A pooled patient-reported outcomes analysis of moderately hypofractionated proton beam therapy and photon-based intensity modulated radiation therapy for low- or intermediate-risk prostate cancer.

BACKGROUND: We sought to characterize and compare late patient-reported outcomes (PROs) after moderately hypofractionated intensity modulated radiation therapy (IMRT) and proton beam therapy (PBT) for localized prostate cancer (PC). METHODS: This multi-institutional analysis included low- or intermediate-risk group PC patients treated with moderately hypofractionated radiation to an intact prostate stratified by treatment modality: IMRT or PBT. The primary outcomes were prospectively collected patient-reported late gastrointestinal (GI) and genitourinary (GU) toxicity assessed by International Prostate Symptom Score (IPSS) and Expanded PC Index Composite (EPIC). Multivariable regression analysis (MVA) controlling for age, race, and risk group tested the effect of time, treatment, and their interaction. RESULTS: 287 IMRT and 485 PBT patients were included. Intermediate risk group (81.2 vs. 68.2%; p < 0.001) and median age at diagnosis (70 vs. 67 years; p < 0.001) were higher in the IMRT group. On MVA, there was no significant difference between modalities. PBT IPSS did not differ from IMRT IPSS at 12 months (odds ratio [OR], 1.19; p = 0.08) or 24 months (OR, 0.99; p = 0.94). PBT EPIC overall GI function at 12 months (OR, 3.68; p = 0.085) and 24 months (OR 2.78; p = 0.26) did not differ from IMRT EPIC overall GI function. At 24 months, urinary frequency was no different between PBT and IMRT groups (OR 0.35; p = 0.096). CONCLUSIONS: This multi-institutional analysis of low- or intermediate-risk PC treated with moderately hypofractionated PBT and IMRT demonstrated low rates of late patient-reported GI and GU toxicities. After covariate adjustment, late GI and GU PROs were not significantly different between PBT or IMRT cohorts.

The Role and Scope of Prehabilitation in Cancer Care.

OBJECTIVES: To recognize cancer prehabilitation as a pretreatment regimen to increase functional status for patients requiring cancer treatment. This article presents current evidence addressing the efficacy and benefits of prehabilitation regimens in different cancer survivor populations. DATA SOURCES: Studies and case reports in the PubMed database. CONCLUSION: Cancer prehabilitation may improve outcomes. Prehabilitation may include targeted or whole-body exercise, nutrition, education, psychologic counseling, and smoking cessation. Opportunities exist to further improve access to and delivery of multimodal prehabilitation, and nurses play a critical role in connecting patients to these services. IMPLICATIONS FOR NURSING PRACTICE: Oncology nurses who are knowledgeable of cancer treatment-related effects are poised to assess survivors for existing impairments, advocate for prehabilitation for existing and potential morbidities, and monitor functional status over time. As patient educators, they are key to informing cancer survivors about the role of prehabilitation.

Treatment Toxicity: Radiation.

Intentional and unintentional radiation exposures have a powerful impact on normal tissue function and can induce short-term and long-term injury to all cell systems. Radiation effects can lead to lifetime-defining health issues for a patient and can produce complications to all organ systems. Providers need to understand acute and late effects of radiation treatment and how the fingerprints of therapy can have an impact on health care in later life. This article reviews current knowledge concerning normal tissue tolerance with therapy.

Prehabilitation for patient positioning: pelvic exercises assist in minimizing inter-fraction sacral slope variability during radiation therapy.

Reproducible patient positioning is essential for precision in radiation therapy (RT) delivery. We tested the hypothesis that a structured daily pre-treatment stretching regimen is both feasible and effective for minimizing variability in positioning, as measured by sacral slope angles (SSA). Eight female subjects undergoing pelvic radiotherapy performed a structured daily hip exercise regimen (extension and external rotation) immediately prior to both simulation imaging and daily treatment, throughout their RT course. This exercising cohort was compared to a retrospective review of 20 subjects (17 women and 3 men) undergoing RT, who had usual care. SSA measurements from daily pre-treatment imaging were compared to SSA measurements from the simulation CT. The average variation in SSA among the intervention subjects was 0.91° (± 0.58°), with a range among subjects of 0.57°-1.27°. The average variation for the control subjects was 2.27° (± 1.43°), ranging 1.22°-5.09°. The difference between the two groups was statistically significant (p = 0.0001). There was a statistically significant SSA variation between groups at each week of treatment. There was no significant variation among the intervention subjects between week 1 and later weeks, whereas subjects in the control group demonstrated significant SSA variation between week 1 and later weeks. We demonstrated a significant decrease in the variability of SSA by implementing a simple pre-treatment exercise program, while control subjects exhibited increasing variation in SSA over the course of treatment. We conclude that there is a potential benefit of prehabilitation during pelvic RT; however, a larger randomized control trial is required to confirm the findings.Clinical Trial: This research project was approved by the University of Massachusetts Medical School IRB (IRB ID H00012353) on January 21, 2017. The study is listed on ClinicalTrials.gov, provided by the U.S. National Library of Medicine, found with identifier NCT03242538.

Positioning of port films for radiation: variability is present.

PURPOSE: Pelvic radiation treatment demands precision and consistency in patient setup for efficacy of therapy and to limit radiation dosage to normal tissue. Despite the use of immobilization devices and positioning techniques, there is still concern for variation in daily setup. The purpose of this retrospective study was to determine the presence and degree of variation in sacral slope in 20 subjects receiving radiation therapy for pelvic malignancies. METHODS: Each of the 20 subjects received between 20 and 25 fractions of external beam radiation treatment to the pelvis. The sacral slope was measured on each of the daily port films taken prior to treatment and compared to the sacral slope angle measured on the initial treatment planning simulation digitally reconstructed radiographic imaging. RESULTS: Compared to this initial imaging, the average sacral slope variation across all 20 subjects was 2.27° (± 1.43°), and the average variation among patients ranged from 1.22° to 5.09°. Variation in sacral slope across all 20 subjects from one treatment day to the next was 2.05° (± 1.47°), and ranged from 0.97° to 3.21°. CONCLUSIONS: This study demonstrates that despite the rigorous use of immobilization devices, there still exists day-to-day variation in sacral slope angle between treatment days and compared to initial baseline imaging off which the treatment plan is developed. There is an on-going study at our institution with an attempt to reduce this variation by offering exercises prior to radiation.

Late acute graft-versus-host disease: a prospective analysis of clinical outcomes and circulating angiogenic factors.

Late acute (LA) graft-versus-host disease (GVHD) is persistent, recurrent, or new-onset acute GVHD symptoms occurring >100 days after allogeneic hematopoietic cell transplantation (HCT). The aim of this analysis is to describe the onset, course, morbidity, and mortality of and examine angiogenic factors associated with LA GVHD. A prospective cohort of patients (n = 909) was enrolled as part of an observational study within the Chronic GVHD Consortium. Eighty-three patients (11%) developed LA GVHD at a median of 160 (interquartile range, 128-204) days after HCT. Although 51 out of 83 (61%) achieved complete or partial response to initial therapy by 28 days, median failure-free survival was only 7.1 months (95% confidence interval, 3.4-19.1 months), and estimated overall survival (OS) at 2 years was 56%. Given recently described alterations of circulating angiogenic factors in classic acute GVHD, we examined whether alterations in such factors could be identified in LA GVHD. We first tested cases (n = 55) and controls (n = 50) from the Chronic GVHD Consortium and then validated the findings in 37 cases from Mount Sinai Acute GVHD International Consortium. Plasma amphiregulin (AREG; an epidermal growth factor [EGF] receptor ligand) was elevated, and an AREG/EGF ratio at or above the median was associated with inferior OS and increased nonrelapse mortality in both cohorts. Elevation of AREG was detected in classic acute GVHD, but not chronic GVHD. These prospective data characterize the clinical course of LA GVHD and demonstrate alterations in angiogenic factors that make LA GVHD biologically distinct from chronic GVHD.

Ipilimumab for Patients with Relapse after Allogeneic Transplantation.

BACKGROUND: Loss of donor-mediated immune antitumor activity after allogeneic hematopoietic stem-cell transplantation (HSCT) permits relapse of hematologic cancers. We hypothesized that immune checkpoint blockade established by targeting cytotoxic T-lymphocyte-associated protein 4 with ipilimumab could restore antitumor reactivity through a graft-versus-tumor effect. METHODS: We conducted a phase 1/1b multicenter, investigator-initiated study to determine the safety and efficacy of ipilimumab in patients with relapsed hematologic cancer after allogeneic HSCT. Patients received induction therapy with ipilimumab at a dose of 3 or 10 mg per kilogram of body weight every 3 weeks for a total of 4 doses, with additional doses every 12 weeks for up to 60 weeks in patients who had a clinical benefit. RESULTS: A total of 28 patients were enrolled. Immune-related adverse events, including one death, were observed in 6 patients (21%), and graft-versus-host disease (GVHD) that precluded further administration of ipilimumab was observed in 4 patients (14%). No responses that met formal response criteria occurred in patients who received a dose of 3 mg per kilogram. Among 22 patients who received a dose of 10 mg per kilogram, 5 (23%) had a complete response, 2 (9%) had a partial response, and 6 (27%) had decreased tumor burden. Complete responses occurred in 4 patients with extramedullary acute myeloid leukemia and 1 patient with the myelodysplastic syndrome developing into acute myeloid leukemia. Four patients had a durable response for more than 1 year. Responses were associated with in situ infiltration of cytotoxic CD8+ T cells, decreased activation of regulatory T cells, and expansion of subpopulations of effector T cells in the blood. CONCLUSIONS: Our early-phase data showed that administration of ipilimumab was feasible in patients with recurrent hematologic cancers after allogeneic HSCT, although immune-mediated toxic effects and GVHD occurred. Durable responses were observed in association with several histologic subtypes of these cancers, including extramedullary acute myeloid leukemia. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01822509.).