Implementation of the REFLECT Communication Curriculum for Clinical Oncology Graduate Medical Education.

Background: Communication and interpersonal skills are essential medical components of oncology patient care. Patients and families rely on physicians for treatment, expertise, guidance, hope, meaning, and compassion throughout a life-threatening illness. A provider's inability to empathize with patients is linked to physician-related fatigue and burnout. Because oncology training programs focus on teaching evidence-based medicine and clinical acumen, little time may be dedicated to professional development and acquisition of interactive skills. Traditional communication courses typically include two components: formal, knowledge-based learning skills, which are gained from didactic lectures, and role-playing, which usually occurs in small groups. We report the implementation of a novel longitudinal communication curriculum for trainees in Oncology. Materials and Methods: At a single-center institution, an innovative communication curriculum titled "REFLECT" (Respect, Empathy, Facilitate Effective Communication, Listen, Elicit Information, Compassion, and Teach Others) was implemented for radiation oncology residents and medical oncology fellows to improve and refine physician/patient interactions. All oncology specialty residents and fellows were eligible to participate in this communication curriculum. The curriculum emphasized a reflective process to guide trainees through challenging scenarios. Results: Since October 2018, this comprehensive course consisted of quarterly (four hour) workshops comprising assigned reading, knowledge assessments, didactic lectures, expert guest lecturers, standardized patient simulations, role-playing, patient/expert panels, coaching, reflective writing, and debriefing/feedback sessions. The curriculum provided longitudinal communication training integrated with the learners' daily physician/patient encounters rather than occasional isolated experiences. Fifteen workshops have been completed. Each focused on navigating challenging situations with patients, loved ones, or colleagues. Conclusions: Future directions of the curriculum will entail improving the communication skills of oncology trainees and gathering communication improvement data to assess the program's success formally.

Physician- and Patient-Reported Outcomes of the MC1635 Phase 3 Trial of Ultrahypofractionated Versus Moderately Hypofractionated Adjuvant Radiation Therapy After Breast-Conserving Surgery.

PURPOSE: Our aim was to report physician- and patient-reported outcomes of patients with localized breast cancer treated with moderate versus ultrahypofractionated whole breast irradiation (WBI) after breast-conserving surgery (BCS). METHODS AND MATERIALS: Between February 2018 and February 2020, patients with localized breast cancer (pT0-3 pN0-1 M0) were offered participation in a phase 3 randomized clinical trial assessing adjuvant moderate hypofractionation (MHF) to 40 Gy in 15 fractions versus ultrahypofractionation (UHF) to 25 Gy in 5 fractions after BCS, with an optional simultaneously integrated boost. Toxicities, cosmesis, and quality of life were assessed at baseline, end of treatment (EOT), and 3 months, 1 year, 2 years, and 3 years from irradiation using validated metric tools. RESULTS: One hundred seven patients were randomized to MHF (n = 54) or UHF (n = 53) adjuvant WBI. The median follow-up was 42.8 months. Grade 2 radiation dermatitis was experienced by 4 patients (7.4%) in the MHF arm and 2 patients (3.7%) in the UHF arm at EOT (P = .726). No grade 3 or higher toxicities were observed. Deterioration of cosmesis by physician assessment was observed in 2 (6.7%) patients treated in the UHF arm and 1 (1.9%) patient treated in the MHF arm at EOT (P = .534), whereas at 3 months, only 1 (1.8%) patient treated in the MHF arm demonstrated deterioration of cosmesis (P = .315). At EOT, 91% and 94% of patients reported excellent/good cosmesis among those treated with MHF and UHF regimens, respectively (P = .550). At 3 months, more patients within the MHF arm reported excellent/good cosmesis compared with those in the UHF arm (100% vs 91%; P = .030). However, the difference in patient-reported cosmesis disappeared at the 1-, 2-, and 3-year time points. CONCLUSIONS: UHF WBI showed similar treatment-related late toxicities and similar provider-scored cosmesis compared with MHF radiation in patients treated adjuvantly after BCS.

Conventional versus hypofractionated postmastectomy proton radiotherapy in the USA (MC1631): a randomised phase 2 trial.

BACKGROUND: Proton therapy is under investigation in breast cancer as a strategy to reduce radiation exposure to the heart and lungs. So far, studies investigating proton postmastectomy radiotherapy (PMRT) have used conventional fractionation over 25-28 days, but whether hypofractionated proton PMRT is feasible is unclear. We aimed to compare conventional fractionation and hypofractionation in patients with indications for PMRT, including those with immediate breast reconstruction. METHODS: We did a randomised phase 2 trial (MC1631) at Mayo Clinic in Rochester (MN, USA) and Mayo Clinic in Arizona (Phoenix, AZ, USA) comparing conventional fractionated (50 Gy in 25 fractions of 2 Gy [relative biological effectiveness of 1·1]) and hypofractionated (40·05 Gy in 15 fractions of 2·67 Gy [relative biological effectiveness of 1·1]) proton PMRT. All patients were treated with pencil-beam scanning. Eligibility criteria included age 18 years or older, an Eastern Cooperative Oncology Group performance status of 0-2, and breast cancer resected by mastectomy with or without immediate reconstruction with indications for PMRT. Patients were randomly assigned (1:1) to either conventional fractionation or hypofractionation, with presence of immediate reconstruction (yes vs no) as a stratification factor, using a biased-coin minimisation algorithm. Any patient who received at least one fraction of protocol treatment was evaluable for the primary endpoint and safety analyses. The primary endpoint was 24-month complication rate from the date of first radiotherapy, defined as grade 3 or worse adverse events occurring from 90 days after last radiotherapy or unplanned surgical interventions in patients with immediate reconstruction. The inferiority of hypofractionation would not be ruled out if the upper bound of the one-sided 95% CI for the difference in 24-month complication rate between the two groups was greater than 10%. This trial is registered with ClinicalTrials.gov, NCT02783690, and is closed to accrual. FINDINGS: Between June 2, 2016, and Aug 23, 2018, 88 patients were randomly assigned (44 to each group), of whom 82 received protocol treatment (41 in the conventional fractionation group and 41 in the hypofractionation group; median age of 52 years [IQR 44-64], 79 [96%] patients were White, two [2%] were Black or African American, one [1%] was Asian, and 79 [96%] were not of Hispanic ethnicity). As of data cutoff (Jan 30, 2023), the median follow-up was 39·3 months (IQR 37·5-61·2). The median mean heart dose was 0·54 Gy (IQR 0·30-0·72) for the conventional fractionation group and 0·49 Gy (0·25-0·64) for the hypofractionation group. Within 24 months of first radiotherapy, 14 protocol-defined complications occurred in six (15%) patients in the conventional fractionation group and in eight (20%) patients in the hypofractionation group (absolute difference 4·9% [one-sided 95% CI 18·5], p=0·27). The complications in the conventionally fractionated group were contracture (five [12%] of 41 patients]) and fat necrosis (one [2%] patient) requiring surgical intervention. All eight protocol-defined complications in the hypofractionation group were due to infections, three of which were acute infections that required surgical intervention, and five were late infections, four of which required surgical intervention. All 14 complications were in patients with immediate expander or implant-based reconstruction. INTERPRETATION: After a median follow-up of 39·3 months, non-inferiority of the hypofractionation group could not be established. However, given similar tolerability, hypofractionated proton PMRT appears to be worthy of further study in patients with and without immediate reconstruction. FUNDING: The Department of Radiation Oncology, Mayo Clinic, Rochester, MN, the Department of Radiation Oncology, Mayo Clinic, Phoenix, AZ, USA, and the US National Cancer Institute.

Dose delivery reproducibility for PBS proton treatment of breast cancer patients with and without mask immobilization.

BACKGROUND: Setup reproducibility of the tissue in the proton beam path is critical in maintaining the planned clinical target volume (CTV) dose coverage and sparing the organs at risk (OAR). In this study, we retrospectively evaluated radiation therapy dose reproducibility for proton pencil beam scanning (PBS) treatment of breast cancer patients with and without mask immobilization. METHODS: Ninety-four patients treated between January 2019 and September 2022 with at least one verification CT scan (V-CT) in treatment position were included for this study. All patients were set up with arms up using the Orfit AIO patient positioning system, with (69 patients) or without (25 patients) mask immobilization in chin, neck, shoulder, upper arm, and chest areas. Two to three enface or near enface single field uniform dose PBS beams were optimized using a commercial treatment planning system. Prescription doses were 25 to 60 GyRBE in 5 to 45 fractions. Treatment plan doses re-calculated on V-CTs were compared to the corresponding planned doses. Cumulative doses were also calculated for patients with at least 3 V-CTs by deform and weighted sum doses from V-CTs to corresponding P-CTs. CTV D95%, ipsilateral-lung V40%, esophagus D0.01cc, and heart mean dose were evaluated and reported as percentages of prescription doses. Differences were large dose deteriorations (LDD) if: (1) CTV (V-CT/cumulative D95%) - (Planned D95%) < - 5%; or (2) Ipsilateral-lung (V-CT/cumulative V40%) - (Planned V40%) > 5%; or (3) Esophagus (V-CT/cumulative D0.01cc) - (Planned D0.01cc) > 10%; or (4) Heart (V-CT/cumulative mean) - (Planned mean) > 1.5%. RESULTS: On average, V-CT/cumulative and planned CTV/OAR dose parameter differences were less than 2.2%/1.7% and 3.4%/3.7% for masked and maskless patients, respectively. The percentages of patients with at least one CTV or OAR V-CT/cumulative dose LDD were 20.3%/25.0% and 72.0%/54.0% for masked and maskless patients, respectively. CONCLUSIONS: On average, masked/maskless setups achieved delivered and planned CTV/OAR dose parameters agreed within 2.2%/3.7% for PBS treatment of breast cancer patients in this study. Maskless patients had higher rate of CTV/OAR LDDs compared to masked patients. Dosimetric differences large enough to raise clinical concerns in either group were able to be addressed with replannings.

Attitudes and Perception of the REFLECT Communication Curriculum for Clinical Oncology Graduate Medical Education.

Communication and interpersonal skills are essential components of oncology patient care. The REFLECT (Respect, Empathy, Facilitate Effective Communication, Listen, Elicit Information, Compassion, and Teach Others) curriculum is a novel framework to improve and refine physician/patient interactions for oncology graduate medical trainees. We seek to evaluate the attitudes and perceptions of the REFLECT communication curriculum among oncology trainees. Seven-question and 8-question Likert scale surveys (1 = not beneficial and 5 = beneficial) were distributed to resident/fellow participants and faculty mentors, respectively. Questions asked trainees and faculty about their perceptions of improvement in communication, handling of stressful situations, the value of the curriculum, and overall impression of the curriculum. Descriptive statistics determined the survey's baseline characteristics and response rates. Kruskal-Wallis rank sum tests were used to compare the distribution of continuous variables. Thirteen resident/fellow participants completed the participant survey. Six (43.6%) Radiation Oncology trainees and 7 (58.3%) Hematology/Oncology fellows completed the trainee survey. Eight (88.9%) Radiation Oncologists and 1 (11.1%) Medical Oncologist completed the observer survey. Faculty and trainees generally felt that the curriculum increased communication skills. Faculty responded more favorably to the program's impact on communication skills (median 5.0 vs. 4.0, p = 0.008). Faculty were more assertive about the curriculum's capabilities to improve a learner's ability to handle stressful situations (median 5.0 vs. 4.0, p = 0.003). Additionally, faculty had a more favorable overall impression of the REFLECT curriculum than the residents/fellows (median 5.0 vs. 4.0, p < 0.001). Radiation Oncology residents felt more strongly that the curriculum enhanced their ability to handle stressful topics, compared to Heme/Onc fellows (median 4.5 vs. 3.0, range 1-5, p = 0.379). Radiation Oncology trainees felt more consistently that the workshops improved their communication skills, compared to Heme/Onc fellows (median 4.5 vs. 3.5, range 1-5, p = 0.410). The overall impression between Rad Onc resident and Heme/Onc fellows was similar (median 4.0, p = 0.586). Conclusions: Overall, the REFLECT curriculum enhanced communication skills of trainees. Oncology trainees and faculty physicians feel that the curriculum was beneficial. As interactive skills and communication is critical to build positive interactions, further work is needed to improve the REFLECT curriculum.

Dosimetric comparison between proton beam therapy, intensity modulated radiation therapy, and 3D conformal therapy for soft tissue extremity sarcoma.

PURPOSE/OBJECTIVES: Proton beam therapy (PBT) may provide a dosimetric advantage in sparing soft tissue and bone for selected patients with extremity soft sarcoma (eSTS). We compared PBT with photons plans generated using intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT). MATERIALS/METHODS: Seventeen patients previously treated with pencil beam scanning PBT were included in this study. Of these patients, 14 treated with pre-operative 50 Gy in 25 fractions were analyzed. IMRT and 3D-CRT plans were created to compare against the original PBT plans. Dose-volume histogram (DVH) indices were evaluated amongst PBT, IMRT, and 3D plans. Kruskal-Wallis rank sum tests were used to get the statistical significance. A p value smaller than .05 was considered to be statistically significant. RESULTS: For the clinical target volume (CTV), D2%, D95%, D98%, Dmin, Dmax, and V50Gy, were assessed. Dmin, D1%, Dmax, Dmean, V1Gy, V5Gy, and V50Gy were evaluated for the adjacent soft tissue. D1%, Dmax, Dmean, and V35-50% were evaluated for bone. All plans met CTV target coverage. The PBT plans delivered less dose to soft tissue and bone. The mean dose to the soft tissue was 2 Gy, 11 Gy, and 13 Gy for PBT, IMRT, and 3D, respectively (p < .001). The mean dose to adjacent bone was 15 Gy, 26 Gy, and 28 Gy for PBT, IMRT, and 3D, respectively (p = .022). CONCLUSION: PBT plans for selected patients with eSTS demonstrated improved sparing of circumferential soft tissue and adjacent bone compared to IMRT and 3D-CRT. Further evaluation will determine if this improved dosimetry correlates with reduced toxicity and improved quality of life.

Pilot/Phase II Trial of Hypofractionated Radiation Therapy to the Whole Breast Alone Before Breast Conserving Surgery.

Purpose: Our purpose was to report the results of a phase II trial of patients with breast cancer treated with hypofractionated whole breast radiation therapy (RT) before breast-conserving surgery (BCS). Methods and materials: Between 2019 and 2020, patients with cT0-T2, N0, M0 breast cancer were enrolled. Patients were treated with hypofractionated whole breast RT, 25 Gy in 5 fractions, 4 to 8 weeks before BCS. Pathologic assessment was performed using the residual cancer burden (RCB). Toxicities were assessed according to Common Terminology Criteria for Adverse Events (version 4). Quality of life was assessed with Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events, The Breast Cancer Treatment Outcome Scale, Linear Analogue Self-Assessment, and Patient-Reported Outcomes Measurement Information System. Results: Twenty-two patients were enrolled. Median follow-up was 7.6 months (range, 0.2-16.8). Seven (32%) and 2 (9%) patients experienced grade 2+ or 3 toxicities, respectively. Overall quality of life Linear Analogue Self-Assessment and Patient-Reported Outcomes Measurement Information System did not change significantly from baseline (P = .21 and P = .72, respectively). There was no clinically significant change (≥1 point) in any of The Breast Cancer Treatment Outcome Scale domains. Only 1 (5%) patient experienced a clinical deterioration that corresponded to a "fair" outcome on the Harvard Cosmesis Scale. At pathologic evaluation, 14 (64%) patients had RCB-0 or RCB-I, including 3 (14%) patients with a pathologic complete response (RCB-0). Eight patients (36%) had RCB-II. No local or distant recurrences have been observed. Conclusions: Extremely hypofractionated whole breast RT before BCS is a feasible approach. There were low rates of toxicities and good cosmesis. Further investigation into this approach with RT before BCS is warranted.

Patient-reported outcomes for patients with breast cancer undergoing radiotherapy: A single-center registry experience.

Background: We present Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) for patients undergoing adjuvant radiotherapy for breast cancer with curative intent. We describe the frequency and severity of PRO-CTCAE and analyze them with respect to dose fractionation. Methods: Patients were included in this study if they were treated with curative intent for breast cancer and enrolled on a prospective registry. Patients must have completed at least one baseline and one post-radiation survey that addressed PRO-CTCAE. For univariate and multivariate analysis, categorical variables were analyzed by Fisher's exact test and continuous variables by Wilcoxon rank sum test. PRO-CTCAE items graded ≥2 and ≥3 were analyzed between patients who received hypofractionation (HF) versus standard conventional fractionation (CF) therapy by the Chi-square test. Results: Three hundred thirty-one patients met inclusion criteria. Pathologic tumor stage was T1-T2 in 309 (94%) patients. Eighty-seven (29%) patients were node positive. Two hundred forty-seven patients (75%) experienced any PRO-CTCAE grade ≥2, and 92 (28%) patients experienced any PRO-CTCAE grade ≥3. CF was found to be associated with an increased risk of grade ≥3 skin toxicity, swallowing, and nausea (all p < 0.01). HF (OR 0.48, p < 0.01) was significant in the multivariate model for decreased risk of any occurrence of PRO-CTCAE ≥3. Conclusions: Our study reports one of the first clinical experiences utilizing multiple PRO-CTCAE items for patients with breast cancer undergoing radiation therapy with curative intent. Compared with CF, HF was associated with a significant decrease in any PRO-CTCAE ≥3 after multivariate analysis.

Unplanned implant removal in locally advanced breast cancer.

Study conducted to determine frequency and timing of unplanned breast implant removal after mastectomy, reconstruction, and postmastectomy radiation (PMRT). From 2010-2017, 52 patients underwent mastectomy, reconstruction, and PMRT. With median follow-up of 3.1 years, 23 patients (44%) experienced implant removal. Implant removal occurred in 9 (17%) patients before starting PMRT and 14 (27%) patients after starting PMRT. Implant removal rates were similar for hypofractionated PMRT compared with standard fractionation and for proton compared with photon PMRT. Implant removal is common for women undergoing mastectomy and reconstruction followed by PMRT. The risk is clinically significant even before starting radiation.

Capsular contracture in the modern era: A multidisciplinary look at the incidence and risk factors after mastectomy and implant-based breast reconstruction.

BACKGROUND: Capsular contracture causes pain, poor cosmesis, and reoperations. This study analyzes its incidence and risk factors in a more modern treatment era. METHODS: Patients undergoing mastectomy with implant reconstruction from 2010 to 18 were reviewed. Univariate and multivariate analysis evaluated rates and risk factors for capsular contracture. RESULTS: Among 451 patients, the majority underwent nipple-sparing mastectomy (262, 58.1%) with one-stage reconstruction (283, 62.7%) utilizing subpectoral implants (353, 77.4%) and acellular dermal matrix (354, 78.5%). Overall capsular contracture incidence was 9.8%; the rate after post-mastectomy radiation therapy (PMRT) was 18.7%, and 7.5% for patients without PMRT. Significant factors included neoadjuvant chemotherapy (P = 0.006), hematoma (P = 0.047), and PMRT (P = 0.001). Multivariate analysis showed that PMRT increased risk of capsular contracture (OR = 3.12, 95% CI 1.55-6.26, P = 0.001), and adjuvant chemotherapy was protective (OR = 0.289, 95% CI 0.114-0.731, P = 0.01). CONCLUSIONS: Incidence of capsular contracture is lower than previously reported. Advancing therapeutic techniques may reduce the risk of this complication.

Practice patterns and recommendations for pediatric image-guided radiotherapy: A Children's Oncology Group report.

This report by the Radiation Oncology Discipline of Children's Oncology Group (COG) describes the practice patterns of pediatric image-guided radiotherapy (IGRT) based on a member survey and provides practice recommendations accordingly. The survey comprised of 11 vignettes asking clinicians about their recommended treatment modalities, IGRT preferences, and frequency of in-room verification. Technical questions asked physicists about imaging protocols, dose reduction, setup correction, and adaptive therapy. In this report, the COG Radiation Oncology Discipline provides an IGRT modality/frequency decision tree and the expert guidelines for the practice of ionizing image guidance in pediatric radiotherapy patients.

Patterns of Failure in Pediatric Rhabdomyosarcoma After Proton Therapy.

PURPOSE: To report on the patterns of failure in children with rhabdomyosarcoma treated with proton therapy. PATIENTS AND METHODS: Between February 2007 and November 2013, 66 children with a median age of 4.1 years (range, 0.6-15.3 years) diagnosed with nonmetastatic rhabdomyosarcoma were treated with proton therapy. Clinical target volume 1 was defined as the prechemotherapy tumor plus a 1-cm anatomically constrained margin. Clinical target volume 2 was defined as the postchemotherapy tumor (or tumor bed) plus a 0.5-cm anatomically constrained margin, further expanded to encompass potential pathways of spread, including soft tissue infiltrated with tumor at diagnosis. RESULTS: Of the 66 children, 11 developed locally progressive disease at a median of 16 months (range, 14-32 months), for an actuarial 2-year local control rate of 88%. Among the children who progressed, median age and tumor size at diagnosis were 6.7 years (range, 0.6-16 years) and 6 cm (range, 2-8 cm), respectively. Of the recurrences, 64% and 36% were embryonal and alveolar, respectively. Disease progression was observed in 7 (64%) parameningeal, 2 (18%) head and neck (other), and 2 (18%) bladder/prostate subsites. At diagnosis, 8 of 11 patients who developed a recurrence were Intergroup Rhabdomyosarcoma Study stage 3, and all 11 were group III. Of the relapses, 100% (11 of 11) were confirmed as in-field within the composite 95% isodose line. One of the 11 patients (9%) developed a new simultaneous regional nodal recurrence outside of the previously treated radiation field. CONCLUSION: Early data suggest that the sharp dosimetric gradient associated with proton therapy is not associated with an increased risk of marginal failure. Routine use of a 0.5- to 1-cm clinical target volume 1/2 margin with highly conformal proton therapy does not compromise local control in children diagnosed with rhabdomyosarcoma with unfavorable risk features.

Fertility in childhood cancer survivors following cranial irradiation for primary central nervous system and skull base tumors.

Recent advances in pediatric cancer treatment have improved disease control and survival outcomes for childhood cancers survivors, including those treated for primary central nervous system and skull base malignancies. Future research in this population will focus on identifying risk factors for infertility, novel screening techniques and recommendations, and quality-of-life outcomes improvement. The purpose of this review is to define the infertility complications observed in pediatric cancer survivors who receive cranial irradiation for central nervous system and skull base malignancies.

Patterns of End-of-Life Care in Children With Advanced Solid Tumor Malignancies Enrolled on a Palliative Care Service.

CONTEXT: Pediatric patients with solid tumors can have a significant symptom burden that impacts quality of life (QoL) and end-of-life care needs. OBJECTIVES: We evaluated outcomes and symptoms in children with solid tumors and compared patterns of end-of-life care after implementation of a dedicated institutional pediatric palliative care (PC) service. METHODS: We performed a retrospective cohort study of children with solid tumors treated at St. Jude Children's Research Hospital, before and after implementation of the institutional QoL/PC service in January 2007. Patients who died between July 2001 and February 2005 (historical cohort; n = 134) were compared with those who died between January 2007 and January 2012 (QoL/PC cohort; n = 57). RESULTS: Median time to first QoL/PC consultation was 17.2 months (range 9-33). At consultation, 60% of children were not receiving or discontinued cancer-directed therapy. Within the QoL/PC cohort, 54 patients had documented symptoms, 94% required intervention for ≥3 symptoms, and 76% received intervention for ≥5 symptoms. Eighty-three percent achieved their preferred place of death. Compared with the historical cohort, the QoL/PC cohort had more end-of-life discussions per patient (median 12 vs. 3; P < 0.001), earlier end-of-life discussions, with longer times before do-not-resuscitate orders (median 195 vs. 2 days; P < 0.001), and greater hospice enrollment (71% vs. 46%, P = 0.002). CONCLUSION: Although children with solid tumor malignancies may have significant symptom burden toward the end of life, positive changes were documented in communication and in places of care and death after implementation of a pediatric PC service.

Prospective evaluation of local control and late effects of conformal radiation therapy in children, adolescents, and young adults with high-grade glioma.

BACKGROUND: A phase II trial of conformal radiotherapy (CRT) for pediatric high-grade glioma (HGG) was performed to evaluate disease control and late effects. METHODS: Between July 1997 and January 2003, 34 pediatric patients (median age, 13.2 ± 6.7 years) with HGG were enrolled on an International Commission on Radiation Units and Measurements Report 50-compliant prospective trial using CRT with a 2 cm clinical target volume margin. Baseline and serial evaluations were performed to assess functional outcomes. RESULTS: Median follow-up for the entire group was 18 months (range, 2-134 months). Twenty (58.8%) patients developed local progression, and 6 (17.6%) patients developed distant progression. Progression-free and overall survival at 10 years were 18.8% ± 6.9% and 16.8% ± 6.5%, respectively. At baseline, 40% of patients evaluated for intelligence quotient (IQ) scored below 85. Measures of cognitive function obtained during the first 12 months fit a mixed model with a quadratic function. The relationship between IQ and time was -1.1883 points/month for the linear term and 0.07728 points/month for the quadratic term (P = .0454). IQ decreased between baseline and 6 months and then increased slightly through 12 months. The opposite was found for (all P values of the quadratic term) activities of daily living (P = .0155), socialization (P = .0049), and the composite score (P = .0257) of adaptive behavior. CONCLUSION: CRT using a 2 cm clinical target volume margin in pediatric HGG demonstrated tumor control comparable to conventional radiation therapy. Disrupted cognitive and adaptive behavioral functioning were present at baseline and throughout the course of disease.

Erythema multiforme, Stevens Johnson syndrome, and toxic epidermal necrolysis syndrome in patients undergoing radiation therapy: a literature review.

OBJECTIVE: Erythema multiforme (EM), Stevens Johnson syndrome (SJS), and toxic epidermal necrolysis syndrome (TENS) are exfoliative disorders that may present as complications in some patients undergoing radiotherapy. The purpose of this literature review was to determine the reported frequency of these exanthemata in irradiated patients. METHODS: A comprehensive search from 1903 to 2011, identified 89 articles with 165 cases. RESULTS: Of 151 evaluable cases, 57 (38%) described EM; 46 (30.5%) SJS; 14 (9%) SJS/TENS overlap; and 34 (22.5%) TENS. Ninety-three percent underwent radiotherapy for either a primary or metastatic malignancy. A majority of patients were simultaneously treated with medications known to precipitate these exanthemata. Of the 61 patients receiving antiepileptic medications during radiotherapy, 48 were treated prophylactically and 13 for seizures, most frequently with phenytoin or phenobarbital. Amifostine was the second most common medication associated with radiotherapy and these reactions. Fourteen (23%) patients on anticonvulsant medication, and 11 (38%) on other medications died compared with 3 (8%) patients treated with radiotherapy alone (P = 0.002). No deaths occurred among irradiated patients receiving amifostine. CONCLUSIONS: EM, SJS, and TENS were rarely reported in patients undergoing radiotherapy alone. The majority of SJS and TENS occurred in irradiated patients with concomitant prescribed medications.

Patterns of recurrence after stereotactic radiosurgery for treatment of meningiomas.

OBJECT: The purpose of this study was to evaluate patterns of failure after stereotactic radiosurgery (SRS) for meningiomas and factors that may influence these outcomes. METHODS: Based on a retrospective chart review, 279 patients were treated with SRS for meningiomas between January 1999 and March 2011 at Wake Forest Baptist Health. Disease progression was determined using serial imaging, with a minimum follow-up of 6 months (median 34.2 months). RESULTS: The median margin dose was 12.0 Gy (range 8.8-20 Gy). Local control rates for WHO Grade I tumors were 96.6%, 84.4%, and 75.7% at 1, 3, and 5 years, respectively. WHO Grade II and III tumors had local control rates of 72.3%, 57.7%, and 52.9% at 1, 3, and 5 years, respectively. Tumors without pathological grading had local control rates of 98.7%, 97.6%, and 94.2% at 1, 3, and 5 years, respectively. Of the local recurrences, 63.1% were classified as marginal (within 2 cm of treatment field). The 1-, 3-, and 5-year rates of distant failure were 6.5%, 10.3%, and 16.6%, respectively, for Grade I tumors and 11.4%, 17.2%, and 22.4%, respectively, for Grade II/III tumors. Tumors without pathological grading had distant failure rates of 0.7%, 3.2%, and 6.5% at 1, 3, and 5 years, respectively. Wilcoxon analysis revealed that multifocal disease (p < 0.001) and high-grade histology (WHO Grade II or III; p < 0.001) were significant predictors of local recurrence. Additionally, male sex was a significant predictor of distant recurrence (p = 0.04). Multivariate analysis also showed that doses greater than or equal to 12 Gy were associated with improved local control (p = 0.015). CONCLUSIONS: In this patient series, 12 Gy was the minimum sufficient margin dose for the treatment of meningiomas. Male sex is a risk factor for distant failure, whereas high-grade histology and multifocal disease are risk factors for local failure.

Breast cancer subtype affects patterns of failure of brain metastases after treatment with stereotactic radiosurgery.

We investigate the variance in patterns of failure after Gamma Knife™ radiosurgery (GKRS) for patients with brain metastases based on the subtype of the primary breast cancer. Between 2000 and 2010, 154 breast cancer patients were treated with GKRS for brain metastases. Tumor subtypes were approximated based on hormone receptor (HR) and HER2 status of the primary cancer: Luminal A/B (HR+/HER2(-)); HER2 (HER2+/HR(-)); Luminal HER2 (HR+/HER2+), Basal (HR(-)/HER2(-)), and then based on HER2 status alone. The median follow-up period was 54 months. Kaplan-Meier method was used to estimate survival times. Multivariable analysis was performed using Cox regression models. Median number of lesions treated was two (range 1-15) with a median dose of 20 Gy (range 9-24 Gy). Median overall survival (OS) was 7, 9, 11 and 22 months for Basal, Luminal A/B, HER2, and Luminal HER2, respectively (p = 0.001), and was 17 and 8 months for HER2+ and HER(-) patients, respectively (p < 0.001). Breast cancer subtype did not predict time to local failure (p = 0.554), but did predict distant brain failure rate (76, 47, 47, 36 % at 1 year for Basal, Luminal A/B, HER2, and Luminal HER2 respectively, p < 0.001). An increased proportion of HER2+ patients experienced neurologic death (46 vs 31 %, p = 0.066). Multivariate analysis revealed that HER2+ patients (p = 0.007) independently predicted for improved survival. Women with basal subtype have high rates of distant brain failure and worsened survival. Our data suggest that differences in biologic behavior of brain metastasis occur across breast cancer subtypes.

Toxic epidermal necrolysis in an irradiated patient treated with a nanocrystalline silver dressing.

Toxic epidermal necrolysis syndrome is a severe exfoliative condition, which may be triggered by anticonvulsant medication. We report a case of toxic epidermal necrolysis syndrome in a 43-year-old female who was receiving radiotherapy for brain metastases from a recurring breast cancer and phenytoin. She had 80% total body surface area involvement and recovered successfully with the application of a nanocrystalline silver dressing.

Survival outcomes in resected extrahepatic cholangiocarcinoma: effect of adjuvant radiotherapy in a surveillance, epidemiology, and end results analysis.

PURPOSE: The benefit of adjuvant radiotherapy (RT) after surgical resection for extrahepatic cholangiocarcinoma has not been clearly established. We analyzed survival outcomes of patients with resected extrahepatic cholangiocarcinoma and examined the effect of adjuvant RT. METHODS AND MATERIALS: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) program between 1973 and 2003. The primary endpoint was the overall survival time. Cox regression analysis was used to perform univariate and multivariate analyses of the following clinical variables: age, year of diagnosis, histologic grade, localized (Stage T1-T2) vs. regional (Stage T3 or greater and/or node positive) stage, gender, race, and the use of adjuvant RT after surgical resection. RESULTS: The records for 2,332 patients were obtained. Patients with previous malignancy, distant disease, incomplete or conflicting records, atypical histologic features, and those treated with preoperative/intraoperative RT were excluded. Of the remaining 1,491 patients eligible for analysis, 473 (32%) had undergone adjuvant RT. After a median follow-up of 27 months (among surviving patients), the median overall survival time for the entire cohort was 20 months. Patients with localized and regional disease had a median survival time of 33 and 18 months, respectively (p<.001). The addition of adjuvant RT was not associated with an improvement in overall or cause-specific survival for patients with local or regional disease. CONCLUSION: Patients with localized disease had significantly better overall survival than those with regional disease. Adjuvant RT was not associated with an improvement in long-term overall survival in patients with resected extrahepatic bile duct cancer. Key data, including margin status and the use of combined chemotherapy, was not available through the SEER database.