Maintenance pembrolizumab therapy in patients with metastatic HER2-negative breast cancer with prior response to chemotherapy.

PURPOSE: Accumulating toxicities hinder indefinite chemotherapy for many patients with metastatic/recurrent HER2-negative breast cancer. We conducted a phase II trial of pembrolizumab monotherapy following induction chemotherapy to determine the efficacy of maintenance immunotherapy in patients with metastatic HER2-negative inflammatory breast cancer (IBC) and non-IBC triple-negative breast cancer (TNBC) and a biomarker study. PATIENTS AND METHODS: Patients with a complete response (CR), partial response (PR), or stable disease (SD) after at least 3 cycles of chemotherapy for HER2-negative breast cancer received pembrolizumab, regardless of programmed death-ligand 1 expression. Pembrolizumab (200 mg) was administered every 3 weeks until disease progression, intolerable toxicity, or 2 years of pembrolizumab exposure. The endpoints included the 4-month disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and response biomarkers in the blood. RESULTS: Of 43 treated patients, 11 had metastatic IBC and 32 non-IBC TNBC. The 4-month DCR was 58.1% (95% CI, 43.4%-72.9%). For all patients, the median PFS was 4.8 months (95% CI, 3.0-7.1 months). The toxicity profile was similar to the previous pembrolizumab monotherapy study. Patients with high T-cell clonality at baseline had a longer PFS with pembrolizumab treatment than did those with low T-cell clonality (10.4 vs. 3.6 months, p = 0.04). Patients who achieved SD also demonstrated a significant increase in T-cell clonality during therapy compared to those who didn't achieve SD (20% vs. 5.9% mean increase, respectively; p = 0.04). CONCLUSIONS: Pembrolizumab monotherapy achieved durable treatment responses. Patients with a high baseline T-cell clonality had prolonged disease control with pembrolizumab.

Short-Term Biomarker Modulation Study of Dasatinib for Estrogen Receptor-Negative Breast Cancer Chemoprevention.

Objective: Risk-reducing therapy with selective estrogen receptor (ER) modulators and aromatase inhibitors reduce breast cancer risk. However, the effects are limited to ER-positive breast cancer. Therefore, new agents with improved toxicity profiles that reduce the risk in ER-negative breast cancers are urgently needed. The aim of this prospective, short-term, prevention study was to evaluate the effect of dasatinib, an inhibitor of the tyrosine kinase Src, on biomarkers in normal (but increased risk) breast tissue and serum of women at high risk for a second, contralateral primary breast cancer. Materials and Methods: Women with a history of unilateral stage I, II, or III ER-negative breast cancer, having no active disease, and who completed all adjuvant therapies were eligible. Patients underwent baseline fine-needle aspiration (FNA) of the contralateral breast and serum collection for biomarker analysis and were randomized to receive either no treatment (control) or dasatinib at 40 or 80 mg/day for three months. After three months, serum collection and breast FNA were repeated. Planned biomarker analysis consisted of changes in cytology and Ki-67 on breast FNA, and changes in serum levels of insulin-like growth factor 1 (IGF-1), IGF-binding protein 1, and IGF-binding protein 3. The primary objective was to evaluate changes in Ki-67 and secondary objective included changes in cytology in breast tissue and IGF-related serum biomarkers. Toxicity was also evaluated. Results: Twenty-three patients started their assigned treatments. Compliance during the study was high, with 86.9% (20/23) of patients completing their assigned doses. Dasatinib was well tolerated and no drug-related grade 3 and 4 adverse events were observed. Since only one patient met the adequacy criteria for the paired FNA sample, we could not evaluate Ki-67 level or cytological changes. No significant change in serum biomarkers was observed among the three groups. Conclusion: Dasatinib was well tolerated but did not induce any significant changes in serum biomarkers. The study could not fulfill its primary objective due to an inadequate number of paired FNA samples. Further, larger studies are needed to evaluate the effectiveness of Src inhibitors in breast cancer prevention.

Phase II Trial of Nelipepimut-S Peptide Vaccine in Women with Ductal Carcinoma In Situ.

NeuVax is a vaccine comprised of the HER2-derived MHC class I peptide E75 (nelipepimut-S, NPS) combined with GM-CSF. We completed a randomized trial of preoperative vaccination with NeuVax versus GM-CSF alone in patients with ductal carcinoma in situ (DCIS). The primary objective was to evaluate for NPS-specific cytotoxic T lymphocyte (CTL) responses. Patients with human leukocyte antigen (HLA)-A2-positive DCIS were enrolled and randomized 2:1 to NeuVax versus GM-CSF alone and received two inoculations prior to surgery. The number of NPS-specific CTL was measured pre-vaccination, at surgery, and 1 and 3 to 6 months post-operation by dextramer assay. Differences in CTL responses between groups and between pre-vaccination and 1-month post-operation were analyzed using a two-sample t test or Wilcoxon rank sum test. The incidence and severity of adverse events were compared between groups. Overall, 45 patients were registered; 20 patients were HLA-A2 negative, 7 declined participation, 1 withdrew, and 4 failed screening for other reasons. The remaining 13 were randomized to NeuVax (n = 9) or GM-CSF alone (n = 4). Vaccination was well-tolerated with similar treatment-related toxicity between groups with the majority (>89%) of adverse events being grade 1. The percentage of NPS-specific CTLs increased in both arms between baseline (pre-vaccination) and 1-month post-operation. The increase was numerically greater in the NPS+GM-CSF arm, but the difference was not statistically significant. NPS+GM-CSF is safe and well-tolerated when given preoperatively to patients with DCIS. In patients with HLA-A2-positive DCIS, two inoculations with NPS+GM-CSF can induce in vivo immunity and a continued antigen-specific T-cell response 1-month postsurgery. PREVENTION RELEVANCE: This trial showed that vaccination of patients with HLA-A2-positive DCIS with NeuVax in the preoperative setting can induce a sustained antigen-specific T-cell response. This provides proof of principle that vaccination in the preoperative or adjuvant setting may stimulate an adaptive immune response that could potentially prevent disease recurrence.

Maternal Embryonic Leucine Zipper Kinase is Associated with Metastasis in Triple-negative Breast Cancer.

Triple-negative breast cancer (TNBC) has high relapse and metastasis rates and a high proportion of cancer stem-like cells (CSC), which possess self-renewal and tumor initiation capacity. MELK (maternal embryonic leucine zipper kinase), a protein kinase of the Snf1/AMPK kinase family, is known to promote CSC maintenance and malignant transformation. However, the role of MELK in TNBC metastasis is unknown; we sought to address this in the current study. We found that MELK mRNA levels were higher in TNBC tumors [8.11 (3.79-10.95)] than in HR+HER2- tumors [6.54 (2.90-9.26)]; P < 0.001]. In univariate analysis, patients with breast cancer with high-MELK-expressing tumors had worse overall survival (P < 0.001) and distant metastasis-free survival (P < 0.01) than patients with low-MELK-expressing tumors. In a multicovariate Cox regression model, high MELK expression was associated with shorter overall survival after adjusting for other baseline risk factors. MELK knockdown using siRNA or MELK inhibition using the MELK inhibitor MELK-In-17 significantly reduced invasiveness, reversed epithelial-to-mesenchymal transition, and reduced CSC self-renewal and maintenance in TNBC cells. Nude mice injected with CRISPR MELK-knockout MDA-MB-231 cells exhibited suppression of lung metastasis and improved overall survival compared with mice injected with control cells (P < 0.05). Furthermore, MELK-In-17 suppressed 4T1 tumor growth in syngeneic BALB/c mice (P < 0.001). Our findings indicate that MELK supports metastasis by promoting epithelial-to-mesenchymal transition and the CSC phenotype in TNBC. Significance: These findings indicate that MELK is a driver of aggressiveness and metastasis in TNBC.

Knowledge, attitudes, and beliefs of oncology trainees on function and cancer rehabilitation medicine.

BACKGROUND: Improved function is associated with reduced morbidity and mortality in patients with cancer. Cancer rehabilitation medicine (CRM) is a subspecialty of physical medicine and rehabilitation (PM&R) that focuses on improving function in patients with cancer. One of the barriers to patients accessing CRM services is the lack of referrals from oncology providers. Understanding the knowledge, attitudes and beliefs of oncology trainees regarding the importance of function and the role of CRM is essential to reducing educational gaps and improving patients' access to essential rehabilitation services. OBJECTIVE: To determine oncology trainees' knowledge, attitude and beliefs about the importance of function and the role of CRM in the care of patients with cancer. SETTING: The study was conducted at a comprehensive cancer center in the United States. INTERVENTION: Descriptive survey study was administered to postgraduate oncology trainees who spent at least 1 day a week providing patient care. MAIN OUTCOME: Participants' report of their knowledge, attitudes, and beliefs on the importance of function and CRM in the care of patients with cancer. RESULTS: The survey was sent to 197 oncology trainees with a response rate of 67% (n = 132) and 126 were ultimately included. All participants believed that function is important in the care of patients with cancer. The majority believed that better function improves treatment tolerance (94%) and survival (84%). Most reported that having CRM physicians (80%) and an inpatient rehabilitation unit (88%) in the oncological setting is important; however, most participants reported that they refer fewer than 25% of their patients to CRM services. Participants with prior exposure to PM&R were significantly more likely to consult PM&R compared to those without exposure (p = .005). Most oncology trainees (81%) believed that education in CRM should be part of their oncology training. CONCLUSION: This study demonstrates that oncology trainees believe that function is important. They also believe that access to CRM would improve treatment tolerance and survival, but most report that they rarely refer patients to CRM services. Most trainees desire increased exposure to CRM during oncology training.

Patient Engagement With Early Stage Advance Care Planning at a Comprehensive Cancer Center.

BACKGROUND: Establishing care preferences and selecting a prepared medical decision-maker (MDM) are basic components of advance care planning (ACP) and integral to treatment planning. Systematic ACP in the cancer setting is uncommon. We evaluated a systematic social work (SW)-driven process for patient selection of a prepared MDM. METHODS: We used a pre/post design, centered on SW counseling incorporated into standard-of-care practice. New patients with gynecologic malignancies were eligible if they had an available family caregiver or an established Medical Power of Attorney (MPOA). Questionnaires were completed at baseline and 3 months to ascertain MPOA document (MPOAD) completion status (primary objective) and evaluate factors associated with MPOAD completion (secondary objectives). RESULTS: Three hundred and sixty patient/caregiver dyads consented to participate. One hundred and sixteen (32%) had MPOADs at baseline. Twenty (8%) of the remaining 244 dyads completed MPOADs by 3 months. Two hundred and thirty-six patients completed the values and goals survey at both baseline and follow-up: at follow-up, care preferences were stable in 127 patients (54%), changed toward more aggressive care in 60 (25%), and toward the focus on the quality of life in 49 (21%). Correlation between the patient's values and goals and their caregiver's/MPOA's perception was very weak at baseline, improving to moderate at follow-up. Patients with MPOADs by study completion had statistically significant higher ACP Engagement scores than those without. CONCLUSION: A systematic SW-driven intervention did not engage new patients with gynecologic cancers to select and prepare MDMs. Change in care preferences was common, with caregivers' knowledge of patients' treatment preferences moderate at best.

Phase I Dose Escalation Study of Topical Bexarotene in Women at High Risk for Breast Cancer.

PREVENTION RELEVANCE: Bexarotene is a rexinoid that has been shown to prevent mammary tumors in mouse models but oral dosing has toxicities. This phase I study evaluates topical bexarotene, as a potential chemoprevention agent, for safety and toxicity in high-risk women for breast cancer.

Associations of Dysnatremia with COVID-19 Status and Mortality.

Background: In patients without COVID-19, dysnatremia is associated with mortality. These relationships are not well established in patients with COVID-19. We tested the hypotheses that patients with COVID-19 were more likely to have dysnatremia than those without COVID-19 and that, among those with COVID-19, dysnatremia is associated with mortality. Methods: We conducted a retrospective observational study of patients admitted to a tertiary care center in the Bronx, New York, during the COVID-19 surge from March 11 to April 26, 2020. Using multinomial logistic regression models, we compared the prevalence of hypernatremia (serum sodium ≥150 mEq/L) and hyponatremia (serum sodium <130 mEq/L) on admission between patients with and without COVID-19. Among patients with COVID-19, we used Cox proportional hazards models to examine the association of dysnatremia with mortality. Results: Compared with those without COVID-19 (n=1265), patients with COVID-19 (n=3345) had a higher prevalence of hypernatremia (7% versus 4%, P<0.001) and hyponatremia (7% versus 6%, P=0.04). In adjusted models, COVID-19-positive patients had a higher likelihood of having hypernatremia (adjusted odds ratio=1.87, 95% CI, 1.3 to 2.57, P=0.001) compared with COVID-19-negative patients, whereas the association between hyponatremia and COVID-19 status was no longer significant (P=0.06). Among patients with COVID-19, 775 (23%) died after a median follow-up of 17 days (IQR 7-27 days). Among nonsurvivors, 15% had hypernatremia and 8% had hyponatremia on admission. Hypernatremia was associated with a higher risk of mortality (adjusted hazard ratio=1.28, 95% CI, 1.01 to 1.63, P=0.04) compared with patients with eunatremia. Conclusions: In patients hospitalized during the spring 2020 COVID-19 surge, COVID-19 status was associated with hypernatremia on admission. Among patients with COVID-19, hypernatremia was associated with higher mortality. Hypernatremia may be a potential prognostic marker for mortality in COVID-19 patients.

Opioid Rotation and Conversion Ratios Used by Palliative Care Professionals: An International Survey.

Background: The opioid rotation ratios (ORRs) and conversion ratios (CRs) used worldwide among palliative care (PC) professionals to perform opioid rotations (ORs) and route conversions may have a wide variation. Methods: We surveyed PC professionals on opioid ratios used through email to the Multinational Association of Supportive Care in Cancer's PC study group and Twitter and Facebook posts between September and November 2020. Results: We received 370 responses from respondents from 53 countries: 276 (76%) were physicians, 46 (13%) advanced practice providers, 39 (11%) pharmacists, and 9 respondents did not report their profession. There were statistically significant variations in median CR from intravenous (IV) to oral morphine (2-3), IV to oral hydromorphone (2-4.5), ORR from IV hydromorphone to oral morphine (10-20), and ORR from transdermal fentanyl mcg/hour to oral morphine (2-3.5) across various groups. Conclusion: This survey highlights the wide variation in ORRs and CRs among PC clinicians worldwide and the need for further research to standardize practice.

Turnaround Times in Melanoma BRAF Testing and the Impact on the Initiation of Systemic Therapy at a Single Tertiary Care Cancer Center.

PURPOSE: The identification of BRAF mutations in melanoma enables targeted therapy and improves patient outcomes. Barriers to BRAF molecular testing affect the quality of care and therapeutic options. METHODS: This retrospective study mapped BRAF testing timelines in adult patients with melanoma at the Princess Margaret Cancer Centre to identify obstacles to timely BRAF reporting and its impact on the initiation of therapy. RESULTS: Sixty-six cases were included. The median time between BRAF request and result was 12 days (95% CI, 8 to 15) when the BRAF test was ordered by pathology, compared with 20 days (95% CI, 16 to 23) if the test was requested by another specialist (P < .001). When the BRAF test and biopsy were performed within the same institution, the BRAF median turnaround time (TAT) was 13 days (95% CI, 6 to 19) compared with 19 days (95% CI, 16 to 21) if the sample was transferred from another institution (P = .02). Forty-seven patients received systemic therapy, and 20 had metastatic disease. In the metastatic subgroup, if the BRAF result was available at the first medical oncology visit, the initiation of treatment was 20 days (95% CI, 9.6 to 30.3), but was delayed to 31 days (95% CI, 10.8 to 51.1) if the BRAF result was not available (P = .03). CONCLUSION: This study showed variations in BRAF test results in TAT. One factor affecting this timeline is the transfer time, which can be streamlined by pathology reflex testing. Delays in TAT affect the timing and type of therapeutic intervention, especially in patients with stage IV disease.

Frequency and Prediction of Burnout Among Physicians Who Completed Palliative Care Fellowship Training - A 10 Year Survey.

CONTEXT: Palliative Care (PC) physicians are vulnerable to burnout given the nature of practice. Reports suggest that burnout frequency is variable across different countries. OBJECTIVE: The main objective of our study was to determine knowledge, attitudes and frequency of burnout among Hospice and Palliative Medicine (HPM) Fellowship graduates trained at a comprehensive cancer center. METHODS: We conducted a survey to determine the knowledge, attitudes, and frequency of burnout in former fellows, consisting of the Maslach Burnout Inventory (MBI) and 41 custom questions. Palliative care fellows who trained at a Comprehensive Cancer Center from 2008 to 2018 were included in the survey. RESULTS: Eighty-four percent of the 52 eligible physicians completed surveys. Median age was 38 years, with 68% females. Seventy-seven percent practiced PC more than 50% of time. Median practice duration was four years, and 84% were board certified. Most common disease types treated were cancer (89%), cardiac (43%) and pulmonary (43%). Burnout rate was high at 52% (n=20). The median scores for emotional exhaustion were 25.5, depersonalization 9, and personal accomplishment 48. Female gender (P=0.07) and having administration as a component in the job description (P=0.044) were associated with risk of burnout. Clinical care setting, work hours/week, frequency of weekend calls, and size of team were not significantly associated with burnout. CONCLUSION: Burnout among former fellows trained in HPM between 2008 and 2018 is high. More research is needed to develop strategies to better prevent and manage burnout among HPM fellowship trained PC physicians.

Place-of-death preferences among patients with cancer and family caregivers in inpatient and outpatient palliative care.

OBJECTIVE: Meeting the preferences of patients is considered an important palliative care outcome. Prior studies reported that more than 80% of patients with terminally ill cancer prefer to die at home. The purpose of this study was to determine place-of-death preference among palliative care patients in the outpatient centre and the palliative care unit (PCU) of a comprehensive cancer centre. METHODS: A cross-sectional anonymous questionnaire was administered to patients with advanced cancer and caregivers (PCU and outpatient centre) between August 2012 and September 2014. PCU patients responded when there was no delirium and the primary caregiver responded when the patient was unable to respond. In the case of outpatients, dyads were assessed. The survey was repeated 1 month later. RESULTS: Overall, 65% preferred home death. There was less preference for home death among PCU patients (58%) than among outpatients (72%). Patient and caregiver agreement regarding preferred place of death for home was 86%. After 1 month, outpatients were significantly more likely than PCU patients to have the same preferred place of death as they had 1 month earlier (96% vs 83%; p=0.003). CONCLUSIONS: Although home was the preferred place of death in our group of patients with advanced cancer and their caregivers, a substantial minority preferred hospital death or had no preference. We speculate that PCU patients' higher preference for hospital death is likely related to more severe distress because they had already tried home care. Personalised assessment of place of death preference for both patient and caregiver is needed.

Outcomes After Breast Radiation Therapy in a Diverse Patient Cohort With a Germline BRCA1/2 Mutation.

PURPOSE: BRCA1/2 pathogenic variant (PV) mutations confer radiation sensitivity preclinically, but there are limited data regarding breast cancer outcomes after radiation therapy (RT) among patients with documented BRCA1/2 PV mutations versus no PV mutations. METHODS AND MATERIALS: This retrospective cohort study included women with clinical stage I-III breast cancer who received definitive surgery and RT and underwent BRCA1/2 genetic evaluation at the The University of Texas MD Anderson Cancer Center. Rates of locoregional recurrence (LRR), disease-specific death (DSD), toxicities, and second cancers were compared by BRCA1/2 PV status. RESULTS: Of the 2213 women who underwent BRCA1/2 testing, 63% self-reported their race as White, 13.6% as Black/African American, 17.6% as Hispanic, and 5.8% as Asian/American Indian/Alaska Native; 124 had BRCA1 and 100 had BRCA2 mutations; and 1394 (63%) received regional nodal RT. The median follow-up time for all patients was 7.4 years (95% confidence interval [CI], 7.1-7.7 years). No differences were found between the groups with and without BRCA1/2 PV mutations in 10-year cumulative incidences of LRR (with mutations: 11.6% [95% CI, 7.0%-17.6%]; without mutations: 6.6% [95% CI, 5.3%-8.0%]; P = .466) and DSD (with mutations: 12.3% [95% CI, 8.0%-17.7%]; without mutations: 13.8% [95% CI, 12.0%-15.8%]; P = .716). On multivariable analysis, BRCA1/2 status was not associated with LRR or DSD, but Black/African American patients (P = .036) and Asians/American Indians/Alaska Native patients (P = .002) were at higher risk of LRR compared with White patients, and Black/African American patients were at higher risk of DSD versus White patients (P = .004). No in-field, nonbreast second cancers were observed in the BRCA1/2 PV group. Rates of acute and late grade ≥3 radiation-related toxicity in the BCRA1/2 PV group were 5.4% (n = 12) and 0.4% (n = 1), respectively. CONCLUSIONS: Oncologic outcomes in a diverse cohort of patients with breast cancer who had a germline BRCA1/2 PV mutation and were treated with RT were similar to those of patients with no mutation, supporting the use of RT according to standard indications in patients with a germline BRCA1/2 PV mutation.

Breast Radiation Therapy-Related Treatment Outcomes in Patients With or Without Germline Mutations on Multigene Panel Testing.

PURPOSE: Multigene panel testing has increased the detection of germline mutations in patients with breast cancer. The implications of using radiation therapy (RT) to treat patients with pathogenic variant (PV) mutations are not well understood and have been studied mostly in women with only BRCA1 or BRCA2 PVs. We analyzed oncologic outcomes and toxicity after adjuvant RT in a contemporary, diverse cohort of patients with breast cancer who underwent genetic panel testing. METHODS AND MATERIALS: We retrospectively reviewed the records of 286 women with clinical stage I-III breast cancer diagnosed from 1995 to 2017 who underwent surgery, breast or chest wall RT with or without regional nodal irradiation, multigene panel testing, and evaluation at a large cancer center's genetic screening program. We evaluated rates of overall survival, locoregional recurrence, disease-specific death, and radiation-related toxicities in 3 groups: BRCA1/2 PV carriers, non-BRCA1/2 PV carriers, and patients without PV mutations. RESULTS: PVs were detected in 25.2% of the cohort (12.6% BRCA1/2 and 12.6% non-BRCA1/2). The most commonly detected non-BRCA1/2 mutated genes were ATM, CHEK2, PALB2, CDH1, TP53, and PTEN. The median follow-up time for the entire cohort was 4.4 years (95% confidence interval, 3.8-4.9 years). No differences were found in overall survival, locoregional recurrence, or disease-specific death between groups (P > .1 for all). Acute and late toxicities were comparable across groups. CONCLUSION: Oncologic and toxicity outcomes after RT in women with PV germline mutations detected by multigene pane testing are similar to those in patients without detectable mutations, supporting the use of adjuvant RT as a standard of care when indicated.

Prognostic Value of Cell-Surface Vimentin-Positive CTCs in Pediatric Sarcomas.

BACKGROUND: Despite advances in care, the 5 year overall survival for patients with relapsed and or metastatic sarcoma remains as low as < 35%. Currently, there are no biomarkers available to assess disease status in patients with sarcomas and as such, disease surveillance remains reliant on serial imaging which increases the risk of secondary malignancies and heightens patient anxiety. METHODS: Here, for the first time reported in the literature, we have enumerated the cell surface vimentin (CSV+) CTCs in the blood of 92 sarcoma pediatric and adolescent and young adult (AYA) patients as a possible marker of disease. RESULTS: We constructed a ROC with an AUC of 0.831 resulting in a sensitivity of 85.3% and a specificity of 75%. Additionally, patients who were deemed to be CSV+ CTC positive were found to have a worse overall survival compared to those who were CSV+ CTC negative. We additionally found the use of available molecular testing increased the accuracy of our diagnostic and prognostic tests. CONCLUSIONS: Our findings indicate that CSV+ CTCs have prognostic value and can possibly serve as a measure of disease burden.

Combination Therapy of Physical Activity and Dexamethasone for Cancer-Related Fatigue: A Phase II Randomized Double-Blind Controlled Trial.

BACKGROUND: Despite the high frequency of cancer-related fatigue (CRF) and its debilitating effects on the quality of life of patients with advanced cancer, there are limited treatment options available. Treatments including physical activity (PA) or dexamethasone (Dex) improve CRF; however, they have lower adherence rates (PA) or long-term adverse effects (Dex). The aim of this study was to determine the feasibility of and preliminary results for the combination of PA and Dex in improving CRF. METHODS: In this phase II randomized controlled trial, patients with advanced cancer and CRF scores of ≥4/10 on the Edmonton Symptom Assessment Scale were eligible. Patients were randomized to standardized PA for 4 weeks with either 4 mg of Dex (LoDex arm) or 8 mg of Dex (HiDex arm) twice a day for 7 days. Feasibility and change in the Functional Assessment of Cancer Illness Therapy-Fatigue subscale (FACIT-F) from baseline to day 8 and day 29 (primary outcome) were assessed. Secondary outcomes included changes in fatigue dimensions (FACIT-General, Patient-Reported Outcomes Measurement Information System [PROMIS]-Fatigue). RESULTS: A total of 60 of 67 (90%) patients were evaluable. All patients were adherent to study medication. We found that 84% and 65% of patients in the LoDex arm and 96% and 68% of patients in the HiDex arm were adherent to aerobic and resistance exercise, respectively. The FACIT-F effect size in the LoDex arm was 0.90 (P<.001) and 0.92 (P<.001) and the effect size in the HiDex arm was 0.86 and 1.03 (P<.001 for both) at days 8 and 29, respectively. We found significant improvements in the Functional Assessment of Cancer Therapy-Physical (P≤.013) and the PROMIS-Fatigue (P≤.003) at days 8 and 29 in both arms. Mixed-model analysis showed a significant improvement in the FACIT-F scores at day 8 (P<.001), day 15 (P<.001), and day 29 (P=.002). Changes in the FACIT-F scores were not significantly different between patients in the 2 arms (P=.86). CONCLUSIONS: Our study found that the combination therapy of PA with Dex was feasible and resulted in the improvement of CRF. The improvement was seen for up to 3 weeks after the discontinuation of Dex. Further larger studies are justified. CLINICALTRIALS: gov identifier: NCT02491632.

A phase II study of talimogene laherparepvec for patients with inoperable locoregional recurrence of breast cancer.

Talimogene laherparepvec (T-VEC) is an immunotherapy that generates local tumor lysis and systemic antitumor immune response. We studied the efficacy of intratumoral administration of T-VEC as monotherapy for inoperable locoregional recurrence of breast cancer. T-VEC was injected intratumorally at 106 PFU/mL on day 1 (cycle 1), 108 PFU/mL on day 22 (cycle 2), and 108 PFU/mL every 2 weeks thereafter (cycles ≥ 3). Nine patients were enrolled, 6 with only locoregional disease and 3 with both locoregional and distant disease. No patient completed the planned 10 cycles or achieved complete or partial response. The median number of cycles administered was 4 (range, 3-8). Seven patients withdrew prematurely because of uncontrolled disease progression, 1 withdrew after cycle 3 because of fatigue, and 1 withdrew after cycle 4 for reasons unrelated to study treatment. Median progression-free survival and overall survival were 77 days (95% CI, 63-NA) and 361 days (95% CI, 240-NA). Two patients received 8 cycles with clinically stable disease as the best response. The most common grade 2 or higher adverse event was injection site reaction (n = 7, 78%). Future studies could examine whether combining intratumoral T-VEC with concurrent systemic therapy produces better outcomes.

Phase II trial of proton therapy versus photon IMRT for GBM: secondary analysis comparison of progression-free survival between RANO versus clinical assessment.

BACKGROUND: This secondary image analysis of a randomized trial of proton radiotherapy (PT) versus photon intensity-modulated radiotherapy (IMRT) compares tumor progression based on clinical radiological assessment versus Response Assessment in Neuro-Oncology (RANO). METHODS: Eligible patients were enrolled in the randomized trial and had MR imaging at baseline and follow-up beyond 12 weeks from completion of radiotherapy. "Clinical progression" was based on a clinical radiology report of progression and/or change in treatment for progression. RESULTS: Of 90 enrolled patients, 66 were evaluable. Median clinical progression-free survival (PFS) was 10.8 (range: 9.4-14.7) months; 10.8 months IMRT versus 11.2 months PT (P = .14). Median RANO-PFS was 8.2 (range: 6.9, 12): 8.9 months IMRT versus 6.6 months PT (P = .24). RANO-PFS was significantly shorter than clinical PFS overall (P = .001) and for both the IMRT (P = .01) and PT (P = .04) groups. There were 31 (46.3%) discrepant cases of which 17 had RANO progression more than a month prior to clinical progression, and 14 had progression by RANO but not clinical criteria. CONCLUSIONS: Based on this secondary analysis of a trial of PT versus IMRT for glioblastoma, while no difference in PFS was noted relative to treatment technique, RANO criteria identified progression more often and earlier than clinical assessment. This highlights the disconnect between measures of tumor response in clinical trials versus clinical practice. With growing efforts to utilize real-world data and personalized treatment with timely adaptation, there is a growing need to improve the consistency of determining tumor progression within clinical trials and clinical practice.