Repeat radiation with bevacizumab and minocycline in bevacizumab-refractory high grade gliomas: a prospective phase 1 trial.

INTRODUCTION: There are no effective treatments for gliomas after progression on radiation, temozolomide, and bevacizumab. Microglia activation may be involved in radiation resistance and can be inhibited by the brain penetrating antibiotic minocycline. In this phase 1 trial, we examined the safety and effect on survival, symptom burden, and neurocognitive function of reirradiation, minocycline, and bevacizumab. METHODS: The trial used a 3 + 3 design for dose escalation followed by a ten person dose expansion. Patients received reirradiation with dosing based on radiation oncologist judgment, bevacizumab 10 mg/kg IV every two weeks, and oral minocycline twice a day. Symptom burden was measured using MDASI-BT. Neurocognitive function was measured using the COGSTATE battery. RESULTS: The maximum tolerated dose of minocycline was 400 mg twice a day with no unexpected toxicities. The PFS3 was 64.6%, and median overall survival was 6.4 months. Symptom burden and neurocognitive function did not decline in the interval between treatment completion and tumor progression. CONCLUSIONS: Minocycline 400 mg orally twice a day with bevacizumab and reirradiation is well tolerated by physician and patient reported outcomes in people with gliomas that progress on bevacizumab.

The Effect of Radiation on Complication Rates and Patient Satisfaction in Breast Reconstruction using Temporary Tissue Expanders and Permanent Implants.

The optimal method of reconstruction following mastectomy for breast cancer patients receiving radiation therapy (RT) is controversial. This study evaluated patient satisfaction and complication rates among patients who received implant-based breast reconstruction. The specific treatment algorithm analyzed included patients receiving mastectomy and immediate temporary tissue expander (TE), followed by placement of a permanent breast implant (PI). If indicated, RT was delivered to the fully expanded TE. Records of 218 consecutive patients with 222 invasive (85%) or in situ (15%) breast lesions from the Salt Lake City region treated between 1998 and 2009 were retrospectively reviewed, 28% of whom received RT. Median RT dose was 50.4 Gy, and 41% received a scar boost at a median dose of 10 Gy. Kaplan-Meier analyses were performed to evaluate the cumulative incidence of surgical complications, including permanent PI removal. Risk factors associated with surgical events were analyzed. To evaluate cosmetic results and patient satisfaction, an anonymous survey was administered. Mean follow-up was 44 months (range 6-144). Actuarial 5-year PI removal rates for non-RT and RT patients were 4% and 22%, respectively. On multivariate analysis (MVA), the only factor associated with PI removal was RT (p = 0.009). Surveys were returned describing the outcomes of 149 breasts. For the non-RT and RT groups, those who rated their breast appearance as good or better were 63% versus 62%, respectively. Under 1/3 of each group was dissatisfied with their reconstruction. RT did not significantly affect patient satisfaction scores, but on MVA RT was the only factor associated with increased PI removal. This reconstruction technique may be considered an acceptable option even if RT is needed, but the increased complication risk with RT must be recognized.

Melanoma, version 4.2014.

The NCCN Guidelines for Melanoma provide multidisciplinary recommendations for the management of patients with melanoma. These NCCN Guidelines Insights highlight notable recent updates. Dabrafenib and trametinib, either as monotherapy (category 1) or combination therapy, have been added as systemic options for patients with unresectable metastatic melanoma harboring BRAF V600 mutations. Controversy continues regarding the value of adjuvant radiation for patients at high risk of nodal relapse. This is reflected in the category 2B designation to consider adjuvant radiation following lymphadenectomy for stage III melanoma with clinically positive nodes or recurrent disease.

Patterns of failure and predictors of outcome in cutaneous malignant melanoma of the scalp.

BACKGROUND: Patients with melanoma of the scalp may have higher failure (recurrence) rates than melanoma of other body sites. OBJECTIVE: We sought to characterize survival and patterns of failure for patients with scalp melanoma. METHODS: Between 1998 and 2010, 250 nonmetastatic patients underwent wide local excision of a primary scalp melanoma. Kaplan-Meier analyses were performed to evaluate overall survival, scalp control, regional neck control, distant metastases-free survival, and disease-free survival. RESULTS: Five-year overall survival was 86%, 57%, and 45% for stages I, II, and III, respectively, and 5-year scalp control rates were 92%, 75%, and 63%, respectively. Five-year distant metastases-free survival for these stages were 92%, 65%, and 45%, respectively. Of the 74 patients who recurred, the site of first recurrence included distant disease in 47%, although 31% recurred in the scalp alone. LIMITATIONS: This is a retrospective review. CONCLUSION: Distant metastases-free survival and overall survival for stage II and III patients with scalp melanoma are poor, and stage III patients experience relatively high rates of scalp failure suggesting that these patients may benefit from additional adjuvant systemic and local therapy. Further research is needed to characterize the environmental, microenvironmental, and genetic causes of the increased aggressiveness of scalp melanoma and to identify more effective treatment and surveillance methods.

Executive Summary of the American Radium Society Appropriate Use Criteria for Neoadjuvant Therapy for Nonmetastatic Pancreatic Adenocarcinoma: Systematic Review and Guidelines.

For patients with locoregionally confined pancreatic ductal adenocarcinoma (PDAC), margin-negative surgical resection is the only known curative treatment; however, the majority of patients are not operable candidates at initial diagnosis. Among patients with resectable disease who undergo surgery alone, the 5-year survival remains poor. Adjuvant therapies, including systemic therapy or chemoradiation, are utilized as they improve locoregional control and overall survival. There has been increasing interest in the use of neoadjuvant therapy to obtain early control of occult metastatic disease, allow local tumor response to facilitate margin-negative resection, and provide a test of time and biology to assist with the selection of candidates most likely to benefit from radical surgical resection. However, limited guidance exists regarding the relative effectiveness of treatment options. In this systematic review, the American Radium Society multidisciplinary gastrointestinal expert panel convened to develop Appropriate Use Criteria evaluating the evidence regarding neoadjuvant treatment for patients with PDAC, including surgery, systemic therapy, and radiotherapy, in terms of oncologic outcomes and quality of life. The evidence was assessed using the Population, Intervention, Comparator, Outcome, and Study (PICOS) design framework and "Preferred Reporting Items for Systematic Reviews and Meta-analyses" 2020 methodology. Eligible studies included phases 2 to 3 trials, meta-analyses, and retrospective analyses published between January 1, 2012 and December 30, 2022 in the Ovid Medline database. A summary of recommendations based on the available literature is outlined to guide practitioners in the management of patients with PDAC.

Consideration of Metastasis-Directed Therapy for Patients With Metastatic Colorectal Cancer: Expert Survey and Systematic Review.

BACKGROUND: A survey of medical oncologists (MOs), radiation oncologists (ROs), and surgical oncologists (SOs) who are experts in the management of patients with metastatic colorectal cancer (mCRC) was conducted to identify factors used to consider metastasis-directed therapy (MDT). MATERIALS AND METHODS: An online survey to assess clinical factors when weighing MDT in patients with mCRC was developed based on systematic review of the literature and integrated with clinical vignettes. Supporting evidence from the systematic review was included to aid in answering questions. RESULTS: Among 75 experts on mCRC invited, 47 (response rate 62.7%) chose to participate including 16 MOs, 16 ROs, and 15 SOs. Most experts would not consider MDT in patients with 3 lesions in both the liver and lung regardless of distribution or timing of metastatic disease diagnosis (6 vs. 36 months after definitive treatment). Similarly, for patients with retroperitoneal lymph node and lung and liver involvement, most experts would not offer MDT regardless of timing of metastatic disease diagnosis. In general, SOs were willing to consider MDT in patients with more advanced disease, ROs were more willing to offer treatment regardless of metastatic site location, and MOs were the least likely to consider MDT. CONCLUSIONS: Among experts caring for patients with mCRC, significant variation was noted among MOs, ROs, and SOs in the distribution and volume of metastatic disease for which MDT would be considered. This variability highlights differing opinions on management of these patients and underscores the need for well-designed prospective randomized trials to characterize the risks and potential benefits of MDT.

Comparisons of short-term outcomes between robot-assisted, video-assisted, and open esophagectomy for resectable esophageal cancer after neoadjuvant treatment: a retrospective study.

Background: Robot-assisted esophagectomy (RAE), video-assisted minimally invasive esophagectomy (VAMIE), and open esophagectomy (OE) all have significant roles in the management of esophageal cancer (EC). Few studies have compared efficacy and safety between RAE, VAMIE, and OE for resectable EC after neoadjuvant treatment. Therefore, this study aimed to explore the short-term outcomes between RAE, VAMIE, and OE for resectable EC after neoadjuvant treatment. Methods: Ninety-eight patients were consecutively enrolled who underwent esophagectomy. A retrospective study was performed including 98 consecutive patients treated from January 2021 to August 2022 who received neoadjuvant treatment (including immunochemotherapy and chemoradiotherapy) followed by RAE, VAMIE or OE. Evaluated endpoints in the present study consisted of pathological outcomes, intraoperative and postoperative outcomes, as well as postoperative complications. Results: No significant differences were seen in the operating time, blood loss, length of intensive care unit (ICU) stay, R0 resection, and number of dissected lymph nodes between the three RAE, VAMIE, or OE groups. The achievement rate of right recurrent laryngeal nerve (RLN) lymph node removal (P=0.01) and the total cost (P<0.001) were higher in RAE. The postoperative hospital stay of OE was longer than the other two groups (P<0.05). There were no significant differences in postoperative complications. Conclusions: Compared to VAMIE, no clear benefit exists for RAE in the treatment of resectable EC after neoadjuvant therapy. OE resulted in a longer hospital stay. Although the rate of successful right RLN node removal was higher with RAE, the clinical relevance for this is yet unclear.

Executive Summary of the American Radium Society® (ARS) Appropriate Use Criteria (AUC) for Non-Operative Management (NOM) for Rectal Adenocarcinoma: Systematic Review and Guidelines.

PURPOSE: For rectal cancer patients, the standard approach of chemotherapy, radiation therapy (RT), and surgery (Trimodality Therapy, TMT) is associated with significant long-term toxicity and/or colostomy for most patients. Patient options focused on quality-of-life (QOL) have dramatically improved, but there remains limited guidance regarding comparative effectiveness. This systematic review and associated guidelines evaluate how various treatment strategies compare to each other in terms of oncologic outcomes and QOL. MATERIALS AND METHODS: Cochrane and PRISMA methodology were used to search for prospective and retrospective trials and meta-analyses of adequate quality within the Ovid Medline database between 1/1/2012-6/15/2023. These studies informed the expert panel, which rated the appropriateness of various treatments in 6 clinical scenarios through a well-established consensus methodology (modified Delphi). RESULTS: The search process yielded 197 articles that advised voting. Increasing data show non-operative management (NOM) and primary surgery result in QOL benefits noted over TMT without detriment to oncologic outcomes. For rectal cancer patients for whom TME would result in permanent colostomy or inadequate bowel continence, NOM was strongly recommended as usually appropriate. Restaging with tumor response assessment 8-12 weeks following completion of RT/CRT was deemed a necessary component of NOM. The panel recommended active surveillance in the setting of a near complete or complete response. In the setting of NOM, 54-56 Gy in 27-33 fractions concurrent with chemotherapy and followed by consolidation chemotherapy was recommended. The panel strongly recommends primary surgery as usually appropriate for a T3N0 high rectal tumor for whom LAR and adequate bowel function is possible, with adjuvant chemotherapy considered if N+. CONCLUSIONS: Recent data supports NOM and primary surgery as important options that should be offered to eligible patients. Considering the complexity of multi-disciplinary management, patients should be discussed in a multi-disciplinary setting and therapy should be tailored to individual patient goals/values.

Melanoma, version 2.2013: featured updates to the NCCN guidelines.

The NCCN Guidelines for Melanoma provide multidisciplinary recommendations on the clinical management of patients with melanoma. This NCCN Guidelines Insights report highlights notable recent updates. Foremost of these is the exciting addition of the novel agents ipilimumab and vemurafenib for treatment of advanced melanoma. The NCCN panel also included imatinib as a treatment for KIT-mutated tumors and pegylated interferon alfa-2b as an option for adjuvant therapy. Also important are revisions to the initial stratification of early-stage lesions based on the risk of sentinel lymph node metastases, and revised recommendations on the use of sentinel lymph node biopsy for low-risk groups. Finally, the NCCN panel reached clinical consensus on clarifying the role of imaging in the workup of patients with melanoma.

Self-expanding stent effects on radiation dosimetry in esophageal cancer.

It is the purpose of this study to evaluate how self-expanding stents (SESs) affect esophageal cancer radiation planning target volumes (PTVs) and dose delivered to surrounding organs at risk (OARs). Ten patients were evaluated, for whom a SES was placed before radiation. A computed tomography (CT) scan obtained before stent placement was fused to the post-stent CT simulation scan. Three methods were used to represent pre-stent PTVs: 1) image fusion (IF), 2) volume approximation (VA), and 3) diameter approximation (DA). PTVs and OARs were contoured per RTOG 1010 protocol using Eclipse Treatment Planning software. Post-stent dosimetry for each patient was compared to approximated pre-stent dosimetry. For each of the three pre-stent approximations (IF, VA, and DA), the mean lung and liver doses and the estimated percentages of lung volumes receiving 5 Gy, 10 Gy, 20 Gy, and 30 Gy, and heart volumes receiving 40 Gy were significantly lower (p-values < 0.02) than those estimated in the post-stent treatment plans. The lung V5, lung V10, and heart V40 constraints were achieved more often using our pre-stent approximations. Esophageal SES placement increases the dose delivered to the lungs, heart, and liver. This may have clinical importance, especially when the dose-volume constraints are near the recommended thresholds, as was the case for lung V5, lung V10, and heart V40. While stents have established benefits for treating patients with significant dysphagia, physicians considering stent placement and radiation therapy must realize the effects stents can have on the dosimetry.

Trends and Outcomes of Salvage Lobectomy for Early-stage Non-Small Cell Lung Cancer.

OBJECTIVES: There is little data describing the outcomes for patients who develop local recurrences after stereotactic body radiation therapy (SBRT), a standard-of-care treatment for patients with early-stage non-small cell lung cancer. One emerging option is salvage lobectomy. We investigated trends in the use of salvage lobectomy after SBRT and described patient outcomes using a nationally representative sample. METHODS: This is a retrospective study using the National Cancer Database of patients with non-small cell lung cancer diagnosed from 2004 to 2017. We used descriptive statistics to describe patients who underwent salvage lobectomy. Kaplan-Meier analysis was used to estimate overall survival (OS). Cox proportional modeling was used to identify factors associated with OS. RESULTS: We identified 276 patients who underwent salvage lobectomy. Ninety-day mortality was 0%. The median survival time for the cohort was 50 months (95% CI, 44 to 58). Median follow-up was 65 months (Interquartile Range: 39 to 96). The factors associated with decreased OS include squamous cell histology (hazard ratio (HR)=1.72, P =0.005) and high grade (1.50, P =0.038). Increased OS was associated with lobectomy performed between 3 and 6 months after SBRT (HR=0.53, P =0.021), lobectomy performed >6 months after SBRT (HR=0.59, P =0.015), and female sex (HR=0.56, P =0.004). CONCLUSIONS: Salvage lobectomy after local failures of SBRT was associated with no perioperative mortality and favorable long-term outcomes. Our data suggest that lobectomy performed within 3 months of SBRT is associated with worse OS.

'CROSS'-ing into the 'Real World': a retrospective cohort study of patients receiving trimodality and bimodality therapy for esophageal cancer.

Background: A standard of care for nonmetastatic esophageal cancer is trimodality therapy consisting of neoadjuvant chemoradiation and esophagectomy, with evidence for improved overall survival versus surgery alone in the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) trial. Patients who receive treatment with curative intent but are poor candidates for or decline surgery receive definitive bimodality therapy. Literature characterizing patients who receive bimodality therapy compared to trimodality therapy, and their relative outcomes, is sparse, especially among patients who are too old or too frail to qualify for clinical trials. In this study, we assess a single-institution real-world dataset of patients receiving bimodality and trimodality management. Methods: Patients treated for clinically resectable, nonmetastatic esophageal cancer between 2009 and 2019 who received bimodality or trimodality therapy were reviewed, generating a dataset of 95 patients. Clinical variables and patient characteristics were assessed for association with modality on multivariable logistic regression. Overall, relapse-free, and disease-free survival were assessed with Kaplan-Meier analyses and Cox proportional modeling. For patients nonadherent to planned esophagectomy, reasons for nonadherence were recorded. Results: Bimodality therapy was associated with greater age-adjusted comorbidity index, worse performance status, higher N-stage, presenting symptom other than dysphagia, and held chemotherapy cycles on multivariable analysis. Compared to bimodality therapy, trimodality therapy was associated with higher overall (3-year: 62% vs. 18%, P<0.001), relapse-free (3-year: 71% vs. 18%, P<0.001), and disease-free (3-year: 58% vs. 12%, P<0.001) survival. Similar results were observed among patients who did not meet CROSS trial qualifying criteria. Only treatment modality was associated with overall survival after adjusting for covariates (HR 0.37, P<0.001, reference group: bimodality). Patient choice accounted for 40% of surgery nonadherence in our population. Conclusions: Patients receiving trimodality therapy were observed to have superior overall survival compared to bimodality therapy. Patient preference for organ-preserving therapies appears to impact resection rate; further characterization of patient decision-making may be helpful. Our results suggest patients who wish to prioritize overall survival should be encouraged to pursue trimodality therapy and obtain early consultation with surgery. Development of evidence-based interventions to physiologically prepare patients before and during neoadjuvant therapy as well as efforts to optimize the tolerability of the chemoradiation plan are warranted.

American Radium Society (ARS) Appropriate Use Criteria (AUC) for Extrahepatic Cholangiocarcinoma.

Although uncommon, extrahepatic cholangiocarcinoma (EHCC) is a deadly malignancy, and the treatment approaches remain controversial. While surgery remains the only cure, few patients are candidates for resection up front, and there are high rates of both local and distant failure following resection. Herein, we systematically review the available evidence regarding treatment approaches for patients with EHCC, including surgery, radiation, and chemotherapy. The evidence regarding treatment outcomes was assessed using the Population, Intervention, Comparator, Outcome, and Study design (PICOS) framework. A summary of recommendations based on the available literature is outlined for specific clinical scenarios encountered by providers in the clinic to guide the management of these patients.

Clinical Reasoning: A 67-Year-Old Woman With Abdominal Pain, Constipation, and Urinary Retention.

Meningeal melanocytomas are an extremely rare, pigmented tumors of the central nervous system (CNS). They generally carry a favorable prognosis, although recurrence and transformation into the more aggressive malignant melanoma has been reported. We present a case of a patient who reported constipation and abdominal pain around the umbilicus, which progressed into cord compression with lower extremity weakness and gait instability. Spinal magnetic resonance imaging (MRI) revealed a tumor at the level of T11, and she underwent gross total resection of the mass. Pathology demonstrated a meningeal melanocytoma with intermediate features. She received post-operative radiation therapy and had stable disease for three years, at which time she developed new weakness and drop metastases. This case represents a rare presentation of a rare disease, in which a spinal cord tumor presented with constipation and abdominal distress. Intradural-extramedullary tumors of the thoracic spine are most commonly nerve sheath tumors or meningiomas, but rare entities such as melanocytomas can present in this location; even more rarely, these tumors can have an aggressive course with delayed recurrence.

The Potential for Overtreatment With Total Neoadjuvant Therapy (TNT): Consider One Local Therapy Instead.

With increased therapeutic options in rectal cancer, a central question has become how to tailor therapy to patient preferences to avoid both over and under treatment. Total Neoadjuvant Therapy (TNT), defined as delivering all planned chemotherapy and radiation therapy (RT) before surgery, was developed with the primary goal of improving overall survival through early elimination of micrometastatic disease. In this narrative review assessing patients with operable adenocarcinoma of the rectum, we sought to evaluate TNT versus alternative options with regard to both quality of life (QoL) and oncologic outcomes. Survey data of patient preferences reveal that an increased focus on QoL when discussing options is essential. While evidence favors TNT improving distant metastases-free survival, this has not yet translated to a clear OS benefit. The improved pathologic complete response rate with TNT compared to short course RT or chemoradiation alone suggests proceeding to surgery might result in overtreatment, lending support to a watch-and-wait option for patients with a goal for nonoperative management if a clinical complete response is achieved. Similarly, for select low-risk patients, surgery may be the only local therapy required allowing for safe omission of RT. In the treatment of rectal cancer, the future appears to be moving toward one local therapy. As an alternative to TNT, there is growing support for the concept we define herein as total definitive therapy instead: chemoradiation followed by consolidation chemotherapy, saving surgery only for incomplete responders rather than as part of the initial treatment plan. Also, selective use of RT should be considered for low-risk patients. By thoroughly assessing how these treatment de-escalation options compare to more traditional treatment algorithms, this narrative review provides guidance on how to honor patient preferences for QoL by avoiding treatments that might offer negligible benefits in oncologic outcomes.

Active Surveillance for Early Stage Lung Cancer.

OBJECTIVES: Data describing outcomes for patients with early stage lung cancer who undergo expectant management is lacking, despite evidence of a sub-population with indolent malignancies. We used the National Cancer Data Base (NCDB) to identify factors associated with active surveillance for early stage lung cancer. Additionally, we sought to describe outcomes of three different care plans: active surveillance, no treatment, and Stereotactic Body Radiation Therapy (SBRT). METHODS: Patients diagnosed in 2010 to 2017 with early stage lung cancer who underwent active surveillance, no treatment, and SBRT were retrospectively identified in the NCDB. Multinomial logistic regression was used to assess care plan selection. Kaplan Meier analysis was used to assess overall survival (OS). RESULTS: We identified 30,107 patients that met our inclusion criteria: 838 (3%) underwent active surveillance, 6388 patients (21%) received no treatment, and 22,881 (76%) underwent SBRT. Black race (relative risk ratio (RRR): 1.66) and older age (RRR: 1.02) were significant positive predictors of active surveillance selection. Conversely, higher tumor stage (RRR: 0.26) and squamous cell carcinoma (RRR: 0.35) were significant negative predictors of active surveillance selection. Kaplan Meier analysis revealed a longer median OS associated with active surveillance compared to no treatment at 49.3 months versus 26.5 months, respectively. SBRT OS was 43.1 months. CONCLUSIONS: We identified a population of lung cancer patients who underwent expectant management with favorable outcomes. Additionally, we identified factors associated with active surveillance selection. The selection of active surveillance over no treatment was associated with significantly longer OS.

Impact of and Response to Cyberattacks in Radiation Oncology.

Cyberattacks on health care facilities are increasing and significantly affecting health care delivery throughout the world. The recent cyberattack on our hospital-based radiation facility exposed vulnerabilities of radiation oncology systems and highlighted the dependence of radiation treatment on integrated and complex radiation planning, delivery and verification systems. After the cyberattack on our health care facility, radiation oncology staff reconstructed patient information, schedules, and radiation plans from existing paper records and physicians developed a system to triage patients requiring immediate transfer of radiation treatment to nearby facilities. Medical physics and hospital information technology collaborated to restore services without access to the system backup or network connectivity. Ultimately, radiation treatments resumed incrementally as systems were restored and rebuilt. The experiences and lessons learned from this response were reviewed. The successes and shortcomings were incorporated into recommendations to provide guidance to other radiation facilities in preparation for a possible cyberattack. Our response and recommendations are intended to serve as a starting point to assist other facilities in cybersecurity preparedness planning. Because there is no one-size-fits-all response, each department should determine its specific vulnerabilities, risks, and available resources to create an individualized plan.

Multiagent Chemotherapy Followed by Stereotactic Body Radiotherapy Versus Conventional Radiotherapy for Resected Pancreas Cancer.

BACKGROUND AND PURPOSE: Chemotherapy followed by margin-negative resection (R0) is the treatment of choice for patients with localized pancreatic ductal adenocarcinoma (PDAC). Neoadjuvant multiagent chemotherapy (MAC) or MAC then radiotherapy (RT) may optimize surgical candidacy. The purpose of this study was to compare pathologic outcomes of MAC followed by conventionally fractionated radiotherapy (CRT) versus stereotactic body radiotherapy (SBRT) for patients with resected PDAC. METHODS: Patients diagnosed with nonmetastatic PDAC between 2012 and 2017 and who received preoperative MAC or MAC+RT were identified in the National Cancer Database. Variables associated with R0 and overall survival were identified with logistic regression and Cox analysis (P<0.05). RESULTS: A total of 5273 patients were identified (MAC: 3900, MAC+CRT: 955, MAC+SBRT: 418). The median RT dose/fraction (fx) in the MAC+CRT and MAC+SBRT cohorts was 50.4 Gy/28 fx and 33 Gy/5 fx. Patients receiving MAC+CRT versus MAC+SBRT had similar rates of ypT3-T4 disease (54% vs. 58%, P=0.187), R0 (87% vs. 84%, P=0.168), and pathologic complete response (pathologic complete response; 6% vs. 4%, P=0.052), however, MAC+CRT was associated with less regional lymphatic disease (ypN+: 28% vs. 41%, P<0.001). The median overall survival of patients receiving MAC+CRT versus MAC+SBRT was 24.6 versus 29.5 months (P=0.045). CONCLUSIONS: For patients with resected PDAC, MAC+CRT, and MAC+SBRT had similar rates of R0 and pathologic complete response, although MAC+CRT was associated with lower ypN+. Prospective evaluation of neoadjuvant RT regimens with attention to radiation therapy design is warranted.

American Radium Society (ARS) Appropriate Use Criteria (AUC) for Locoregional Gastric Adenocarcinoma: Systematic Review and Guidelines.

OBJECTIVE: The objective of this study was to systematically evaluate the data regarding the use of neoadjuvant, perioperative, surgical, and adjuvant treatment options in localized gastric cancer patients and to develop Appropriate Use Criteria recommended by a panel of experts convened by the American Radium Society. METHODS: Preferred reporting items for systematic reviews and meta-analyses methodology was used to develop an extensive analysis of peer-reviewed phase 2/2R/3 trials, as well as meta-analyses found within the Ovid Medline database between 2010 and 2020. The expert panel then rated the appropriateness of various treatments in 5 representative clinical scenarios through a well-established consensus methodology (modified Delphi). RESULTS: For patients with medically operable locally advanced gastric cancer, the strongest recommendation was for perioperative chemotherapy based on high-quality data. Acceptable alternatives included surgery followed by either chemotherapy or concurrent chemoradiotherapy (CRT). For patients with upfront resection of stages I to III gastric cancer (no neoadjuvant therapy), the group strongly recommended adjuvant therapy with either chemotherapy alone or CRT, based on high-quality data. For patients with locally advanced disease who received preoperative chemotherapy without tumor regression, the group strongly recommended postoperative chemotherapy or postoperative CRT. Finally, for medically inoperable gastric cancer patients, there was moderate consensus recommending definitive concurrent CRT. CONCLUSIONS: The addition of chemotherapy and/or radiation, either in the neoadjuvant, adjuvant, or perioperative setting, results in improved survival rates for patients compared with surgery alone. For inoperable patients, definitive CRT is a reasonable treatment option, though largely palliative.

Initial experience and clinical comparison of two image guidance methods for SBRT treatment: 4DCT versus respiratory-triggered imaging.

For Stereotactic Body Radiation Therapy (SBRT) treatment of lung and liver, we quantified the differences between two image guidance methods: 4DCT and ExacTrac respiratory-triggered imaging. Five different patients with five liver lesions and one lung lesion for a total of 19 SBRT delivered fractions were studied. For the 4DCT method, a manual registration process was used between the 4DCT image sets from initial simulation and treatment day to determine the required daily image-guided corrections. We also used the ExacTrac respiratory-triggered imaging capability to verify the target positioning, and calculated the differences in image guidance shifts between these two methods. The mean (standard deviation) of the observed differences in image-guided shifts between 4DCT and ExacTrac respiratory-triggered image guidance was left/right (L/R) = 0.4 (2.0) mm, anterior/posterior (A/P) = 1.4 (1.7) mm, superior/inferior (S/I) = 2.2 (2.0) mm, with no difference larger than 5.0 mm in any given direction for any individual case. The largest error occurred in the S/I direction, with a mean of 2.2 mm for the six lesions. This seems reasonable, because respiratory motion and the resulting imaging uncertainties are most pronounced in this S/I direction. Image guidance shifts derived from ExacTrac triggered imaging at two extreme breathing phases (i.e., full exhale vs. full inhale), agreed well (less than 2.0 mm) with each other. In summary, two very promising image guidance methods of 4DCT and ExacTrac respiratory-triggered imaging were presented and the image guidance shifts were comparable for the patients evaluated in this study.