Constance Barysauskas

Retrospective cohort study evaluating the impact of intraperitoneal morcellation on outcomes of localized uterine leiomyosarcoma.

Uterine leiomyosarcoma (ULMS) is identified in 0.1% to 0.2% of hysterectomy specimens of presumed leiomyoma. To date, there is no preoperative technique that reliably differentiates ULMS from uterine leiomyoma. Increasing use of minimally invasive approaches for the management of leiomyomas may result in inadvertently morcellated ULMS with resultant intraperitoneal dissemination of tumor. The objective of this study was to assess the impact of intraperitoneal morcellation on the outcomes of patients with ULMS.

Impact of contact precautions on falls, pressure ulcers and transmission of MRSA and VRE in hospitalized patients

BACKGROUND Hospitals use contact precautions to prevent the spread of meticillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). There is concern that contact precautions may have adverse effects on the safety of isolated patients. In November 2010, the infection control policy at an academic medical centre was modified, and contact precautions were discontinued for patients colonized or infected with MRSA or VRE (MRSA/VRE patients). AIM To assess the rates of falls and pressure ulcers among MRSA/VRE patients and other adult medical-surgical patients, as well as changes in MRSA and VRE transmission before and after the policy change. METHODS A single-centre retrospective hospital-wide cohort study was performed from 1st November 2009 to 31st October 2011. FINDINGS Rates of falls and pressure ulcers were significantly higher among MRSA/VRE patients compared with other adult medical-surgical patients before the policy change (falls: 4.57 vs 2.04 per 1000 patient-days, P < 0.0001; pressure ulcers: 4.87 vs 1.22 per 1000 patient-days, P < 0.0001) and after the policy change (falls: 4.82 vs 2.10 per 1000 patient-days, P < 0.0001; pressure ulcers: 4.17 vs 1.19 per 1000 patient-days, P < 0.0001). No significant differences in the rates of falls and pressure ulcers among MRSA/VRE patients were found after the policy change compared with before the policy change. There was no overall change in MRSA or VRE hospital-acquired transmission. CONCLUSION MRSA/VRE patients had higher rates of falls and pressure ulcers compared with other adult medical-surgical patients. Rates were not affected by removal of contact precautions, suggesting that other factors contribute to these complications. Further research is required among this population to prevent complications.

Immunotherapy with single agent nivolumab for advanced leiomyosarcoma of the uterus: Results of a phase 2 study

Immunotherapy has changed the therapeutic landscape in oncology. Advanced uterine leiomyosarcoma (ULMS) remains an incurable disease in most cases, and despite new drug approvals, improvements in overall survival have been modest at best. The goal of this study was to evaluate programmed‐death 1 (PD‐1) inhibition with nivolumab in this patient population.

Long-term follow-up results of the multicenter phase II trial of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of standard tyrosine kinase inhibitor therapy.

BACKGROUND This investigator-initiated trial provided the justification for the phase III GRID study resulting in worldwide regulatory approval of regorafenib as a third-line therapy for patients with metastatic gastrointestinal stromal tumors (GIST). We report the genotype analyses, long-term safety, and activity results from this initial trial of regorafenib in GIST. PATIENTS AND METHODS The trial was conducted between February 2010 and January 2014, among adult patients with metastatic GIST, after failure of at least imatinib and sunitinib. Patients received regorafenib orally, 160 mg once daily, days 1-21 of a 28-day cycle. Clinical benefit rate (CBR), defined as complete or partial response (PR), or stable disease lasting ≥16 weeks per RECIST 1.1, progression-free survival (PFS), overall survival (OS), long-term safety data, and metabolic response by functional imaging were assessed. RESULTS Thirty-three patients received at least one dose of regorafenib. The median follow-up was 41 months. CBR was documented in 25 of 33 patients [76%; 95% confidence interval (CI) 58% to 89%], including six PRs. The median PFS was 13.2 months (95% CI 9.2-18.3 months) including four patients who remained progression-free at study closure, each achieving clinical benefit for more than 3 years (range 36.8-43.5 months). The median OS was 25 months (95% CI 13.2-39.1 months). Patients whose tumors harbored a KIT exon 11 mutation demonstrated the longest median PFS (13.4 months), whereas patients with KIT/PDGFRA wild-type, non-SDH-deficient tumors experienced a median 1.6 months PFS (P < 0.0001). Long-term safety profile is consistent with previous reports; hand-foot skin reaction and hypertension were the most common reasons for dose reduction. Notably, regorafenib induced objective responses and durable benefit in SDH-deficient GIST. CONCLUSIONS Long-term follow-up of patients with metastatic GIST treated with regorafenib suggests particular benefit among patients with primary KIT exon 11 mutations and those with SDH-deficient GIST. Dose modifications are frequently required to manage treatment-related toxicities. CLINICAL TRIAL NUMBER NCT01068769.

Oral adverse events in cancer patients treated with VEGFR-directed multitargeted tyrosine kinase inhibitors

OBJECTIVES This study characterized the incidence and clinical features of oral adverse events among cancer patients who received VEGFR-directed multitargeted tyrosine kinase inhibitor (VR-TKI) therapies. METHODS Electronic medical records of adult cancer patients treated with sunitinib, sorafenib, regorafenib, pazopanib, cabozantinib, imatinib, and bevacizumab therapy at Dana-Farber Cancer Institute from 2009 to 2012 were reviewed. Data collected included patient characteristics, oral and non-oral adverse events, and time to onset. Time oral adverse event-free was the primary outcome. RESULTS A total of 747 patients with 806 individual courses of therapy were treated for a median of 3.9months with sunitinib (n=161), sorafenib (n=172), regorafenib (n=15), pazopanib (n=132), cabozantinib (n=23), imatinib (n=144), or bevacizumab (n=159) for lung cancer (21%), gastrointestinal stromal tumor (15%), and metastatic renal cell carcinoma (13%). An oral adverse event was reported in 23.7% of patients at a median of 1.9months after starting therapy. The most commonly reported oral adverse event was oral mucosal sensitivity (dysesthesia), occurring in 12% of patients, typically without clinical findings. Multivariate models showed patients who received VR-TKI therapy were at greater risk of any oral adverse event compared with patients treated with imatinib or bevacizumab. Patients receiving VR-TKI therapy who developed an oral adverse event were also at increased risk for hand-foot skin reaction (15.9%). CONCLUSIONS VR-TKI associated oral adverse events are characterized primarily by dysesthesia with lack of clinical signs. Oral dysesthesia is more commonly associated with VR-TKIs than with bevacizumab or imatinib. Management is largely empirical and requires further investigation.

A Prospective Controlled Trial of an Electronic Hand Hygiene Reminder System

A prospective controlled trial conducted in two intensive care units found that an electronic hand hygiene reminder system that provides real-time feedback on overall unit-wide hand hygiene performance can increase hand hygiene activity.

Acute gastrointestinal toxicity and bowel bag dose-volume parameters for preoperative radiation therapy for retroperitoneal sarcoma

PURPOSE Acute gastrointestinal (GI) toxicity has been studied in GI and gynecological (GYN) cancers, with volume receiving 15 Gy (V15) <830 mL, V25 <650 mL, and V45 <195 mL identified as dose constraints for the peritoneal space (bowel bag [BB]). There are no reported constraints derived from retroperitoneal sarcoma (RPS), and prospective trials for RPS have adopted some of the GI and GYN constraints. This study quantified GI toxicity during preoperative radiation therapy (RT) for RPS, assessed toxicity using published constraints, and evaluated predictors for toxicity. METHODS AND MATERIALS From 2003 to 2013, 56 patients with RPS underwent preoperative RT at 2 institutions. Toxicity was scored using Radiation Therapy Oncology Group criteria for upper and lower acute GI toxicity. BB was contoured on planning computed tomography scans per Radiation Therapy Oncology Group atlas guidelines with review by a radiologist. Relationships among toxicity, clinical factors, and BB dose were analyzed. RESULTS Three patients (5%) developed grade ≥3 acute GI toxicity: 2 grade 3 toxicities (anorexia and nausea) and 1 grade 5 toxicity (tumor-bowel fistula). Thirty-six patients (64%) had grade 2 toxicity (nausea, 55%; diarrhea, 23%; pain, 20%). Tumor size was the only significant clinical predictor of grade ≥2 acute GI toxicity. Larger mean BB volumes predicted for grade ≥2 toxicity (P = .001). On receiver operating characteristics analysis, V30 was the best discriminator for toxicity (P = .0001). Median BB V15 was 1375 mL; 75% of patients had V15 ≥830 mL. Median V25 was 1083 mL; 68% had V25 ≥650 mL. Median V45 was 575 mL; 82% had V45 ≥195 mL. V25 ≥650 mL was significantly associated with grade ≥2 toxicity (P = .01). CONCLUSIONS Among patients treated with preoperative RT for RPS, significant acute GI toxicity was very low despite BB dose exceeding established constraints for most cases. Acceptable dose constraints for RPS may be higher than those for GI or GYN cancers. Further assessment of dose-volume constraints for RPS is needed.

Comparison of performance of various tumor response criteria in assessment of sunitinib activity in advanced gastrointestinal stromal tumors.

PURPOSE To compare the performance of various tumor response criteria (TRC) in the assessment of patients with advanced gastrointestinal stromal tumor (GIST) treated with sunitinib after failure of imatinib. METHODS Sixty-two participants with advanced GIST in two clinical trials received oral sunitinib after prior failure of imatinib (median duration 24 weeks; interquartile range 14-56) and were followed with contrast-enhanced computed tomography at baseline and thereafter at median intervals of 6 weeks (IRQ 6-9). Tumor response was prospectively determined using Response Evaluation Criteria in Solid Tumors (RECIST) 1.0, and retrospectively reassessed for comparison using RECIST 1.1, Choi criteria, and modified Choi (mChoi) criteria using the original target lesions. For mChoi criteria, progressive disease was defined as 20% increase in sum of the longest dimension, similar to RECIST 1.1. Clinical benefit rate (CBR; complete response, partial response, or stable disease ≥12 weeks) and progression-free survival were compared between various TRCs using kappa statistics. RESULTS While partial response as the best response was more frequent by Choi and mChoi criteria (50% each) than RECIST 1.1 (15%) and RECIST 1.0 (13%), CBR was similar between various TRCs (overall CBR 60%-77%, 77%-94% agreement between all TRC pairs). Time to best response was shorter for Choi and mChoi criteria (median 11 weeks each) compared to RECIST 1.1 and RECIST 1.0 (median 25 and 24 weeks, respectively). PFS was similar for RECIST 1.1, RECIST 1.0, and mChoi (median 35 weeks each), and shortest for Choi criteria (median 23 weeks). CONCLUSIONS CBR was similar among the various TRCs, although Choi criteria led to earlier determination of disease progression. Therefore, RECIST 1.1 and mChoi criteria may be preferred for response assessment in patients with advanced GIST.

Localized Adult Ewing Sarcoma: Favorable Outcomes with Alternating Vincristine, Doxorubicin, Cyclophosphamide, and Ifosfamide, Etoposide (VDC/IE)‐Based Multimodality Therapy

BACKGROUND In children with localized Ewing sarcoma (ES), addition of ifosfamide and etoposide to cyclophosphamide, doxorubicin, and vincristine (VDC/IE) improved 5-year overall survival (OS) to 70%-80%. Prior to delivery of VDC/IE in adults, 5-year OS was <50%. We reviewed our institutional outcomes for adults with ES who received VDC/IE-based treatment. MATERIALS AND METHODS Between 1997-2013, 67 adults with localized ES were treated with curative intent. Local recurrence-free survival (LRFS), progression-free survival (PFS), and OS were determined using Kaplan-Meier method; comparisons were assessed with log-rank. Proportional hazard models were used to determine predictive factors. RESULTS All patients received VDC/IE (median 14 cycles.) Local therapy was surgery for 33, radiation therapy for 17, or both for 17. Median follow-up for living patients was 5.2 years. Six patients had disease progression on therapy. Site of first failure was local for three, local and distant for two, and distant for ten. Five-year LRFS was 91%; 5-year LRFS was 96% for nonpelvic disease and 64% for pelvic disease (p = .003). Five-year PFS was 66%, and 5-year OS was 79%. On multivariate analysis, pelvic site had a 3.3 times increased risk of progression (p = .01). CONCLUSION Survival for adults with localized ES treated with VDC/IE-based multimodality therapy appears to be better than historical data and similar to excellent outcomes in children. Pelvic site of disease remains a predictor of worse outcome. Given the paucity of literature for adult ES, these data help validate VDC/IE-based therapy as an appropriate treatment approach for this rare disease in adults. IMPLICATIONS FOR PRACTICE Ewing sarcoma (ES) is rare in adults. Treatment approaches for adults have been extrapolated from the pediatric experience, and there is a sense that adults fare less well than children. We reviewed treatment outcomes in adults with localized ES treated with cyclophosphamide, doxorubicin, and vincristine in alternation with ifosfamide and etoposide (VDC/IE) as part of multimodality therapy. Survival outcomes appear to be better than historical data for adults and similar to the excellent outcomes for children. These data help validate VDC/IE-based therapy as an appropriate treatment approach for this rare disease in adults.

Oncology Patient Portal Enrollment at a Comprehensive Cancer Center: A Quality Improvement Initiative

PURPOSE Patient portals (PPs) provide patients access to their electronic health record and may facilitate active engagement in their care. Because PP use has not been well studied among patients with cancer, we sought to: understand the willingness of patients with cancer to use the PP, identify barriers to PP use, and improve PP accessibility. MATERIALS AND METHODS As part of an institutional quality improvement initiative, we used a stakeholder-driven approach to examine PP use at the Dana-Farber Cancer Institute (Boston, MA). We conducted a survey across all ambulatory oncology practices as well as staff and patient focus groups in one ambulatory practice. We deployed three interventions to address barriers: staff education, staff-assisted enrollment support, and independent enrollment support. RESULTS In October 2015, 1,019 (87%) of 1,178 eligible patients completed the survey (PP enrolled, 57%; non-PP enrolled, 43%). PP-enrolled patients reported reviewing test results and appointment schedules. Non-PP-enrolled patients cited difficult PP enrollment, lack of computer access, and concern about sharing data electronically as barriers to PP enrollment. Focus groups (staff, n = 20; patient representatives, n = 5) also identified lack of awareness of PP benefits as a barrier. The interventions, deployed from November to December 2015, increased PP enrollment from 47% to 53% by January 2016. CONCLUSION Patients with cancer want to communicate with their team through the PP, but barriers to enrollment impede use. Straightforward system-level interventions may increase enrollment. Further work is necessary to ascertain the degree to which increased PP enrollment leads to greater engagement and better outcomes.