Improvement In Performance Status Research Articles

Meta-analysis of the effect of sophora flavescens on tumor metastasis-induced bone neuropathic pain.

Tumor metastasis to bone is a critical and painful stage in cancer progression, significantly affecting patients' quality of life. Traditional treatments for bone neuropathic pain often exhibit limited efficacy and undesirable side effects. Sophora flavescens, an herb used in traditional Chinese medicine, has shown potential analgesic and anti-cancer properties, but the existing evidence is fragmented and inconsistent. In accordance with PRISMA guidelines, an extensive literature search was performed across PubMed, Web of Science, and Cochrane Library databases, Embase, Medline, CNKI, VIP, Wanfang Database, CBMdisc to identify relevant studies. The inclusion criteria focused on randomized controlled trials (RCTs) investigating the use of Sophora flavescens for bone neuropathic pain. Data related to pain intensity, mechanisms of action, and safety were extracted and analyzed using meta-analysis techniques. The quality of the studies was assessed using the Cochrane Risk of Bias tool. Seven studies met the inclusion criteria, involving a total of 463 patients with bone neuropathic pain induced by tumor metastasis. The meta-analysis revealed a significant overall reduction in pain intensity for patients treated with Sophora flavescens compared to control groups (mean difference = 26.45, 95% CI: 13.89, 39.00, P < 0.0001). Specifically, the Karnofsky Performance Status (KPS) increase rate showed a combined risk ratio of 1.62 (95% CI: 1.32, 1.99, P < 0.0001), indicating improved performance status with treatment. Pain scores also significantly decreased (mean difference = 26.45, 95% CI: 13.89, 39.00, P < 0.0001) despite substantial heterogeneity among studies (I2 = 91%). Funnel plots suggested minimal publication bias, and sensitivity analyses confirmed the stability of these results. The included studies reported minimal adverse effects, indicating good tolerability of Sophora flavescens. Sophora flavescens demonstrates significant potential as an adjunctive therapy for managing bone neuropathic pain induced by tumor metastasis, offering substantial pain relief with minimal adverse effects.

CTNI-54. RESPONSE BY RANO2.0 CRITERIA IN ONC201 (DORDAVIPRONE)-TREATED PATIENTS WITH RECURRENT H3 K27M-MUTANT DIFFUSE MIDLINE GLIOMA

Abstract PURPOSE Response assessment in neuro-oncology (RANO) 2.0 is a recently established response assessment for glial tumors that is agnostic to WHO grade. This updated response assessment includes quantitative evaluation of enhancing and non-enhancing disease and recommendations to account for pseudoprogression. This analysis evaluated response to ONC201 by RANO2.0 in recurrent, H3K27M-mutant diffuse midline glioma (DMG), which was previously assessed by RANO-HGG/RANO-LGG (Arrillaga-Romany, JCO, 2024). METHODS Fifty patients with recurrent H3 K27M-mutant DMG were selected based on criteria designed with input from regulators to evaluate objective response to ONC201 monotherapy. Patients had contrast-enhancing, measurable, progressive disease, and were ≥90 days from radiation, with adequate washout from other anti-cancer therapies. Diffuse intrinsic pontine glioma, primary spinal tumors, leptomeningeal spread, or CSF-disseminating tumors were ineligible. Response was assessed using RANO2.0 criteria by two-party blinded independent central review. RESULTS Best response by RANO2.0 included one complete response (CR, 2.0%), nine partial responses (PR, 18.0%), and four minor responses (MR, 8.0%). Overall response rate (CR+PR+MR) by RANO2.0 criteria was 28.0% (n=14; 95%CI, 16-42). Disease control rate (CR+PR+MR+SD) was 40.0% (n=20; 26-55). Median duration of response was 10.4 months (95%CI, 7.4-15.4). Median time to response was 4.6 months (range, 1.6-15.9). 6- and 12-month progression free survival rates were 32.0% (95%CI, 19-47) and 27.0% (15-41), respectively. RANO2.0 response as a time-varying covariate was significantly associated with overall survival in a multivariate analysis considering baseline performance score, multiple enhancing target lesions, enhancing tumor size, and number of prior recurrences (HR [95%CI], 0.22 [0.08–0.58]; p=0.0023). Patients with an objective response by RANO2.0 were more likely to be alive at 12 (100%) and 24 (86%) months, have reduced corticosteroid usage, and have improved performance status. Responses occurred at a higher rate among patients with a higher performance score and fewer target lesions. CONCLUSIONS RANO2.0 assessment of ONC201-treated patients suggests durable and clinically meaningful efficacy in recurrent H3K27M-mutant DMG.

Successful Allogeneic Hematopoietic Cell Transplantation for Patients with IL10RA Deficiency in Japan.

IL10RA (IL10 receptor subunit alpha) deficiency is an autosomal recessive disease that causes inflammatory bowel disease during early infancy. Its clinical course is often fatal and the only curative treatment is allogeneic hematopoietic cell transplantation (HCT). In Japan, only case reports are available, and there are no comprehensive reports of treatment outcomes. We retrospectively analyzed patients with IL10RA deficiency in Japan. Two newly identified and five previously reported patients were included in this study. Five patients underwent HCT; one untransplanted patient survived to age 14, and one died of influenza encephalopathy before transplantation. All five HCT recipients underwent HCT at the age before 2 years. They all were conditioned with fludarabine/busulfan- or fludarabine /melphalan-based regimens. The donor source was human leukocyte antigen haploidentical donor bone marrow (BM) for two patients and unrelated umbilical cord blood (CB) for two patients. One patient experienced graft failure with unrelated CB and required a second transplant with unrelated BM. All patients who underwent HCT survived and demonstrated an improved performance status. In cases of IL10RA deficiency, the need for transplantation should be promptly assessed, and early transplantation should be considered. (190/250).

Effectiveness and safety of bortezomib-dexamethasone regimen in patients with multiple myeloma: A prospective observational study

Background: Bortezomib and dexamethasone (BD) regimen offers a promising therapeutic approach in multiple myeloma (MM) by inhibiting the proteolytic pathway of tumor cells. Aims and Objectives: This study aims to assess the safety profile and treatment outcomes of MM patients undergoing the BD regimen. Materials and Methods: This prospective observational study included MM patients who received BD regimen. Patients received bortezomib (1.3 mg/m2 intravenous) weekly for 4 weeks along with dexamethasone (40 mg orally) weekly for 4 weeks. Clinical assessments were performed after each cycle, and adverse drug reactions were graded according to National Cancer Institute criteria. Treatment outcomes were evaluated after the 4th cycle based on specific parameters. Results: Thirty-seven patients, with a mean age of 56.2 years, predominantly male (56.8%), were included. Common symptoms included bone pain, fatigue, weight loss, and appetite loss. Toxicities were mainly grade 1 and 2, with peripheral neuropathy (PN) being the most prevalent. The BD regimen exhibited a response rate of 65%, accompanied by significant improvements in bone marrow plasma cells, β2 microglobulin, immunoglobulin assay, and erythrocyte sedimentation rate. In addition, treatment improved performance status, in 51.4% of patients achieving scores above 90 on the Karnofsky scale. Conclusion: The BD regimen demonstrated notable efficacy and tolerability in MM treatment. However, it is associated with a higher risk of PN.

Effect of change in ECOG performance status at diagnosis and relapse in patients with acute myeloid leukemia.

e19007 Background: ECOG performance status (PS) is often utilized in treatment decision-making for patients with acute myeloid leukemia (AML). Patients with relapsed or refractory (R/R) disease have a particularly poor prognosis and require complex treatment decisions that weight patient preference, disease risk and PS. Currently, limited data exist on changes in performance status from initial diagnosis to the time when R/R AML is found. It would be interesting to characterize whether patients with R/R AML have worse performance status due to progression of disease or stable or improved performance status after initial therapy. Given there are additional factors such as induction chemotherapy that impact performance status at R/R disease, we were also interested in characterizing the association of PS in R/R AML with short and long term survival. Methods: We utilized an institutional database from University of Washington/Fred Hutchinson Cancer Center to retrospectively identify patients with AML or other high-grade myeloid neoplasms (≥10% blasts) who received both induction and salvage chemotherapy between January 1, 2008 through December 1, 2021. Patients with missing performance status at R/R were excluded. Salvage treatment was divided into high (cytarabine greater than 1g/m2/dose), intermediate (7+3 or similar), or reduced intensity (i.e., hypomethylating agents). The McNemar test was used for matched-pair analysis of PS at two timepoints. The Kaplan-Meier method was used for overall survival (OS). Univariate and multivariable linear regression models were used to evaluate associations with 4 week survival. All statistical analyses were performed using R 4.2.1 (2022). Results: Of the patients identified (n = 614), only patients with PS documented at R/R (n = 51) were included in the analysis (baseline characteristics in Table 1). No significant change was identified in PS at diagnosis versus R/R (PS≤1 66.7% vs 70.6%, p = 0.80). Better performance status (PS≤1) at R/R was correlated with improved OS (11.4 months vs 2.33 months, p = 0.003). The 4-week unadjusted mortality rate was 8.5% for patients with PS≤1, and 33.3% for patients with PS &gt; 1 (p = 0.04). Poor performance status (PS &gt; 1) at R/R was associated with significantly increased 4 week mortality (OR 5.5, 95% CI 1.2-30.9), even after adjustment for age and ELN2017 risk (OR 6.2, 95% CI 1.1-41.3). When OS was further stratified by chemotherapy intensity, patients with PS≤1 (n = 36) treated with high intensity chemotherapy (n = 22) had improved OS (14.1 vs 4.3 months, p = 0.007). Conclusions: PS tends to be stable at R/R disease, and poor PS is associated with very poor survival. Further work is needed to characterize the patients with R/R AML who benefit from intensive re-induction chemotherapy.

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: Diffuse large B cell lymphoma (DLBCL) is an aggressive but potentially curable malignancy. Nearly one-third of patients are >75 y, and advanced age is an adverse prognostic variable. R-miniCHOP, a dose attenuated version of standard R-CHOP, offers a 2-year progression-free survival (PFS) of 47% based on phase II data (Peyrade F et al, 2011). For comparison, patients age 60-80 have about a 75% 2-year overall survival (OS) with R-CHOP chemotherapy (Coiffier B et al., 2002). A key dilemma is identifying which older patients with DLBCL should be considered for curative intent chemoimmunotherapy. The FIL (Fondazione Italiana Linfomi; Italian Lymphoma Foundation) has developed a tool accounting for age, comorbidities, and ability to perform daily and instrumental activities to classify patients as fit, unfit, or frail (Tucci A et al, 2015), with a key observation being improved survival when curative intent chemoimmunotherapy was delivered to fit and unfit patients. (Merli F et al., 2021). However, there is no prospective validation of frailty assessment and treatment outcomes. Epigenetic deregulation is a feature of DLBCL in older patients. Pre-clinical models show that pre-treatment with hypomethylating agents improves the anti-tumor effect of the agents contained in R-CHOP (Clozel T et al., 2013). Early studies of azacitidine with R-CHOP showed promising efficacy and acceptable toxicity (Martin P et al., 2022). The availability of oral azacitidine is appealing, reduces the infusion burden of treatment, and is agnostic to cell-of-origin. Methods: S1918 is a randomized trial of R-miniCHOP ± oral azacitidine in patients >75 y with newly diagnosed aggressive B-cell non Hodgkin lymphomas (NCT04799275). This is the first randomized study in this population conducted in North America by the National Clinical Trials Network (NCTN) and will enroll 384 patients. Patients receive prephase therapy with prednisone 60–100 mg × 4–7 days to improve performance status and decrease early treatment-related mortality (Owens CN et al., 2015; Pfreundschuh M et al., 2008). A safety run-in has been completed. The phase II objective is to determine if oral azacitidine + R-miniCHOP should be tested further against R-miniCHOP based on estimates of 1-year PFS. The phase III objective is to compare OS at 2 years between arms. S1918 incorporates the FIL Tool for baseline frailty assessment and a serial comprehensive geriatric assessment to evaluate effects of therapy on quality of life and functional status. Key correlative tests include circulating tumor DNA (ctDNA) assays to explore if ctDNA quantity and methylation patterns correlate with response. S1918 has potential to impact future trial design and change the standard of care for patients > 75 y with aggressive lymphoma with its randomized design, incorporation of baseline frailty and geriatric assessments, and utilization of ctDNA correlatives. The research was funded by: NIH/NCI grants U10CA180888, U10CA180819, U10CA180820, and U10CA180821; and in part by Celgene Corporation (now part of Bristol-Myers Squibb). Keywords: aggressive B-cell non-Hodgkin lymphoma, combination therapies, ongoing trials Conflicts of interests pertinent to the abstract. E. A. Brem Consultant or advisory role Bayer, TG Therapeutics, Astra Zeneca, BeiGene Honoraria: Astra Zeneca, BeiGene, SeaGen, Morphosys/Incyte, Pharmacyclics/Janssen P. Caimi Research funding: Abbvie, ADC Therapeutics, Genentech, Consultancy: Abbvie, ADC Therapeutics, Beigene, BMS, Genentech, Incyte, Kite, Lilly, MEI Pharma, Novartis, Takeda R. L. Olin Consultant or advisory role Actinium, Servier Research funding: Cellectis B. Kahl Consultant or advisory role Genentech, BMS J. P. Leonard Consultant or advisory role Roche/Genentech, BMS/Celgene

Palliative extracranial radiotherapy in patients receiving immunotherapy for non-small cell lung cancer: a narrative review.

Role of radiotherapy (RT) in the era of immuno-oncology (IO) in advanced non-small cell lung cancer (NSCLC) is rapidly changing. RT is not only intended for addressing palliation symptoms but also is considered as a potential tool potentializing an immunogenic effect of given drugs. However, the best timing, techniques, doses, volumes, and its use for asymptomatic patients is a subject of research. We performed a review on the role of palliative RT schedules in combination with IO for advanced NSCLC. Indications in symptomatic and asymptomatic patients, outcomes, toxicity, and possible developments are discussed. A literature search was conducted in MEDLINE and PubMed databases and clinicaltrials.gov using the keywords 'lung cancer' AND "immunotherapy" AND 'radiotherapy' OR "palliative radiotherapy". Body of evidence indicate that palliative RT used in combination with IO is effective in terms of symptom management and safe; does not increase the risk of serious side effects, including serious pulmonary toxicity. We have limited data evidencing improvement of survival by addition of short ablative RT dose to one site of the disease to IO in oligometastatic NSCLC. Some data indicate that short ablative doses of stereotactic body radiation therapy (SBRT) are more effective with regard to treatment response and survival than protracted RT schedule with lower fractional doses. However, this may be a selection bias of better prognostic patients who underwent SBRT. The use of steroids being a potential concern during IO should not be prohibited if clinically indicated during palliative RT. Its detrimental effect shown in some studies may also be a result of selection bias, because steroids given for not cancer-related causes during IO did not decrease survival. RT for symptom management may be used during, directly before or after IO. This has a potential to ease symptom burdens and improve performance status (PS). However, still more studies are needed to establish optimal guidelines in asymptomatic patients for appropriate timing, volumes, dose, and fractionation schedules of palliative RT use in combination with IO.

Radiotherapy Versus Chemoradiation in Elderly Head-and-Neck Squamous Cell Carcinoma Patients – A Retrospective International Multicenter Study

<h3>Purpose/Objective(s)</h3> While the proportion of elderly head-and-neck squamous cell carcinoma (HNSCC) patients is increasing, the evidence regarding the ideal treatment for this patient cohort is limited. The benefit of concomitant chemotherapy (CT) has been reported to decrease in elderly HNSCC patients; however, it remains unknown whether modern supportive treatments, state-of-the art radiotherapy (RT) techniques and the generally improved performance status of elderly patients nowadays may have altered this observation. <h3>Materials/Methods</h3> Elderly (≥65 years) patients with locoregionally advanced HNSCCs of the oral cavity, oropharynx, hypopharynx or larynx (cT3-4 and/or cN+) receiving definitive RT, with or without concomitant CT, between 2005 and 2019 were eligible for this analysis. Exclusion criteria were recurrent HNSCCs, distant metastases at the time of RT, or HNSCCs from the nasopharynx, salivary glands or the skin. <h3>Results</h3> A total of 824 elderly HNSCC patients from nine tertiary cancer centers met the inclusion criteria and were analyzed. The median age amounted to 72 years (range 65-96 years), and 568 patients (80% of the patients with known ECOG status, n=708) exhibited an ECOG performance status of 0 or 1. The median age-adjusted Charlson Comorbidity Index (CCI) ranged at 4 points (IQR 3-5). Only a minority of HNSCCs (n=140, 17%) exhibited p16 positivity. About half of the cohort suffered from oropharyngeal carcinomas (n=418, 51%), followed by cancers of the hypopharynx (n=151, 18%), oral cavity (n=124, 15%), larynx (n=102, 12%) and multi-level carcinomas (n=29, 4%). A positive smoking history was present in 473 patients (70% of the patients with known smoking status, n=674). Seven hundred thirty-six (89%) of the analyzed patients completed the pre-specified RT dose. OS/PFS amounted to 71%/56% at 1 year, 56%/45% at 2 years, and 46%/38% at 3 years, respectively. Chemoradiation (CRT) resulted in significantly improved OS (HR=0.49, <i>p</i><0.05) and PFS (HR=0.53, <i>p</i><0.05) compared to RT. Even for patients aged ≥75 years (n=329), CRT was associated with superior OS (HR=0.57, <i>p</i><0.05) and PFS (HR=0.61, <i>p</i><0.05). However, patients receiving concomitant CT were significantly younger (<i>p</i><0.05), exhibited a better ECOG performance status (<i>p</i><0.05) and fewer comorbidities (<i>p</i><0.05). In order to control for these disparities, a matched-pair analysis with the matching variables ECOG, CCI and age was conducted, resulting in 98 matching pairs (n=196): Here, both OS (HR=0.44, <i>p</i><0.05) and PFS (HR=0.45, <i>p</i><0.05) remained superior in the CRT compared to the RT group. <h3>Conclusion</h3> This analysis suggests a benefit of concomitant CT in elderly HNSCC patients receiving RT and does not support the usage of a strict age cut-off for CT. Structured assessment of patient performance and comorbidities may help to guide treatment decisions regarding CRT in elderly HNSCC patients.

Role Of Palliative Radiotherapy In Improving Performance Status And Quality Of Life In Patients With Metastatic Spinal Cord Compression.

Palliative radiotherapy in patients with metastatic spinal cord compression is a well known treatment modality but little is known whether it improves quality of life and performance status. Our study focusses on analyzing the impact of palliative radiotherapy on these two parameters in patients with metastatic spinal cord compression. We performed a prospective observational study from August 2020 to April 2021 to assess consecutive patients presenting to emergency department with suspected MSCC. We enrolled 24 patients in the study, and they were evaluated for their performance status and quality of life using ECOG and FACIT PAL 14 scores respectively. Palliative radiotherapy was administered, and the patients were followed up four to six weeks later. Their ECOG and FACIT-PAL 14 scores before and after receiving palliative radiotherapy were analyzed. The mean age of the patients was 48 (IQR 35-62), with 14 (58%) being male. 1 patient died soon after admission. Median dose fractionation was 2000 cGy. Median (IQR) of ECOG performance status score on admission and follow up was 2.5 (1.0-3.7) and 1.5 (1.0-3.7), p=0.719, respectively. Median (IQR) FACIT-PAL 14 score on admission and follow up were 35.5 (34.0-37.6) and 36.5 (30.2-44.7), p=0.277, respectively. Our results indicate that there was no statistically significant difference in the median ECOG performance status and FACIT PAL 14 scores before and after the administration of palliative radiotherapy. Our study indicates that palliative radiotherapy in patients with metastatic spinal cord compression had little benefit in objectively improving quality of life and performance status using the well-known and widely used scores. This lack of response could be due to delayed presentation of the patients. Earlier involvement of palliative care team could have improved both these parameters. Further research with larger population of patients over a longer period is needed to further assess these outcomes.

Is comprehensive geriatric testing guiding in the identification of multiple myeloma patients who are candidates for autologous stem cell transplantation? A prospective analysis.

Multiple myeloma (MM) is a hematological malignancy of older adults. This study aimed to investigate the differences in performance, comorbidity scores, and comprehensive geriatric assessment (CGA) before and after induction therapy in newly diagnosed MM patients, as well as the factors that may be associated with improved performance status after induction therapy. Thirty-seven consecutive patients aged 50years and older, who were newly diagnosed with MM, were included in the study. The patients underwent performance status evaluation and CGA when first diagnosed and after 4 cycles of induction chemotherapy. The performance status of 11 patients (40.7%) changed after induction therapy. Improvement in performance status was significantly lower in patients who were frail according to the Fried frailty criteria and IMWG scores (60% vs. 25%, p = 0.04), (30.0% vs. 6.2%, p = 0.02), taking more than 2 medications due to comorbidities (p = 0.01, confidence interval 0.06-0.09) and those with renal involvement (80.0% vs. 18.7%, p = 0.002). Those with bone involvement were more prevalent among the patients whose performance status improved (87.5% and 50.0%, p = 0.03). This study demonstrated that performance status might improve after induction therapy. Results suggest that CGA before induction therapy can predict performance status change. These results might have implications for predicting at the time of diagnosis, whether an MM patient can be a transplant candidate after induction therapy.

Improving performance status documentation using an electronic medical record tool.

309 Background: Performance status (PS) is used regularly in oncology care to select appropriate cancer treatment, track changes in level of functioning, and determine clinical trial eligibility. In addition, the American Society of Clinical Oncology (ASCO)/Oncology Nursing Society (ONS) Chemotherapy Administration Safety Standards requires that on each clinical encounter, staff performs and documents a patient assessment that includes 8 elements; one of which is PS. Currently, little instruction is provided on how to utilize and record a more standardized criteria, such as PS with either ECOG or Karnofsky scores, in the electronic medical record (EMR) which results in suboptimal documentation. We assessed documentation of PS before and after implementation of a tool within the EMR at our outpatient cancer center. Methods: Using the Plan-Do-Study-Act (PDSA) technique, a quality improvement project was developed to determine if our center was consistent with the ASCO/ONS guidelines. An EMR tool was developed that enabled clinicians to standardize PS documentation within an encounter via population of a flowsheet to improve compliance. Clinicians were educated on guidelines and utilization of the PS tool and data was collected pre- and post- implementation. A survey was developed and administered to assess PS tool use and to learn of any barriers to implementation. Based on survey results, we created a reminder tip sheet for clinicians to utilize the PS tool; a subsequent chart review was completed. Results: In a random pre-study 50 chart review, 0% of encounters in our lung and breast clinic had PS documented. At the time of pre-tool implementation, due to the lack of a retrievable flowsheet, we did not obtain a reliable PS documentation percentage. After education and tool implementation, 2481 random encounters were evaluated of which 315 encounters (12.6%) documented PS and used the PS tool. A total of 7 (35%) clinicians completed the survey: 4 physicians and 3 advanced practice registered nurses. Of those who responded, 57% used the PS tool, 71% used a note template with ECOG PS embedded, and 85.7% were willing to alter their note template to incorporate ECOG PS. Barriers identified included: limited time, workflow constraints and redundant documentation. After tip sheet implementation, 66% of encounters documented PS; however, only 6 out of those 33 encounters (18%) documented PS using the PS EMR tool. Conclusions: Documentation support tools help facilitate care and enable measurement of guideline concordance, but once implemented it can be challenging to maintain adherence. Although this study improved overall PS documentation (0 to 66%), we were only able to demonstrate a 6% increase in the use of our PS documentation tool. While PS tool implementation was feasible, adoption of the additional tool was not universal. We aim to gather additional clinician input to improve PS documentation completion and guideline adherence.

Efficacy and safety of herbal formulas with the function of gut microbiota regulation for gastric and colorectal cancer: A systematic review and meta-analysis.

BackgroundCurrently, gastric cancer (GC) and colorectal cancer (CRC) are the most common causes of cancer-related mortality worldwide. Gut microbiota is closely related to the occurrence of GC and CRC and the efficacy of chemotherapy. This study is aimed at evaluating the efficacy and safety of herbal formulas with the function of gut microbiota regulation (HFGMR) in the treatment of GC and CRC and to assess the quality of the synthesized evidence.MethodsA comprehensive search was performed on eight electronic databases, PubMed, EMBASE, CENTRAL, Web of Science, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang database, Chinese Scientific Journals Database, and two registries, Chinese Clinical Trial Registry and ClinicalTrials.gov, from their initiation to January 2022. Randomized controlled trials (RCTs) studying the therapeutic effects of HFGMR were included. We used Stata 16 for data synthesis and Risk of Bias 2 (RoB 2) for methodological quality evaluation and assessed the quality of the synthesized evidence in the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.ResultsFifty-three RCTs involving 4,478 patients were included. These trials involve seven herbal formulas that could regulate the gut microbiota of Bifidobacterium, Lactobacillus, Escherichia coli, Bacteroides, and Enterococcus faecalis. The meta-analysis results were subgrouped to three different stages in GC and CRC. 1) For the perioperative stage, HFGMR combined with conventional therapy could shorten the time to bowel sound recovery by 1.63 h [mean difference (MD) = −1.63, 95% confidence interval (CI) (−2.62, −0.65)], the time to first flatus by 9.69 h [MD = −9.69, 95% CI (−10.89, −8.48)], and the duration of hospitalization by 2.91 days [MD = −2.91, 95% CI (−4.01, −1.80)] in GC. There were no significant differences in outcomes of gastrointestinal function recovery and adverse events in CRC. 2) For postoperative patients, combined with adjuvant chemotherapy, HFGMR could decrease the incidence of diarrhea, nausea and vomiting, anorexia, and peripheral neurotoxicity in GC; boost Karnofsky performance status (KPS) improvement rate [risk ratio (RR) = 1.96, 95% CI (1.38, 2.79)]; and decrease the incidence of leucopenia and nausea and vomiting in CRC. 3) For advanced stage, HFGMR can significantly improve the objective response rate (ORR) [RR = 1.35, 95% CI (1.19~1.53)], disease control rate (DCR) [RR = 1.14, 95% CI (1.05~1.23)], and KPS improvement rate [RR = 1.56, 95% CI (1.17, 2.09)] and decrease the incidence of leucopenia, neutropenia, anemia, nausea and vomiting, diarrhea, and fatigue in GC. There were no significant differences in ORR [RR = 1.32, 95% CI (0.94~1.86)] and DCR [RR = 1.22, 95% CI (0.99~1.50)], but they can improve the KPS response rate [RR = 1.62, 95% CI (1.13, 2.32)] and decrease the incidence of myelosuppression, nausea and vomiting, diarrhea, and hepatic and renal dysfunction in CRC.ConclusionThis study indicates that herbal formulas that could regulate the composition and proportion of gut microbiota have a positive effect in three stages (perioperative, postoperative, and advanced) of GC and CRC. They could promote the recovery of postoperative gastrointestinal function, increase tumor response, improve performance status, and reduce the incidence of adverse events. Herbal formulas exerted anti-cancer efficacy through multiple mechanisms and pathways; among them, the regulation of gut microbiota has not been paid enough attention. To further support the conclusion and better understand the role of gut microbiota in the treatment of GC and CRC, more rigorously designed, large-scale, and multicenter RCTs that focus on herbal formulas and gut microbiota are needed in the future.

The feasibility of weekly paclitaxel in improving performance status(PS) of advanced non-small cell lung cancer (NSCLC) patients with poor performance status: A single-arm phase two trial.

e21155 Background: Treatment of driver mutation negative metastatic NSCLC with poor PS (Eastern Cooperative Oncology Group[ECOG] PS of ≥2) is controversial. Preliminary data suggests poor PS patients also benefit from chemotherapy, with toxicity being a valid concern. We hypothesize PS of a patient may improve with chemotherapy if poor PS is due to high tumor burden rather than comorbidities. We designed a phase II single arm study to assess the feasibility of using abbreviated chemotherapy to improve the PS of stage IIIC/IV NSCLC patients of ECOG PS≥2. Methods: Adult patients with age≤65 years, Charlson’s comorbidity index &lt; 9, serum albumin≥3.5g/dl, adequate bone marrow and organ function, &amp; ECOG PS≥2 as judged by the worst score of three independent physicians were administered 3 doses of weekly paclitaxel at 60mg/m2/dose. ECOG PS was again assessed at 4th week. Primary end point was an improvement in ECOG PS by 1 point at 4th week assessment. Secondary endpoints were toxicity by Common Terminology Criteria for Adverse Events (CTCAE v 5.0), quality of life(QOL)assessment at baseline and 4 weeks by European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC QLQ-C30) and its lung cancer module, EORTC QLQ-LC13. Optimal Simon’s 2 stage design was used. In the first stage, 18 pts were to be accrued; if ≤ 2 responses were observed the study would be stopped. Else, 25 additional pts would be recruited to a total of 43 patients. The null hypothesis would have been rejected if ≥ 7 responses were observed. This design yielded a type I error rate of 0.05 and 80% power. Results: A total of 46 patients were included in the study, median age 56years(interquartile range 54-59), 34(74%) male, 12(26%) had comorbid conditions, 34(74%) had extrathoracic disease, squamous cell carcinoma was the most common histology(41%). ECOG PS distribution shown in table. Overall, 11 out of 46 patients(24%) showed improved PS, fulfilling primary end point. Further 7 patients had improved in PS beyond the time point of 4 weeks. Due to improved PS, 16 patients(35%) were able to receive standard platinum doublet. Any grade toxicity was seen in 85% of patients and 20% had grade 3/4 (most common: anemia and diarrhea). At a median follow up of 4.8m (95 % CI: 3.27-14.9), the median progression free survival was 3.3 months (95% CI: 2.36-5.6) and median overall survival 6.8months (95% CI 2.47-8.8). QOL improved significantly for global QOL, role functioning, pain, dyspnea, insomnia, pain in chest, pain in other parts &amp; worsened for alopecia and sore mouth. Conclusions: Use of abbreviated chemotherapy is a useful, well tolerated strategy in carefully selected poor PS stage IIIC/IV NSCLC patients that leads to meaningful improvement in QOL. Clinical trial information: CTRI/2020/01/022617. [Table: see text]

Response to epithelial growth factor receptor inhibitor (EGFRi) treatment in patients with early-onset, treatment-naïve metastatic colorectal cancer (mCRC): An ARCAD database analysis.

3572 Background: Early onset colorectal cancer (eoCRC: disease diagnosed &lt; 50) has been increasing over the past 2 decades. Currently, standard treatment recommendations for eoCRC patients (pts) with metastatic disease does not differ from late-onset CRC (loCRC) pts although outcomes data in eoCRC pts is limited. Methods: Individual patient data on 5,761 treatment-naive metastatic eoCRC pts was pooled from 8 phase II and III randomized EGFRi studies (2000 - 2012) from the ARCAD mCRC database. The distribution of demographics, clinicopathological features, and biomarkers were summarized by age groups. Progression-free survival (PFS) was compared between age groups by stratified Cox models, adjusting for potential confounders. Predictive value of age group was evaluated by testing interaction effect between treatment and age variables based on a subset of trials with concurrent randomizations between regimens with and without EGFRi Results: eoCRC (n=756) were more evenly distributed between gender, had improved performance status (PS), increased likelihood of metastatic resection, and distant lymph node metastasis, but were less likely to have lung metastasis or KRAS mutation compared to loCRC (n=5,005, table 1). eoCRC and loCRC patients had similar distribution of primary tumor sidedness, primary resection, liver and/or peritoneal involvement, number of metastatic sites involved, and BRAF mutations (MT). No difference in PFS for eoCRC versus loCRC pts was noted (7.8 vs. 7.9 months [M], adjusted hazard ratio [HRadj], 1.02, 95% confidence interval [CI], 0.93-1.11). Among pts with KRAS wild type (WT) and left sided primary tumors, univariable analysis of EGFRi demonstrated improved mPFS in loCRC (9.9 vs 8.5M, HR = 0.74, p&lt;0.001), but this benefit was not seen in eoCRC (8.3 vs 8.9 months, HR 1.20, p=0.36). The same pattern was observed upon multivariable analysis (Table). Conclusions: In our pooled analysis, EGFRi + chemotherapy significantly improved PFS in treatment-naïve loCRC patients but not in left sided, KRAS WT, eoCRC patients. Further validation in an independent cohort is warranted. [Table: see text]

Review of Current Principles of the Diagnosis and Management of Brain Metastases.

Brain metastases are the most common intracranial tumors and are increasing in incidence as overall cancer survival improves. Diagnosis of brain metastases involves both clinical examination and magnetic resonance imaging. Treatment may involve a combination of surgery, radiotherapy, and systemic medical therapy depending on the patient’s neurologic status, performance status, and overall oncologic burden. Advances in these domains have substantially impacted the management of brain metastases and improved performance status and survival for some patients. Indications for surgery have expanded with improved patient selection, imaging, and intraoperative monitoring. Robust evidence supports the use of whole brain radiotherapy and stereotactic radiosurgery, for both standalone and adjuvant indications, in almost all patients. Lastly, while systemic medical therapy has historically provided little benefit, modern immunotherapeutic agents have demonstrated promise. Current investigation seeks to determine the utility of neoadjuvant radiotherapy and laser interstitial thermal therapy, which have shown benefit in limited studies to date. This article provides a review of the epidemiology, pathology, diagnosis, and treatment of brain metastases and the corresponding supporting evidence.

PO-633-03 RIGHT VENTRICULAR PRESSURE ANALYSIS ASSESSING THE IMPACT OF DIFFERENT PACING STRATEGIES DURING A LEFT VENTRICULAR ASSIST DEVICE SPEED OPTIMIZATION STUDY

CRT restores ventricular synchrony and improves outcomes in advanced heart failure. It is unknown if the benefit of CRT persists post LVAD; recent data suggest improved performance status and quality of life with RV-only versus biventricular (BiV) pacing. The mechanism underlying this observation is uncertain.

A systematic review of endotracheal stenting in patients with locally advanced thyroid cancer.

Locally aggressive thyroid cancer can result in airway obstruction secondary to tracheal compression or vocal cord palsy. A tracheal stent provides an alternative to surgical resection, tracheostomy or conservative management in patients with compressive symptoms. This systematic review synthesises the current evidence associated with tracheal stenting in locally advanced thyroid cancer. We conducted a systematic review of tracheal stenting in locally advanced thyroid cancers. We searched MEDLINE, Embase and Web of Science for studies until 22 September 2020. Inclusion criteria were studies involving patients who had received tracheal stents to treat laryngotracheal stenosis secondary to locally advanced thyroid cancer. Single case reports or single cases were not included. We assessed studies for data on the performance of tracheal stenting; defined as symptomatic relief, spirometry data, complication rates and mortality. We also extracted data pertaining to the use of different types of stent. We identified eight full-text articles from 325 titles found in our search. These were all single-centre retrospective studies that lacked homogeneity of thyroid cancer histotypes. The number of patients in each study ranged from 4 to 35 patients. Stenting improved performance status (two of two studies), symptoms (five of five studies) and spirometry (two of three studies). The most common complications were tracheal granulation, tumour overgrowth, stent migration and sputum retention. There is a lack of evidence in the literature of tracheal stents in locally advanced thyroid cancer. However, the evidence available suggests tracheal stenting may be a useful treatment adjunct in advanced thyroid cancer-causing symptomatic airway obstruction.

Chronic lymphocytic leukaemia/small lymphocytic lymphoma treatment with rituximab and high-dose methylprednisolone, revisited.

High‐dose methylprednisolone plus rituximab (R‐HDMP) is a useful treatment in chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) patients unfit for chemo‐immunotherapy and has proven its utility on the treatment of CLL/SLL complicated by auto‐immune cytopenias. We performed a retrospective, single‐centre study, of CLL/SLL patients treated with R‐HDMP for 9 years. Thirty‐nine patients were included, median age at time of treatment was 77 years. Most patients had stage Rai III/IV and Binet C disease. Twenty‐eight patients had relapsed/refractory disease at time of treatment with a median of 1 previous line of therapy; 53.8% had prior exposure to fludarabine and 25% to rituximab. Grade 3–4 neutropenia and thrombocytopenia were recorded in 10.2% and 17.9% patients, respectively. While on treatment, 51.3% had documented infectious complications, but no other non‐haematological toxicities grades 3–4 were identified. Overall response rate was 64%. Median overall survival and progression‐free survival were 24 and 13 months, respectively. Twenty four patients relapsed and 16 received another line of treatment after R‐HDMP, with median time to next treatment of 13.5 months. Thirteen out of the 24 patients improved performance status and were subsequently considered fit for chemo‐immunotherapy. R‐HDMP is a valuable option for elderly and frail patients, with low risk of severe myelotoxicity and other severe adverse events. It was shown to work as a bridge to other lines of treatment, including chemo‐immunotherapy.

Cutaneous squamous cell carcinoma metastatic to the axilla and groin: Outcomes and prognostic factors.

This study examined the clinical outcomes and prognostic factors of patients with metastatic cutaneous SCC metastatic to the axilla and groin when managed with curative-intent lymphadenectomy and received (neo)adjuvant treatment. We conducted a single institution retrospective review. Patients who had nodal disease without distant spread were 18 years or older with no non-cutaneous primary identified. From January 2000 to July 2015, 78 patients were treated for axilla (64, 82%) or inguinal (14, 18%) involvement with cSCC. The median age was 75.5 years (range: 29-95), and 8 patients (11%) were immunosuppressed. The median size of the largest node was 45 mm (range: 8-135), and extracapsular extension was found in 63 (81%) cases. A majority of patients were treated with surgery alone (21, 26.9%) and surgery with adjuvant radiation therapy (54, 69%). The 2-year OS and PFS were 50% (95% CI: 40%-63%) and 43% (95% CI: 33%-56%), and 5-year OS and PFS were 33% (95% CI:23%-47%) and 32% (95% CI:22%-46%) respectively in the entire cohort. On univariable analysis, factors associated with longer OS were as follows: younger age (HR 1.1, 95% CI: 0.9-1.3 P = 0.021), improved performance status (HR 1.5, 95% CI:1.0-2.3 P = 0.026), lack of immunosuppression (HR 3.3, 95% CI: 1.5-7.3 P = 0.001), lower lymph node ratio (HR 1.2, 95% CI:1.0-1.3 P = 0.007), lower number of positive nodes (HR 1.1, 95% CI:1.0-1.2 P = 0.004) and the use of radiation therapy (HR 0.5, 95% CI:0.3-0.9 P = 0.012). Metastasis to the axilla and groin with cSCC has poor outcomes with standard treatment. The addition of immunotherapy warrants investigation.

S1918: A Phase II/III Randomized Study of R-Minichop with or without Oral Azacitidine (CC-486) in Participants Age 75 Years or Older with Newly Diagnosed Diffuse Large B Cell Lymphoma, Grade IIIb Follicular Lymphoma, Transformed Lymphoma, and High-Grade B-Cell Lymphomas with MYC and BCL2 and/or BCL6 Rearrangements

S1918: A Phase II/III Randomized Study of R-Minichop with or without Oral Azacitidine (CC-486) in Participants Age 75 Years or Older with Newly Diagnosed Diffuse Large B Cell Lymphoma, Grade IIIb Follicular Lymphoma, Transformed Lymphoma, and High-Grade B-Cell Lymphomas with MYC and BCL2 and/or BCL6 Rearrangements