Citations

TPS11578 Background: Conventional chondrosarcoma (cCS) accounts for ̃25% of primary bone cancers and is the second most common primary bone tumor after osteosarcoma. Surgical resection is the primary treatment for localized disease. No FDA approved therapy exists for advanced disease and chemotherapy has marginal efficacy with ORR < 12%. IDH1/2 mutation is seen in 50% of cases. Epigenetic dysregulation is central to oncogenesis in both IDH1/2 mutant and wild-type CS. Pre-clinical studies from our group show that combination treatment with HDAC and DNMT inhibitors is significantly more effective at suppressing the growth of CS models in vitro and in vivo compared to either therapy alone. The combination regimen mediates anti-tumor effects on CS by induction of apoptosis, induction of tumor suppressor genes (eg. E-cadherin), the induction of interferon responsive genes (eg. IRF7, OASL, ISG15, DDX58) and reversal of global hypomethylated state. Based on these findings we have designed a phase 2 clinical trial with an HDAC inhibitor (belinostat) and a DNMT inhibitor (guadecitabine) in patients with advanced cCS. Methods: NCI # 10330 is a single-arm, multi-center, Simon 2-stage, phase 2 clinical trial evaluating belinostat and guadecitabine in patients with advanced cCS. Eligible patients will have biopsy proven cCS which is measurable by RECIST v1.1 and amenable to biopsy, ECOG PS ≤ 2, any number of prior treatments (including none). Patients will receive guadecitabine 45 mg/m2 SC followed by belinostat 1000 mg/m2 IV once daily on days 1-5 of a 28-day cycle. A safety lead-in and continuous toxicity monitoring rule will be applied. The primary endpoint will be ORR. Since chemotherapy is associated with an ORR of 8-12% and targeted agents have shown an ORR of 0% in cCS, we will consider an ORR of 8% as inactive while an ORR of 28% will suggest promising activity. A Simon 2-stage design is employed. The design calls for 26 patients. If ≥ 2 responses are observed among 13 patients in stage I, the study will proceed to full accrual. If ≥ 5 responses are seen among 26 patients, the study treatment is considered promising. This design has 85% power with α of 0.054 to test for a response rate of 8% vs 28%. Secondary objectives include safety, tolerability and PFS. All patients will undergo pre-treatment and on-treatment tumor biopsies. Paired tissue will be used for correlative analysis including: 1) whole exome sequencing/RNAseq to evaluate changes in gene expression in response to treatment, 2) multiplex IHC to interrogate the effect of combination therapy on tumor immune microenvironment and 3) a global DNA methylation assay to better understand the changes in epigenetic landscape in response to treatment. This study is open throughout the ETCTN (NCT04340843). Six of the planned 26 patients in the safety lead-in have been enrolled without DLT. Further accrual is on hold pending completion of the safety lead-in. Clinical trial information: 04340843.

11505 Background: AL3818 (Catequentinib, Anlotinib) is a novel, orally administered, small molecule tyrosine kinase inhibitor. The primary objective of this Phase 3 study is to evaluate the efficacy of AL3818 monotherapy in patients (pts) with synovial sarcoma (SS) comparing with dacarbazine in randomization setting. Methods: Patients with a diagnosis of synovial sarcoma requiring second line or further line treatment were eligible for enrollment. The regimen was a 21-day cycle with oral AL3818 administered on 14 days on and 7 days off. This phase 3 trial is randomized in 2:1 ratio of AL3818 comparing to dacarbazine with option of crossover after PD of dacarbazine treatment. Progression free survival (PFS) with Log Rank test is the primary endpoint and this trial for SS is currently completed enrolled in US and Italy. Results: Total 79 pts initiated treatment and are evaluable, 52 received AL3818 as treatment arm (T), and 27 received dacarbazine (D) as control arm (C). Arms T/C median ages were 40.5/42.0 years (range: 18-70+) and 20/16 (38.5%/59.3%) were male. Overall, PFS was 2.89 months (95% CI: 2.73 – 6.87) for AL3818 and 1.64 (95% CI: 1.45 – 2.70) for D. The PFS of study met the primary endpoint with a p-value of 0.0015 and a HR of 0.449 (95% CI: 0.270– 0.744). At the month 4, 6, and 12, the percentages of progression free patients for AL3818 were 48.1%, 42.3% and 26.9%; and for D were 14.85%, 11.1% and 3.7%. For grade 3 treatment-related adverse events, 12(23.1%) of pts experienced for AL3818 and 7(25.9%) of pts experienced for D. The most common AL3818 related grade 3 AEs were diarrhea (5.8%) and hypertension (3.8%). Conclusions: This phase III trial demonstrates improved disease control and superior progression free survival for AL3818 vs dacarbazine in advanced SS. In addition, the study further confirms the acceptable benefit-risk profile of AL3818 from the prior randomized Phase 2b soft tissue sarcoma study (NCT02449343). AL3818 is a meaningful treatment option for pts with advanced SS. Clinical trial information: NCT 03016819 Clinical trial information: NCT03016819.

11503 Background: EHE is a rare vascular cancer arising in liver, lung, soft tissue and bone. The natural history of metastatic disease varies considerably from indolent growth over years to rapid growth with fatal outcome in months. Treatment of patients (pts) with metastatic EHE with antiangiogenic therapy induces tumor response in a minority of pts, and median PFS is 6-12 months. TAZ-CAMTA1 translocation results in activation of MAPK pathway and is an oncogenic driver in EHE. We sought to evaluate the effect of MEK inhibition using trametinib in pts with unresectable EHE. Methods: A phase 2 trial of trametinib 2 mg daily was conducted in pts with EHE though the Experimental Therapeutics Clinical Trials Network supported by NCI in collaboration with SARC. Additional support was provided by the EHE Rare Cancer Charity and the EHE Foundation. Pts had to have evidence of objective tumor progression or EHE-related pain requiring narcotics for relief prior to enrollment. Presence of TAZ-CAMTA1 translocation was analyzed by fusion-FISH after enrollment. Primary trial endpoint was objective response rate (ORR) per RECIST1.1 with at least 1 objective response required in the 1st 13 pts to expand enrollment to 27. The trial was amended after stage 1 to continue enrollment to 27 pts with TAZ-CAMTA1 detected by FISH with goal of >4 objective responses in this group. Secondary objectives were PFS and OS rates, safety and change in pt-reported global health and pain scores per PROMIS questionnaires. Results: 43 pts were enrolled between 6/2017 – 9/2020 across 10 sites and 41 started therapy. TAZ-CAMTA1 fusion was detected in 26, not detected in 7, test failed in 5 and was not performed due to insufficient tumor in 5. Median pt age was 54 (range 22-81 yrs) and 11 were >65 yrs; 25 were female; ECOG was 0 in 23, 1 in 16 and 2 in 3 pts. Most pts experienced reduction in tumor size. ORR per RECIST was 7% (3/41); in pts with TAZ-CAMTA1 detected, the ORR was 0% (0/26). Mean pain intensity and interference scores had a statistically significant improvement and global quality of life scores did not statistically change after 4 weeks of therapy. 17 pts remained on treatment > 6 months and 7 > 12 months. 25 pts stopped trametinib due to EHE progression, 6 died during treatment, 6 withdrew from treatment, 3 stopped drug due to adverse event and 1 is on treatment. The most common AEs related to trametinib were rash, fatigue, nausea/vomiting, diarrhea, alopecia and edema; Grade >3 AEs included anemia, dyspnea, hypoxia, hypotension, syncope and dermatitis. Conclusions: To our knowledge, this is the largest prospective clinical study focused on pts with EHE. Although the trial did not meet the ORR goal, stable disease > 6 months was seen in 40% of pts, and EHE-related pain improved on treatment. Trametinib was associated with expected cutaneous and GI adverse effects. Additional pt-reported outcomes and biomarkers of inflammation are undergoing analysis. Clinical trial information: NCT03148275.

e18739 Background: Hair loss is a well-known side effect of chemotherapy. The Paxman Hair Loss Prevention System, a scalp cooling device, has been shown to be effective in reducing chemotherapy induced alopecia in patients receiving chemotherapy (Nangia, JAMA, 2017). The National Comprehensive Cancer Network and the European Society for Medical Oncology guidelines have recommended scalp cooling as category 2A and 2B options, respectively. Methods: The real world use of scalp cooling using the Paxman device, as documented by orders through the Paxman Hub during the years of 2017-2020 was summarized. Descriptive statistics were used to summarize demographics and utilization. Results: Data from 6649 patients who used scalp cooling were reviewed. Patients with breast cancer were the most common users of scalp cooling (78%, n=5197) followed by gynecology (12%, n=775), gastrointestinal (3%, n=201), lung (1%, n=81) and genitourinary (1%, n=52). The majority of patients were between the ages of 45-65 (55%), followed by 65-74 (18%), older than 75 (5%), and 25-44 (2%). Average number (#) of cycles of cooling completed was 6.53 (range of average # of cycles 4.50-12). Scalp cooling with this device was commonly used in 39 out of 50 states. Conclusions: This is the largest report of scalp cooling usage in the real world setting in the USA, including scalp cooling usage in older adults. Uptake of scalp cooling across various cancers has not been uniform and this deserves further study.

Background: Surviving critical illness often creates a lasting psychological impact, including depression, anxiety, and post-traumatic stress. Memories of frightening and delusional experiences are the largest potentially modifiable risk factor, but currently, there is no proven intervention to improve these inciting factors. Psychological support based on positive suggestion is a psychotherapeutic approach that can be provided even to patients in altered cognitive states and is therefore a viable psychotherapy intervention throughout the ICU stay. Traditional ICU care team members have limited time and training to provide such psychological support to patients. Doulas are trained supportive companions who have been effectively used to provide patient advocacy and emotional support in other clinical settings and may address this need. Our aim was to train and implement a psychological support based on positive suggestion program for the critically ill using doulas, and measure acceptance of this intervention through stakeholder feedback. Methods: Doula training included three objectives: an introduction to ICU practice structure and policies; education about fundamental aspects of critical care conditions and procedures; and didactic and hands-on learning experiences in effective use of psychological support based on positive suggestion in the critically ill. Doulas were evaluated at the end of their training and during subsequent clinical activities using competency-based assessments as well as through survey-based questions and interviews with key stakeholders. Results: The ICU doulas performed psychological support based on positive suggestion on 43 critically ill patients in the ICU setting. Stakeholder feedback from nurses, patients, and patient families was positive. The majority (28/32) of surveyed bedside ICU nurses reported that the doulas’ involvement was helpful for both patients and nurses alike. All interviewed family members offered positive comments about the ICU doula presence and of the 40 patients who recalled the intervention 37 found it comforting. Conclusions: Our program successfully trained two doulas to work effectively in the ICU setting performing patient-centered psychological support based on positive suggestion interventions. Their training improved their skill sets and was reported as beneficial by patients, families, and critical care nursing. This training program offers a proof of concept that could be applied in other medical centers, bringing doulas more commonly into the ICU practice to help humanize the experience for patients, families, and medical teams.

Background: Food protein‐induced enterocolitis syndrome (FPIES) is a non-immunoglobulin E mediated food allergy that typically presents with repetitive emesis and may be associated with lethargy, marked pallor, hypotension, hypothermia, and/or diarrhea. Although many foods are known to cause FPIES, peanut-triggered FPIES is emerging due to changes in the feeding practice guidelines, which recommends early peanut introduction in infants. Objective: We aimed to characterize peanut-triggered acute FPIES cases in our pediatric population and to describe their attributes, treatment, and outcomes. We hypothesized that increases in the incidence of peanut-triggered FPIES coincided with implementation of the guidelines for early peanut introduction. Methods: A retrospective chart review was conducted of pediatric patients who presented to Phoenix Children’s Hospital Emergency Department and subspecialty clinics during a 6-year period (January 2013 to September 2019). Results: Thirty-three cases of patients with acute FPIES were identified, five of which were peanut triggered. In those patients with peanut-triggered FPIES, the median age for peanut introduction was 7 months (range, 5‐24 months). Two patients had positive peanut skin-prick test results. All five cases were identified in the past 2 years (2018 to 2019). No peanut-triggered reactions were documented in the preceding 4-year period (2013 to 2017). Conclusion: Peanut may be an emerging trigger of acute FPIES, coinciding with an earlier introduction of peanut in the infant diet after implementation of the new addendum guidelines for the prevention of peanut allergy. Oats and rice were the most common triggers of acute FPIES in our cohort. Further study will help clarify the significance and reproducibility of these findings.

Abstract Purpose: This open-label, multicenter, phase IB/II study evaluated sapanisertib, a dual inhibitor of mTOR kinase complexes 1/2, plus exemestane or fulvestrant in postmenopausal women with hormone receptor–positive (HR+)/HER2-negative (HER2−) advanced/metastatic breast cancer. Patients and Methods: Eligible patients had previously progressed on everolimus with exemestane/fulvestrant and received ≤3 (phase IB) or ≤1 (phase II) prior chemotherapy regimens. Patients received sapanisertib 3 to 5 mg every day (phase IB), or 4 mg every day (phase II) with exemestane 25 mg every day or fulvestrant 500 mg monthly in 28-day cycles. Phase II enrolled parallel cohorts based on prior response to everolimus. The primary objective of phase II was to evaluate antitumor activity by clinical benefit rate at 16 weeks (CBR-16). Results: Overall, 118 patients enrolled in phase IB (n = 24) and II (n = 94). Five patients in phase IB experienced dose-limiting toxicities, at sapanisertib doses of 5 mg every day (n = 4) and 4 mg every day (n = 1); sapanisertib 4 mg every day was the MTD in combination with exemestane or fulvestrant. In phase II, in everolimus-sensitive versus everolimus-resistant cohorts, CBR-16 was 45% versus 23%, and overall response rate was 8% versus 2%, respectively. The most common adverse events were nausea (52%), fatigue (47%), diarrhea (37%), and hyperglycemia (33%); rash occurred in 17% of patients. Molecular analysis suggested positive association between AKT1 mutation status and best treatment response (complete + partial response; P = 0.0262). Conclusions: Sapanisertib plus exemestane or fulvestrant was well tolerated and exhibited clinical benefit in postmenopausal women with pretreated everolimus-sensitive or everolimus-resistant breast cancer.

AbstractBackgroundMargins in transoral surgery for tonsil cancer can be limited by oropharyngeal wall thickness (OWT), but the normal range is not well established.MethodsIn 240 noncancer subjects, OWT was measured bilaterally in the vicinity of the tonsils with MRI. Statistical analysis was performed to assess for interaction of age, sex, location, and obesity.ResultsMean(SD) OWT measured 3.4(0.6) mm posteriorly, 3.7(2.0) mm between the styloglossus and stylopharyngeus, and 5.3(0.8) mm laterally. OWT was greater in men, correlated with obesity, decreased posteriorly and laterally in the 60–80 versus 40–59 year age groups, and increased when styloglossus/stylopharyngeus were closer. OWT was <5 mm in 36.7%–97.9% of locations, with the largest percentage below this threshold located posteriorly.ConclusionsOWT is frequently <5 mm, particularly in the posterior and intermuscular areas, suggesting that a smaller surgical margin may need to be accepted in transoral tonsil cancer surgery for anatomic reasons.