. There is a significant body of literature evaluating the effectiveness of various treatments in preventing, mitigating, or treating radiation-induced normal tissue injury. Whereas some reviews have focused on a specific disease site or agent, this critical review focuses on a mechanistic classification of activity and assesses multiple agents across different disease sites. The classification of agents used herein further offers a useful framework to organize the multitude of treatments that have been studied. Many commonly available treatments have demonstrated benefit in prevention, mitigation, and/or treatment of radiation toxicity and warrant further investigation. These drug-based approaches to radioprotection and radiation injury mitigation and treatment represent an important method of making radiation therapy safer.

The Business Case for Palliative Care: Translating Research Into Program Development in the U.S.

Specialist palliative care (PC) often embraces a "less is more" philosophy that runs counter to the revenue-centric nature of most health care financing in the U.S. A special business case is needed in which the financial benefits for organizations such as hospitals and payers are aligned with the demonstrable clinical benefits for patients. Based on published studies and our work with PC programs over the past 15 years, we identified 10 principles that together form a business model for specialist PC. These principles are relatively well established for inpatient PC but are only now emerging for community-based PC. Three developments that are key for the latter are the increasing penalties from payers for overutilization of hospital stays, the variety of alternative payment models such as accountable care organizations, which foster a population health management perspective, and payer-provider partnerships that allow for greater access to and funding of community-based PC.