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Purpose: This updated report on stereotactic radiosurgery (SRS) and stereotactic body radiation therapy (SBRT) is part of a series of consensus-based white papers previously published addressing patient safety. Since the first white papers were published, SRS and SBRT technology and procedures have progressed significantly such that these procedures are now more commonly used. The complexity and submillimeter accuracy, and delivery of a higher dose per fraction requires an emphasis on best practices for technical, dosimetric, and quality assurance. Therefore, quality and patient safety considerations for these techniques remain an important area of focus., Method: The American Society for Radiation Oncology convened a task force to assess the original SRS/SBRT white paper and update content where appropriate. Recommendations were created using a consensus-building methodology and task force members indicated their level of agreement based on a 5-point Likert scale, from "strongly agree" to "strongly disagree." A prespecified threshold of ≥75% of raters who select "strongly agree" or "agree" indicated consensus., Summary: This white paper builds on the previous version and uses of other guidance documents to broadly address SRS and SBRT delivery, primarily focusing on processes related to quality and safety. SRS and SBRT require a team-based approach, staffed by appropriately trained and credentialed specialists as well as significant personnel resources, specialized technology, and implementation time. A thorough feasibility analysis of resources is required to achieve the clinical and technical goals and thoroughly discussed with all personnel before undertaking new disease sites. A comprehensive quality assurance program must be developed, using established treatment guidelines, to ensure SRS and SBRT are performed in a safe and effective manner. Patient safety in SRS/SBRT is everyone's responsibility and professional organizations, regulators, vendors, and end-users must demonstrate a clear commitment to working together to ensure the highest levels of safety., (Copyright © 2022 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: Twitter is an increasingly popular social media platform within the health care community. The objective of this analysis is to characterize the profile of radiation oncology-related tweets and Twitter users over the past 6 years., Methods and Materials: Using the web-based social media analytics platform Symplur Signals, we filtered tweets containing at least 1 of the following hashtags or key words: #radonc, #radiationoncology, "rad onc," or "radiation oncology." We evaluated radiation oncology-related Twitter activity between October 2014 and March 2020 for tweet frequency, tweet content, and individuals or groups posting tweets. We identified the most influential Twitter users contributing to radiation oncology-related tweets., Results: From 2014 to 2020, the quarterly volume of radiation oncology-related tweets increased from 5027 to 29,763. Physicians contributed the largest growth in tweet volume. Academic radiation oncologists comprise 60% of the most influential Twitter accounts responsible for radiation oncology-related content. The number of radiation-oncology resident physicians on Twitter increased from 25 to 328 over the past 6 years, and 20% of radiation-oncology residency programs have a Twitter account. Seventy-one percent of radiation oncology-related tweets generated direct communication via mentions, and 59% of tweets contain links to external sources, including scientific articles., Conclusions: The number of physicians contributing radiation oncology-related Twitter content has increased significantly in recent years. Academic radiation oncologists are the primary influencers of radiation oncology-related Twitter activity. Twitter is used by radiation oncologists to both professionally network and discuss findings related to the field. There remains the opportunity for radiation oncologists to broaden their audience on Twitter to encompass a more diverse community, including patients., (Copyright © 2020 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Introduction: Clinical variables describing the natural history and longitudinal therapy outcomes of stage IV anaplastic lymphoma kinase gene rearrangement positive (ALK-positive) NSCLC and their relationship with long-term overall survival (OS) have not previously been described in detail., Methods: Patients with stage IV NSCLC treated with an ALK inhibitor at the University of Colorado Cancer Center from 2009 through November 2017 were identified retrospectively. OS curves were constructed by using Kaplan-Meier methods. Multivariate Cox proportional hazard analysis was used to determine the relationship of variables with OS., Results: Of the 110 patients with ALK-positive NSCLC who were identified, 105 received crizotinib as their initial ALK inhibitor. With a median follow-up time of 47 months, the median OS time from diagnosis of stage IV disease was 81 months (6.8 years). Brain metastases at diagnosis of stage IV disease (hazard ratio = 1.01, p = 0.971) and year of stage IV presentation (p = 0.887) did not influence OS. More organs with tumor at diagnosis of stage IV disease was associated with worse OS (HR = 1.49 for each additional organ with disease, including the CNS [p = 0.002]). Each additional month of pemetrexed-based therapy was associated with a 7% relative decrease in risk of death., Conclusion: Patients with stage IV ALK-positive NSCLC can have prolonged OS. Brain metastases at diagnosis of stage IV disease does not influence OS. Having more organs involved with tumor at stage IV presentation is associated with worse outcomes. Prolonged benefit from pemetrexed is associated with better outcomes., (Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Introduction: Retrospective studies have evaluated the approach of stereotactic radiotherapy (SRT) to address oligoprogression in patients with EGFR mutant NSCLC on TKI therapy, it has never been prospectively studied., Materials and Methods: We treated 25 patients with EGFR mutant NSCLC on erlotinib who had 3 or fewer sites of extra-cranial progression with SRT to progressing sites, followed by re-initiation of erlotinib., Results: Median PFS from the initiation of SRT was 6 months (95% CI 2.5 to 11.6) and median OS was 29 months (95% CI 21.7 to 36.3). Neither baseline nor changes in the Veristrat proteomic predicted PFS., Conclusions: SRT and TKI continuation may be considered for select patients with EGFR mutant NSCLC and oligo-progression on EGFR TKI therapy., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: Stereotactic radiosurgery (SRS) represents an expanding approach for neurosurgeons and radiation oncologists. We evaluate educational gaps of senior residents drawn from each specialty as part of a focused SRS course. We also evaluate the strengths and limitations of SRS training in current residency programs of the course residents and faculty., Methods: The American Association of Neurological Surgeons and American Society of Radiation Oncology jointly held a senior resident course in SRS. Residents were nominated by program directors from across the United States. Thirty residents were chosen to participate in the course. The residents were surveyed before and after the course. Faculty (n = 14) were also surveyed to ascertain their perspectives on current training in SRS., Results: Most (96.7%) of the residents planned to perform SRS when finished, and 94% anticipated SRS indications to expand. Regarding SRS technique, 47% reported average/above average understanding of intracranial SRS; only 17% expressed similar understanding of spinal SRS. Before the course, 76.6% noted below average/average ability to recognize and manage SRS complications. Twenty-three percent of the faculty indicated that graduating residents from their programs were unprepared to perform radiosurgery. Residents' self-assessed understanding of brain SRS indication (P = 0.000693), SRS techniques (P = 0.000021), spinal SRS indications (P = 0.000050), spinal SRS techniques (P = 0.000019), and complication recognition and management (P = 0.00033) significantly improved following the course., Conclusions: Knowledge and training gaps in SRS appear evident to the senior residents and faculty of both specialties. We believe that other educational opportunities for SRS experience are necessary to optimize clinical competency, as well as meet future clinical staffing needs for this expanding, multidisciplinary approach. Further evaluation of gaps in SRS is necessary through a larger, nationwide survey of U.S. neurosurgeons, program directors, and residents., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: We hypothesized that high-dose stereotactic body radiation therapy (SBRT) would lead to faster time to nadir and lower nadir values compared with conventional radiation therapy experiences. We now report prostate-specific antigen (PSA) kinetics following high-dose SBRT in patients treated with radiation alone., Methods and Materials: Ninety-one patients were enrolled on the phase 1/2 dose escalation study of SBRT for localized prostate cancer. All patients with at least 36 months of follow-up and without hormone therapy were included in this analysis (n = 47). Treatment response parameters evaluated include time to nadir, nadir value, occurrence of PSA bounces (rise of ≥0.2 ng/mL followed by a subsequent fall), magnitude of bounces, duration of bounces, and correlation of bounces with clinical outcomes., Results: Median follow-up was 42 months (range, 36-78 months). Treatment dose levels were 45 Gy (n = 10), 47.5 Gy (n = 8), and 50 Gy (n = 29) in 5 fractions. Biochemical control rate was 98%. Median PSA at follow-up was 0.10 ± 0.20 ng/mL. Median time to nadir was 36 ± 11 months. A total of 24/47 (51.1%) patients had ≥1 PSA bounce. Median magnitude of PSA rise during bounce was 0.50 ± 1.2 ng/mL. Median time to first bounce was 9 ± 7.0 months. Median bounce duration was 3 ± 2.3 months for the first bounce and 6 ± 5.2 months for subsequent bounces. Prostate volumes <30 mL were associated with a decreased likelihood of bounce (P = .0202), and increasing prostate volume correlated with increasingly likelihood of having ≥2 bounces (P = .027). Patients reaching PSA nadir of ≤0.1 ng/mL were less likely to experience any bounce (P = .0044)., Conclusions: Compared with other SBRT experiences, our study demonstrated a higher PSA bounce rate, a similar or shorter median time to bounce, and a very low nadir. Prostate volume appears correlated with bounce., (Copyright © 2016. Published by Elsevier Inc.)

Objectives: Current guidelines support the use of screening for early detection in breast, prostate, colorectal and cervical cancer. The purpose of this study was to evaluate whether insurance status predicts for more advanced disease in these four currently screened cancers., Study Design: The Surveillance, Epidemiology, and End Results (SEER) database was queried for breast, prostate, colorectal and cervix in patients aged 18-64 years. The database was queried from 2007 to 2011, with 425,614 patients with known insurance status included., Methods: Multinomial logistic regression was used to evaluate insurance status and cancer presentation., Results: Under multivariate analysis for breast cancer, uninsured patients more often had invasive disease (odds ratio [OR]: 1.55), T- (OR: 2.00), N- (OR: 1.59) stage, and metastatic disease (OR: 3.48), and were more often high-grade (OR: 1.21). For prostate cancer, uninsured patients again presented more commonly with higher T-stage (OR: 1.45), nodal (OR: 2.90) and metastatic (OR: 4.98) disease, in addition to higher prostate-specific antigen (OR: 2.85) and Gleason score (OR: 1.65). Colorectal cancer had similar findings with uninsured individuals presenting with more invasive disease (OR: 1.78), higher T (OR: 1.86), N (OR: 1.22), and M (OR: 1.58) stage, in addition to higher carcinoembryonic antigen levels (OR: 1.66). Similar results were seen for cervical cancer with uninsured having higher T (OR: 2.03), N (OR: 1.21), and M (OR: 1.45) stage., Conclusion: In the four cancers detected by screening exams, those without health insurance present with more advanced disease, with higher stage and grade, and more elevated tumour markers., (Copyright © 2016 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Purpose: To highlight 5 interventions that patients should question, as part of the Choosing Wisely campaign. This initiative, led by the American Board of Internal Medicine Foundation, fosters conversations between physicians and patients about treatments and tests that may be overused, unnecessary, or potentially harmful., Methods and Materials: Potential items were initially compiled using an online survey. They were then evaluated and refined by a work group representing the American Society for Radiation Oncology (ASTRO) Clinical Affairs and Quality, Health Policy, and Government Relations Councils. Literature reviews were carried out to support the recommendation and narrative, as well as to provide references for each item. A final list of 5 items was then selected by the ASTRO Board of Directors., Results: ASTRO's 5 recommendations for the Choosing Wisely campaign are the following: (1) Don't initiate whole-breast radiation therapy as a part of breast conservation therapy in women age ≥50 with early-stage invasive breast cancer without considering shorter treatment schedules; (2) don't initiate management of low-risk prostate cancer without discussing active surveillance; (3) don't routinely use extended fractionation schemes (>10 fractions) for palliation of bone metastases; (4) don't routinely recommend proton beam therapy for prostate cancer outside of a prospective clinical trial or registry; and (5) don't routinely use intensity modulated radiation therapy to deliver whole-breast radiation therapy as part of breast conservation therapy., Conclusions: The ASTRO list for the Choosing Wisely campaign highlights radiation oncology interventions that should be discussed between physicians and patients before treatment is initiated. These 5 items provide opportunities to offer higher quality and less costly care.

Purpose: Image segmentation methods were studied to delineate liver lesions in (18)F-fluoro-2-deoxy-glucose positron emission tomographic (FDG-PET) images. The goal of this study was to identify a clinically practical, semiautomated FDG-PET avid volume segmentation method to improve the accuracy of liver tumor contouring for treatment planning in stereotactic body radiation therapy (SBRT)., Methods and Materials: Pretreatment PET-CT image sets for 26 patients who received SBRT to 28 liver lesions were delineated using the following 3 methods: (1) Percent threshold with respect to background corrected maximum standard uptake values (SUV; threshold values varied from 10% to 50% with 10% increments); (2) threshold 3 standard deviations above mean background SUV (3σ); and (3) a gradient-based method that detects the edge of the FDG-PET avid lesion (edge). For each lesion, semiautomatically generated contours were evaluated with respect to reference contours manually drawn by 3 radiation oncologists. Two similarity metrics, Dice coefficient, and mean minimal distance (MMD), were employed to assess the volumetric overlap and the mean Euclidian distance between semiautomatically and observer-drawn contours., Results: Mean Dice and MMD values for 10%, 20%, 30% threshold, 3σ, and edge varied from 0.69 to 0.73, and from 3.44 mm to 3.94 mm, respectively (ideal Dice and MMD values are 1 and 0 mm, respectively). A statistically significant difference was not observed among 10%, 20%, 30% threshold, 3σ, and edge methods, whereas 40% and 50% methods had inferior Dice and MMD values., Conclusions: Three PET segmentation methods were identified above as potential tools to accelerate liver lesion delineation. The edge method appears to be the most practical for clinical implementation as it does not require calculation of SUV statistics. However, the performance of all segmentation methods showed large lesion-to-lesion fluctuations. Therefore, such methods may be suitable for generating initial estimates of FDG-PET avid volumes rather than being surrogates for manual volume delineation., (© 2014.)

Introduction: Induction chemotherapy in patients with bulky small cell lung cancer (SCLC) could lead to decreased tumor burden, smaller radiation fields, and less pulmonary toxicity. This study compared radiation therapy (RT) plans based on pre- and postchemotherapy computed tomography (CT) scans of patients with SCLC to estimate the reduced risk of radiation pneumonitis (RP) after receiving chemotherapy., Methods: Between 2003 and 2009, 23 patients with stage IV SCLC were treated with chemotherapy alone (no surgery or RT) and had computed tomography scans pre- and post two cycles of platin-based chemotherapy. Simulated RT plans were created as if to deliver 45 Gy to the thoracic disease. The percent of lung receiving ≥20 Gy (V20), mean lung dose, and normal tissue complication probability (NTCP) was evaluated in patients who had a partial response (≥30% volumetric reduction) in gross tumor volume., Results: One (4.3%) patient had a complete response, 18 (78.3%) had a partial response, and four (17.4%) had stable disease. Among 18 responders, the absolute decrease in V20 was 7.4% (p < 0.01), in mean lung dose was 3.3 Gy (p < 0.01), and in NTCP was 5.5% (p < 0.01). Patients with a prechemotherapy V20 ≥35% versus V20 less than 35% had an average absolute reduction in NTCP of 10% versus 2% (p < 0.01)., Conclusion: Patients with limited stage SCLC with a V20 ≥35% may benefit from induction chemotherapy as there is an estimated reduction of RP of 10%. This reduction in risk of RP after induction chemotherapy should be weighed against risks and benefits of delaying upfront RT.

Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) delivers inhibitory signals to activated T cells. CTLA4 is constitutively expressed on regulatory CD4(+) T cells (Tregs), but its role in these cells remains unclear. CTLA4 blockade has been shown to induce antitumor immunity. In this study, we examined the effects of anti-CTLA4 antibody on the endogenous CD4(+) T cells in cancer patients. We show that CTLA4 blockade induces an increase not only in the number of activated effector CD4(+) T cells, but also in the number of CD4(+) FoxP3(+) Tregs. Although the effects were dose-dependent, CD4(+) FoxP3(+) regulatory T cells could be expanded at lower antibody doses. In contrast, expansion of effector T cells was seen only at the highest dose level studied. Moreover, these expanded CD4(+) FoxP3(+) regulatory T cells are induced to proliferate with treatment and possess suppressor function. Our results demonstrate that treatment with anti-CTLA4 antibody does not deplete human CD4(+) FoxP3(+) Tregs in vivo, but rather may mediate its effects through the activation of effector T cells. Our results also suggest that CTLA4 may inhibit Treg proliferation similar to its role on effector T cells. This study is registered at http://www.clinicaltrials.gov/ct2/show/NCT00064129, registry number NCT00064129.

Aggressive surgical and radiotherapeutic management of a patient with desmoplastic malignant melanoma arising from the mucosa of the oral cavity has resulted in disease-free survival of more than 2(1/2) years after diagnosis. This case represents only the tenth reported instance of desmoplastic malignant melanoma arising from the oral cavity and only the third for which survival has exceeded 2 years. Details of the clinical, histopathologic, and therapeutic features of the case are provided to augment the paucity of literature available to clinicians managing this rare disease.

Permissive hypercapnia (acceptance of raised concentrations of carbon dioxide in mechanically ventilated patients) may be associated with increased survival as a result of less ventilator-associated lung injury. Conversely, hypocapnia is associated with many acute illnesses (eg, asthma, systemic inflammatory response syndrome, pulmonary oedema), and is thought to reflect underlying hyperventilation. Accumulating clinical and basic scientific evidence points to an active role for carbon dioxide in organ injury, in which raised concentrations of carbon dioxide are protective, and low concentrations are injurious. We hypothesise that therapeutic hypercapnia might be tested in severely ill patients to see whether supplemental carbon dioxide could reduce the adverse effects of hypocapnia and promote the beneficial effects of hypercapnia. Such an approach could also expand our understanding of the pathogenesis of disorders in which hypocapnia is a constitutive element.

Prolactin (PRL) is an immunomodulator that has been demonstrated to enhance immune responses both in vitro and in vivo. Prolactin enhances the proliferative response of lymphoid cells to both nonspecific mitogens and specific antigens and increases their production of IL-2 and interferon-gamma. Studies were performed to examine whether recombinant human prolactin (r-hPRL) also acts as a growth factor for B cell hybridomas. Prolactin was able to stimulate proliferation of murine B cell hybridomas in a dose-dependent manner and enhanced their proliferation in response to IL-4, IL-5, and IL-6. This increase in proliferation resulted in an overall increase in antibody production. Studies were also undertaken to examine the effect of PRL with transforming growth factor beta (TGF-beta), an immunosuppressive cytokine. Hybridoma cell lines incubated with TGF-beta demonstrated a dose-dependent decrease in proliferation. Variability in the degree of inhibition was observed among the various hybridomas in their responsiveness to TGF-beta. The addition of r-hPRL to the cultures reversed the antiproliferative effects of TGF-beta. The mechanism by which PRL can overcome the anti-proliferative effect of TGF-beta is under investigation. These findings provide an additional rationale for using r-hPRL clinically in immunosuppressed patients in certain disease settings such as AIDS and cancer, where overexpression of TGF-beta has been implicated in disease development and progression.

Several reports have suggested that preoperative nociceptive block may reduce postoperative pain, analgesic requirements, or both, beyond the anticipated duration of action of the analgesic agents. We have investigated, in a double-blind, placebo-controlled study, pre-emptive analgesia and the respiratory effects of preoperative administration of a multimodal antinociceptive regimen. Thirty patients undergoing thoracotomy were allocated randomly to two groups. Before surgery, the treatment group (n = 15) received morphine 0.15 mg kg-1 i.m. with perphenazine 0.03 mg kg-1 i.m. and a rectal suppository of indomethacin 100 mg, while the placebo group (n = 15) received midazolam 0.05 mg kg-1 i.m. and a placebo rectal suppository. After induction of anaesthesia, the treatment group received intercostal nerve block with 0.5% bupivacaine and adrenaline 1:200,000 (3 ml) in the interspace of the incision and in the two spaces above and two spaces below. The placebo group received identical injections but with normal saline only. The treatment group consumed significantly less morphine by patient-controlled analgesia in the first 6 h after operation, but the total dose of morphine consumed on days 2 and 3 after surgery was significantly greater in the treatment group. There were no differences between the groups in postoperative VAS scores (at rest or after movement), PaCO2 values or postoperative spirometry. However, pain thresholds to pressure applied at the side of the chest contralateral to the site of incision decreased significantly from preoperative values on days 1 and 2 after surgery in both groups. The results of this study do not support the preoperative use of this combined regimen for post-thoracotomy pain.

Progressive extension contracture of the wrist of a 19-year-old female patient was noted at operation to be due to shortening of the extensor carpi radialis longus and extensor carpi radialis brevis. Satisfactory wrist motion was restored with Z-plasty tendon lengthening of these two muscles. There was no apparent abnormality of the muscle bellies and no identifiable cause of the muscular contracture. A review of the literature revealed no previously reported cases of this kind.