Publications by authors named "Christopher L Hallemeier"

93 Publications

Predicting Adverse Pathologic Features and Clinical Outcomes of Resectable Pancreas Cancer With Preoperative CA 19-9.

Front Oncol 2021 11;11:651119. Epub 2021 May 11.

Department of Radiation Oncology, Mayo Clinic, Rochester, MN, United States.

Background: We evaluated preoperative CA 19-9 levels in patients with resected pancreatic cancer to analyze whether they were predictive of clinical outcomes and could help select patients for additional therapy. We hypothesized that elevated CA 19-9 would be associated with worse pathologic findings and oncologic outcomes.

Methods: This study assessed 509 patients with non-metastatic pancreatic adenocarcinoma who underwent resection at our institution from 1995-2011 and had preoperative CA 19-9 recorded. No patients received neoadjuvant therapy. CA 19-9 level was analyzed as a continuous and a dichotomized (> . ≤ 55 U/mL) variable using logistic and Cox models.

Results: Median follow-up was 7.8 years, and the median age was 66 years (33-90). 64% of patients had elevated preoperative CA 19-9 (median: 141 U/mL), that did not correlate with bilirubin level or tumor size. Most patients had ≥ T3 tumors (72%) and positive lymph nodes (62%). The rate of incomplete (R1 or R2) resection was 19%. Increasing preoperative CA 19-9 was associated with extra-pancreatic extension (p=0.0005), lymphovascular space invasion (p=0.0072), incomplete resection [HR (95% CI) 2.0 (1.2-3.5)], and lower OS [HR = 1.6 (1.3-2.0)]. Each doubling in preoperative CA 19-9 value was associated with an 8.3% increased risk of death [HR = 1.08 (1.02-1.15)] and a 10.0% increased risk of distant recurrence [HR = 1.10 (1.02-1.19)]. Patients classified as non-secretors had comparable outcomes to patients with normal CA 19-9.

Conclusions: Elevated preoperative CA 19-9 level was associated with adverse pathologic features, incomplete resection, and inferior clinical outcomes. Neither tumor size nor bilirubin confound an elevated CA 19-9 level. Preoperative CA 19-9 level may help select patients for additional therapy.
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http://dx.doi.org/10.3389/fonc.2021.651119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147692PMC
May 2021

Liver Metastasis-Directed Ablative Radiotherapy in Pancreatic Cancer Offers Prolonged Time Off Systemic Therapy in Selected Patients: Data From a Multi-institutional Retrospective Study.

Pancreas 2021 May-Jun 01;50(5):736-743

Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA.

Objectives: We evaluated the outcomes of metastatic pancreatic cancer (MPC) patients who underwent liver metastases (LMs)-directed ablative radiotherapy (RT) and sought to characterize patients with more favorable prognosis.

Methods: A retrospective analysis of 76 MPC patients who underwent ablative RT (median dose, 50 Gy) to LM at 3 academic centers between 2008 and 2018 was performed. Endpoints were local control (LC), progression-free survival, and overall survival (OS) since RT.

Results: Median follow-up was 10.9 months. Liver metastases were metachronous in 68%. Before RT, LM was responsive/stable on chemotherapy (CTX) in 36% whereas progressive in 43%. Median carbohydrate antigen 19-9 (CA 19-9) at RT was 334 U/mL. After RT, 32% had ≥6 months of CTX break. Twelve-month outcomes were: LC, 66%; progression-free survival, 7%; and OS, 38%. On multivariable analysis, Eastern Cooperative Oncology Group 2-3 (hazard ratio [HR], 13.49; P < 0.01), progressive LM on CTX (HR, 3.26; P < 0.01), and higher CA 19-9 (log10 scale; HR, 1.39; P < 0.01) at RT predicted worse OS.

Conclusions: Ablative RT to LM in setting of MPC may offer LC of systemic disease and thus quality time off CTX. Selected patients with good performance status, stable/responsive LM on CTX, and lower CA 19-9 have more favorable prognosis.
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http://dx.doi.org/10.1097/MPA.0000000000001822DOI Listing
May 2021

Malignancies diagnosed before and after anal squamous cell carcinomas: A SEER registry analysis.

Cancer Med 2021 Jun 7;10(11):3575-3583. Epub 2021 May 7.

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, USA.

Background: Increased risk of a second primary malignancy (SPM) before or after diagnosis of anal squamous cell carcinoma (ASCC) has been reported in a previous single-institution study. We hypothesize that patients diagnosed with ASCC are at increased risk for developing SPMs before or after the diagnosis of ASCC. The primary objective of this study was to identify the diagnoses of cancer most likely to occur as SPMs before or after ASCC.

Methods: This work employs the Surveillance, Epidemiology, and End Results (SEER) Program registry data to conduct a US-population-based study of patients diagnosed with ASCC between 1975 and 2016. In patients diagnosed with ASCC, we evaluated the risk of SPMs and the risk of developing ASCC as an SPM after another cancer using standardized incidence ratios (SIR) for all SPMs by calculating the ratio of observed events in the ASCC cohort compared to expected (O/E) events in a matched reference cohort of the general population.

Results: A total of 7,594 patients with primary ASCC were included. Patients with ASCC were at increased risk of the diagnosis of an SPM (SIR = 1.45), particularly cancers of the lung, vulva, oropharynx, or colon. Patients with ASCC had an increased rate of previous malignancy (SIR = 1.23), especially Kaposi sarcoma or vulvar cancer. Overall elevated incidence of SPMs was unrelated to prior radiation treatment. Radiation treatment was associated with increased risk for SPMs in the female genital system but appeared protective against prostate cancer as SPMs.

Conclusions: Our findings support increased surveillance and screening for second malignancies in patients with these diagnoses, as patients with ASCC are often either survivors of a prior cancer diagnosis or are at increased risk of developing later malignancies.
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http://dx.doi.org/10.1002/cam4.3909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178496PMC
June 2021

Intensity modulated radiotherapy for anal canal squamous cell carcinoma: A 16-year single institution experience.

Clin Transl Radiat Oncol 2021 May 23;28:17-23. Epub 2021 Feb 23.

Department of Radiation Oncology, Mayo Clinic, Rochester, MN, United States.

Introduction: To report long-term efficacy and adverse events (AEs) associated with intensity modulated radiotherapy (IMRT) for patients with anal canal squamous cell carcinoma (ASCC).

Materials And Methods: This was a retrospective review of patients with ASCC who received curative-intent IMRT and concurrent chemotherapy (98%) between 2003 and 2019. Overall survival (OS), colostomy-free survival (CFS), and progression-free survival (PFS) were estimated using the Kaplan-Meier method. The cumulative incidence of local recurrence (LR), locoregional recurrence (LRR), and distant metastasis (DM) were reported. Acute and late AEs were recorded per National Cancer Institute Common Terminology Criteria for AEs.

Results: 127 patients were included. The median patient age was 63 years (interquartile range [IQR] 55-69) and 79% of patients were female. 33% of patients had T3-4 disease and 68% had clinically involved pelvic or inguinal lymph nodes (LNs).The median patient follow-up was 47 months (IQR: 28-89 months). The estimated 4-year OS, CFS, and PFS were 81% (95% confidence interval [CI]: 73%-89%), 77% (95% CI: 68%-86%), and 78% (95% CI: 70%-86%), respectively. The 4-year cumulative incidences of LR, LRR, and DM were 3% (95% CI: 1%-9%), 9% (95% CI: 5%-17%), and 10% (95% CI: 6%-18%), respectively. Overall treatment duration greater than 39 days was associated with an increased risk of LRR (Hazard Ratio [HR]: 5.2, 95% CI: 1.4-19.5, p = 0.015). The most common grade 3+ acute AEs included hematologic (31%), gastrointestinal (GI) (17%), dermatologic (16%), and pain (15%). Grade 3+ late AEs included: GI (3%), genitourinary (GU) (2%), and pain (1%). Current smokers were more likely to experience grade 3+ acute dermatologic toxicity compared to former or never smokers (34% vs. 7%, p < 0.001).

Conclusions: IMRT was associated with favorable toxicity rates and long-term efficacy. These data support the continued utilization of IMRT as the preferred treatment technique for patients with ASCC.
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http://dx.doi.org/10.1016/j.ctro.2021.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943964PMC
May 2021

Chemoradiotherapy for patients with locally advanced or unresectable extra-hepatic biliary cancer.

J Gastrointest Oncol 2020 Dec;11(6):1408-1420

Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.

Background: Although surgical resection is the preferred curative-intent treatment option for patients with non-metastatic, extra-hepatic biliary cancer (EBC), radiotherapy (RT) or chemoradiotherapy (CRT) may be utilized in select cases when surgical resection is not feasible. The purpose of this study is to report the efficacy and adverse events (AEs) associated with CRT for patients with locally advanced and unresectable EBC.

Methods: This was a retrospective cohort study of patients with EBC, including extra-hepatic cholangiocarcinoma or gallbladder cancer, deemed inoperable who received RT between 1998 and 2018. The median RT dose was 50.4 Gy in 28 fractions and 94% received concurrent 5-fluorouracil. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS) from the start of RT. The cumulative incidence of local progression (LP), locoregional progression (LRP), and distant metastasis (DM) were reported with death as a competing risk. Cox proportional hazards regression models were used to assess for correlation between patient and treatment characteristics and outcomes.

Results: Forty-eight patients were included for analysis. The median OS was 12.0 months [95% confidence interval (CI): 2.3-73.2 months]. The 2-, 3-, and 5-year OS were 33% (95% CI: 22-50%), 20% (95% CI: 11-36%), and 7% (95% CI: 2-20%), respectively. The 2-year PFS, LP, LRP, and DM were 21% (95% CI: 12-36%), 27% (95% CI: 17-44%), 31% (95% CI: 20-48%), and 33% (95% CI: 22-50%), respectively. On univariate analysis, biologically effective dose (BED) >59.5 Gy was associated with improved OS [hazard ratio (HR): 0.40, 95% CI: 0.18-0.92, P=0.03] and PFS (HR: 0.37, 95% CI: 0.16-0.84, P=0.02) and primary tumor size (per 1 cm increase) was associated with worsened PFS (HR: 1.29, 95% CI: 1.02-1.63, P=0.04). BED >59.5 Gy remained associated with PFS on multivariate analysis (HR: 0.34, 95% CI: 0.15-0.78, P=0.01). Treatment-related grade 3+ acute and late gastrointestinal AEs occurred in 13% and 17% of patients, respectively.

Conclusions: RT is associated with 3- and 5-year survival in a subset of patients with unresectable EBC. Further exploration of the role of RT as part of a multi-modality curative treatment strategy is warranted.
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http://dx.doi.org/10.21037/jgo-20-245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807283PMC
December 2020

Randomized Trials for Esophageal, Liver, Pancreas, and Rectal Cancers.

Int J Radiat Oncol Biol Phys 2021 Feb;109(2):305-311

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, New Jersey. Electronic address:

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http://dx.doi.org/10.1016/j.ijrobp.2020.09.033DOI Listing
February 2021

Margin negative resection and pathologic downstaging with multiagent chemotherapy with or without radiotherapy in patients with localized pancreas cancer: A national cancer database analysis.

Clin Transl Radiat Oncol 2021 Mar 16;27:15-23. Epub 2020 Dec 16.

Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06520, USA.

Purpose: Margin-negative (R0) resection is the only potentially curative treatment for patients with pancreatic ductal adenocarcinoma (PDAC). Pre-operative multi-agent chemotherapy alone (MAC) or MAC followed by pre-operative radiotherapy (MAC + RT) may be used to improve resectability and potentially survival. However, the optimal pre-operative regimen is unknown.

Methods: Patients with non-metastatic PDAC from 2006 to 2016 who received pre-operative MAC or MAC + RT before oncologic resection were identified in the National Cancer Database. Univariable and multivariable (MVA) associates with R0 resection were identified with logistic regression, and survival was analyzed secondarily with the Kaplan Meier method and Cox regression analysis.

Results: 4,599 patients were identified (MAC: 3,109, MAC + RT: 1,490). Compared to those receiving MAC, patients receiving MAC + RT were more likely to have cT3-4 disease (76% vs 64%, p < 0.001) and cN + disease (33% vs 29%, p = 0.010), but were less likely to have ypT3-4 disease (59% vs 74%, p < 0.001) and ypN + disease (32% vs 55%, p < 0.001) and more likely to have a pathologic complete response (5% vs 2%, p < 0.001) and R0 resection (86% vs 80%, p < 0.001). On MVA, MAC + RT (OR 1.58, 95% CI 1.33-1.89, p < 0.001), evaluation at an academic center (OR 1.33, 95% CI 1.14-1.56, p < 0.001), and female sex (OR 1.43, 95% CI 1.23-1.67, p < 0.001) were associated with higher odds of R0 resection, while cT3-4 disease (OR 0.81, 95% CI 0.68-0.96, p = 0.013) was associated with lower odds of R0 resection.

Conclusion: For patients with localized PDAC who receive pre-operative MAC, the addition of pre-operative RT was associated with improved rates of R0 resection and pathologic response.
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http://dx.doi.org/10.1016/j.ctro.2020.12.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772693PMC
March 2021

Costs of Definitive Chemoradiation, Surgery, and Adjuvant Radiation Versus De-Escalated Adjuvant Radiation per MC1273 in HPV+ Cancer of the Oropharynx.

Int J Radiat Oncol Biol Phys 2021 Jun 23;110(2):396-402. Epub 2020 Dec 23.

Division of Radiation Oncology, University of Tennessee, Knoxville, Tennessee. Electronic address:

Purpose: De-escalated treatment for human papillomavirus (HPV)+ oropharynx squamous cell carcinoma (OPSCC) has shown promising initial results. Health-care policy is increasingly focusing on high-value care. This analysis compares the cost of care for HPV+ OPSCC treated with definitive chemoradiation (CRT), surgery and adjuvant radiation (RT), and surgery and de-escalated CRT on MC1273.

Methods And Materials: MC1273 is a prospective, phase 2 study evaluating adjuvant CRT to 30 to 36 Gy plus docetaxel for HPV+ OPSCC after surgery for high-risk patients. Matched standard-of-care control groups were retrospectively identified for patients treated with definitive CRT or adjuvant RT. Standardized costs were evaluated before radiation, during treatment (during RT), and at short-term (6 month) and long-term (7-24 month) follow-up periods.

Results: A total of 56 definitive CRT, 101 adjuvant RT, and 66 MC1273 patients were included. The CRT arm had more T3-4 disease (63% vs 17-21%) and higher N2c-N3 disease (52% vs 20-24%) vs both other groups. The total treatment costs in the CRT, adjuvant RT, and MC1273 groups were $47,763 (standard deviation [SD], $19,060], $57,845 (SD, $17,480), and $46,007 (SD, $9019), respectively, and the chemotherapy and/or RT costs were $39,936 (SD, $18,480), $26,603 (SD, $12,542), and $17,864 (SD, $3288), respectively. The per-patient, per-month, average short-term follow-up costs were $3860 (SD, $10,525), $1072 (SD, $996), and $972 (SD, $833), respectively, and the long-term costs were $978 (SD, $2294), $485 (SD, $1156), and $653 (SD, $1107), respectively. After adjustment for age, T-stage, and N-stage, treatment costs remained lower for CRT and MC1273 versus adjuvant RT ($45,450 and $47,114 vs $58,590, respectively; P < .001), whereas the total per-patient, per-month follow-up costs were lower in the MC1273 study group and adjuvant RT versus CRT ($853 and $866 vs $2030, respectively; P = .03).

Conclusions: MC1273 resulted in 10% and 20% reductions in global costs compared with standard-of-care adjuvant RT and definitive CRT treatments. Substantial cost savings may be an added benefit to the already noted low toxicity and maintained quality of life of treatment per MC1273.
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http://dx.doi.org/10.1016/j.ijrobp.2020.12.021DOI Listing
June 2021

Proton beam radiotherapy for esophagus cancer: state of the art.

J Thorac Dis 2020 Nov;12(11):7002-7010

Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.

The majority of esophageal cancer patients are diagnosed with locoregionally confined disease, which is often amenable to curative intent therapy. Chemoradiotherapy (CRT) improves overall survival (OS) in stage II and III esophagus cancer in the neoadjuvant and definitive settings. Due to the close proximity of organs at risk (OARs), including lungs, heart, stomach, bowel, kidneys, and spinal cord, esophageal CRT can result in profound acute and late toxicities. Acute toxicities can include esophagitis, nausea, vomiting, fatigue, and cytopenias. Late complications may also occur months or years after completion of thoracic radiotherapy, including significant cardiac, pulmonary, liver, kidney, or bowel toxicities, which can be life-threatening or fatal. Photon-based radiotherapy exposes OARs to significant doses of radiation, whereas proton beam therapy (PBT) has unique physical properties, as it lacks an exit dose. This allows PBT to deliver, a more conformal dose to the target and minimize the volume of OARs exposed to radiation. This dosimetric advantage may portend an increased therapeutic ratio of CRT for esophagus cancer. The objective of this review is to discuss the evolution of photon and proton-based radiotherapy techniques, rationale, dosimetric and clinical studies comparing outcomes of photon- and proton-based techniques, ongoing prospective trials, and future directions of PBT as a means of reducing toxicity and improving oncologic outcomes for patients with esophagus cancer.
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http://dx.doi.org/10.21037/jtd-2019-cptn-06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711403PMC
November 2020

Multi-institutional Evaluation of Curative Intent Chemoradiotherapy for Patients With Clinical T1N0 Esophageal Adenocarcinoma.

Adv Radiat Oncol 2020 Sep-Oct;5(5):951-958. Epub 2020 Apr 27.

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Purpose: To evaluate the safety and efficacy of definitive chemoradiotherapy (CRT) for patients with clinical T1N0M0 esophageal adenocarcinoma.

Methods And Materials: This was a retrospective study of patients with clinical T1N0 adenocarcinoma of the esophagus treated with curative-intent CRT between 2004 and 2017 at 2 tertiary care centers. Patients received CRT instead of esophagectomy owing to medical comorbidities or patient preference. Toxicities were evaluated according to Common Terminology Criteria for Adverse Events version 4.03. The Kaplan-Meier method was used to estimate overall, progression-free, and disease-specific survivals.

Results: Twenty-eight patients were included for analysis. Median age was 76 years (range 55-90). The majority of patients were male (93%) and had a history of Barrett's esophagus (71%). Tumor characteristics included distal esophagus location (93%), clinical stage T1b (86%), and median length of 2 cm (range, 1-9). Prior endoscopic resection was performed in 57%.The median follow-up was 44 months (range, 4-146). The acute grade 3 adverse events were observed in 7 patients (25%). One patient died of complications potentially related to chemoradiation. Eight patients (29%) had disease progression at a median of 7.6 months after CRT. First site of progression was local only (14%), local and regional (11%), or distant (4%). Salvage locally directed treatment was performed in 3 of 4 patients with local-only recurrence. The 3-year overall survival, progression-free, and disease-specific rates were 78%, 62%, and 81%, respectively.

Conclusion: CRT is a safe and effective curative treatment strategy for select patients with clinical T1N0M0 esophageal adenocarcinoma.
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http://dx.doi.org/10.1016/j.adro.2020.03.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557140PMC
April 2020

Acute Toxicities and Short-Term Patient Outcomes After Intensity-Modulated Proton Beam Radiation Therapy or Intensity-Modulated Photon Radiation Therapy for Esophageal Carcinoma: A Mayo Clinic Experience.

Adv Radiat Oncol 2020 Sep-Oct;5(5):871-879. Epub 2020 May 19.

Department of Radiation Oncology, Mayo Clinic Hospital, Phoenix, Arizona.

Purpose: Intensity modulated proton beam radiation therapy (IMPT) has a clinically significant dosimetric advantage over intensity modulated photon radiation therapy (IMRT) for the treatment of patients with esophageal cancer, particularly for sparing the heart and lungs. We compared acute radiation therapy-related toxicities and short-term clinical outcomes of patients with esophageal cancer who received treatment with IMPT or IMRT.

Methods And Materials: We retrospectively reviewed the electronic health records of consecutive adult patients with esophageal cancer who underwent concurrent chemoradiotherapy with IMPT or IMRT in the definitive or neoadjuvant setting from January 1, 2014, through June 30, 2018, with additional follow-up data collected through January 31, 2019. Treatment-related toxicities were evaluated per the Common Terminology Criteria for Adverse Events, version 4. Survival outcomes were estimated with the Kaplan-Meier method.

Results: A total of 64 patients (32 per group) were included (median follow-up time: 10 months for IMPT patients vs 14 months for IMRT patients). The most common radiation therapy regimen was 45 Gy in 25 fractions, and 80% of patients received a simultaneous integrated boost to a median cumulative dose of 50 Gy. Similar numbers of IMPT patients (n = 15; 47%) and IMRT patients (n = 18; 56%) underwent surgery ( = .07), with no difference in pathologic complete response rates (IMPT: n = 5; 33% vs IMRT: n = 7; 39%; = .14). At 1 year, the clinical outcomes also were similar for IMPT and IMRT patients, respectively. Local control was 92% versus 84% ( = .87), locoregional control 92% versus 80% ( = .76), distant metastasis-free survival 87% versus 65% ( = .08), progression-free survival 71% versus 45% ( = .15), and overall survival 74% versus 71% ( = .62). The rate of acute treatment-related grade 3 toxicity was similar between the groups ( = .71).

Conclusions: In our early experience, IMPT is a safe and effective treatment when administered as part of definitive or trimodality therapy. Longer follow-up is required to evaluate the effectiveness of IMPT.
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http://dx.doi.org/10.1016/j.adro.2020.04.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557123PMC
May 2020

Clinical Implementation of Preoperative Short-Course Pencil Beam Scanning Proton Therapy for Patients With Rectal Cancer.

Adv Radiat Oncol 2020 Sep-Oct;5(5):865-870. Epub 2020 May 22.

Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.

Purpose: For treatment of rectal cancer, pencil beam scanning proton therapy (PBS-PT) may reduce radiation exposure to normal tissues compared with 3-dimensional conformal photon radiation therapy (3DCRT) or volumetric modulated arc photon radiation therapy (VMAT). The purpose of this study was to report the clinical implementation and dosimetric analysis of preoperative short-course PBS-PT for rectal cancer.

Methods And Materials: Eleven patients with stage IIA-IVB rectal cancer received preoperative short-course (25 Gy in 5 fx) PBS-PT between 2018 and 2019 preceding curative-intent total mesorectal excision. PBS-PT plans were generated using single-field optimization with 2 posterior-oblique fields. Verification computed tomography scans were performed on the first 3 days of treatment. Each patient had a backup 3DCRT and VMAT plan.

Results: Clinical target volume coverage was similar between PBS-PT, 3DCRT, and VMAT. PBS-PT had statistically significant reductions in dose to the small bowel, large bowel, bladder, and femoral heads across multiple dosimetric parameters. All patients completed PBS-PT as planned without need for replanning. All computed tomography verification scans demonstrated good target coverage with clinical target volume V100 > 95%.

Conclusions: Preoperative short-course PBS-PT has been successfully implemented and offers a significant reduction of dose to normal tissues. Prospective studies are warranted to evaluate if dosimetric advantages translate into clinical benefit.
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http://dx.doi.org/10.1016/j.adro.2020.05.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557137PMC
May 2020

Patient-Reported Quality of Life Before and After Chemoradiation for Intact Pancreas Cancer: A Prospective Registry Study.

Pract Radiat Oncol 2021 Jan-Feb;11(1):e63-e69. Epub 2020 Jul 23.

Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota. Electronic address:

Purpose: Our purpose was to determine the effect of chemoradiotherapy (CRT) on patient-reported quality of life (QOL) for patients with intact pancreas cancer.

Methods And Materials: We reviewed a prospective QOL registry for patients with intact, clinically localized pancreatic ductal adenocarcinoma treated with CRT between June 2015 and November 2018. QOL was assessed pre-CRT (immediately before CRT, after neoadjuvant chemotherapy) and at the completion of CRT with the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) and its component parts: FACT-General (FACT-G) and hepatobiliary cancer subscore (HCS). A minimally important difference from pre-CRT was defined as ≥ 6, 5, and 8 points for FACT-G, HCS, and FACT-Hep, respectively.

Results: Of 157 patients who underwent CRT, 100 completed both pre- and post-CRT surveys and were included in the primary analysis. Median age at diagnosis was 65 years (range, 23-90). National Comprehensive Cancer Network resectability status was resectable (3%), borderline resectable (40%), or locally advanced (57%). Folinic acid, 5-fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) (75%) or gemcitabine and nab-paclitaxel (42%) were given for a median of 6 cycles (range, 0-42) before CRT. Radiation therapy techniques included 3-dimensional conformal (22%), intensity modulated photon (55%), and intensity modulated proton (23%) radiation therapy to a median dose of 50 Gy (range, 36-62.5). Concurrent chemotherapy was most commonly capecitabine (82%). Sixty-three patients (63%) had surgery after CRT. The mean decline in FACT-G, HCS subscale, and FACT-Hep from pre- to post-CRT was 3.5 (standard deviation [SD], 13.7), 1.7 (SD 7.8), and 5.2 (SD 19.4), respectively. Each of these changes were statistically significant, but did not meet the minimally important difference threshold. Pancreatic head tumor location was associated with decline in FACT-Hep. Nausea was the toxicity with the greatest increase from pre- to post-CRT by both physician-assessment and patient-reported QOL.

Conclusions: For patients with intact pancreatic adenocarcinoma, modern CRT is well tolerated with minimal decline in QOL during treatment.
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http://dx.doi.org/10.1016/j.prro.2020.06.011DOI Listing
July 2020

Carbon Ion Radiotherapy in the Treatment of Pancreatic Cancer: A Review.

Pancreas 2020 07;49(6):737-743

Department of Radiation Oncology, Mayo Clinic, Rochester, MN.

Pancreatic cancer is the fourth most common cause of cancer-related morality worldwide, and the prognosis remains poor despite aggressive therapy. Carbon ion radiotherapy has favorable radiobiological and physical characteristics in the treatment, including a higher linear energy transfer and higher relative biological effectiveness, which increase the cell kill while potentially reducing toxicities to nearby normal tissues. Although small, early clinical studies have shown promise in both the resectable and unresectable settings to improve local control and overall survival while minimizing toxicities. Currently, there are several trials, including 2 sponsored by institutions in the United States, investigating the role of carbon ion radiotherapy for the treatment of locally advanced pancreatic cancer.
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http://dx.doi.org/10.1097/MPA.0000000000001566DOI Listing
July 2020

Time to Reconsider Staging Laparoscopy in Pancreatic Cancer?

J Clin Oncol 2020 09 23;38(25):2944-2945. Epub 2020 Jun 23.

Gabrielle W. Peters, MD, Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT; Christopher L. Hallemeier, MD, Department of Radiation Oncology, Mayo Clinic, Rochester, MN; and Krishan R. Jethwa, MD, Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT.

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http://dx.doi.org/10.1200/JCO.20.00996DOI Listing
September 2020

Patterns of inguinal lymph node metastases in anal canal cancer and recommendations for elective clinical target volume (CTV) delineation.

Radiother Oncol 2020 08 15;149:128-133. Epub 2020 May 15.

Department of Radiation Oncology, Mayo Clinic, Rochester, USA. Electronic address:

Purpose: Optimal clinical target volume (CTV) for inguinal lymph node irradiation in anal cancer remains uncertain. This study documents the location of radiographically involved inguinal lymph nodes and proposes guidelines for CTV delineation.

Materials And Methods: Patients with anal canal squamous cell carcinoma with inguinal lymph node metastases were identified. Criteria for lymph node involvement included: >15 mm short axis or suspicious morphology on CT or MRI, increased avidity on 18-FDG-PET, or positive biopsy. Distances from center of involved nodes to femoral vessels and inferior pubic symphysis were measured.

Results: Forty patients with 79 inguinal lymph nodes were included. Relative to right femoral vessels, nodes were located: 12:00 (n = 6); 1:00 (n = 28); 2:00 (n = 35), 3:00 (n = 5); 4:00 (n = 1); 10:00 (n = 1); 11:00 (n = 3). No nodes were identified lateral or posterior to vessels. Published AGITG guidelines covered 68% of nodes anteriorly and 85% medially. Margins from nearest femoral vessel to cover 95% of nodes were 30 mm anteriorly and 26 mm medially. Inferior margin to cover 95% of nodes was 14 mm below inferior pubic symphysis. Proposed borders include cranial, where external iliac vessels leave bony pelvis; caudal, 14 mm below inferior pubic symphysis; posterior, posterior border of femoral vessels; lateral, lateral border of femoral vessels; anterior, 30 mm margin on femoral vessels and medial, 26 mm margin on femoral vessels, including radiographically suspicious nodes.

Conclusions: Published guidelines for inguinal CTV in anal cancer may result in inadequate coverage of high risk areas. Updated guidelines based on this study ensure coverage of at-risk areas.
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http://dx.doi.org/10.1016/j.radonc.2020.05.018DOI Listing
August 2020

Managing treatment-related uncertainties in proton beam radiotherapy for gastrointestinal cancers.

J Gastrointest Oncol 2020 Feb;11(1):212-224

Department of Radiation Oncology, Mayo Clinic Phoenix, Phoenix, AZ, USA.

In recent years, there has been rapid adaption of proton beam radiotherapy (RT) for treatment of various malignancies in the gastrointestinal (GI) tract, with increasing number of institutions implementing intensity modulated proton therapy (IMPT). We review the progress and existing literature regarding the technical aspects of RT planning for IMPT, and the existing tools that can help with the management of uncertainties which may impact the daily delivery of proton therapy. We provide an in-depth discussion regarding range uncertainties, dose calculations, image guidance requirements, organ and body cavity filling consideration, implanted devices and hardware, use of fiducials, breathing motion evaluations and both active and passive motion management methods, interplay effect, general IMPT treatment planning considerations including robustness plan evaluation and optimization, and finally plan monitoring and adaptation. These advances have improved confidence in delivery of IMPT for patients with GI malignancies under various scenarios.
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http://dx.doi.org/10.21037/jgo.2019.11.07DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052758PMC
February 2020

The emerging role of proton therapy for esophagus cancer.

J Gastrointest Oncol 2020 Feb;11(1):144-156

Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.

Chemoradiotherapy (CRT) plays an essential role in the treatment of esophageal cancer as either curative or neoadjuvant therapy. When delivered with conventional photon-based techniques, multiple adjacent organs at risk including the heart, lungs, kidneys, liver, stomach, and bowel, receive considerable radiation dose which may contribute to acute and late adverse events (AEs). Proton beam therapy (PBT) offers a reduction in radiation exposure to these organs and potentially an improvement in the therapeutic ratio. Herein we discuss the emerging role of PBT for esophageal cancer, including rationale, treatment planning, early dosimetric and clinical comparisons of PBT with photon-based techniques, ongoing prospective trials, and potential areas of opportunity for the incorporation of PBT with the goal of improving outcomes for patients with esophageal cancer.
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http://dx.doi.org/10.21037/jgo.2019.11.04DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052753PMC
February 2020

A brief overview of the use of proton beam radiotherapy for gastrointestinal cancers.

J Gastrointest Oncol 2020 Feb;11(1):139-143

Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA. (Email:

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http://dx.doi.org/10.21037/jgo.2019.07.06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052778PMC
February 2020

Neutrophil to lymphocyte ratio as a prognostic marker in metastatic gallbladder cancer.

HPB (Oxford) 2020 10 28;22(10):1490-1495. Epub 2020 Feb 28.

Department of Oncology, Mayo Clinic, Rochester, MN, USA. Electronic address:

Background: Neutrophil-to-lymphocyte ratio (NLR) has been used as an inflammation based prognostic marker for various malignancies. This study evaluated the association between NLR and overall survival (OS) in patients with metastatic gallbladder cancer (GBC) METHODS: An optimal cut off point for NLR was identified by plotting spline-based hazard ratio curves to identify a threshold effect and patients were divided into two groups, ≥5 or <5. Kaplan-Meier curves were plotted for NLR≥5 and NLR<5 and OS between the two groups.

Results: Of the 231 patients included, 138 (60%) had NLR <5 and 93 (40%) had NLR ≥5. There were no significant differences noted in gender, race, and administration of chemotherapy between the two groups. On univariable analysis, patients with NLR ≥5 had a significantly poor OS compared to those with NLR <5 (Median OS: 3.6 vs 8.7 months, p < 0.001). On multivariable analysis, adjusting for age, performance status, albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, bilirubin, platelet count and no administration of chemotherapy, NLR of ≥5 was associated with a worse OS compared to NLR <5 (HR: 1.70, 95%CI:1.20-2.39, p < 0.05).

Conclusion: The current study demonstrates that NLR ≥5 is an independent predictor of poor prognosis in patients with metastatic GBC.
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http://dx.doi.org/10.1016/j.hpb.2020.02.002DOI Listing
October 2020

Association of tumor genomic factors and efficacy for metastasis-directed stereotactic body radiotherapy for oligometastatic colorectal cancer.

Radiother Oncol 2020 05 27;146:29-36. Epub 2020 Feb 27.

Department of Radiation Oncology, Mayo Clinic, Rochester, United States. Electronic address:

Purpose/objective(s): To report tumor genomic factors associated with overall survival (OS) and local failure (LF) for patients with colorectal cancer (CRC) who received metastasis-directed stereotactic body radiation therapy (SBRT).

Materials/methods: This was a retrospective review of patients with CRC who received metastasis-directed SBRT. Tumor genomic alterations were identified through KRAS, BRAF, or a 50-gene next generation sequencing panel. OS and LF were estimated using Kaplan-Meier and competing-risk methods.

Results: Eighty-five patients and 109 lesions were treated between 2008 and 2018. The median patient follow-up was 50 months (IQR: 28-107). The median and 5-year OS was 34 months and 26% (95% CI: 16-41%), respectively. The 2-year cumulative incidence of LF was 30% (95% CI: 23-41%). Univariate associates with OS included patient age ≥60 years, bone metastasis, increasing tumor size, KRAS mutation, and combined KRAS and TP53 mutation, while increasing tumor size, bone metastasis, biologically effective dose <100 Gy, and combined KRAS and TP53 mutation were associated with LF. Multivariate associates with OS included patient age ≥60 years (HR: 2.4, 95% CI: 1.2-4.8, p = 0.01), lesion size per 1 cm (HR: 1.3, 95% CI: 1.1-1.5, p < 0.01), and KRAS mutation (HR: 2.2, 95% CI: 1.2-4.3, p < 0.01), while no multivariable model for LF retained more than a single variable.

Conclusion: Genomic factors, in particular KRAS and TP53 mutation, may assist in patient selection and radiotherapeutic decision-making for patients with oligometastatic CRC. Prospective validation, ideally with genomic correlation of all irradiated metastases, is warranted.
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http://dx.doi.org/10.1016/j.radonc.2020.02.008DOI Listing
May 2020

Gastrointestinal Cancers: Moving the Needle for Rectal, Gastroesophageal, Pancreaticobiliary, and Liver Cancers.

Int J Radiat Oncol Biol Phys 2020 03;106(4):653-662

Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Rutgers University, New Brunswick, New Jersey. Electronic address:

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http://dx.doi.org/10.1016/j.ijrobp.2019.12.011DOI Listing
March 2020

Cystic Lymph Node Metastases From HPV-Associated Squamous Cell Carcinoma of the Anal Canal.

Pract Radiat Oncol 2020 Mar - Apr;10(2):e111-e115. Epub 2019 Dec 19.

Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota. Electronic address:

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http://dx.doi.org/10.1016/j.prro.2019.12.008DOI Listing
November 2020

Prediction of Severe Lymphopenia During Chemoradiation Therapy for Esophageal Cancer: Development and Validation of a Pretreatment Nomogram.

Pract Radiat Oncol 2020 Jan - Feb;10(1):e16-e26. Epub 2019 Jul 29.

Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Electronic address:

Introduction: In patients with esophageal cancer, occurrence of severe radiation-induced lymphopenia during chemoradiation therapy has been associated with worse progression-free and overall survival. The aim of this study was to develop and validate a pretreatment clinical nomogram for the prediction of grade 4 lymphopenia.

Methods And Materials: A development set of consecutive patients who underwent chemoradiation therapy for esophageal cancer and an independent validation set of patients from another institution were identified. Grade 4 lymphopenia was defined as an absolute lymphocyte count nadir during chemoradiation therapy of <0.2 × 10/μL. Multivariable logistic regression analysis was used to create a prediction model for grade 4 lymphopenia in the development set, which was internally validated using bootstrapping and externally validated by applying the model to the validation set. The model was presented as a nomogram yielding 4 risk groups.

Results: Among 860 included patients, 322 (37%) experienced grade 4 lymphopenia. Higher age, larger planning target volume in interaction with lower body mass index, photon- rather than proton-based therapy, and lower baseline absolute lymphocyte count were predictive in the final model (corrected c-statistic, 0.76). External validation in 144 patients, among whom 58 (40%) had grade 4 lymphopenia, yielded a c-statistic of 0.71. Four nomogram-based risk groups yielded predicted risk rates of 10%, 24%, 43%, and 70%, respectively.

Conclusions: A pretreatment clinical nomogram was developed and validated for the prediction of grade 4 radiation-induced lymphopenia during chemoradiation therapy for esophageal cancer. The nomogram can risk stratify individual patients suitable for lymphopenia-mitigating strategies or potential future therapeutic approaches to ultimately improve survival.
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http://dx.doi.org/10.1016/j.prro.2019.07.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564893PMC
June 2020

A Comparison of Patient-Reported Health-Related Quality of Life During Proton Versus Photon Chemoradiation Therapy for Esophageal Cancer.

Pract Radiat Oncol 2019 Nov 13;9(6):410-417. Epub 2019 Jul 13.

Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota. Electronic address:

Purpose: The purpose of this study was to compare Functional Assessment of Cancer Therapy-Esophagus (FACT-E) questionnaire changes during proton (PRT) or photon (XRT) chemoradiation therapy (CRT) for esophageal cancer (EC).

Methods And Materials: We reviewed patients enrolled in a prospective registry who received preoperative or definitive CRT for EC. Patients completed the FACT-E before CRT and during the last week of CRT. Analysis of variance testing was used to assess associations between patient and treatment characteristics and FACT-E score changes.

Results: One hundred twenty-five patients completed a baseline and posttreatment FACT-E; 63 received XRT and 62 received PRT. The mean age was 65 years; the PRT group was older (68 vs 64 years, P = .0063). The following characteristics were similar between cohorts: 83% male, 78% adenocarcinoma, and 89% stage II-III. The radiation therapy prescription dose was higher in the PRT group (≥50 Gy in 94% vs 67%, P < .0001), whereas the median clinical target volume was smaller in the PRT group (553 vs 668 cm, P = .013). Most (96%) received concurrent weekly carboplatin-paclitaxel. The mean FACT-E score was 136.3 (standard deviation [SD] 21.0) at baseline and 119.6 (SD 24.8) post-CRT, with mean change of -16.7 (SD 19.8). Baseline scores were comparable between XRT and PRT groups (135.9 vs 136.7, P = .82). On univariate and multivariate analyses, less mean decline in FACT-E score was observed for PRT versus XRT (-12.7 vs -20.6, P = .026) and for trimodality versus definitive therapy (-13.0 vs -22.5, P = .008).

Conclusions: For patients receiving CRT for EC, PRT was associated with less decline in FACT-E scores compared with XRT.
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http://dx.doi.org/10.1016/j.prro.2019.07.003DOI Listing
November 2019

Local excision for patients with stage I anal canal squamous cell carcinoma can be curative.

J Gastrointest Oncol 2019 Apr;10(2):171-178

Department of Medical Oncologyy, Mayo Clinic, Rochester, MN, USA.

Background: Definitive concurrent chemoradiation is the current standard of care for all stage I anal canal squamous cell carcinoma. Local excision as primary treatment for selected stage I lesions has been reported in the literature but is not currently recommended by major guidelines. We herein compared the oncologic outcomes of patients with stage I anal canal squamous cell carcinoma treated with local excision alone versus chemoradiation to determine if there are any significant differences in outcomes including disease free survival, overall survival (OS) and local failure rate.

Methods: A retrospective review of all patients treated for stage I anal canal squamous cell carcinoma between 1990 and 2016 was conducted. Data collected included baseline demographics, staging studies, pathology, treatment received, relapse pattern and survival.

Results: A total of 57 patients were treated for stage I anal canal squamous cell carcinoma between 1990 and 2016; 13 were treated with local excision alone and 44 were treated with chemoradiation therapy. Baseline characteristics in both cohorts of patients were comparable. Median follow-up duration of the local excision and the chemoradiation cohorts were 106 and 70 months, respectively. Of the 13 patients in local excision cohort, two patients had disease recurrence, at 21 and 97 months from the diagnosis. Both patients were long term survivors with salvage treatment. In chemoradiation cohort, 1 out of 44 patients had a local recurrence at 1 year who underwent curative resection. Five-year progression free survival (PFS) of subjects in local excision cohort and chemoradiation cohort were 91% and 83%, respectively (P=0.57).

Conclusions: Local excision as primary treatment may be safe and effective for a selected group of stage I anal canal squamous cell carcinoma patients.
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http://dx.doi.org/10.21037/jgo.2018.12.12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6465491PMC
April 2019

Controversy in the Treatment of Localized Hepatocellular Carcinoma.

Int J Radiat Oncol Biol Phys 2018 12;102(5):1404

Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.

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http://dx.doi.org/10.1016/j.ijrobp.2018.08.042DOI Listing
December 2018

Long-term Clinical Outcomes and Safety Profile of SBRT for Centrally Located NSCLC.

Adv Radiat Oncol 2019 Apr-Jun;4(2):422-428. Epub 2019 Jan 24.

Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.

Purpose: Previous studies suggest that stereotactic body radiation therapy (SBRT) is associated with higher toxicity rates for central lung tumors relative to peripheral tumors when using 3 fraction SBRT. The initial results from Radiation Therapy Oncology Group study 0813 suggest a safe toxicity profile of SBRT administered in 5 fractions for central non-small cell lung cancer (NSCLC). We reviewed our institutional data to evaluate the safety and efficacy of SBRT for central NSCLC.

Methods And Materials: We reviewed our prospectively collected SBRT database for patients with central NSCLC who received SBRT between 2008 and 2014. The most frequent dose and fractionations were 50 Gy in 5 fractions (59%) and 48 Gy in 4 fraction (30%). Local control (LC), regional control, metastasis-free survival, and overall survival were calculated using Kaplan-Meier estimates. The National Cancer Institute Common Terminal Criteria for Adverse Events were used for toxicity grading.

Results: A total of 110 central lung tumors in 103 patients were included. The median age was 74 years (range, 40-95 years), and the median follow-up time of living patients was 50 months. The mean tumor size was 20 mm (range, 5-70 mm). The 5 year rate of LC, regional control, and distant control was 89%, 77%, and 82%, respectively. The median and 5-year overall survival were 3.5 years and 35%, respectively. No treatment variables were associated with tumor control or other clinical outcomes. A single patient experienced grade 3 radiation pneumonitis (0.97%). The rate of late toxicity grade ≥3 was 9.7% (grade 3, 7.7%; grade 4, 0.97%; grade 5, 0.97%) and included pneumonitis (3.9%), bronchial necrosis (2.9%), myocardial dysfunction (1.9%), and worsening heart failure (0.97%).

Conclusions: SBRT for central NSCLC provides high rates of LC. Despite excellent LC, patients remain at risk for regional and distant failure. The rate of grade 3 pneumonitis was consistent with that of prior reports. We observed low rates of grade 4-5 toxicity potentially attributable to SBRT. Our results contribute to the growing body of data in support of the safety of SBRT for central NSCLC.
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http://dx.doi.org/10.1016/j.adro.2019.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460233PMC
January 2019