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Purpose:In this prospective trial, we sought to assess the feasibility of concurrent administration of ipilimumab and radiation as adjuvant, neoadjuvant, or definitive therapy in patients with regionally advanced melanoma.Patients and Methods:Twenty-four patients in two cohorts were enrolled and received ipilimumab at 3 mg/kg every 3 weeks for four doses in conjunction with radiation; median dose was 4,000 cGy (interquartile range, 3,550–4,800 cGy). Patients in cohort 1 were treated adjuvantly; patients in cohort 2 were treated either neoadjuvantly or as definitive therapy.Results:Adverse event profiles were consistent with those previously reported with checkpoint inhibition and radiation. For the neoadjuvant/definitive cohort, the objective response rate was 64% (80% confidence interval, 40%–83%), with 4 of 10 evaluable patients achieving a radiographic complete response. An additional 3 patients in this cohort had a partial response and went on to surgical resection. With 2 years of follow-up, the 6-, 12-, and 24-month relapse-free survival for the adjuvant cohort was 85%, 69%, and 62%, respectively. At 2 years, all patients in the neoadjuvant/definitive cohort and 10/13 patients in the adjuvant cohort were still alive. Correlative studies suggested that response in some patients were associated with specific CD4+ T-cell subsets.Conclusions:Overall, concurrent administration of ipilimumab and radiation was feasible, and resulted in a high response rate, converting some patients with unresectable disease into surgical candidates. Additional studies to investigate the combination of radiation and checkpoint inhibitor therapy are warranted.

Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver tumor and remains a fatal malignancy in the majority of patients. Approximately 20%-30% of patients are eligible for resection, which is considered the only potentially curative treatment; and, after resection, a median survival of 53 months has been reported when sequenced with adjuvant capecitabine. For the 70%-80% of patients who present with locally unresectable or distant metastatic disease, systemic therapy may delay progression, but survival remains limited to approximately 1 year. For the past decade, doublet chemotherapy with gemcitabine and cisplatin has been considered the most effective first-line regimen, but results from the recent use of triplet regimens and even immunotherapy may shift the paradigm. More effective treatment strategies, including those that combine systemic therapy with locoregional therapies like radioembolization or hepatic artery infusion, have also been developed. Molecular therapies, including those that target fibroblast growth factor receptor and isocitrate dehydrogenase, have recently received US Food and Drug Administration approval for a defined role as second-line treatment for up to 40% of patients harboring these actionable genomic alterations, and whether they should be considered in the first-line setting is under investigation. Furthermore, as the oncology field seeks to expand indications for immunotherapy, recent data demonstrated that combining durvalumab with standard cytotoxic therapy improved survival in patients with ICC. This review focuses on the current and future strategies for ICC treatment, including a summary of the primary literature for each treatment modality and an algorithm that can be used to drive a personalized and multidisciplinary approach for patients with this challenging malignancy.

The NCCN Guidelines for Hepatobiliary Cancers focus on the screening, diagnosis, staging, treatment, and management of hepatocellular carcinoma (HCC), gallbladder cancer, and cancer of the bile ducts (intrahepatic and extrahepatic cholangiocarcinoma). Due to the multiple modalities that can be used to treat the disease and the complications that can arise from comorbid liver dysfunction, a multidisciplinary evaluation is essential for determining an optimal treatment strategy. A multidisciplinary team should include hepatologists, diagnostic radiologists, interventional radiologists, surgeons, medical oncologists, and pathologists with hepatobiliary cancer expertise. In addition to surgery, transplant, and intra-arterial therapies, there have been great advances in the systemic treatment of HCC. Until recently, sorafenib was the only systemic therapy option for patients with advanced HCC. In 2020, the combination of atezolizumab and bevacizumab became the first regimen to show superior survival to sorafenib, gaining it FDA approval as a new frontline standard regimen for unresectable or metastatic HCC. This article discusses the NCCN Guidelines recommendations for HCC.

Purpose Stereotactic body radiation therapy (SBRT) and stereotactic ablative body radiation therapy is being increasingly used for pancreatic cancer (PCa), particularly in patients with locally advanced and borderline resectable disease. A wide variety of dose fractionation schemes have been reported in the literature. This HyTEC review uses tumor control probability models to evaluate the comparative effectiveness of the various SBRT treatment regimens used in the treatment of patients with localized PCa. Methods and Materials A PubMed search was performed to review the published literature on the use of hypofractionated SBRT (usually in 1-5 fractions) for PCa in various clinical scenarios (eg, preoperative [neoadjuvant], borderline resectable, and locally advanced PCa). The linear quadratic model with α/β= 10 Gy was used to address differences in fractionation. Logistic tumor control probability models were generated using maximum likelihood parameter fitting. Results After converting to 3-fraction equivalent doses, the pooled reported data and associated models suggests that 1-year local control (LC) without surgery is ≈79% to 86% after the equivalent of 30 to 36 Gy in 3 fractions, showing a dose response in the range of 25 to 36 Gy, and decreasing to less than 70% 1-year LC at doses below 24 Gy in 3 fractions. The 33 Gy in 5 fraction regimen (Alliance A021501) corresponds to 28.2 Gy in 3 fractions, for which the HyTEC pooled model had 77% 1-year LC without surgery. Above an equivalent dose of 28 Gy in 3 fractions, with margin-negative resection the 1-year LC exceeded 90%. Conclusions Pooled analyses of reported tumor control probabilities for commonly used SBRT dose-fractionation schedules for PCa suggests a dose response. These findings should be viewed with caution given the challenges and limitations of this review. Additional data are needed to better understand the dose or fractionation-response of SBRT for PCa.

Purpose:In this prospective trial, we sought to assess the feasibility of concurrent administration of ipilimumab and radiation as adjuvant, neoadjuvant, or definitive therapy in patients with regionally advanced melanoma.Patients and Methods:Twenty-four patients in two cohorts were enrolled and received ipilimumab at 3 mg/kg every 3 weeks for four doses in conjunction with radiation; median dose was 4,000 cGy (interquartile range, 3,550–4,800 cGy). Patients in cohort 1 were treated adjuvantly; patients in cohort 2 were treated either neoadjuvantly or as definitive therapy.Results:Adverse event profiles were consistent with those previously reported with checkpoint inhibition and radiation. For the neoadjuvant/definitive cohort, the objective response rate was 64% (80% confidence interval, 40%–83%), with 4 of 10 evaluable patients achieving a radiographic complete response. An additional 3 patients in this cohort had a partial response and went on to surgical resection. With 2 years of follow-up, the 6-, 12-, and 24-month relapse-free survival for the adjuvant cohort was 85%, 69%, and 62%, respectively. At 2 years, all patients in the neoadjuvant/definitive cohort and 10/13 patients in the adjuvant cohort were still alive. Correlative studies suggested that response in some patients were associated with specific CD4+ T-cell subsets.Conclusions:Overall, concurrent administration of ipilimumab and radiation was feasible, and resulted in a high response rate, converting some patients with unresectable disease into surgical candidates. Additional studies to investigate the combination of radiation and checkpoint inhibitor therapy are warranted.

Purpose: We previously reported on the clinical outcomes of treating oligometastases with radiation using an elective simultaneous integrated boost technique (SIB), delivering higher doses to known metastases and reduced doses to adjacent bone or nodal basins. Here we compare outcomes of oligometastases receiving radiation targeting metastases alone (MA) versus those treated via an SIB. Methods: Oligometastatic patients with ≤5 active metastases treated with either SIB or MA radiation at two institutions from 2013 to 2019 were analyzed retrospectively for treatment-related toxicity, pain control, and recurrence patterns. Tumor metastasis control (TMC) was defined as an absence of progression in the high dose planning target volume (PTV). Marginal recurrence (MR) was defined as recurrence outside the elective PTV but within the adjacent bone or nodal basin. Distant recurrence (DR) was defined as any recurrence that is not within the PTV or surrounding bone or nodal basin. The outcome rates were estimated using the Kaplan–Meier method and compared between the two techniques using the log-rank test. Results: 101 patients were treated via an SIB to 90 sites (58% nodal and 42% osseous) and via MA radiation to 46 sites (22% nodal and 78% osseous). The median follow-up among surviving patients was 24.6 months (range 1.4–71.0). Of the patients treated to MA, the doses ranged from 18 Gy in one fraction (22%) to 50 Gy in 10 fractions (50%). Most patients treated with an SIB received 50 Gy to the treated metastases and 30 Gy to the elective PTV in 10 fractions (88%). No acute grade ≥3 toxicities occurred in either cohort. Late grade ≥3 toxicity occurred in 3 SIB patients (vocal cord paralysis and two vertebral body compression), all related to the high dose PTV and not the elective volume. There was similar crude pain relief between cohorts. The MR-free survival rate at 2 years was 87% (95% CI: 70%, 95%) in the MA group and 98% (95% CI: 87%, 99%) in the SIB group (p = 0.07). The crude TMC was 89% (41/46) in the MA group and 94% (85/90) in the SIB group. There were no significant differences in DR-free survival (65% (95% CI: 55–74%; p = 0.24)), disease-free survival (60% (95% CI: 40–75%; p = 0.40)), or overall survival (88% (95% CI: 73–95%; p = 0.26)), between the MA and SIB cohorts. Conclusion: Both SIB and MA irradiation of oligometastases achieved high rates of TMC and similar pain control, with a trend towards improved MR-free survival for oligometastases treated with an SIB. Further investigation of this technique with prospective trials is warranted.

Objectives Expert abstraction of acute toxicities is critical in oncology research but is labor-intensive and variable. We assessed the accuracy of a natural language processing (NLP) pipeline to extract symptoms from clinical notes compared to physicians. Materials and Methods Two independent reviewers identified present and negated National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0 symptoms from 100 randomly selected notes for on-treatment visits during radiation therapy with adjudication by a third reviewer. A NLP pipeline based on Apache clinical Text Analysis Knowledge Extraction System was developed and used to extract CTCAE terms. Accuracy was assessed by precision, recall, and F1. Results The NLP pipeline demonstrated high accuracy for common physician-abstracted symptoms, such as radiation dermatitis (F1 0.88), fatigue (0.85), and nausea (0.88). NLP had poor sensitivity for negated symptoms. Conclusion NLP accurately detects a subset of documented present CTCAE symptoms, though is limited for negated symptoms. It may facilitate strategies to more consistently identify toxicities during cancer therapy.

PURPOSE Patients undergoing outpatient radiotherapy (RT) or chemoradiation (CRT) frequently require acute care (emergency department evaluation or hospitalization). Machine learning (ML) may guide interventions to reduce this risk. There are limited prospective studies investigating the clinical impact of ML in health care. The objective of this study was to determine whether ML can identify high-risk patients and direct mandatory twice-weekly clinical evaluation to reduce acute care visits during treatment. PATIENTS AND METHODS During this single-institution randomized quality improvement study (ClinicalTrials.gov identifier: NCT04277650 ), 963 outpatient adult courses of RT and CRT started from January 7 to June 30, 2019, were evaluated by an ML algorithm. Among these, 311 courses identified by ML as high risk (> 10% risk of acute care during treatment) were randomized to standard once-weekly clinical evaluation (n = 157) or mandatory twice-weekly evaluation (n = 154). Both arms allowed additional evaluations on the basis of clinician discretion. The primary end point was the rate of acute care visits during RT. Model performance was evaluated using receiver operating characteristic area under the curve (AUC) and decile calibration plots. RESULTS Twice-weekly evaluation reduced rates of acute care during treatment from 22.3% to 12.3% (difference, −10.0%; 95% CI, −18.3 to −1.6; relative risk, 0.556; 95% CI, 0.332 to 0.924; P = .02). Low-risk patients had a 2.7% acute care rate. Model discrimination was good in high- and low-risk patients undergoing standard once-weekly evaluation (AUC, 0.851). CONCLUSION In this prospective randomized study, ML accurately triaged patients undergoing RT and CRT, directing clinical management with reduced acute care rates versus standard of care. This prospective study demonstrates the potential benefit of ML in health care and offers opportunities to enhance care quality and reduce health care costs.

Purpose The National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0 is the standard for oncology toxicity encoding and grading, despite limited validation. We assessed interrater reliability (IRR) in multireviewer toxicity identification. Methods and Materials Two reviewers independently reviewed 100 randomly selected notes for weekly on-treatment visits during radiation therapy from the electronic health record. Discrepancies were adjudicated by a third reviewer for consensus. Term harmonization was performed to account for overlapping symptoms in CTCAE. IRR was assessed based on unweighted and weighted Cohen’s kappa coefficients. Results Between reviewers, the unweighted kappa was 0.68 (95% confidence interval, 0.65-0.71) and the weighted kappa was 0.59 (0.22-1.00). IRR was consistent between symptoms noted as present or absent with a kappa of 0.6 (0.66-0.71) and 0.6 (0.65-0.69), respectively. Conclusions Significant discordance suggests toxicity identification, particularly retrospectively, is a complex and error-prone task. Strategies to minimize IRR, including training and simplification of the CTCAE criteria, should be considered in trial design and future terminologies.

Background: Adjuvant chemotherapy (AC) after chemoradiation (CRT) and surgery for locoregionally advanced rectal cancer (LARC) is a standard of care in the United States. This study examined the role, optimal regimen, and duration of AC using data from the largest integrated health system in the United States. Patients and Methods: Using the Veterans Affairs Central Cancer Registry, patients with stage II–III rectal cancer diagnosed in 2001 through 2011 who received neoadjuvant CRT and surgery with or without AC were identified. Kaplan-Meier analysis, log-rank tests, and propensity score (PS) adjustment analysis were used to assess survival. Results: A total of 866 patients were identified; 417 received AC and 449 did not (observation [OBS] group). Median follow-up was 109 months. Median disease-specific survival (DSS) was not reached. Six-year DSS was 73.7%; 79.5% for the AC group versus 68.0% for the OBS group. PS-matched analysis for DSS favored AC (P=.0002). Median overall survival (OS) was 90.8 months. Six-year OS was 56.7%; 64.3% for AC versus 49.6% for OBS. In PS-matched analysis, median OS was 117.4 months for AC and 74.3 months for OBS (PP=.023). No difference in DSS or OS was seen with single-agent versus multiagent AC. Conclusions: In this population of patients with LARC treated with neoadjuvant CRT and surgery, OS and DSS were improved among those treated with AC versus OBS. DSS benefits were seen with ≥4 months of AC. No additional benefit was observed with multiagent therapy. In the absence of phase III data, these findings support the use of AC for LARC.

176 Background: Response to neoadjuvant chemotherapy and radiation therapy in the treatment of locally advanced rectal cancer is heterogenous and prognostic of clinical outcomes, necessitating the need for predictive biomarkers to guide personalized treatment recommendations. Sensitivity to a given chemotherapy in patient-derived organoids predicts patient response to that chemotherapy, establishing it as a promising model for efforts to ascertain predictive biomarkers and personalize treatment decisions. This study assessed the feasibility of obtaining patient-derived rectal organoids from standard of care pre-treatment proctoscopy biopsies. Methods: In this clinical trial (NCT04371198), biopsies were obtained from patients with stage II rectal adenocarcinoma prior to receipt of neoadjuvant therapy. Tissue samples were mechanically and enzymatically dissociated to obtain a single cell suspension. Cells were then mixed with matrigel at a ratio of 2,000 cells:5 µL Matrigel in a 50ul dome and plated on a 24 well tissue culture plate with colorectal cancer organoid media at 37oC/5% CO2. Established patient-derived organoids were then used to perform drug screens with clinically-applicable chemotherapeutics including oxaliplatin, irinotecan and 5-FU, followed by high throughput drug screen using our recently published MicroOrganoSpheres platform using the NCI Approved Oncology Drugs Set VI* library. Results: Of the 20 patients enrolled, 17 (85%) patient-derived organoids were created from pre-treatment specimens. 15 (88%) of these samples were successfully established as defined by the ability to passage organoids for at least two passages. All established samples were used to perform standard of care drug screens and high throughout drug screens, which demonstrated differences in drug sensitivities among the samples. Moreover, within two weeks of receiving the sample, four established quickly enough to complete drug screening with oxaliplatin, SN38, and 5-Fluorouracil. Conclusions: These results demonstrate the feasibility of establishing patient-derived rectal organoids from biopsy specimens obtained by proctoscopy, and reinforce the utility of patient-derived organoids as a tractable ex vivo platform to personalize rectal cancer treatment. Planned future directions include in vitro determination of radiation therapy sensitivity as well as systematic assessment of the correlation between individual patients and their organoid model. Clinical trial information: NCT04371198 .

Objective. The purpose of this study was to investigate whether, compared with traditional criteria, the modified Response Evaluation Criteria in Solid Tumors version 1.1 for immune-based therapeutics (iRECIST) improves prediction of local tumor control and survival in patients with hepatocellular carcinoma (HCC) treated with stereotactic body radiotherapy (SBRT). Materials and Methods. Fifty-one HCC lesions (mean size, 3.1 cm) treated with SBRT in 41 patients (mean age, 67 years) were retrospectively included. Each patient underwent CT or MRI before SBRT and at least once after SBRT. Best overall response was categorized using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), iRECIST, World Health Organization (WHO) criteria, modified Response Evaluation Criteria in Solid Tumors (mRECIST), and European Association for the Study of the Liver (EASL) criteria. Lesions were then classified as local tumor control (i.e., stable disease, partial response, or complete response) or local treatment failure (i.e., progressive disease) by each tumor response criteria. Proportions of local tumor control were compared using the McNemar exact test. The 1-year overall survival was estimated using the Kaplan-Meier method. Results. The median follow-up after SBRT was 21.0 months. The local tumor control rate was 94.1% (48/51) by iRECIST, 88.2% (45/51) by RECIST 1.1, 72.5% (37/51) by WHO criteria, 80.4% (41/51) by mRECIST, and 72.5% (37/51) by EASL criteria. The local tumor control rate was significantly higher according to iRECIST compared with WHO (p = 0.0010) and EASL (p = 0.0225) criteria. The 1-year survival rate for patients with local tumor control according to iRECIST (86.4%) was higher (although not statistically significant) compared with the 1-year survival rate for patients with local tumor control according to the other response criteria. Conclusion. iRECIST may provide more robust interpretation of HCC response after SBRT, yielding improved prediction of local tumor control and 1-year survival rates compared with traditional criteria.

Hepatocellular carcinoma is a rising cause of morbidity and mortality in the USA and around the world. Surgical resection and liver transplantation are the preferred management strategies; however, less than 30% of patients are eligible for surgery. Stereotactic body radiation therapy is a promising local treatment option for non-surgical candidates. Local control rates between 95 and 100% have been reported at 1-2 years post-treatment, and classical radiation-induced liver disease described with conventional radiation is an unlikely complication from stereotactic radiotherapy. Enrollment in randomized trials will be essential in establishing the role of stereotactic radiation in treatment paradigms for hepatocellular carcinoma.

Background Although the management of localized anal canal squamous cell carcinomas is well established, the role of pelvic chemoradiation (CRT) in the treatment of patients presenting with synchronous metastatic (stage IV) disease is poorly defined. This study used a national cancer database to compare the overall survival (OS) rates of patients with synchronous metastatic disease receiving CRT to the pelvis and patients treated with chemotherapy (CT) alone. Methods This study included adult patients with anal canal squamous cell carcinomas presenting with synchronous metastases diagnosed from 2004 to 2012. Multiple imputation and 2:1 propensity score matching were used to create a matched data set for testing. The proportional hazards model was used to estimate the hazard ratio (HR) for the effect of the treatment group on OS. With only patients in the matched data set, the OS of the treatment groups was estimated with the Kaplan-Meier method by treatment group. Results This study started with an unmatched data set of 978 patients, and 582 patients were selected for the matched data set: 388 in the CRT group and 194 in the CT-alone group. The HR for the group effect was 0.75 (95% confidence interval [CI], 0.61-0.92; P = .006). The median OS was 21.1 months in the CRT group (95% CI, 17.4-24.0 months) and 14.6 months in the CT group (95% CI, 12.2-18.4 months). The corresponding 5-year OS rates were 23% (95% CI, 18%-28%) and 14% (95% CI, 7%-21%), respectively. Conclusions In this large series analyzing OS in patients with stage IV anal cancer, CRT was associated with improved OS in comparison with CT alone. Because of the lack of prospective data in this setting, this evidence will help to guide treatment approaches in this group of patients.

Standard therapy for locally advanced rectal cancer includes neoadjuvant chemoradiation and surgery. Complete response (CR) rates after chemoradiation can be as high as 29%, suggesting that nonoperative management (NOM) may be reasonable with appropriately selected patients. We sought to identify potential NOM candidates.Using the Veterans Administration Central Cancer Registry, patients with stage II to III rectal cancer receiving chemoradiation with or without subsequent surgery were identified. Clinical CR (cCR) was assessed by physical examination, endoscopy, or imaging. Kaplan-Meier and log-rank tests were used to assess survival; multivariate analysis was performed using Cox proportional hazards.A total of 1313 patients were identified. Of these, 313 received chemoradiation alone (CRT cohort); 1000 received chemoradiation followed by surgery (CRT + S cohort). Median follow-up was 67.2 months. Median overall survival (OS) was 68.5 months. Median OS was 30.6 months for CRT and 89.3 months for CRT + S (P .001). Median disease-specific survival (DSS) was 44.8 months for CRT and not reached (NR) for CRT + S (P .001). Sixty-five CRT patients (20.8%) had a cCR. Median OS for CRT cCR patients was 73.5 months (P = .128 vs CRT + S); median DSS was NR (P = .161 vs CRT + S). One hundred thirty-seven (10.5%) CRT + S patients had a pathologic CR (pCR). Median OS with pCR was 133.7 months (P .001 vs CRT cCR), and median DSS was NR (P = .276 vs CRT cCR).CRT patients with cCR had similar OS and DSS versus CRT + S patients and similar DSS versus CRT + S patients with a pCR. This suggests that patients with locally advanced rectal cancer with a cCR to CRT have an excellent prognosis and may be candidates for organ preservation.

Purpose/objective(s) Management of HCC without surgical resection or transplantation is poorly defined with no standard. Stereotactic body radiation therapy (SBRT) or hypofractionated image-guided radiotherapy (HIGRT), is an evolving, non-invasive, therapeutic option for patients with HCC delivering ablative doses with modest toxicity. Materials/methods We retrospectively identified all patients with unresectable, non-metastatic HCC treated with SBRT/HIGRT who presented to our University and Veterans Affairs (VA) radiation oncology departments from 2013 to 2019. Primary study endpoints included freedom from local progression, progression free survival, overall survival, and treatment-related toxicity. Results 149 patients were included in our analysis with median delivered radiation dose of 50 Gy in 5 fractions. This included a total of 172 treatment courses, as 21 patients received more than one course (19 patients received 2 courses; 2 patients received 3 courses). Twenty-two of the re-treatment courses were to previously unirradiated lesions, while one course was delivered to a previously treated lesion exhibiting local progression. Sixty-nine percent (69%) of patients were Child-Pugh A and 89% had a baseline ALBI grade of 1-2 prior to treatment. A majority of patients (59%) had a single lesion with a median size of 2.70 cm (Q1 2.00, Q3 3.95). Fifty-seven percent (57%) of patients received a biologically effective dose (BEDα/β = 10) of at least 75 Gy and 48% of patients had undergone prior liver-directed therapy. All patients completed their intended treatment course with 1 patient (0.7%) experiencing Grade 3+ acute and 4 patients (2.6%) experiencing Grade 3+ late toxicities. Fifteen treatment courses (8.7%) resulted in non-classical radiation-induced liver disease (RILD), defined as an increase of 2 or more points in Child-Pugh score following radiation. With median follow up of 40 months, median overall survival was 25 months (95% CI 18-30 months). The 2-year freedom from local progression was 75% (95% CI 65-83%) overall, 64% (95% CI 48-77%) among patients who received BED ≤75 Gy and 86% (95% CI 72-93%) among those who received BED > 75 Gy. Median progression free survival was not reached. During the study period, 8.1% of patients developed regional nodal progression and 18.8% developed distant metastatic disease (42.9% osseous, 50.0% lung, 46.4% soft tissue/peritoneal/other involvement; multiple patients with more than one site of metastatic involvement). Conclusion SBRT/HIGRT results in high rates of local control with minimal treatment related toxicities. Randomized, prospective trials should seek to establish SBRT/HIGRT as a standard local therapeutic option for patients with unresectable, non-metastatic HCC.

Background: Colorectal cancer is the third most common cancer in the United States and associated with significant morbidity and mortality. Within colorectal cancer histologies, squamous cell carcinomas (SCC) are rare compared to adenocarcinomas, with only about 200 cases reported to date. Because rectal SCC is rarely encountered, there is a lack of literature and clinical consensus surrounding its optimal treatment approach. Staging and management of SCC can be partly analogous to both rectal adenocarcinoma and anal canal SCC, which leads to a dilemma in how to best approach these patients. As large randomized prospective trials are unrealistic in the setting of this rare malignancy, this study evaluates an institutional experience and reviews the existing literature to help guide future management approaches. Methods: This retrospective study compared various treatment regimens for rectal SCC patients treated at Duke University Medical Center from January 1, 1980 through December 31, 2016. Patients ≥18 years old with histologically confirmed, nonmetastatic rectal SCC were included. Due to small sample size, all statistical analyses were descriptive. For our systematic review, a comprehensive search of PubMed from 1933 to March 2018 was performed, with selected articles referenced to ensure all relevant publications were included. A qualitative analysis was performed to examine patient diagnoses, treatments, and disease- and treatment-related outcomes. Results: Eight patients were included. Three patients underwent initial, curative attempt surgery and two of these patients required colostomy. With follow-up ranging from 7.1 to 31.5 months, one patient was alive with no evidence of disease while two developed local/regional recurrences. Five patients received definitive chemoradiation. Of these, three patients developed local/regional and/or metastatic recurrence. Two patients achieved complete response on imaging and currently remain disease-free (follow-up of 31.5 and 33.6 months). Conclusions: Although the review of our institutional experience is limited by small numbers, our analysis suggests that definitive chemoradiation therapy is the preferred treatment approach to rectal SCC based on improved disease-related outcomes, sphincter preservation and morbidity profiles. This conclusion is supported by a systematic literature review.

Purpose: To perform a multi-institutional analysis of patients with synchronous prostate and rectosigmoid cancers.Materials and Methods: A retrospective review of Duke University and Durham Veterans Affairs Medical Center records was performed for men with both prostate and rectosigmoid adenocarcinomas from 1988 to 2017. Synchronous presentation was defined as symptoms, diagnosis, or treatment of both cancers within 12 months of each other. The primary study endpoint was overall survival. Univariate and multivariable Cox regression was performed.Results: Among 31,883 men with prostate cancer, 330 (1%) also had rectosigmoid cancer and 54 (16%) of these were synchronous. Prostate cancer was more commonly the initial diagnosis (59%). Fifteen (28%) underwent prostatectomy or radiotherapy before an established diagnosis of rectosigmoid cancer. Stage I, II–III, or IV rectosigmoid cancer was present in 26, 57, and 17% of men, respectively. At a median follow-up of 43 months, there were 18 deaths due rectosigmoid cancer and two deaths due to prostate cancer. Crude late grade ≥3 toxicities include nine (17%) gastrointestinal and six (11%) genitourinary. Two anastomotic leaks following low anterior resection occurred in men who received a neoadjuvant radiotherapy prostate dose of 70.6–76.4 Gy. Rectosigmoid cancer stages II–III (HR 4.3, p = 0.02) and IV (HR 16, p < 0.01) as well as stage IV prostate cancer (HR 31, p < 0.01) were associated with overall survival on multivariable analysis.Conclusions: Synchronous rectosigmoid cancer is a greater contributor to mortality than prostate cancer. Men aged ≥45 with localized prostate cancer should undergo colorectal cancer screening prior to treatment to evaluate for synchronous rectosigmoid cancer.

Pancreas stereotactic body radiotherapy treatment planning requires planners to make sequential, time consuming interactions with the treatment planning system (TPS) to reach the optimal dose distribution. We seek to develop a reinforcement learning (RL)-based planning bot to systematically address complex tradeoffs and achieve high plan quality consistently and efficiently. The focus of pancreas SBRT planning is finding a balance between organs-at-risk sparing and planning target volume (PTV) coverage. Planners evaluate dose distributions and make planning adjustments to optimize PTV coverage while adhering to OAR dose constraints. We have formulated such interactions between the planner and the TPS into a finite-horizon RL model. First, planning status features are evaluated based on human planner experience and defined as planning states. Second, planning actions are defined to represent steps that planners would commonly implement to address different planning needs. Finally, we have derived a reward system based on an objective function guided by physician-assigned constraints. The planning bot trained itself with 48 plans augmented from 16 previously treated patients and generated plans for 24 cases in a separate validation set. All 24 bot-generated plans achieve similar PTV coverages compared to clinical plans while satisfying all clinical planning constraints. Moreover, the knowledge learned by the bot can be visualized and interpreted as consistent with human planning knowledge, and the knowledge maps learned in separate training sessions are consistent, indicating reproducibility of the learning process., Comment: 13 pages, 5 figures, and a table. Submitted to International Journal of Radiation Oncology Biology Physics

Purpose Patients undergoing radiotherapy (RT) or chemoradiotherapy (CRT) may require emergency department evaluation or hospitalization. Early identification may direct preventative supportive care, improving outcomes and reducing health care costs. We developed and evaluated a machine learning (ML) approach to predict these events. Methods A total of 8,134 outpatient courses of RT and CRT from a single institution from 2013 to 2016 were identified. Extensive pretreatment data were programmatically extracted and processed from the electronic health record (EHR). Training and internal validation cohorts were randomly generated (3:1 ratio). Gradient tree boosting (GTB), random forest, support vector machine, and least absolute shrinkage and selection operator logistic regression approaches were trained and internally validated based on area under receiver operating characteristic (AUROC) curve. The most predictive ML approach was also evaluated using only disease- and treatment-related factors to assess predictive gain of extensive EHR data. Results All methods had high predictive accuracy, particularly GTB (validation AUROC, 0.798). Extensive EHR data beyond disease and treatment information improved accuracy (delta AUROC, 0.056). A Youden-based cutoff corresponded to validation sensitivity of 81.0% (175 of 216 courses with events) and specificity of 67.3% (1,218 of 1811 courses without events). Interpretability is an important advantage of GTB. Variable importance identified top predictive factors, including treatment (planned RT and systemic therapy), pretreatment encounters (emergency department visits and admissions in the year before treatment), vital signs (weight loss and pain score in the year before treatment), and laboratory values (albumin level at weeks before treatment). Conclusion ML predicts emergency visits and hospitalization during cancer therapy. Incorporating predictions into clinical care algorithms may help direct personalized supportive care, improve quality of care, and reduce costs. A prospective trial investigating ML-assisted direction of increased clinical assessments during RT is planned.

Purpose Imaging parameters from 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) before and after chemoradiation therapy (CRT) for anal canal cancer correlate with clinical outcomes. This prospective, hypothesis-generating pilot study investigates the relationship between interim PET imaging during CRT for anal canal cancer and clinical outcome. Methods and Materials From June 2012 to August 2015, 30 patients with anal canal cancer were enrolled in a prospective clinical study of PET prior to and during CRT after ∼30 Gy. PET parameters of the primary site included maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). MTV and TLG were calculated based on 40% SUVmax (MTV40, TLG40) or SUV 2.5 (MTV2.5, TLG2.5) thresholds for pretreatment and interim images. Absolute and change in PET parameters were assessed for association with freedom from local and regional recurrence (FFLR) using single-predictor Cox regression models. Local and regional recurrence were primary and nodal (in-field) recurrences, respectively. Results Twenty-three patients were eligible for analysis. Patients were excluded with nonsquamous cell histology, recurrent anal cancer, and incomplete studies due to treatment toxicity or patient choice. Median follow-up was 2.5 years. Pretreatment MTV40 (HR 1.4 [95% CI 1.02-2.05]), interim MTV2.5 (1.4 [1.04-1.89]), and interim TLG2.5 (1.1 [1.01-1.21]) were associated with FFLR. Conclusions In this prospective pilot study, interim PET parameters were associated with FFLR. These results warrant further investigation assessing the value of interim PET as a biomarker of response in the treatment of patients with anal cancer.

This review summarizes the relevant literature on the use of total neoadjuvant therapy (TNT) for patients with locally advanced rectal cancer. It highlights the most notable literature published and briefly discusses future directions. Recent randomized trials evaluating TNT show improved rates of pathologic complete response and patient treatment tolerance with this approach. The rationale for TNT includes the poor patient tolerance of adjuvant chemotherapy and the persistent risk of distant disease in patients with locally advanced rectal cancer, despite improvements in local control. Randomized trials have focused on short-term pathologic endpoints. Ongoing phase 3 trials are evaluating long-term disease-related outcomes, allowing for a more thorough evaluation of this treatment paradigm. TNT may also facilitate organ preservation in appropriately selected patients.

Hepatocellular carcinoma (HCC) is increasing in incidence and mortality. Although the prognosis remains poor, long-term survival has improved from 3% in 1970 to an 18% 5-year survival rate today. This is likely because of the introduction of well tolerated, oral antiviral therapies for hepatitis C. Curative options for patients with HCC are often limited by underlying liver dysfunction/cirrhosis and medical comorbidities. Less than one-third of patients are candidates for surgery, which is the current gold standard for cure. Nonsurgical treatments include embolotherapies, percutaneous ablation, and ablative radiation. Technological advances in radiation delivery in the past several decades now allow for safe and effective ablative doses to the liver. Conformal techniques allow for both dose escalation to target volumes and normal tissue sparing. Multiple retrospective and prospective studies have demonstrated that hypofractionated image-guided radiation therapy, used as monotherapy or in combination with other liver-directed therapies, can provide excellent local control that is cost effective. Therefore, as the HCC treatment paradigm continues to evolve, ablative radiation treatment has moved from a palliative treatment to both a "bridge to transplant" and a definitive treatment.

Objective: To design a deep transfer learning framework for modeling fluence map predictions for stereotactic body radiation therapy (SBRT) of adrenal cancer and similar sites that usually have a small number of cases. Approach: We developed a transfer learning framework for adrenal SBRT planning that leverages knowledge in a pancreas SBRT planning model. Treatment plans from the two sites had different dose prescriptions and beam settings but both prioritized gastrointestinal sparing. A base framework was first trained with 100 pancreas cases. This framework consists of two convolutional neural networks (CNN), which predict individual beam doses (BD-CNN) and fluence maps (FM-CNN) sequentially for 9-beam intensity-modulated radiation therapy (IMRT) plans. Forty-five adrenal plans were split into training/validation/test sets with the ratio of 20/10/15. The base BD-CNN was re-trained with transfer learning using 5/10/15/20 adrenal training cases to produce multiple candidate adrenal BD-CNN models. The base FM-CNN was directly used for adrenal cases. The deep learning (DL) plans were evaluated by several clinically relevant dosimetric endpoints, producing a percentage score relative to the clinical plans. Main results: Transfer learning significantly reduced the number of training cases and training time needed to train such a DL framework. The adrenal transfer learning model trained with 5/10/15/20 cases achieved validation plan scores of 85.4/91.2/90.7/89.4, suggesting that model performance saturated with 10 training cases. Meanwhile, a model using all 20 adrenal training cases without transfer learning only scored 80.5. For the final test set, the 5/10/15/20-case models achieved scores of 73.5/75.3/78.9/83.3. Significance: It is feasible to use deep transfer learning to train an IMRT fluence prediction framework. This technique could adapt to different dose prescriptions and beam configurations. This framework potentially enables DL modeling for clinical sites that have a limited dataset, either due to few cases or due to rapid technology evolution.

PURPOSE/OBJECTIVE(S) Radiation is increasingly used to treat oligometastatic patients (OM). Following metastasis directed radiation therapy, progression in nearby nodal basins or bones is common. We previously reported clinical outcomes of OM treated with an elective simultaneous integrated boost (SIB) technique delivering higher doses to known metastases and reduced doses to adjacent bones/nodal basins. Here we compare outcomes of OM receiving radiation to metastases alone (MA) versus those treated via an SIB. We hypothesized that use of SIB would maintain treated metastasis control (TMC) while reducing MR. MATERIALS/METHODS OM patients with ≤5 active metastases treated with either SIB or MA at our IRB approved sites from 2013-2018 were analyzed for toxicities, pain control, and recurrence patterns. TMC was defined as absence of progression in high dose planning target volume (PTV). Marginal recurrence (MR) was defined as recurrence outside elective PTV, but within the adjacent bone or nodal chain. Distant recurrence (DR) was defined as any recurrence outside of the treatment PTVs not meeting other criteria. Outcome rates were estimated using the Kaplan-Meier method. Patients treated with the two techniques were compared using the log rank test. RESULTS 101 patients were treated to 90 SIB (58% nodal and 42% osseous) and 46 MA (22% nodal and 78% osseous) sites. The most common primary tumors were prostate (37%), lung (15%), and breast (7%). Median follow up among surviving patients was 24.6 months (range 1.4-71.0). Of the MA treated patients, doses ranged from 18 Gy in 1 fraction (22%) to 50 Gy in 10 fractions (50%). Most patients treated with SIB received 50 Gy to the treated metastases and 30 Gy to the elective PTV in 10 fractions (88%). No patients in either cohort experienced acute grade ≥3 toxicity. Late grade ≥3 toxicity occurred in 3 SIB patients (vocal cord paralysis n = 1, vertebral body compression n = 2) and no MA patients. There was similar crude pain relief between cohorts: 82% with MA (9/11 patients reporting improved pain) and 86% with SIB (19/22). Crude MR were more frequent in the MA group 13% (n = 6) compared to SIB group 2% (n = 2). MR-free survival at 2 years was 87% (95% CI: 70%, 95%) in the MA group and 98% (95% CI: 87%, 99%) in the SIB group (P = 0.07). Crude TMC was 89% (41/46) in the MA group and 94% (85/90) in the SIB group. There were no significant differences found in DR-free survival (P = 0.24) or Disease-free survival (P = 0.4) and Overall survival (P = 0.26) between MA and SIB cohorts. CONCLUSION Both SIB and MA irradiation of OM achieved high rates of TMC and similar pain control, with a trend towards improved MR-free survival for OM treated with SIB. Although more late grade 3 toxicities were seen in the SIB cohort, these were mechanistically related to the high dose PTV and not the elective volume, with differences in treated metastasis location/characteristics. Further investigation of this technique with prospective trials is warranted.

PURPOSE/OBJECTIVE(S) Mortality prediction is critical to appropriate cancer care planning. This has become a topic of interest, with machine learning (ML) tools demonstrating accurate binary predictions for mortality at specific time points. There are limited prospective data validating the clinical utility of health care ML tools. We previously developed a ML algorithm which predicts risk of acute care (ER visits or hospitalizations). SHIELD-RT was a randomized controlled study which demonstrated that a ML algorithm could direct supplemental clinic visits to reduce the rate of acute care during RT from 22% to 12%. While the algorithm was trained for acute care visits, we sought to determine whether ML risk would facilitate multiple clinical uses through survival prediction in this prospective study. MATERIALS/METHODS Patients who initiated RT from 1/7/2019-6/30/19 at a single institution were evaluated during the first week of treatment by the electronic health record-based ML algorithm. High risk patients (> 10% risk of acute visit) were randomized to standard weekly evaluations (S) or twice weekly evaluations (TW). Patient, disease, and treatment factors were collected prospectively. Survival was recorded retrospectively. Unadjusted OS was estimated with the Kaplan Meier method and compared between arms with the log rank test. Cox proportional hazards models were used to estimate the association of covariates with OS after adjustment for study arm. Hazard ratios (HRs) and 95% confidence intervals (CIs) are reported. RESULTS Patients undergoing 311 distinct courses were randomized to S (n = 157) or TW (n = 154) evaluations. The 1-year OS was similar for those who underwent S (58%, 95% CI 50%-65%) or TW (66%, 95% CI 58%-73%) evaluations, P = 0.35. ML risk on a continuous basis was significantly associated with survival (HR 4.27, 95% CI 0.98-18.6, P = 0.05). Other factors associated with OS included age (HR 1.01, 95% CI 1.00-1.03, P = 0.04), palliative treatment vs curative treatment (HR 6.59 (95% CI 4.62-9.41, < 0.001), widely metastatic disease vs no metastatic disease (HR 6.86, 95% CI 4.74-9.92, P < 0.001). Treatment of certain disease sites were also associated with OS: brain metastases (HR 5.00, 95% CI 3.16-7.93, P < 0.001), bone metastases (HR 4.69, 95% CI 3.09-7.12, P < 0.001), thoracic (HR 2.44, 95% CI 1.61-3.7, P < 0.001), head and neck cancer (HR 0.44, 95% CI 0.22-0.91, P = 0.03), genitourinary cancer (HR 0.32, 95% CI 0.12-0.85, P = 0.02). Admission during RT + 15 days was associated with decreased OS (HR 2.32, 95% CI 1.58-3.40, P < 0.001). CONCLUSION Our ML algorithm, developed to predict acute care, also predicted OS. This supports the correlation between the two event types and demonstrates the utility of ML to provide multiple predictive functions. Implementation of predictive ML algorithms into oncology clinical workflows may aid in prognostication to guide personalized patient care and influence treatment decisions. (NCT03775265).

Purpose/Objective(s) To date there is no clear standard non-surgical therapeutic option for HCC patients. Ablative radiation therapy (SBRT/HIGRT) is an emerging non-invasive treatment for patients with HCC. However, there is concern about the risk for radiation-induced liver toxicity following radiation in patients with decompensated liver function (Child-Pugh B/C). Materials/Methods We retrospectively identified all patients with unresectable, non-metastatic HCC treated with SBRT/HIGRT and underlying Child-Pugh B or C liver function prior to radiation therapy at our University and Veterans Affairs (VA) radiation oncology departments from 2014 to 2019. Primary endpoints included treatment-related toxicity, as well as, evaluation of dosimetric parameters for OAR. Results 38 patients (39 treatment courses) were included. Most patients (97%) had Child-Pugh B7-B9 (62% CP B7, 21% CP B8, 15% CP B9) or ALBI grade 2-3 (69% ALBI grade 2, 31% ALBI grade 3) liver disease prior to radiation therapy. A single patient had Child-Pugh C10 liver function. The most commonly utilized regimens include 50 Gy in either 5 or 10 fractions. The median delivered dose was 50 Gy (range 30-50) in an average of 7.5 fractions (range 5-10). Most patients had a single lesion (63%) with a median lesion size of 3.2 cm (range 1.10-7.40 cm). The mean liver dose was 9.40 Gy (range 3.38-23.94) with a liver D800cc of 4.14 Gy (range 0.35-17.31). All patients completed their intended treatment course with a median follow up of 43 months. Four (10.3%) treatment courses resulted in non-classical radiation-induced liver disease (RILD) (defined as an increase of 2 or more points in Child-Pugh score), compared to 8.3% for patients with Child-Pugh A liver function treated during a similar time period. Otherwise, one patient (2.6%) experienced acute grade 3+ (non-RILD) hepatobiliary toxicity (transient transaminitis). Two-year freedom from local progression was 73% (95% CI 37-90%), median overall survival 12 months (95% CI 5-25 months), and median progression free-survival was not reached. Conclusion Ablative radiation therapy as definitive management for patients with unresectable, non-metastatic HCC appears to be reasonably well tolerated in patients with decompensated liver function at baseline (Child-Pugh B7-B9), with low rates of RILD and encouraging local control. With careful selection, these patients appear to be reasonable candidates for consideration of SBRT/HIGRT. Our analysis did not include enough patients with Child-Pugh C10+ disease to draw meaningful conclusions.

Purpose/objective(s) Patients undergoing radiotherapy during the COVID-19 pandemic have experienced unique changes to care, including increased use of telehealth for radiotherapy on-treatment visits (OTVs). The objective of this study was to determine telehealth utilization and provider perceptions towards effectively assessing, managing and treating patients via telehealth OTVs during the pandemic. Materials/methods As part of this IRB-approved single institution study, a survey was developed to capture the percentage of OTVs that were conducted via telehealth and provider perceptions on management effectiveness. Participants included attending and resident physicians and advanced practice providers (APPs). Likert scale questions assessed the provider perceptions in the following areas: ability to fully evaluate patient, manage symptoms, minimize acute care, and prevent COVID19 exposure. The survey was sent at 3 timepoints: April 15th, May 22nd, and December 18, 2020 (1, 2, and 7 months since declaration of COVID-19 as a national emergency). Respondents were not linked across the 3 surveys. Response frequencies and percentages are presented for each survey and global trends in responses are described. Results Surveys were sent to 34 radiation oncology providers. 22 (65%), 20 (59%), and 21 (62%) participants responded to the April, May, and December survey, respectively. 13, 12, 13 attending physicians; 8, 6, and 3 resident physicians; and 2, 2, and 5 APPs responded to the 3 surveys, respectively. In the April survey 59% of respondents indicated that 75-100% of patients were evaluated weekly by telehealth. This percentage dropped to 8% in May and 0% in December. Most respondents reported agreement with the ability to fully evaluate patients (70% vs 55%; 55%), manage symptoms (80% vs 59%; 60%) and minimize acute care (70% vs 64%; 60%) with in-person OTVs (% December vs April; May). Agreement of an appropriate balance of patient care and COVID-19 risk prevention dropped from 86% in April to 75% in May and 68% in December. Respondents reported a preference for patient-specific management strategies (telehealth vs in-person visits) at all time points (95% in April and May; 90% in December). Conclusion Based on our results, telehealth was widely used during the beginning of the pandemic, but shifted to essentially zero by December 2020. The increase of in person visits by December appears to correlate with agreement to fully evaluate a patient, manage symptoms, and minimize acute care. However, as in person OTVs increased, there was more concern for COVID-19 prevention by providers. By implementing systems into our electronic medical record that can accurately predict patients that may imminently require acute intervention, we may strike a balance of providing the best care for our cancer patients and minimize exposure risk.

277 Background: Oncology telehealth (TH) services may improve access, mitigate care delays, and augment care in select settings. However, logistical and workflow barriers hinder the sustainable adoption of TH services by providers. We created a novel oncology TH nurse (OTN) position to address these barriers. Methods: An OTN was introduced into oncology provider groups (physician + advanced practice provider) in a staggered, opt-in fashion across the Duke Cancer Institute between 9/2020 and 12/2020. The OTN performed individualized interventions to decrease provider burden, improve TH workflows, and increase TH utilization. Specific interventions performed by the OTN were recorded. We monitored the primary outcome, TH utilization, as a proportion of all visits at baseline (month 0) and 3 months post-OTN intervention. Patient TH satisfaction surveys were reviewed at baseline and 3 months post-OTN intervention. Provider surveys were sent 3 months post-OTN intervention. Results: The OTN was implemented across 10 provider groups and 25 providers [gastrointestinal (GI) medical oncology (n = 10), thoracic medical oncology (n = 3), melanoma medical oncology (n = 3), adult bone marrow transplant (n = 2), lung cancer screening (n = 2), melanoma surgical oncology (n = 1), hematological malignancies (n = 1), head and neck medical oncology (n = 1), central nervous system radiation oncology (n = 1), and GI radiation oncology (n = 1)]. 25 providers utilized 1 or more OTN interventions: support for patients on the TH platform (n = 13), construction of TH clinic schedule templates (n = 6), creation of workflows to order and obtain outside imaging/labs (n = 5), provider TH education (n = 4), creation of Epic SmartPhrases (n = 4), and identifying patients appropriate for TH (n = 3). Baseline TH utilization was 15.6% of all visits, and 3-month post-OTN utilization was 23.8%. TH patient satisfaction data was available for 10 providers at baseline and 13 providers at 3 months post-OTN. Patients’ global approval rating of TH was 85.0% at baseline and 98.5% at month 3. 16/25 providers returned the post-intervention survey. Providers requested continued assistance from the OTN for supporting patients on the TH platform (43.5%), staff TH education (43.5%), provider TH education (25%), creation of SmartPhrases (25%), and creation of TH clinic templates (13%). Providers requested new additional OTN support to 1) order and retrieve imaging/laboratory tests for TH visits and 2) explore patients' willingness to undergo TH visits. Conclusions: OTN interventions were individualized to providers and evolved over time. While TH utilization was increased at 3 months post-OTN, it is possible that utilization was confounded by the dynamic COVID-19 pandemic and provider/patient preferences over time. Nevertheless, these results demonstrate feasibility of OTN implementation and provide support for this novel role in promoting TH services in oncology.

Purpose Treatment planning for pancreas stereotactic body radiation therapy (SBRT) is a challenging task, especially with simultaneous integrated boost treatment approaches. We propose a deep learning (DL) framework to accurately predict fluence maps from patient anatomy and directly generate intensity modulated radiation therapy plans. Methods and Materials The framework employs 2 convolutional neural networks (CNNs) to sequentially generate beam dose prediction and fluence map prediction, creating a deliverable 9-beam intensity modulated radiation therapy plan. Within the beam dose prediction CNN, axial slices of combined structure contour masks are used to predict 3-dimensional (3D) beam doses for each beam. Each 3D beam dose is projected along its beam’s-eye-view to form a 2D beam dose map, which is subsequently used by the fluence map prediction CNN to predict its fluence map. Finally, the 9 predicted fluence maps are imported into the treatment planning system to finalize the plan by leaf sequencing and dose calculation. One hundred patients receiving pancreas SBRT were retrospectively collected for this study. Benchmark plans with unified simultaneous integrated boost prescription (25/33 Gy) were manually optimized for each case. The data set was split into 80/20 cases for training and testing. We evaluated the proposed DL framework by assessing both the fluence maps and the final predicted plans. Further, clinical acceptability of the plans was evaluated by a physician specializing in gastrointestinal cancer. Results The DL-based planning was, on average, completed in under 2 minutes. In testing, the predicted plans achieved similar dose distribution compared with the benchmark plans (-1.5% deviation for planning target volume 33 V33Gy), with slightly higher planning target volume maximum (+1.03 Gy) and organ at risk maximum (+0.95 Gy) doses. After renormalization, the physician rated 19 cases clinically acceptable and 1 case requiring minor improvement. Conclusions The DL framework can effectively plan pancreas SBRT cases within 2 minutes. The predicted plans are clinically deliverable, with plan quality approaching that of manual planning.

Purpose Bolus-tracked multiphasic contrast computed tomography (CT) is often used in diagnostic radiology to enhance the visibility of pancreas tumors, but is uncommon in radiation therapy pancreas CT simulation, and its impact on gross tumor volume (GTV) delineation is unknown. This study evaluates the lesion conspicuity and consistency of pancreas stereotactic body radiation therapy (SBRT) GTVs contoured in the different contrast phases of triphasic CT simulation scans. Methods and materials Triphasic, bolus-tracked planning CT simulation scans of 10 consecutive pancreas SBRT patients were acquired, yielding images of the pancreas during the late arterial (LA), portal venous (PV), and either the early arterial or delayed phase. GTVs were contoured on each phase by a gastrointestinal-specialized radiation oncologist and reviewed by a fellowship-trained abdominal radiologist who specializes in pancreatic imaging. The volumes of the registered GTVs, their overlap ratio, and the 3-dimensional margin expansions necessary for each GTV to fully encompass GTVs from the other phases were calculated. The contrast difference between tumor and normal pancreas was measured, and 2 radiation oncologists rank-ordered the phases according to their value for the lesion-contouring task. Results Tumor-to-pancreas enhancement was on average much larger for the LA and PV than the delayed phase or early arterial phases; the LA and PV phases were also consistently preferred by the radiation oncologists. Enhancement differences among the phases resulted in highly variable GTV volumes with no observed trends. Overlap ratios ranged from 18% to 75% across all 3 phases, improving to 43% to 91% when considering only the preferred LA and PV phases. GTV expansions necessary to encompass all GTVs ranged from 0.3 to 1.8 cm for all 3 phases, improving slightly to 0.1 to 1.4 cm when considering just the LA and PV phases. Conclusions For pancreas SBRT, we recommend combining the GTVs from a multiphasic CT simulation with bolus-tracking, including, at a minimum, a Boolean "OR" of the LA and PV phases.

Gastric adenocarcinoma is the fifth most common cancer worldwide and is often diagnosed at a late stage with nearly 50% of patients having locally advanced, unresectable, or metastatic disease at the time of presentation. Efforts to improve outcomes in patients with resected and unresectable gastric cancer with various chemotherapy and radiation regimens are ongoing. Appropriate evaluation and management is often not straightforward and requires the input of a multidisciplinary team. There is no consensus as to the best approach for treatment of gastric cancer; however, the available data and our institutional approach to the management of gastric cancer are discussed.

The treatment of locally advanced rectal cancer (LARC) has benefited from improved surgical techniques and from the implementation of neoadjuvant chemoradiotherapy (CRT), which have markedly decreased the rates of local recurrence. However, distant metastatic disease remains the most significant cause of death for these patients. Although adjuvant chemotherapy (ChT) after neoadjuvant CRT and definitive surgery is commonly recommended, the value of adjuvant systemic therapy remains less clear. Trials evaluating adjuvant ChT for rectal cancer have been handicapped by poor compliance rates and inconsistent survival results. Shifting systemic therapy delivery to the neoadjuvant setting has the promise to improve compliance rates, reduce toxicity, and decrease distant relapse rates. Recently, multiple prospective trials have reported on the use of total neoadjuvant therapy (TNT) for patients with LARC, incorporating both ChT and CRT in the neoadjuvant setting. Here, the authors review the promising results from those trials. Because the studies have largely focused on pathologic outcomes (primarily pathologic complete response rates), ongoing phase 2 and 3 trials are now underway assessing the long-term disease-related outcomes with TNT. In addition to improving survival, TNT has the potential to increase the pool of patients with LARC who are eligible for organ preservation, which is also being evaluated. Cancer 2017;123:1497-1506. © 2017 American Cancer Society.

Purpose Diffusion-weighted Magnetic Resonance Imaging (DWI) has been shown to be a powerful tool for cancer detection with high tumor-to-tissue contrast. This study aims to investigate the feasibility of developing a four-dimensional DWI technique (4D-DWI) for imaging respiratory motion for radiation therapy applications. Materials/methods Image acquisition was performed by repeatedly imaging a volume of interest (VOI) using an interleaved multislice single-shot echo-planar imaging (EPI) 2D-DWI sequence in the axial plane. Each 2D-DWI image was acquired with an intermediately low b-value (b = 500 s/mm2 ) and with diffusion-encoding gradients in x, y, and z diffusion directions. Respiratory motion was simultaneously recorded using a respiratory bellow, and the synchronized respiratory signal was used to retrospectively sort the 2D images to generate 4D-DWI. Cine MRI using steady-state free precession was also acquired as a motion reference. As a preliminary feasibility study, this technique was implemented on a 4D digital human phantom (XCAT) with a simulated pancreas tumor. The respiratory motion of the phantom was controlled by regular sinusoidal motion profile. 4D-DWI tumor motion trajectories were extracted and compared with the input breathing curve. The mean absolute amplitude differences (D) were calculated in superior-inferior (SI) direction and anterior-posterior (AP) direction. The technique was then evaluated on two healthy volunteers. Finally, the effects of 4D-DWI on apparent diffusion coefficient (ADC) measurements were investigated for hypothetical heterogeneous tumors via simulations. Results Tumor trajectories extracted from XCAT 4D-DWI were consistent with the input signal: the average D value was 1.9 mm (SI) and 0.4 mm (AP). The average D value was 2.6 mm (SI) and 1.7 mm (AP) for the two healthy volunteers. Conclusion A 4D-DWI technique has been developed and evaluated on digital phantom and human subjects. 4D-DWI can lead to more accurate respiratory motion measurement. This has a great potential to improve the visualization and delineation of cancer tumors for radiotherapy.

Aim: The aim of this study was to evaluate deformable image registration (DIR)-based motion estimation of the liver for four-dimensional-computed tomography (4D-CT) and 4D-magnetic resonance imaging (MRI). Methods: Five liver cancer patients were included. Each patient was imaged with 4D-CT and 4D-MRI under an Institutional Review Board-approved protocol. Motion estimation of the liver was obtained by performing DIR on 4D-CT and 4D-MRI. A region of interest (ROI) encompassing the expert-determined gross tumor volume was used as surrogate to evaluate the accuracy of the motion estimation. ROI motion trajectories were estimated by averaging the displacement vector fields (DVFs) within the ROI during the breathing cycles for 4D-CT and 4D-MRI and were compared to those extracted from cine MR. Target registration error (TRE), correlation coefficient (CC) for phase agreement, difference in phase at maximum displacement (ΔPmax), and Dice's Similarity Coefficient (DSC) for overall motion agreement were determined. Results: As compared to 4D-CT, 4D-MRI resulted in smaller TRE in DVFs (anterior-posterior [AP]: 1.0 ± 0.4 mm vs. 1.5 ± 0.5 mm, superior-inferior [SI]: 1.9 ± 0.7 mm vs. 2.2 ± 0.8 mm), greater CC (AP: 0.67 ± 0.32 vs. 0.49 ± 0.26, SI: 0.84 ± 0.15 vs. 0.58 ± 0.28), smaller ΔPmax (AP: 1.4 ± 1.7 vs. 2.0 ± 1.0, SI: 0.4 ± 0.9 vs. 1.2 ± 0.8), and greater DSC (AP: 0.67 ± 0.08 vs. 0.61 ± 0.11, SI: 0.73 ± 0.12 vs. 0.67 ± 0.10). Conclusion: 4D-MRI can potentially provide more realistic respiratory DVFs of the liver than 4D-CT.