Skin-directed radiation therapy for cutaneous lymphoma: The Mayo Clinic experience.

BACKGROUND: Focal or total skin radiation therapy can be used to treat mild to refractory cutaneous T-cell lymphoma. OBJECTIVE: To report the broad therapeutic benefit of radiation therapy for cutaneous T-cell lymphoma. METHODS: Retrospective, single-institution review of outcomes for skin-directed radiation therapy. RESULTS: Skin-directed radiation therapy showed a 99% response rate and 80% complete response rate after treatment regardless of involvement, severity, histopathologic subtype, dose, or fractionation. The overall in-field recurrence rate was 15%, and median time to recurrence was 296 days (range, 1-1884 days). Focal and hypofractionated regimens were similarly associated with disease response and rare toxicity. Short-term rates of secondary skin cancer after treatment were comparable to expected incidence in a patient population without radiation. LIMITATIONS: Large total number of treatments courses compared with overall number of patients. Heterogenous mix of treatment regimens (no standardization of dose or fraction number). CONCLUSIONS: Radiation therapy is a well-tolerated treatment option for properly selected patients with cutaneous T-cell lymphoma.

Effect of Doxepin Mouthwash or Diphenhydramine-Lidocaine-Antacid Mouthwash vs Placebo on Radiotherapy-Related Oral Mucositis Pain: The Alliance A221304 Randomized Clinical Trial.

Importance: Oral mucositis causes substantial morbidity during head and neck radiotherapy. In a randomized study, doxepin mouthwash was shown to reduce oral mucositis-related pain. A common mouthwash comprising diphenhydramine-lidocaine-antacid is also widely used. Objective: To evaluate the effect of doxepin mouthwash or diphenhydramine-lidocaine-antacid mouthwash for the treatment of oral mucositis-related pain. Design, Setting, and Participants: A phase 3 randomized trial was conducted from November 1, 2014, to May 16, 2016, at 30 US institutions and included 275 patients who underwent definitive head and neck radiotherapy, had an oral mucositis pain score of 4 points or greater (scale, 0-10), and were followed up for a maximum of 28 days. Interventions: Ninety-two patients were randomized to doxepin mouthwash (25 mg/5 mL water); 91 patients to diphenhydramine-lidocaine-antacid; and 92 patients to placebo. Main Outcome and Measures: The primary end point was total oral mucositis pain reduction (defined by the area under the curve and adjusted for baseline pain score) during the 4 hours after a single dose of doxepin mouthwash or diphenhydramine-lidocaine-antacid mouthwash compared with a single dose of placebo. The minimal clinically important difference was a 3.5-point change. The secondary end points included drowsiness, unpleasant taste, and stinging or burning. All scales ranged from 0 (best) to 10 (worst). Results: Among the 275 patients randomized (median age, 61 years; 58 [21%] women), 227 (83%) completed treatment per protocol. Mucositis pain during the first 4 hours decreased by 11.6 points in the doxepin mouthwash group, by 11.7 points in the diphenhydramine-lidocaine-antacid mouthwash group, and by 8.7 points in the placebo group. The between-group difference was 2.9 points (95% CI, 0.2-6.0; P = .02) for doxepin mouthwash vs placebo and 3.0 points (95% CI, 0.1-5.9; P = .004) for diphenhydramine-lidocaine-antacid mouthwash vs placebo. More drowsiness was reported with doxepin mouthwash vs placebo (by 1.5 points [95% CI, 0-4.0]; P = .03), unpleasant taste (by 1.5 points [95% CI, 0-3.0]; P = .002), and stinging or burning (by 4.0 points [95% CI, 2.5-5.0]; P < .001). Maximum grade 3 adverse events for the doxepin mouthwash occurred in 3 patients (4%); diphenhydramine-lidocaine-antacid mouthwash, 3 (4%); and placebo, 2 (2%). Fatigue was reported by 5 patients (6%) in the doxepin mouthwash group and no patients in the diphenhydramine-lidocaine-antacid mouthwash group. Conclusions and Relevance: Among patients undergoing head and neck radiotherapy, the use of doxepin mouthwash or diphenhydramine-lidocaine-antacid mouthwash vs placebo significantly reduced oral mucositis pain during the first 4 hours after administration; however, the effect size was less than the minimal clinically important difference. Further research is needed to assess longer-term efficacy and safety for both mouthwashes. Trial Registration: ClinicalTrials.gov Identifier: NCT02229539.

A Curative-Intent Trimodality Approach for Isolated Abdominal Nodal Metastases in Metastatic Colorectal Cancer: Update of a Single-Institutional Experience.

BACKGROUND: The purpose of this study was to define survival rates in patients with isolated advanced abdominal nodal metastases secondary to colorectal cancer (CRC), treated with curative-intent trimodality therapy. MATERIALS AND METHODS: Sixty-five patients received trimodality therapy, defined as chemotherapy delivered with external beam radiotherapy (EBRT) followed by lymphadenectomy and intraoperative radiotherapy (IORT). Infusional 5-fluorouracil was the most common radiosensitizer used (63%, 41 patients). The median dose of EBRT was 50 Gy, and the median dose of IORT was 12.5 Gy. We evaluated time to distant metastasis, toxicities, local failure within the EBRT field, recurrence within the IORT field, and survival. RESULTS: Fifty-two percent of patients were male; patients' median age was 50.5 years. All patients had an Eastern Cooperative Oncology Group score ≤1. Twenty-nine patients had right-sided colon cancer, 22 had left-sided colon cancer, and 14 had rectal primaries. The median time from initial CRC diagnosis to development of abdominal nodal metastatic disease was 20.6 months (95% confidence interval [CI], 21.2-40.8 months). Seventy-eight percent (51 patients) had para-aortic nodal metastases, 15% (10 patients) had mesenteric nodal metastases, and 6% (4 patients) had both. With a median follow-up of 77.6 months, the median overall survival and 5-year estimated survival rate were 55.4 months (95% CI, 47.2-80.9 months) and 45%, respectively. The median progression-free survival was 19.3 months (95% CI, 16.5-32.8 months). Twenty-six (40%) patients never developed distant disease. The outcome was not affected by disease sidedness or rectal primary. Treatment was well tolerated without grade 3 or 4 toxicities. CONCLUSION: Trimodality therapy produces sustainable long-term survival in selected patients with metastatic CRC presenting with isolated retroperitoneal or mesenteric nodal relapse. IMPLICATIONS FOR PRACTICE: This article reports a unique trimodality approach incorporating external beam radiotherapy with radiosensitizing chemotherapy, surgical resection, and intraoperative radiotherapy provides durable survival benefit with significant curative potential for patients with metastatic colorectal cancer who present with isolated abdominal nodal (mesenteric and/or retroperitoneal) recurrence.

Large B-cell transformation in nodular lymphocyte-predominant Hodgkin lymphoma: 40-year experience from a single institution.

A number of reports have shown a propensity of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) to transform into diffuse large B-cell lymphoma (DLBCL). Long-term data on the incidence and outcomes of transformed NLPHL are lacking. A comprehensive analysis of the actively maintained Mayo Clinic Lymphoma Database was performed. Between 1970 and 2011, 222 consecutive adult patients with new untreated NLPHL were identified. Median age at diagnosis was 40 years, and 146 (66%) were males. The median follow-up was 16 years. Seventeen patients (7.6%) developed a transformation to DLBCL. The median time to transformation was 35 months (range, 6-268 months). Based on the observed 17 transformations during 2304 patient-years of follow-up, the rate of transformation was 0.74 per 100 patient-years. In a multivariate analysis, use of any prior chemotherapy ( ITALIC! P= .04) and splenic involvement ( ITALIC! P= .03) were significantly associated with increased risk of transformation. The 5-year overall survival (OS) in those with transformed disease was 76.4%, and transformation did not adversely affect OS when compared with patients who did not experience transformation. In this large single-institution cohort with long-term follow-up, the risk of transformation was lower than that observed in other low-grade lymphomas.

Repeated measures analyses of dermatitis symptom evolution in breast cancer patients receiving radiotherapy in a phase 3 randomized trial of mometasone furoate vs placebo (N06C4 [alliance]).

PURPOSE: Radiotherapy-related dermatological toxicities over time have not been well quantified. We examined during and immediately following radiation therapy skin toxicities over time in a randomized study of mometasone furoate vs placebo during breast radiotherapy. MATERIAL AND METHODS: Patients with breast cancer undergoing radiotherapy to the breast or chest wall were randomized. Symptoms related to skin toxicity were addressed weekly using provider-reported Common Terminology Criteria for Adverse Events (CTCAE v3.0) and 4 patient-reported outcomes (PRO) surveys. We applied repeated measures and risk analysis methodologies. RESULTS: One hundred seventy-six patients were enrolled. By CTCAE, significant differences favoring mometasone were detected over time in all toxicities except skin striae, atrophy, and infection. Statistically significant differences between arms at baseline but not over time occurred for all Linear Analog Self-Assessment. Statistically significant differences occurred for all symptoms in the temporal profile of symptoms as measured by PRO surveys (all P < .001). CONCLUSIONS: The use of longitudinal methods enhanced the ability of PRO tools to detect differences between study arms. Our results strengthened the conclusions of the original report that mometasone reduced acute skin toxicities. PRO surveys can accurately assess patients' experiences of symptom type and intensity over time and should be included in future clinical trials. For radiotherapy-related dermatological toxicity, we hypothesized that clinically significant differences over time, if any, can be found by repeated measures. We examined the acute skin toxicities in a randomized study of mometasone vs placebo during breast radiotherapy. For secondary end points, we showed that longitudinal methods enhanced the detection of differences between study arms and strengthened the conclusions from the original report. Frequent patient-reported outcome surveys over time should be included in future clinical trials.

Predictors of pretransplant dropout and posttransplant recurrence in patients with perihilar cholangiocarcinoma.

UNLABELLED: We have previously reported excellent outcomes with liver transplantation for selected patients with early-stage perihilar cholangiocarcinoma (CCA) following neoadjuvant chemoradiotherapy. Our aim was to identify predictors of dropout before transplantation and predictors of cancer recurrence after transplantation. We reviewed all patients with unresectable perihilar CCA treated with neoadjuvant chemoradiation in anticipation for transplantation between 1993 and 2010. Predictors were identified by univariate and multivariate Cox regression analysis of clinical variables. In total, 199 patients were enrolled, of whom 62 dropped out and 131 underwent transplantation at our institution, with six undergoing transplantation elsewhere. Predictors of dropout were carbohydrate antigen 19-9 (CA 19-9) ≥ 500 U/mL (hazard ratio [HR] 2.3; P = 0.04), mass ≥ 3 cm (HR 2.1; P = 0.05), malignant brushing or biopsy (HR 3.6; P = 0.001), and Model for End-Stage Liver Disease (MELD) score ≥ 20 (HR 3.5; P = 0.02). Posttransplant, recurrence-free 5-year survival was 68%. Predictors of recurrence were elevated CA 19-9 (HR 1.8; P = 0.01), portal vein encasement (HR 3.3; P = 0.007), and residual tumor on explant (HR 9.8; P < 0.001). Primary sclerosing cholangitis (PSC), age, history of cholecystectomy, and waiting time were not independent predictors. CONCLUSION: Outcome following neoadjuvant chemoradiation and liver transplantation for perihilar CCA is excellent. Risk of dropout is related to patient and tumor characteristics and this can be used to guide patient counseling before enrollment. Recurrence risk is mostly associated with presence of residual cancer on explant. Patients with PSC do not have an independent survival advantage over de novo patients, but present with more favorable tumor characteristics.

Assessment of patient-reported measures of bowel function before and after pelvic radiotherapy: an ancillary study of the North Central Cancer Treatment Group study N00CA.

PURPOSE: The Bowel Function Questionnaire (BFQ) has been used in clinical trials to assess symptoms during and after pelvic radiotherapy (RT). This study evaluated the importance of symptoms in the BFQ from a patient perspective. METHODS: Patients reported presence or absence of symptoms and rated importance of symptoms at baseline, 4 weeks after completion of pelvic RT, and 12 and 24 months after RT. The BFQ measured overall quality of life (QOL) and symptoms of nocturnal bowel movements, incontinence, clustering, need for protective clothing, inability to differentiate stool from gas, liquid bowel movements, urgency, cramping, and bleeding. Bowel movement frequency also was recorded. A content validity questionnaire (CVQ) was used to rate symptoms as "not very important," "moderately unimportant," "neutral," "moderately important," or "very important." RESULTS: Most of the 125 participating patients rated all symptoms as moderately or very important. Generally, patients gave similar ratings for symptom importance at all study points, and ratings were independent of whether the patient experienced the symptom. Measures of greatest importance (moderately or very important) at baseline were ability to control bowel movements (94 %), not having to wear protective clothing (90 %), and not having rectal bleeding (94 %). With the exception of need for protective clothing, the presence of a symptom at 4 weeks was associated with significantly worse QOL (P < .01 for all). CONCLUSIONS: The BFQ has excellent content validity. Patients rated most symptoms as moderately or very important, indicating the BFQ is an appropriate tool for symptom assessment during and after pelvic RT.

Assessment of long-term rectal function in patients who received pelvic radiotherapy: a pooled North Central Cancer Treatment Group trial analysis, N09C1.

PURPOSE: Pelvic radiotherapy (PRT) is known to adversely affect bowel function (BF) and patient well-being. This study characterized long-term BF and evaluated quality of life (QOL) in patients receiving PRT. METHODS: Data from 252 patients were compiled from two North Central Cancer Treatment Group prospective studies, which included assessment of BF and QOL by the BF questionnaire (BFQ) and Uniscale QOL at baseline and 12 and 24 months after completion of radiotherapy. BFQ scores (sum of symptoms), Uniscale results, adverse-event incidence, and baseline demographic data were compared via t test, χ (2), Fisher exact, Wilcoxon, and correlation methodologies. RESULTS: The total BFQ score was higher than baseline at 12 and 24 months (P < 0.001). More patients had five or more symptoms at 12 months (13 %) and 24 months (10 %) than at baseline (2 %). Symptoms occurring in greater than 20 % of patients at 12 and 24 months were clustering, stool-gas confusion, and urgency. Factors associated with worse BF were female sex, rectal or gynecologic primary tumors, prior anterior resection of the rectum, and 5-fluorouracil chemotherapy. Patients experiencing grade 2 or higher acute toxicity had worse 24-month BF (P values, <.001-.02). Uniscale QOL was not significantly different from baseline at 12 or 24 months, despite worse BFQ scores. CONCLUSIONS: PRT was associated with worse long-term BF. Worse BFQ score was not associated with poorer QOL. Further research to characterize the subset of patients at risk of significant decline in BF is warranted.

Low-Dose Hypofractionated Total Skin Electron Beam Therapy for Adult Cutaneous T-Cell Lymphoma.

PURPOSE: Historically, the standard of care for total skin electron beam therapy (TSEBT) delivered 30 to 36 Gy over 5 to 10 weeks. Given the high risk of relapse, a majority of patients require additional treatments. Therefore, attempts to use a shortened course of TSEBT have been investigated. METHODS AND MATERIALS: We conducted a single-institution retrospective review to evaluate disease response, control, and toxicity using a low-dose, hypofractionated course of TSEBT (HTSEBT) in patients with mycosis fungoides. RESULTS: Forty patients received 57 courses of HTSEBT. Median dose (Gy)/fractionation was 12/3, spanning a median time of 2.4 weeks. Overall response rate of patients assessed (n = 54) was 100%. Thirty-one courses (57.4%) resulted in a complete response and 23 courses (42.6%) resulted in a partial response. Cumulative incidence of progressive skin disease at 3 months was 37.2%, at 6 months, 56.9%, and at 1 year, 81.5%. Of the 40 patients treated with a first course of HTSEBT, 31 received subsequent courses of radiotherapy. Cumulative incidence of subsequent treatment was 28.0% at 3 months, 46.8% at 6 months, and 70.0% at 1 year. Patients who underwent repeat courses of HTSEBT continued to have similar treatment responses to repeat courses without increased toxicities. Toxicities from all courses were acceptable with the exception of 1 patient, who experienced grade 4 skin toxicity (moist desquamation requiring hospitalization). CONCLUSIONS: Low-dose HTSEBT provides good palliation in patients with cutaneous T-cell lymphoma with a satisfactory response and toxicity profile. HTSEBT allows therapy to be completed in far fewer treatments. Low-dose HTSEBT is an appropriate treatment option for patients unable to come for daily treatment. HTSEBT provides a way to decrease exposure to other patients and staff during public health emergencies such as the coronavirus disease 2019 (COVID-19) pandemic.

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

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.

Reducing Heart Dose with Protons and Cardiac Substructure Sparing for Mediastinal Lymphoma Treatment.

PURPOSE: Electrocardiogram-gated computed tomography with coronary angiography can be used for cardiac substructure sparing (CSS) optimization, which identifies and improves avoidance of cardiac substructures when treating with intensity modulated radiotherapy (IMRT). We investigated whether intensity modulated proton therapy (IMPT) would further reduce dose to cardiac substructures for patients with mediastinal lymphoma. PATIENTS AND METHODS: Twenty-one patients with mediastinal lymphoma were enrolled and underwent electrocardiogram-gated computed tomography angiography during or shortly after simulation for radiotherapy planning. Thirteen patients with delineated cardiac substructures underwent comparative planning with both IMPT and IMRT. Plans were normalized for equivalent (95%) target volume coverage for treatment comparison. RESULTS: Thirteen patients met criteria for this study. The median size of the mediastinal lymphadenopathy was 7.9 cm at the greatest diameter. Compared with IMRT-CSS, IMPT-CSS significantly reduced mean dose to all cardiac substructures, including 3 coronary arteries and 4 cardiac valves. Use of IMPT significantly reduced average whole-heart dose from 9.6 to 4.9 Gy (P < .0001), and average mean lung dose was 9.7 vs 5.8 Gy (P < .0001). Prospectively defined clinically meaningful improvement was observed in at least 1 coronary artery in 9 patients (69%), at least 1 cardiac valve in 10 patients (77%), and whole heart in all 13 patients. CONCLUSIONS: For patients with mediastinal lymphoma, IMPT-CSS treatment planning significantly reduced radiation dose to cardiac substructures. The significant improvements outlined in this study for proton therapy suggest possible clinical improvement in alignment with previous analyses of CSS optimization.

Electrocardiogram-Gated Computed Tomography with Coronary Angiography for Cardiac Substructure Delineation and Sparing in Patients with Mediastinal Lymphomas Treated with Radiation Therapy.

PURPOSE: (1) Demonstrate feasibility of electrocardiogram-gated computed tomography with coronary angiography (E-CTA) in treatment planning for mediastinal lymphoma and (2) assess whether inclusion of cardiac substructures in the radiation plan optimization (CSS optimization) results in increased cardiac substructure sparing. METHODS AND MATERIALS: Patients with mediastinal lymphomas requiring radiation therapy were prospectively enrolled in an observational study. Patients completed a treatment planning computed tomography scan and E-CTA in the deep inspiration breath hold position. Avoidance structures (eg, coronary arteries and cardiac valves) were created in systole and diastole and then merged into a single planning organ-at-risk volume based on a cardiac substructure contouring atlas. In the photon cohort, 2 volumetric modulated arc therapy plans were created per patient with and without CSS optimization. Dosimetric endpoints were compared. RESULTS: In the photon cohort, 7 patients were enrolled. For all 7 patients, the treating physician elected to use the CSS optimization plan. At the individual level, 2 patients had reductions of 10.8% and 16.2% of the right coronary artery receiving at least 15 Gy, and 1 had a reduction of 9.6% of the left anterior descending artery receiving 30 Gy. No other differences for coronary arteries were detected between 15 and 30 Gy. Conversely, 5 of 7 patients had >10% reductions in dose between 15 to 30 Gy to at least 1 cardiac valve. The greatest reduction was 22.8% of the aortic valve receiving at least 30 Gy for 1 patient. At the cohort level, the maximum, mean, and 5-Gy increment analyses were nominally similar between planning techniques for all cardiac substructures and the lungs. CONCLUSIONS: Cardiac substructure delineation using E-CTA was feasible, and inclusion in optimization led to modest improvements in sparing of radiosensitive cardiac substructures for some patients.

A Comparison of Grade 4 Lymphopenia With Proton Versus Photon Radiation Therapy for Esophageal Cancer.

PURPOSE: Grade 4 lymphopenia (G4L) during radiation therapy (RT) is associated with higher rates of distant metastasis and decreased overall survival in a number of malignancies, including esophageal cancer (EC). Through a reduction in integral radiation dose, proton RT (PRT) may reduce G4L relative to photon RT (XRT). The purpose of this study was to compare G4L in patients with EC undergoing PRT versus XRT. METHODS AND MATERIALS: Patients receiving curative-intent RT and concurrent chemotherapy for EC were identified. Lymphocyte nadir was defined as the lowest lymphocyte count during RT. G4L was defined as absolute lymphocyte count <200/mm3. Univariate and multivariable logistic regression analyses (MVA) were performed to assess patient and treatment factors associated with lymphopenia. A propensity-matched (PM) cohort was created using logistic regression, including baseline covariates. RESULTS: A total of 144 patients met the inclusion criteria. The median age was 66 years (range, 32-85 years). Of these patients, 79 received XRT (27% 3-dimensional chemo-RT and 73% intensity modulated RT) and 65 received PRT (100% pencil-beam scanning). Chemotherapy consisted of weekly carboplatin and paclitaxel (99%). There were no significant differences in baseline characteristics between the groups, except for age (median 4 years older in the PRT cohort). G4L was significantly higher in patients who received XRT versus those who received PRT (56% vs 22%; P < .01). On MVA, XRT (odds ratio [OR]: 5.13; 95% confidence interval [CI], 2.35-11.18; P < .001) and stage III/IV (OR: 4.54; 95% CI, 1.87-11.00; P < .001) were associated with G4L. PM resulted in 50 PRT and 50 XRT patients. In the PM cohort, G4L occurred in 60% of patients who received XRT versus 24% of patients who received PRT. On MVA, XRT (OR: 5.28; 95% CI, 2.14-12.99; P < .001) and stage III/IV (OR: 3.77; 95% CI, 1.26-11.30; P = .02) were associated with G4L. CONCLUSIONS: XRT was associated with a significantly higher risk of G4L in comparison with PRT. Further work is needed to evaluate a potential association between RT modality and antitumor immunity as well as long-term outcomes.

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

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 cm3, 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.

N-Acetylcysteine Rinse for Thick Secretion and Mucositis of Head and Neck Chemoradiotherapy (Alliance MC13C2): A Double-Blind Randomized Clinical Trial.

OBJECTIVE: To determine whether N-acetylcysteine rinse was safe and could improve thickened secretions and dry mouth during and after radiotherapy. PATIENTS AND METHODS: We designed a prospective pilot double-blind, placebo-controlled randomized clinical trial (Alliance MC13C2). Adult patients (age ≥18 years) were enrolled if they underwent chemoradiotherapy (≥60 Gy). Patients initiated testing rinse within 3 days of starting radiotherapy. With swish-and-spit, they received 10% N-acetylcysteine (2500 mg daily) or placebo rinse solution 5 times daily during radiotherapy and 2 weeks postradiotherapy. The primary aim was to evaluate N-acetylcysteine in improvement of saliva viscosity with the Groningen Radiotherapy-Induced Xerostomia questionnaire. Secondary aims included evaluating xerostomia improvement by the same questionnaire and with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck-35 Questions survey and adverse-event profiles. The type I error rate was 20%. RESULTS: Thirty-two patients undergoing chemoradiotherapy were enrolled. Baseline characteristics were balanced for placebo (n=17) and N-acetylcysteine (n=15). N-acetylcysteine was better for improving sticky saliva (area under curve, P=.12). Scores of multiple secondary end points favored N-acetylcysteine, including sticky saliva daytime (P=.04), daytime and total xerostomia (both P=.02), pain (P=.18), and trouble with social eating (P=.15). Repeated measures models confirmed the findings. Taste was a major dissatisifer for N-acetylcysteine rinse; however, both testing rinses were safe and well tolerated overall. CONCLUSION: Our pilot data showed that N-acetylcysteine rinse was safe and provided strong evidence of potential efficacy for improving thickened saliva and xerostomia by patient-reported outcome. A confirmatory phase 3 trial is required. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02123511.

Technique for the administration of high-dose-rate brachytherapy to the bile duct using a nasobiliary catheter.

PURPOSE: Cholangiocarcinoma patients who are potential candidates for liver transplantation may be treated with high-dose-rate (HDR) brachytherapy using a minimally invasive nasobiliary catheter in an effort to escalate the radiotherapy dose to the tumor and maximize local control rates. This work describes the equipment, procedures, and quality assurance (QA) that enables successful administration. METHODS AND MATERIALS: This work describes the nasobiliary catheter placement, simulation, treatment planning, treatment delivery, and QA. In addition, a chart review was performed of all patients who received endoscopic retrograde cholangiopancreatography for HDR bile duct brachytherapy at our institution from 2007 to 2017. The review evaluated how many patients were treated and the number of patients who could not be treated because of anatomic and/or equipment limitations. RESULTS: From 2007 to 2017, 122 cholangiocarcinoma patients have been treated with HDR brachytherapy using a nasobiliary catheter. Three patients underwent catheter placement but did not receive brachytherapy treatment due to catheter migration between placement and treatment or because the HDR afterloader was unable to extend the source wire into the treatment site. Periodic QA is recommended for ensuring whether the HDR afterloader is capable of extending the source wire through an extensive and curved path. CONCLUSIONS: Intraluminal HDR brachytherapy with a nasobiliary catheter can be successfully administered. Procedures and QA are described for ensuring safety and overcoming technical challenges.

Treatment options for hepatobiliary and pancreatic cancer.

Hepatobiliary and pancreatic cancers account for 4% of all cancers in the United States. Traditionally, these cancers have had a high mortality rate and have been poorly responsive to therapy. Because of a growing number of treatment options, patients are now living longer. For hepatocellular carcinoma, a broad number of treatment options are available, including surgery, ablation, embolization, systemic therapy, and liver transplantation. Treatment options for cholangiocarcinoma include surgery, systemic therapy, and liver transplantation. For pancreatic cancer, surgery, radiation, and systemic therapy all have potential roles. This review provides an updated summary of diagnosis and assessment together with treatment options for this group of cancers.

Long-term Treatment Outcomes for Locally Advanced Esophageal Cancer: A Single-Institution Experience.

OBJECTIVES: To determine long-term outcomes in patients with locally advanced esophageal carcinoma treated with trimodality therapy (chemoradiotherapy [CRT] and surgery, TMT) or definitive CRT. METHODS: We retrospectively identified patients with advanced esophageal carcinoma treated with curative intent at our institution between 1998 and 2004. Identified patients were separated into 3 groups: patients who received TMT, patients who received CRT, and patients who began treatment with trimodality intent but did not undergo surgery (PTMT). Local control, overall survival (OS), and distant metastasis-free survival were compared using Kaplan-Meier statistics. RESULTS: Among the 265 patients included, median follow-up was 6.4 years for surviving patients and 1.7 years for all patients. Type of esophageal cancer was adenocarcinoma in 213 patients (80%) and squamous cell carcinoma in 46 patients (17%). Treatment groups comprised 169 patients (64%) completing TMT, 46 patients medically unable to undergo surgery after neoadjuvant therapy (PTMT), and 50 (19%) who underwent CRT. Median OS was 20.5 months; actuarial 5- and 10-year OS were 27% and 12%, respectively. The TMT group had the highest 5- and 10-year OS (32% and 19%, respectively). Local control rates at 2, 5, and 10 years for all patients were 80%, 70%, and 69%, respectively. By treatment modality, 5-year local control was best (82%) for TMT, compared with 60% for CRT and 40% for PTMT groups (P<0.001). CONCLUSIONS: Patients who completed TMT had the best local control and long-term OS. In the context of TMT, surgery seemed more beneficial in patients with esophageal adenocarcinoma versus squamous cell carcinoma.