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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.

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.

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.

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.

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.

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) 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.

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 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: To perform a multi-institutional analysis following treatment of limited osseous and/or nodal metastases in patients using a novel hypofractionated image-guided radiotherapy with simultaneous-integrated boost (HIGRT-SIB) technique. Methods: Consecutive patients treated with HIGRT-SIB for ≤5 active metastases at Duke University Medical Center or Durham Veterans' Affairs Medical Center between 2013 and 2018 were analyzed to determine toxicities and recurrence patterns following treatment. Most patients received 50 Gy to the PTVboost and 30 Gy to the PTVelect simultaneously in 10 fractions. High-dose treatment volume recurrence (HDTVR) and low-dose treatment volume recurrence (LDTVR) were defined as recurrences within PTVboost and PTVelect, respectively. Marginal recurrence (MR) was defined as recurrence outside PTVelect, but within the adjacent bone or nodal chain. Distant recurrence (DR) was defined as recurrences not meeting HDTVR, LDTVR, or MR criteria. Freedom from pain recurrence (FFPR) was calculated in patients with painful osseous metastases prior to HIGRT-SIB. Outcome rates were estimated at 12 months using the Kaplan-Meier method. Results: Forty-two patients met inclusion criteria with 59 sites treated with HIGRT-SIB (53% nodal and 47% osseous). Median time from diagnosis to first metastasis was 31 months and the median age at HIGRT-SIB was 69 years. The most common primary tumors were prostate (36%), gastrointestinal (24%), and lung (24%). Median follow-up was 11 months. One acute grade ≥3 toxicity (febrile neutropenia) occurred after docetaxel administration immediately following HIGRT-SIB. Four patients developed late grade ≥3 toxicities: two ipsilateral vocal cord paralyzes and two vertebral compression fractures. The overall pain response rate was 94% and the estimated FFPR at 12 months was 72%. The estimated 12 month rate of HDTVR, LDTVR, MR, and DR was 3.6, 6.2, 7.6, and 55.8%, respectively. DR preceded MR, HDTVR, or LDTVR in each instance. The estimated 12 month probability of in-field and marginal control was 90.0%. Conclusion: Targeting areas at high-risk for occult disease with a lower radiation dose, while simultaneously boosting gross disease with HIGRT in patients with limited osseous and/or nodal metastases, has a high rate of treated metastasis control, a low rate of MR, acceptable toxicity, and high rate of pain palliation. Further investigation with prospective trials is warranted.

The NCCN Guidelines for Hepatobiliary Cancers provide treatment recommendations for cancers of the liver, gallbladder, and bile ducts. The NCCN Hepatobiliary Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel’s discussion and updated recommendations regarding systemic therapy for first-line and subsequent-line treatment of patients with hepatocellular carcinoma.

Purpose This guideline systematically reviews the evidence for treatment of pancreatic cancer with radiation in the adjuvant, neoadjuvant, definitive, and palliative settings and provides recommendations on indications and technical considerations. Methods and Materials The American Society for Radiation Oncology convened a task force to address 7 key questions focused on radiation therapy, including dose fractionation and treatment volumes, simulation and treatment planning, and prevention of radiation-associated toxicities. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. Results The guideline conditionally recommends conventionally fractionated or stereotactic body radiation for neoadjuvant and definitive therapy in certain patients and conventionally fractionated regimens for adjuvant therapy. The task force suggests a range of appropriate dose-fractionation schemes and provides recommendations on target volumes and sequencing of radiation and chemotherapy. Motion management, daily image guidance, use of contrast, and treatment with modulated techniques are all recommended. The task force supported prophylactic antiemetic medication, and patients may also benefit from medications to reduce acid secretion. Conclusions The role of radiation in the management of pancreatic cancer is evolving, with many ongoing areas of active investigation. Radiation therapy is likely to become even more important as new systemic therapies are developed and there is increased focus on controlling local disease. It is important that the nuances of available data are discussed with patients and families and that care be coordinated in a multidisciplinary fashion.

BACKGROUND Short-course radiotherapy (SC-RT) and long-course chemoradiotherapy (LC-CRT) are accepted neoadjuvant treatments of rectal cancer. In the current study, the authors surveyed US radiation oncologists to assess practice patterns and attitudes regarding SC-RT and LC-CRT for patients with rectal cancer. METHODS The authors distributed a survey to 1701 radiation oncologists regarding treatment of neoadjuvant rectal cancer. Respondents were asked questions regarding the number of patients with rectal cancer treated, preference for SC-RT versus LC-CRT, and factors influencing regimen choice. RESULTS Of 1659 contactable physicians, 182 responses (11%) were received. Approximately 83% treated at least 5 patients with rectal cancer annually. The majority of responding radiation oncologists (96%) preferred neoadjuvant LC-CRT for the treatment of patients with locally advanced rectal cancer and 44% never used SC-RT. Among radiation oncologists using SC-RT, respondents indicated they would not recommend this regimen for patients with low (74%) or bulky tumors (70%) and/or concern for a positive circumferential surgical resection margin (69%). The most frequent reasons for not offering SC-RT were insufficient downstaging for sphincter preservation (53%) and a desire for longer follow-up (45%). Many radiation oncologists indicated they would prescribe SC-RT for patients not receiving chemotherapy (62%) or patients with a geographic barrier to receiving LC-CRT (82%). Patient comorbidities appeared to influence regimen preferences for 79% of respondents. Approximately 20% of respondents indicated that altered oncology care reimbursement using capitated payment by diagnosis would impact their consideration of SC-RT. CONCLUSIONS US radiation oncologists rarely use neoadjuvant SC-RT despite 3 randomized controlled trials demonstrating no significant differences in outcome compared with LC-CRT. Further research is necessary to determine whether longer follow-up coupled with the benefits of lower cost, increased patient convenience, and lower acute toxicity will increase the adoption of SC-RT by radiation oncologists in the United States. Cancer 2017;123:1434–1441. © 2016 American Cancer Society.

Pancreatic cancer is a formidable malignancy with poor outcomes. The majority of patients are unable to undergo resection, which remains the only potentially curative treatment option. The management of locally advanced (unresectable) pancreatic cancer is controversial; however, treatment with either chemotherapy or chemoradiation is associated with high rates of local tumor progression and metastases development, resulting in low survival rates. An emerging local modality is stereotactic body radiation therapy (SBRT), which uses image-guided, conformal, high-dose radiation. SBRT has demonstrated promising local control rates and resultant quality of life with acceptable rates of toxicity. Over the past decade, increasing clinical experience and data have supported SBRT as a local treatment modality. Nevertheless, additional research is required to further evaluate the role of SBRT and improve upon the persistently poor outcomes associated with pancreatic cancer. This review discusses the existing clinical experience and technical implementation of SBRT for pancreatic cancer and highlights the directions for ongoing and future studies.

Colorectal cancer has a high global incidence, and standard treatment employs a multimodality approach. In addition to cure, minimizing treatment-related toxicity and improving the therapeutic ratio is a common goal. The following article addresses the potential of omitting radiotherapy in select rectal cancer patients. Omission of radiotherapy in rectal cancer is analyzed in the context of historical findings, as well as more recent data describing risk stratification of stage II–III disease, surgical optimization, imaging limitations, improvement in systemic chemotherapeutic agents, and contemporary studies evaluating selective omission of radiotherapy. A subset of rectal cancer patients exists that may be considered low to intermediate risk for locoregional recurrence. With appropriate staging, surgical technique, and possibly improved systemic therapy, it may be feasible to selectively omit radiotherapy in these patients. Current imaging limitations as well as evidence of increased locoregional recurrence following radiotherapy omission lend us to continue supporting the standard treatment of approach of neoadjuvant chemoradiation therapy followed by surgical resection until additional improvements and prospective evidence can support otherwise.

Purpose This prospective study seeks to extract semiquantitative positron emission tomography (PET) features from 18F-fluorodeoxyglucose PET scans performed before and during neoadjuvant chemoradiotherapy for esophageal cancer and to compare their accuracy in predicting histopathologic response. Methods and Materials From 2012 to 2016, 26 patients with esophageal cancer underwent pretreatment and intratreatment PET scans during chemoradiotherapy followed by surgery. Median patient age was 63 years (interquartile range, 58-68 years); 26 patients had esophageal adenocarcinoma, and 3 had esophageal squamous cell carcinoma. The intratreatment PET scan was performed at a median of 32.4 Gy (interquartile range, 30.6-32.4 Gy). PET features of the primary site including maximum standardized uptake value (SUV), SUV mean, metabolic tumor volume, and total lesion glycolysis were extracted from the pretreatment and intratreatment PET scans. Patients were histopathologic responders if there was complete or near-complete tumor response by modified Ryan scheme. Mean values of PET features were compared between histopathologic responders and nonresponders. The area under the receiver operating characteristic curve (AUC) was used to compare the accuracy of PET features in predicting histopathologic response. Results Eleven patients (42%) were histopathologic responders. PET features most discriminatory of histopathologic response on AUC analysis were volumetric PET features from the intratreatment PET including metabolic tumor volume based on manual contour (AUC, 0.73; 95% confidence interval, 0.52-0.93) and total lesion glycolysis based on semiautomatic 40% SUV threshold (AUC, 0.73; 95% confidence interval, 0.53-0.94). Conclusions Volumetric PET features from the intratreatment PET were the most accurate predictors of histopathologic response.

Surgery has long been the primary curative modality for localized rectal cancer. Neoadjuvant chemoradiation has significantly improved local control rates and, in a significant minority, eradicated all disease. Patients who achieve a pathologic complete response to neoadjuvant therapy have an excellent prognosis, although the combination treatment is associated with long-term morbidity. Because of this, a nonoperative management (NOM) strategy has been pursued to preserve sphincter function in select patients. Clinical and radiographic findings are used to identify patients achieving a clinical complete response to chemoradiation, and they are then followed with intensive surveillance. Incomplete, nonresponding and those demonstrating local progression are referred for salvage with standard surgery. Habr-Gama and colleagues have published extensively on this treatment strategy and have laid the groundwork for this approach. This watch-and-wait strategy has evolved over time, and several groups have now reported their results, including recent prospective experiences. Although initial results appear promising, several significant challenges remain for NOM of rectal cancer. Further study is warranted before routine implementation in the clinic.

The role of adjuvant radiation therapy (RT) in the treatment of resected, locally advanced colon cancer is unclear. One randomized controlled trial (Intergroup-0130) addressed this question but failed to meet its accrual goals. Since this trial, few attempts have been made to reassess the role of RT in this clinical setting. Sixty-two patients with non-metastatic, American Joint Committee on Cancer 7th edition stage T4 colonic adenocarcinoma were treated at our institution between 2000 and 2013. All underwent curative-intent surgery. Sixteen patients underwent resection only, 33 patients received adjuvant chemotherapy (ChT), and 13 patients received adjuvant chemoradiation therapy (CRT). Patients receiving adjuvant CRT were more likely to have T4b (vs. T4a) disease and were more likely to undergo R1 or R2 resection compared with those receiving adjuvant ChT alone. Despite this, multivariate analysis demonstrated that treatment with adjuvant CRT (vs. adjuvant ChT) enhanced locoregional control and disease-free survival (hazard ratio 0.044 and 0.145, respectively; p

Radiation therapy is associated with acute treatment-related complications that can lead to decreased quality of life (QOL). Exercise has been shown in other cancer treatment settings to improve negative outcomes. We conducted a prospective pilot study to explore the association between exercise, patient-reported outcomes, and acute radiation therapy toxicities.Women receiving curative breast radiation therapy were enrolled. Each patient completed an exercise behavior/QOL survey before or during the first week of treatment and again during the last week of treatment. Exercise behavior was quantified with the Godin Leisure Time Exercise Questionnaire (metabolic equivalent [MET] hours per week). Measurements to evaluate upper extremity lymphedema and shoulder range of motion were completed. Skin toxicity was assessed weekly. Patient-reported outcomes were measured using standardized questionnaires.Forty-five patients were enrolled. Mean patient age was 54 (range, 28-73) years. Mean METs in the exercise cohort (≥9 METs/wk) was 21 per week (range, 11-38, n = 14); 3 per week (range, 0-8, n = 25) in the nonexercise cohort (9 METs/wk). Women in the exercise cohort showed improvements in treatment-induced quality of life and fatigue (not significant) despite more extensive surgical, medical, and radiation treatment. No differences in treatment-related toxicities, pain, or sleep scores were noted. Lymphedema was mild (3 cm) in the entire patient cohort.The vast majority of current exercise oncology literature implicates physical activity as an independent predictor of QOL in cancer patients. Our study noted similar trends, but they were not statistically significant. This may be due to our finding that patient-reported outcomes with radiation therapy are relatively high compared with other treatment modalities and remain stable throughout treatment. Thus, it may be that radiation therapy has a limited impact on QOL in breast cancer patients. Exercise may be best used as a targeted therapy in patients at high risk for poor QOL or radiation-related toxicities at baseline.

Purpose/Objectives: RT is associated with acute treatment-related complications that can lead to poor quality of life (QOL) and fatigue. Exercise has been shown in other cancer treatment settings to improve negative outcomes. We conducted a prospective pilot study to explore the association between exercise, patient-reported outcomes (PROs), and radiation therapy (RT) toxicities. Materials/Methods: Patients with surgically excised ductal carcinoma in situ or invasive breast carcinoma receiving curative radiation were enrolled. Each patient completed an exercise behavior/QOL survey at two time points: before the patient’s 5th fraction of radiation and during the last week of treatment. Limb girth measurements to evaluate lymphedema and assessment of shoulder range of motion (ROM) were completed on all patients at the same two time points. Skin toxicity was assessed weekly throughout radiotherapy. Exercise behavior was quantified with the Godin Leisure Time Exercise Questionnaire (metabolic equivalent [MET] hours per week). Patients with >7 METs/week were designated the exercise cohort (n=10) and those with Results: Median patient age was 56 (range 28-70) years. Median MET in the exercise cohort was 12.9/week (range 7.5-35.0, n=10); 0.0/week in the non-exercise cohort (range 0-5.8, n=10). Women in the exercise cohort experienced significant improvement in depression scores over the course of treatment as compared to those who did not exercise (p=0.013). Those in the exercise cohort also reported less fatigue on the FACT-Fatigue subscale at treatment completion (exercise: 133.0; non-exercise: 121.0) (p=0.6). In addition, only 30% of exercisers suffered from grade 2 dermatitis compared to 70% of non-exercisers (p=0.2), despite a similar body mass index (26.4 exercise cohort versus 28.1 non-exercise). Exercisers also had greater ROM in the affected (91.7 vs. 85.2%, p=0.1) and contralateral shoulder (95 vs. 90%, p=0.048) at treatment completion. No differences in pain or sleep scores were noted and lymphedema was mild ( Conclusion: The vast majority of current exercise oncology literature indicates that physical activity is an independent predictor of quality of life metrics in cancer patients. Our study notes a trend towards improved outcomes with increased exercise during radiation therapy, suggesting that accrual of additional patients to our pilot study is worthwhile. Ultimately, a concurrent exercise intervention may improve quality of life and reduce acute toxicity in patients undergoing breast radiation treatment. Citation Format: Ritu Arya, Lee W Jones, Rachel C Blitzblau, Manisha Palta, Lisa Massa, Gloria Broadwater, Janet K Horton. The association between exercise behavior and patient-reported outcomes in women with early breast cancer receiving locoregional radiation therapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-12-07.

BACKGROUND: Breast cancer treatment contributes the greatest proportion of cancer-related health care spending in the United States. Locoregional therapy comprises a significant share of these costs. We hypothesized that among eligible women with early-stage breast cancer treated with lumpectomy, evidence-based utilization of hypofractionated whole breast radiation or omission of radiotherapy could substantially reduce cancer-related treatment costs. METHODS: Using the National Cancer Data Base which captures approximately 70% of all newly diagnosed cancers in the United States, we identified 43,247 women with clinically node-negative, T1-T2 invasive breast cancers treated with lumpectomy during 2011. Women with DCIS, those treated with mastectomy, accelerated partial breast irradiation (APBI), or unknown or questionable radiation regimens were excluded. Adjuvant radiation was categorized into the following regimens: conventionally fractionated whole breast irradiation therapy (CF-WBI) [25-40 fractions, 45-66 Gy], hypofractionated whole-breast irradiation (HF-WBI) [15-24 fractions, 40-58 Gy), and lumpectomy without radiation (no RT). Women were considered eligible for no RT if ≥70 years with T1N0, ER+ breast cancers, and for HF-WBI if ≥50 years, with T1-T2 N0 invasive breast cancer. Treatment costs were calculated using Medicare Physician Fee Schedule payment information for 2011, and based on average current procedural codes billed per regimen. Costs per patient were estimated as follows: CF-WBI $13,358.37, HF-WBI $8,327.98, and lumpectomy without RT $0. Actual treatment costs were compared to evidence-based, reduced-cost radiation regimens for which patients were potentially eligible. RESULTS: Median patient age was 63 years (range 19-90). Median tumor size was 1.2 cm. Of the total study cohort, 84.5% was eligible for HF-WBI, and 22.3% for no RT. Among the 36,562 (84.5%) patients eligible for treatment with HF-WBI, 28,383 (77.6%) received radiation therapy. Of these, 22,653 (79.8%) received CF-WBI, 5,289 (18.6%) received HF-WBI, and 441 (1.6%) received accelerated partial breast irradiation (APBI). Among 9,651 women ≥70 years with ER+ tumors eligible for no-RT, 4,245 (44.0%) received CF-WBI, 1,768 (18.3%) received HF-WBI, 153 (1.6%) received APBI, and 3,485 (36.1%) received no RT. 26% of women received the least expensive evidence-based radiation regimen for which they were eligible, while 67% of patients were treated with more costly radiation regimens. Estimated costs of actual treatment were $420.2 million during 2011, compared to $256.2 million had women been treated with the least expensive radiation regimen for which they were eligible. This translates into an annual cost savings of $164.0 million, a 39% reduction in costs. CONCLUSIONS: Utilization of evidence-based adjuvant radiation following lumpectomy is associated with reductions in cancer-related costs in the locoregional treatment of early-stage breast cancer. Although treatment decisions should not be driven by health care costs alone, consideration of hypofractionated regimens or omission of radiotherapy for patients that fit evidence-based eligibility criteria could translate into dramatic reductions in annual health care spending. Citation Format: Rachel A Greenup, Rachel Blitzblau, Kevin Houck, Janet Horton, Lynn Howie, Manisha Palta, Aimee Mackey, Randy Scheri, Julie A Sosa, Alphonse G Taghian, Jeffrey Peppercorn, Barbara L Smith, E Shelley Hwang. Adjuvant radiation after lumpectomy: A cost comparison of treatment patterns in 43,247 women from the National Cancer Data Base [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-10-02.

Background: Large randomized controlled trials have shown that hypofractionated whole breast irradiation (HF-WBI) is not inferior to or more toxic than conventionally fractionated whole breast irradiation (CF-WBI) for the treatment of early-stage breast cancer. Royal Marsden data were published in 2006 (10-yr), the Ontario trial was reported in 2002 (5-yr) and 2010 (10-yr), and the UK START trials were published in 2006 (5-yr) and 2013 (10-yr). We utilized the National Cancer Data Base (NCDB) to evaluate patterns of radiotherapy fractionation for early-stage, node-negative breast cancer in the U.S. We hypothesized that HF-WBI use would increase over time in response to emerging data supporting its use in this population. Methods: We conducted a retrospective, population-based cohort study of women >18 years diagnosed with T1-2N0 invasive breast carcinoma and treated with breast-conserving surgery between 2004 and 2011. Radiotherapy was categorized as accelerated partial breast irradiation (APBI; 38-40 Gy/1-10 fractions), HF-WBI (40-56 Gy/15-24 fractions) or CF-WBI (50-66 Gy/25-40 fractions). Patients treated with alternate fractionation were excluded. Patterns of breast radiotherapy fractionation were compared using the chi-square test. Multivariable logistic regression was performed for patients diagnosed in 2011, the year with the highest levels of HF-WBI utilization. Results: 217,789 patients in the NCDB met inclusion criteria. HF-WBI use increased over time, rising from 2.1% among eligible patients in 2004 to 15.1% in 2011, while APBI use remained low at 30 years. Table 1 shows frequency of HF-WBI use over time by center type. On multivariate analysis of patients diagnosed in 2011, the following factors were associated with higher use of HF-WBI: treatment at an academic center, older patient age, hormone receptor positivity, pT1 tumor size, and rural residence (Table 2). Table 1: % HF-WBI use Community Cancer CenterComprehensive Community Cancer CenterAcademic Center20040.9%1.7%3.8%20051.6%2.1%3.8%20061.2%2.0%4.6%20071.5%2.8%7.1%20082.9%5.3%10.8%20093.9%8.5%14.7%20105.8%10.7%16.4%20119.6%13.9%20.5% Table 2. Multivariate analysis, year 2011 (n=5568) OR95% CIAcademic Center vs. Community Cancer Center3.062.324.02Academic Center vs. Comprehensive Community Cancer Center1.781.532.08Patient age, 50-90 vs. 18-492.371.863.01T2 vs. T10.540.460.63HER2+ vs. Hormone Receptor +/HER2-0.750.590.97ER-/PR-/HER2- vs. Hormone Receptor +/HER2-0.660.520.84Rural vs. urban2.681.694.24 Conclusions: Utilization of HF-WBI in the US is rising, but remains low overall despite level I evidence showing its non-inferiority to CF-WBI. Given the advantages of HF-WBI in terms of patient convenience and potential healthcare system costs, further research is indicated to explore disparities in HF-WBI utilization in the US and to guide education of breast cancer providers. Citation Format: Yvonne M Mowery, Rachel A Greenup, Kevin Houck, Manisha Palta, Janet K Horton, Eun-Sil S Hwang, Julie A Sosa, Rachel C Blitzblau. Low utilization of hypofractionated radiotherapy for the treatment of early-stage breast cancer in the US [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-15-10.

The NCCN Guidelines for Hepatobiliary Cancers provide treatment recommendations for cancers of the liver, gallbladder, and bile ducts. The NCCN Hepatobiliary Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding locoregional therapy for treatment of patients with hepatocellular carcinoma.

The treatment of esophageal cancer with radiation therapy presents many challenges. The propensity of esophageal cancer to invade and spread within the submucosa with resultant lymph node involvement requires particular attention to areas of elective coverage beyond the gross tumor. Moreover, the intimate association of the esophagus and gastroesophageal junction with adjacent organs in the thoracic cavity and upper abdomen dictates attention to normal tissue constraints. Although most patients receive preoperative chemoradiation, patients treated postoperatively may require larger treatment fields, further increasing treatment-related normal tissue toxicities. This chapter will discuss the rationale of radiation treatment field design and dose for esophageal cancer patients based on thoracic anatomy, imaging, and patterns of spread/failure, as well as practical considerations for patient simulation and treatment.

Radiotherapy is an integral part of achieving long-term cure in a number of intrathoracic malignancies. This chapter will provide an overview of the epidemiology of heart disease after radiotherapy, with specific focus on clinical data from Hodgkin lymphoma and breast cancer survivors. As clinical manifestation of heart disease can take years, if not decades, to manifest, animal models can assist in our understanding of the pathogenesis as well as the cellular and molecular mechanisms of radiation-induced heart disease, elucidating opportunities for intervention and prevention. Finally, recommendations for monitoring patients after radiotherapy and management of cardiac disease in patients with prior thoracic/breast neoplasms will be discussed.

Although esophageal cancer represents only 6 % of all gastrointestinal malignancies diagnosed in the United States, it remains a highly lethal disease and the seventh most common cause of cancer death in males. Rates of squamous cell carcinoma have been declining, while the incidence of esophageal adenocarcinoma is increasing with rising rates of gastroesophageal reflux disease (GERD) and associated risk factors. Although the overall prognosis of esophageal cancer patients is poor, particularly with more advanced disease, trimodality therapy with radiation, chemotherapy, and surgery has improved outcomes. This chapter reviews the clinical data underlying the current management of esophageal cancer.

BACKGROUND The Cancer and Leukemia Group B (CALGB) 9343 randomized phase 3 trial established lumpectomy and adjuvant therapy with tamoxifen alone, rather than both radiotherapy and tamoxifen, as a reasonable treatment course for women aged >70 years with clinical stage I (AJCC 7th edition), estrogen receptor-positive breast cancer. An analysis of the Surveillance, Epidemiology, and End Results (SEER) registry was undertaken to assess practice patterns before and after the publication of this landmark study. METHODS The SEER database from 2000 to 2009 was used to identify 40,583 women aged ≥70 years who were treated with breast-conserving surgery for clinical stage I, estrogen receptor-positive and/or progesterone receptor-positive breast cancer. The percentage of patients receiving radiotherapy and the type of radiotherapy delivered was assessed over time. Administration of radiotherapy was further assessed across age groups; SEER cohort; and tumor size, grade, and laterality. RESULTS Approximately 68.6% of patients treated between 2000 and 2004 compared with 61.7% of patients who were treated between 2005 and 2009 received some form of adjuvant radiotherapy (P < .001). Coinciding with a decline in the use of external beam radiotherapy, there was an increase in the use of implant radiotherapy from 1.4% between 2000 and 2004 to 6.2% between 2005 to 2009 (P < .001). There were significant reductions in the frequency of radiotherapy delivery over time across age groups, tumor size, and tumor grade and regardless of laterality (P < .001 for all). CONCLUSIONS Randomized phase 3 data support the omission of adjuvant radiotherapy in elderly women with early-stage breast cancer. Analysis of practice patterns before and after the publication of these data indicates a significant decline in radiotherapy use; however, nearly two-thirds of women continue to receive adjuvant radiotherapy. Cancer 2015;121:188–93. © 2014 American Cancer Society.

Purpose To evaluate the relationship between liver tumor motion and diaphragm motion. Methods and Materials Fourteen patients with hepatocellular carcinoma (10 of 14) or liver metastases (4 of 14) undergoing radiation therapy were included in this study. All patients underwent single-slice cine–magnetic resonance imaging simulations across the center of the tumor in 3 orthogonal planes. Tumor and diaphragm motion trajectories in the superior–inferior (SI), anterior–posterior (AP), and medial–lateral (ML) directions were obtained using an in-house-developed normalized cross-correlation–based tracking technique. Agreement between the tumor and diaphragm motion was assessed by calculating phase difference percentage, intraclass correlation coefficient, and Bland-Altman analysis ( D i f f ). The distance between the tumor and tracked diaphragm area was analyzed to understand its impact on the correlation between the 2 motions. Results Of all patients, the mean (±standard deviation) phase difference percentage values were 7.1% ± 1.1%, 4.5% ± 0.5%, and 17.5% ± 4.5% in the SI, AP, and ML directions, respectively. The mean intraclass correlation coefficient values were 0.98 ± 0.02, 0.97 ± 0.02, and 0.08 ± 0.06 in the SI, AP, and ML directions, respectively. The mean Diff values were 2.8 ± 1.4 mm, 2.4 ± 1.1 mm, and 2.2 ± 0.5 mm in the SI, AP, and ML directions, respectively. Tumor and diaphragm motions had high concordance when the distance between the tumor and tracked diaphragm area was small. Conclusions This study showed that liver tumor motion had good correlation with diaphragm motion in the SI and AP directions, indicating diaphragm motion in the SI and AP directions could potentially be used as a reliable surrogate for liver tumor motion.

BACKGROUND Patterns of failure after neoadjuvant chemoradiotherapy and surgery for esophageal cancer are poorly defined.

33 Background: Synchronous prostate cancer (PC) and rectosigmoid (RS) cancer (RSC) is a challenging clinical situation. Methods: A retrospective review of Duke University and Durham VA charts was performed for men with adenocarcinomas of the prostate and RS colon from 1988-2017. Synchronous presentation was defined as symptoms, diagnosis (dx), or treatment (tx) of PC/RSC within 12 months. The primary endpoint was overall survival (OS), calculated from latest dx date. Univariate and multivariate (MVA) Cox regression was performed using STATA 15.1. Results: Among 31,883 men with PC identified, 330 (1%) also had RSC. 54 (16%) were considered synchronous (median age 67, IQR 62-72). PC was more commonly the first dx (59%), and 15 (28%) underwent prostatectomy (n=13) or radiotherapy (RT, n=2) before a dx of synchronous RSC. 26%, 57%, and 17% had stage I, II-III, and IV RSC, respectively. Prostatectomy, LAR, APR, and combined surgery for both PC/RSC was performed in 17 (31%), 24 (44%), 10 (19%), and 2 (4%) men, respectively. 35 (65%) received RT with median RS dose of 50.4 Gy (IQR 50.4-54 Gy) and prostate boost to 66 Gy (IQR 61-72 Gy). 34 (63%) received 5-FU based chemotherapy, 23 (43%) received ADT, and 9 (17%) received no PC-specific tx. After a median follow up of 43 (IQR 21-93) months, there were 34 deaths: 18 (53%) due to RSC, 2 (6%) due to PC, 3 (9%) due to grade 5 toxicity, 7 (21%) due to another malignancy, and 4 (12%) due to unknown cause without recurrence. Grade 5 toxicities resulted from sequential hepatectomy/LAR, combined prostatectomy/APR, and myocardial infarction while on ADT. Crude late grade ≥3 toxicities include 9 (17%) GI and 6 (11%) GU. Two anastomotic leaks

SUMMARY The management of rectal adenocarcinoma and the role of radiation in the adjuvant and neoadjuvant setting is evolving. Randomized clinical trials established the role of neoadjuvant chemoradiation (CRT), primarily in patients with T3/T4 and/or node-positive tumor presentations. Clinical trials comparing short-course radiotherapy with long-course CRT have been undertaken, and data supporting treatment with definitive CRT-reserving surgery for salvage is emerging. Clinical research to enhance the efficacy of the 5-fluorouracil-based CRT platform is being investigated, incorporating a variety of chemotherapeutics and targeted agents.

Purpose Several recent series evaluating external beam accelerated partial breast irradiation (PBI) have reported adverse cosmetic outcomes, possibly related to large volumes of normal tissue receiving near-prescription doses. We hypothesized that delivery of external beam PBI in a single fraction to the preoperative tumor volume would be feasible and result in a decreased dose to the uninvolved breast compared with institutional postoperative PBI historical controls. Methods and Materials A total of 17 patients with unifocal Stage T1 breast cancer were identified. Contrast-enhanced subtraction magnetic resonance images were loaded into an Eclipse treatment planning system and used to define the target volumes. A "virtual plan" was created using four photon beams in a noncoplanar beam arrangement and optimized to deliver 15 Gy to the planning target volume. Results The median breast volume was 1,713 cm 3 (range: 1,014–2,140), and the median clinical target volume was 44 cm 3 (range: 26–73). In all cases, 100% of the prescription dose covered 95% of the clinical target volume. The median conformity index was 0.86 (range: 0.70–1.12). The median percentage of the ipsilateral breast volume receiving 100% and 50% of the prescribed dose was 3.8% (range: 2.2–6.9) and 13.3% (range: 7.5–20.8) compared with 18% (range: 3–42) and 53% (range: 24–65) in the institutional historical controls treated with postoperative external beam PBI ( p = .002). The median maximum skin dose was 9 Gy. The median dose to 1 and 10 cm 3 of skin was 6.7 and 4.9 Gy. The doses to the heart and ipsilateral lung were negligible. Conclusion Preoperative PBI resulted in a substantial reduction in ipsilateral breast tissue dose compared with postoperative PBI. The skin dose appeared reasonable, given the small volumes. A prospective Phase I trial evaluating this technique is ongoing.

Ampullary carcinoma is a rare malignancy. Despite radical resection, survival rates remain low with high rates of local failure. We performed a single-institution outcomes analysis to define the role of concurrent chemoradiotherapy (CRT) in addition to surgery. A retrospective analysis was performed of all patients undergoing potentially curative pancreaticoduodenectomy for adenocarcinoma of the ampulla of Vater at Duke University Hospitals between 1976 and 2009. Time-to-event analysis was performed comparing all patients who underwent surgery alone to the cohort of patients receiving CRT in addition to surgery. Local control (LC), disease-free survival (DFS), overall survival (OS), and metastases-free survival (MFS) were estimated using the Kaplan–Meier method. A total of 137 patients with ampullary carcinoma underwent Whipple procedure. Of these, 61 patients undergoing resection received adjuvant (n = 43) or neoadjuvant (n = 18) CRT. Patients receiving chemoradiotherapy were more likely to have poorly differentiated tumors (P = .03). Of 18 patients receiving neoadjuvant therapy, 67% were downstaged on final pathology with 28% achieving pathologic complete response (pCR). With a median follow-up of 8.8 years, 3-year local control was improved in patients receiving CRT (88% vs 55%, P = .001) with trend toward 3-year DFS (66% vs 48%, P = .09) and OS (62% vs 46%, P = .074) benefit in patients receiving CRT. Long-term survival rates are low and local failure rates high following radical resection alone. Given patterns of relapse with surgery alone and local control benefit in patients receiving CRT, the use of chemoradiotherapy in selected patients should be considered.