Integration of Telemedicine Consultation Into a Tertiary Radiation Oncology Department: Predictors of Use, Treatment Yield, and Effects on Patient Population.

PURPOSE: The COVID-19 pandemic led to rapid expansion of telemedicine. The implications of telemedicine have not been rigorously studied in radiation oncology, a procedural specialty. This study aimed to evaluate the characteristics of in-person patients (IPPs) and virtual patients (VPs) who presented to a large cancer center before and during the pandemic and to understand variables affecting likelihood of receiving radiotherapy (yield) at our institution. METHODS: A total of 17,915 patients presenting for new consultation between 2019 and 2021 were included, stratified by prepandemic and pandemic periods starting March 24, 2020. Telemedicine visits included video and telephone calls. Area deprivation indices (ADIs) were also compared. RESULTS: The overall population was 56% male and 93% White with mean age of 63 years. During the pandemic, VPs accounted for 21% of visits, were on average younger than their in-person (IP) counterparts (63.3 years IP v 62.4 VP), and lived further away from clinic (215 miles IP v 402 VP). Among treated VPs, living closer to clinic was associated with higher yield (odds ratio [OR], 0.95; P < .001). This was also seen among IPPs who received treatment (OR, 0.96; P < .001); however, the average distance from clinic was significantly lower for IPPs than VPs (205 miles IP v 349 VP). Specialized radiotherapy (proton and brachytherapy) was used more in VPs. IPPs had higher ADI than VPs. Among VPs, those treated had higher ADI (P < .001). CONCLUSION: Patient characteristics and yield were significantly different between IPPs and VPs. Telemedicine increased reach to patients further away from clinic, including from rural or health care-deprived areas, allowing access to specialized radiation oncology care. Telemedicine has the potential to increase the reach of other technical and procedural specialties.

Defining Minimum Treatment Parameters of Ablative Radiation Therapy in Patients With Hepatocellular Carcinoma: An Expert Consensus.

PURPOSE: External beam radiation therapy (EBRT) is a highly effective treatment in select patients with hepatocellular carcinoma (HCC). However, the Barcelona Clinic Liver Cancer system does not recommend the use of EBRT in HCC due to a lack of sufficient evidence and intends to perform an individual patient level meta-analysis of ablative EBRT in this population. However, there are many types of EBRT described in the literature with no formal definition of what constitutes "ablative." Thus, we convened a group of international experts to provide consensus on the parameters that define ablative EBRT in HCC. METHODS AND MATERIALS: Fundamental parameters related to dose, fractionation, radiobiology, target identification, and delivery technique were identified by a steering committee to generate 7 Key Criteria (KC) that would define ablative EBRT for HCC. Using a modified Delphi (mDelphi) method, experts in the use of EBRT in the treatment of HCC were surveyed. Respondents were given 30 days to respond in round 1 of the mDelphi and 14 days to respond in round 2. A threshold of ≥70% was used to define consensus for answers to each KC. RESULTS: Of 40 invitations extended, 35 (88%) returned responses. In the first round, 3 of 7 KC reached consensus. In the second round, 100% returned responses and consensus was reached in 3 of the remaining 4 KC. The distribution of answers for one KC, which queried the a/b ratio of HCC, was such that consensus was not achieved. Based on this analysis, ablative EBRT for HCC was defined as a BED10 ≥80 Gy with daily imaging and multiphasic contrast used for target delineation. Treatment breaks (eg, for adaptive EBRT) are allowed, but the total treatment time should be ≤6 weeks. Equivalent dose when treating with protons should use a conversion factor of 1.1, but there is no single conversion factor for carbon ions. CONCLUSIONS: Using a mDelphi method assessing expert opinion, we provide the first consensus definition of ablative EBRT for HCC. Empirical data are required to define the a/b of HCC.

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.

Sublobar Resection, Stereotactic Body Radiation Therapy, and Percutaneous Ablation Provide Comparable Outcomes for Lung Metastasis-Directed Therapy.

BACKGROUND: Prolonged survival of patients with metastatic disease has furthered interest in metastasis-directed therapy (MDT). RESEARCH QUESTION: There is a paucity of data comparing lung MDT modalities. Do outcomes among sublobar resection (SLR), stereotactic body radiation therapy (SBRT), and percutaneous ablation (PA) for lung metastases vary in terms of local control and survival? STUDY DESIGN AND METHODS: Medical records of patients undergoing lung MDT at a single cancer center between January 2015 and December 2020 were reviewed. Overall survival, local progression, and toxicity outcomes were collected. Patient and lesion characteristics were used to generate multivariable models with propensity weighted analysis. RESULTS: Lung MDT courses (644 total: 243 SLR, 274 SBRT, 127 PA) delivered to 511 patients were included with a median follow-up of 22 months. There were 47 local progression events in 45 patients, and 159 patients died. Two-year overall survival and local progression were 80.3% and 63.3%, 83.8% and 9.6%, and 4.1% and 11.7% for SLR, SBRT, and PA, respectively. Lesion size per 1 cm was associated with worse overall survival (hazard ratio, 1.24; P = .003) and LP (hazard ratio, 1.50; P < .001). There was no difference in overall survival by modality. Relative to SLR, there was no difference in risk of local progression with PA; however, SBRT was associated with a decreased risk (hazard ratio, 0.26; P = .023). Rates of severe toxicity were low (2.1%-2.6%) and not different among groups. INTERPRETATION: This study performs a propensity weighted analysis of SLR, SBRT, and PA and shows no impact of lung MDT modality on overall survival. Given excellent local control across MDT options, a multidisciplinary approach is beneficial for patient triage and longitudinal management.

American Radium Society Appropriate Use Criteria for the use of liver-directed therapies for nonsurgical management of liver metastases: Systematic review and guidelines.

The liver is a common site of cancer metastases. Systemic therapy is widely accepted as the standard treatment for liver metastases (LM), although select patients with liver oligometastases may be candidates for potentially curative liver resection. Recent data support the role of nonsurgical local therapies such as ablation, external beam radiotherapy, embolization, and hepatic artery infusion therapy for management of LM. Additionally, for patients with advanced, symptomatic LM, local therapies may provide palliative benefit. The American Radium Society gastrointestinal expert panel, including members representing radiation oncology, interventional radiology, surgical oncology, and medical oncology, performed a systemic review and developed Appropriate Use Criteria for the use of nonsurgical local therapies for LM. Preferred Reporting Items for Systematic reviews and Meta-Analyses methodology was used. These studies were used to inform the expert panel, which then rated the appropriateness of various treatments in seven representative clinical scenarios through a well-established consensus methodology (modified Delphi). A summary of recommendations is outlined to guide practitioners on the use of nonsurgical local therapies for patients with LM.

Comparing Oncologic Outcomes and Toxicity for Combined Modality Therapy vs. Carbon-Ion Radiotherapy for Previously Irradiated Locally Recurrent Rectal Cancer.

No standard treatment paradigm exists for previously irradiated locally recurrent rectal cancer (PILRRC). Carbon-ion radiotherapy (CIRT) may improve oncologic outcomes and reduce toxicity compared with combined modality therapy (CMT). Eighty-five patients treated at Institution A with CIRT alone (70.4 Gy/16 fx) and eighty-six at Institution B with CMT (30 Gy/15 fx chemoradiation, resection, intraoperative electron radiotherapy (IOERT)) between 2006 and 2019 were retrospectively compared. Overall survival (OS), pelvic re-recurrence (PR), distant metastasis (DM), or any disease progression (DP) were analyzed with the Kaplan-Meier model, with outcomes compared using the Cox proportional hazards model. Acute and late toxicities were compared, as was the 2-year cost. The median time to follow-up or death was 6.5 years. Median OS in the CIRT and CMT cohorts were 4.5 and 2.6 years, respectively (p ≤ 0.01). No difference was seen in the cumulative incidence of PR (p = 0.17), DM (p = 0.39), or DP (p = 0.19). Lower acute grade ≥ 2 skin and GI/GU toxicity and lower late grade ≥ 2 GU toxicities were associated with CIRT. Higher 2-year cumulative costs were associated with CMT. Oncologic outcomes were similar for patients treated with CIRT or CMT, although patient morbidity and cost were lower with CIRT, and CIRT was associated with longer OS. Prospective comparative studies are needed.

Determinants of Long-term Survival Decades After Esophagectomy for Esophageal Cancer.

BACKGROUND: Long-term survival in esophagectomy patients with esophageal cancer is low due to tumor-related characteristics, with few reports of modifiable variables influencing outcome. We identified determinants of overall survival, time to recurrence, and disease-free survival in this patient cohort. METHODS: Adult patients who underwent esophagectomy for primary esophageal cancer from January 5, 2000, through December 30, 2010, at our institution were identified. Univariate Cox models and multivariable logistic regression analyses were used to identify associations between modifiable and unmodifiable patient and clinical variables and outcome of survival for the total cohort and a subgroup with locally advanced disease. RESULTS: We identified 870 patients with esophageal cancer who underwent esophagectomy. The median follow-up time was 15 years, and the 15-year overall survival rate was 25.2%, survival free of recurrence was 57.96%, and disease-free survival was 24.21%. Decreased overall survival was associated with the following unmodifiable variables: older age, male sex, active smoking status, history of coronary artery disease, advanced clinical stage, and tumor location. Decreased overall survival was associated with the following modifiable variables: use of neoadjuvant therapy, advanced pathologic stage, resection margin positivity, surgical reintervention, and blood transfusion requirement. The overall survival probability 6 years after esophagectomy was 0.920 (95% CI, 0.895-0.947), and time-to-recurrence probability was 0.988 (95% CI, 0.976-1.000), with a total of 17 recurrences and 201 deaths. CONCLUSIONS: Once patients survive 5 years, recurrence is rare. Long-term survival can be achieved in high-volume centers adhering to National Comprehensive Cancer Network guidelines using multidisciplinary care teams that is double what has been previously reported in the literature from national databases.

Association of Radiotherapy Duration With Clinical Outcomes in Patients With Esophageal Cancer Treated in NRG Oncology Trials: A Secondary Analysis of NRG Oncology Randomized Clinical Trials.

Importance: For many types of epithelial malignant neoplasms that are treated with definitive radiotherapy (RT), treatment prolongation and interruptions have an adverse effect on outcomes. Objective: To analyze the association between RT duration and outcomes in patients with esophageal cancer who were treated with definitive chemoradiotherapy (CRT). Design, Setting, and Participants: This study was an unplanned, post hoc secondary analysis of 3 prospective, multi-institutional phase 3 randomized clinical trials (Radiation Therapy Oncology Group [RTOG] 8501, RTOG 9405, and RTOG 0436) of the National Cancer Institute-sponsored NRG Oncology (formerly the National Surgical Adjuvant Breast and Bowel Project, RTOG, and Gynecologic Oncology Group). Enrolled patients with nonmetastatic esophageal cancer underwent definitive CRT in the trials between 1986 and 2013, with follow-up occurring through 2014. Data analyses were conducted between March 2022 to February 2023. Exposures: Treatment groups in the trials used standard-dose RT (50 Gy) and concurrent chemotherapy. Main Outcomes and Measures: The outcomes were local-regional failure (LRF), distant failure, disease-free survival (DFS), and overall survival (OS). Multivariable models were used to examine the associations between these outcomes and both RT duration and interruptions. Radiotherapy duration was analyzed as a dichotomized variable using an X-Tile software to choose a cut point and its median value as a cut point, as well as a continuous variable. Results: The analysis included 509 patients (median [IQR] age, 64 [57-70] years; 418 males [82%]; and 376 White individuals [74%]). The median (IQR) follow-up was 4.01 (2.93-4.92) years for surviving patients. The median cut point of RT duration was 39 days or less in 271 patients (53%) vs more than 39 days in 238 patients (47%), and the X-Tile software cut point was 45 days or less in 446 patients (88%) vs more than 45 days in 63 patients (12%). Radiotherapy interruptions occurred in 207 patients (41%). Female (vs male) sex and other (vs White) race and ethnicity were associated with longer RT duration and RT interruptions. In the multivariable models, RT duration longer than 45 days was associated with inferior DFS (hazard ratio [HR], 1.34; 95% CI, 1.01-1.77; P = .04). The HR for OS was 1.33, but the results were not statistically significant (95% CI, 0.99-1.77; P = .05). Radiotherapy duration longer than 39 days (vs ≤39 days) was associated with a higher risk of LRF (HR, 1.32; 95% CI, 1.06-1.65; P = .01). As a continuous variable, RT duration (per 1 week increase) was associated with DFS failure (HR, 1.14; 95% CI, 1.01-1.28; P = .03). The HR for LRF 1.13, but the result was not statistically significant (95% CI, 0.99-1.28; P = .07). Conclusions and Relevance: Results of this study indicated that in patients with esophageal cancer receiving definitive CRT, prolonged RT duration was associated with inferior outcomes; female patients and those with other (vs White) race and ethnicity were more likely to have longer RT duration and experience RT interruptions. Radiotherapy interruptions should be minimized to optimize outcomes.

Risk stratification of postoperative cardiopulmonary toxicity after trimodality therapy for esophageal cancer.

Purpose/objective: Postoperative toxicity for esophageal cancer impacts patient quality of life and potentially overall survival (OS). We studied whether patient and toxicity parameters post-chemoradiation therapy predict for post-surgical cardiopulmonary total toxicity burden (CPTTB) and whether CPTTB was associated with short and long-term outcomes. Materials/methods: Patients had biopsy-proven esophageal cancer treated with neoadjuvant chemoradiation and esophagectomy. CPTTB was derived from total perioperative toxicity burden (Lin et al. JCO 2020). To develop a CPTTB risk score predictive for major CPTTB, recursive partitioning analysis was used. Results: From 3 institutions, 571 patients were included. Patients were treated with 3D (37%), IMRT (44%), and proton therapy (19%). 61 patients had major CPTTB (score ≥ 70). Increasing CPTTB was predictive of decreased OS (p<0.001), lengthier post-esophagectomy length of stay (LOS, p<0.001), and death or readmission within 60 days of surgery (DR60, p<0.001). Major CPTTB was also predictive of decreased OS (hazard ratio = 1.70, 95% confidence interval: 1.17-2.47, p=0.005). The RPA-based risk score included: age ≥ 65, grade ≥ 2 nausea or esophagitis attributed to chemoradiation, and grade ≥ 3 hematologic toxicity attributed to chemoradiation. Patients treated with 3D radiotherapy had inferior OS (p=0.010) and increased major CPTTB (18.5% vs. 6.1%, p<0.001). Conclusion: CPTTB predicts for OS, LOS, and DR60. Patients with 3D radiotherapy or age ≥ 65 years and chemoradiation toxicity are at highest risk for major CPTTB, predicting for higher short and long-term morbidity and mortality. Strategies to optimize medical management and reduce toxicity from chemoradiation should be strongly considered.

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.

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.

Imaging Features in the Liver after Stereotactic Body Radiation Therapy.

Historically, radiation therapy was not considered in treatment of liver tumors owing to the risk of radiation-induced liver disease. However, development of highly conformed radiation treatments such as stereotactic body radiation therapy (SBRT) has increased use of radiation therapy in the liver. SBRT is indicated in treatment of primary and metastatic liver tumors with outcomes comparable to those of other local therapies, especially in treatment of hepatocellular carcinoma. After SBRT, imaging features of the tumor and surrounding background hepatic parenchyma demonstrate a predictable pattern immediately after treatment and during follow-up. The goals of SBRT are to deliver a lethal radiation dose to the targeted liver tumor and to minimize radiation dose to normal liver parenchyma and other adjacent organs. Evaluation of tumor response after SBRT centers on changes in size and enhancement; however, these changes are often delayed secondary to the underlying physiologic effects of radiation. Knowledge of the underlying pathophysiologic mechanisms of SBRT should allow better understanding of the typical imaging features in detection of tumor response and avoid misinterpretation from common pitfalls and atypical imaging findings. Imaging features of radiation-induced change in the surrounding liver parenchyma are characterized by a focal liver reaction that can potentially be mistaken for no response or recurrence of tumor. Knowledge of the pattern and chronology of this phenomenon may allay any uncertainty in assessment of tumor response. Other pitfalls related to fiducial marker placement or combination therapies are important to recognize. The authors review the basic principles of SBRT and illustrate post-SBRT imaging features of treated liver tumors and adjacent liver parenchyma with a focus on avoiding pitfalls in imaging evaluation of response. Online supplemental material is available for this article. ©RSNA, 2022.

FDG-PET Predicts Neoadjuvant Therapy Response and Survival in Borderline Resectable/Locally Advanced Pancreatic Adenocarcinoma.

BACKGROUND: Neoadjuvant therapy (NAT) is used in borderline resectable/locally advanced (BR/LA) pancreatic ductal adenocarcinoma (PDAC). Anatomic imaging (CT/MRI) poorly predicts response, and biochemical (CA 19-9) markers are not useful (nonsecretors/nonelevated) in many patients. Pathologic response highly predicts survival post-NAT, but is only known postoperatively. Because metabolic imaging (FDG-PET) reveals primary tumor viability, this study aimed to evaluate our experience with preoperative FDG-PET in patients with BR/LA PDAC in predicting NAT response and survival. METHODS: We reviewed all patients with resected BR/LA PDAC who underwent NAT with FDG-PET within 60 days of resection. Pre- and post-NAT metabolic (FDG-PET) and biochemical (CA 19-9) responses were dichotomized in addition to pathologic responses. We compared post-NAT metabolic and biochemical responses as preoperative predictors of pathologic responses and recurrence-free survival (RFS) and overall survival (OS). RESULTS: We identified 202 eligible patients. Post-NAT, 58% of patients had optimization of CA 19-9 levels. Major metabolic and pathologic responses were present in 51% and 38% of patients, respectively. Median RFS and OS times were 21 and 48.7 months, respectively. Metabolic response was superior to biochemical response in predicting pathologic response (area under the curve, 0.86 vs 0.75; P<.001). Metabolic response was the only univariate preoperative predictor of OS (odds ratio, 0.25; 95% CI, 0.13-0.40), and was highly correlated (P=.001) with pathologic response as opposed to biochemical response alone. After multivariate adjustment, metabolic response was the single largest independent preoperative predictor (P<.001) for pathologic response (odds ratio, 43.2; 95% CI, 16.9-153.2), RFS (hazard ratio, 0.37; 95% CI, 0.2-0.6), and OS (hazard ratio, 0.21; 95% CI, 0.1-0.4). CONCLUSIONS: Among patients with post-NAT resected BR/LA PDAC, FDG-PET highly predicts pathologic response and survival, superior to biochemical responses alone. Given the poor ability of anatomic imaging or biochemical markers to assess NAT responses in these patients, FDG-PET is a preoperative metric of NAT efficacy, thereby allowing potential therapeutic alterations and surgical treatment decisions. We suggest that FDG-PET should be an adjunct and recommended modality during the NAT phase of care for these patients.

Vaginal Sparing Radiotherapy Using IMPT and Daily Dilator Placement for Women with Anal Cancer.

Sexual dysfunction is a common toxicity and detrimental for the quality of life of women treated with chemoradiotherapy for anal cancer. Sexual dysfunction occurs because the vagina is closely approximated to the anal canal and typically receives substantial doses of radiation. Strategies for mitigation have largely been focused on posttreatment therapy and symptom management. The use of daily vaginal dilator placement during radiotherapy to mitigate dose to the vagina has been previously explored with modest gains, while proton therapy is under active investigation for the treatment of anal cancer. Use of proton therapy for anal cancer reduces dose to some organs at risk but may inadvertently increase vaginal toxicity if the proton beam terminates in the vaginal tissue. Herein, we present the case histories of 2 women treated for squamous cell carcinoma of the anal canal with the novel combination of intensity-modulated proton therapy and daily vaginal dilator placement to maximally reduce dose to the vagina and protect it from areas of increased energy deposition at the end of the proton range.

A Critical Review of the Role of Local Therapy for Oligometastatic Gastrointestinal Cancer.

PURPOSE: The purpose of this critical review is to provide an overview of the role and outcomes associated with the use of local therapy for patients with oligometastatic gastrointestinal cancers. METHODS AND MATERIALS: A review of clinical data was performed to describe outcomes associated with the use of systemic therapy and/or locoregional therapies for patients with oligometastatic gastrointestinal cancers including esophagus, gastric, liver, biliary, pancreas, colorectal, and anal canal. RESULTS: This review describes outcomes associated with current first line systemic therapy and oligometastasis directed locoregional therapy for patients with gastrointestinal cancers. Available data suggest that for well-selected patients among each gastrointestinal disease subsite, the use of local therapy is associated with favorable disease control and possible survival benefit. CONCLUSIONS: These data emphasize the importance of multidisciplinary collaboration and consideration of radiation therapy for patients with oligometastatic gastrointestinal cancers to improve locoregional control and progression-free survival. Multiple trials are ongoing to determine whether metastasis-directed radiation therapy improves overall survival.

Patterns of Recurrence After Primary Local Therapy for Pancreatic Ductal Adenocarcinoma - A Critical Review of Rationale and Target Delineation for (Neo)Adjuvant Radiation Therapy.

PURPOSE: The purpose of this work was to describe pancreatic ductal adenocarcinoma (PDAC) patterns of locoregional spread and recurrence to help guide clinicians on (neo)adjuvant radiation therapy (RT) planning strategies and target volume delineation. METHODS AND MATERIALS: A comprehensive review of clinical data was performed to describe PDAC patterns of locoregional spread, including extrapancreatic tumor extension, perineural invasion, regional lymph node involvement, and patterns of disease recurrence as influenced by (neo)adjuvant treatment strategy. RESULTS: This review describes PDAC patterns of spread, disease progression, and evolving treatment techniques. Based upon this data, we advocate for inclusion of elective at-risk regions of extrapancreatic extension, perineural invasion, and lymphatic spread for patients receiving neoadjuvant RT. CONCLUSIONS: This review provides a nuanced description of PDAC patterns of spread and recurrence to guide clinicians on target volume delineation and planning strategies to maximize the effectiveness of neo(adjuvant) RT delivery for patients with PDAC. Further prospective studies are needed to better define the optimal RT dose, fractionation regimens, and target volumes to be used in the (neo)adjuvant setting.

Re-resection of Microscopically Positive Margins Found on Intraoperative Frozen Section Analysis Does Not Result in a Survival Benefit in Patients Undergoing Surgery and Intraoperative Radiation Therapy for Locally Recurrent Rectal Cancer.

BACKGROUND: Intraoperative frozen-section analysis provides real-time margin resection status that can guide intraoperative decisions made by the surgeon and radiation oncologist. For patients with locally recurrent rectal cancer undergoing surgery and intraoperative radiation therapy, intraoperative re-resection of positive margins to achieve negative margins is common practice. OBJECTIVE: This study aimed to assess whether re-resection of positive margins found on intraoperative frozen-section analysis improves oncologic outcomes. DESIGN: This is a retrospective cohort study. SETTINGS: This study was an analysis of a prospectively maintained multicenter database. PATIENTS: All patients who underwent surgical resection of locally recurrent rectal cancer with intraoperative radiation therapy between 2000 and 2015 were included and followed for 5 years. Three groups were compared: initial R0 resection, initial R1 converted to R0 after re-resection, and initial R1 that remained R1 after re-resection. Grossly positive margin resections (R2) were excluded. MAIN OUTCOME MEASURES: The primary outcome measures were 5-year overall survival, recurrence-free survival, and local re-recurrence. RESULTS: A total of 267 patients were analyzed (initial R0 resection, n = 94; initial R1 converted to R0 after re-resection, n = 95; initial R1 that remained R1 after re-resection, n = 78). Overall survival was 4.4 years for initial R0 resection, 2.7 years for initial R1 converted to R0 after re-resection, and 2.9 years for initial R1 that remained R1 after re-resection ( p = 0.01). Recurrence-free survival was 3.0 years for initial R0 resection and 1.8 years for both initial R1 converted to R0 after re-resection and initial R1 that remained R1 after re-resection ( p ≤ 0.01). Overall survival did not differ for patients with R1 and re-resection R1 or R0 ( p = 0.62). Recurrence-free survival and freedom from local re-recurrence did not differ between groups. LIMITATIONS: This study was limited by the heterogeneous patient population restricted to those receiving intraoperative radiation therapy. CONCLUSIONS: Re-resection of microscopically positive margins to obtain R0 status does not appear to provide a significant survival advantage or prevent local re-recurrence in patients undergoing surgery and intraoperative radiation therapy for locally recurrent rectal cancer. See Video Abstract at http://links.lww.com/DCR/B886 . LA RERESECCIN DE LOS MRGENES MICROSCPICAMENTE POSITIVOS ENCONTRADOS DE MANERA INTRAOPERATORIA MEDIANTE LA TCNICA DE CRIOSECCIN, NO DA COMO RESULTADO UN BENEFICIO DE SUPERVIVENCIA EN PACIENTES SOMETIDOS A CIRUGA Y RADIOTERAPIA INTRAOPERATORIA PARA EL CNCER RECTAL LOCALMENTE RECIDIVANTE: ANTECEDENTES:El análisis de la ténica de criosección para los margenes positivos encontrados de manera intraoperatoria proporciona el estado de la resección del margen en tiempo real que puede guiar las decisiones intraoperatorias tomadas por el cirujano y el oncólogo radioterapeuta. Para los pacientes con cáncer de recto localmente recurrente que se someten a cirugía y radioterapia intraoperatoria, la re-resección intraoperatoria de los márgenes positivos para lograr márgenes negativos es una práctica común.OBJETIVO:Evaluar si la re-resección de los márgenes positivos encontrados en el análisis de la ténica por criosecciónde manera intraoperatorios mejora los resultados oncológicos.DISEÑO:Estudio de cohorte retrospectivo.AJUSTES:Análisis de una base de datos multicéntrica mantenida de forma prospectiva.POBLACIÓN:Todos los pacientes que se sometieron a resección quirúrgica de cáncer de recto localmente recurrente con radioterapia intraoperatoria entre 2000 y 2015 fueron incluidos y seguidos durante 5 años. Se compararon tres grupos: resección inicial R0, R1 inicial convertido en R0 después de la re-resección y R1 inicial que permaneció como R1 después de la re-resección. Se excluyeron las resecciones de márgenes macroscópicamente positivos (R2).PRINCIPALES MEDIDAS DE RESULTADO:Supervivencia global a cinco años, supervivencia sin recidiva y recidiva local.RESULTADOS:Se analizaron un total de 267 pacientes (resección inicial R0 n = 94, R1 inicial convertido en R0 después de la re-resección n = 95, R1 inicial que permaneció como R1 después de la re-resección n = 78). La supervivencia global fue de 4,4 años para la resección inicial R0, 2,7 años para la R1 inicial convertida en R0 después de la re-resección y 2,9 años para la R1 inicial que permaneció como R1 después de la re-resección ( p = 0,01). La supervivencia libre de recurrencia fue de 3,0 años para la resección inicial R0 y de 1,8 años para el R1 inicial convertido en R0 después de la re-resección y el R1 inicial que permaneció como R1 después de la re-resección ( p ≤ 0,01). La supervivencia global no difirió para los pacientes con R1 y re-resección R1 o R0 ( p = 0,62). La supervivencia libre de recurrencia y la ausencia de recurrencia local no difirieron entre los grupos.LIMITACIONES:Población de pacientes heterogénea, restringida a aquellos que reciben radioterapia intraoperatoria.CONCLUSIONES:La re-resección de los márgenes microscópicamente positivos para obtener el estado R0 no parece proporcionar una ventaja de supervivencia significativa o prevenir la recurrencia local en pacientes sometidos a cirugía y radioterapia intraoperatoria para el cáncer de recto localmente recurrente. Consulte Video Resumen en http://links.lww.com/DCR/B886 . (Traducción-Dr. Daniel Guerra ).

Hepatocellular carcinoma downstaging for liver transplantation in the era of systemic combined therapy with anti-VEGF/TKI and immunotherapy.

Hepatocellular carcinoma remains a global health challenge affecting close to 1 million cases yearly. Liver transplantation provides the best long-term outcomes for those meeting strict criteria. Efforts have been made to expand these criteria, whereas others have attempted downstaging approaches. Although locoregional approaches to downstaging are appealing and have demonstrated efficacy, limitations and challenges exists including poor imaging modality to assess response and appropriate endpoints along the process. Recent advances in systemic treatments including immune checkpoint inhibitors alone or in combination with tyrosine kinase inhibitors have prompted the discussion regarding their role for downstaging disease prior to transplantation. Here, we provide a review of prior locoregional approaches for downstaging, new systemic agents and their role for downstaging, and finally, key and critical considerations of the assessment, endpoints, and optimal designs in clinical trials to address this key question.