Performance Status Scale Scores Research Articles

A Comparative Analysis of Vitamin D Status among Tuberculosis Patients and Healthy Household Contacts: A Case–Control Study from Central India

Background and Objectives: When it comes to the nature of the relationship between tuberculosis (TB) and Vitamin D, the available literature offers contradictory findings. The purpose of this study was to assess the relationship between Vitamin D and TB, as well as the relationship between Vitamin D and functional capacity in TB patients from Central India. Materials and Methods: This case–control study comprised 400 participants divided into two equal groups: cases (200 TB patients) and controls (200 healthy household contacts). The study involved subjecting participants to standard laboratory tests in accordance with the management guidelines implemented by the institute. Abbott Architect i1000SR PLUS was used to test the Vitamin D levels while the Karnofsky Performance Status Scale score was used for the functional capacity of cases. Vitamin D levels were categorized into deficient, insufficient, and sufficient for every participant. Information related to the study was noted down on a structured pro forma. Results: The difference in Vitamin D values between the two groups was statistically significant, with 62.5% of deficient patients in the case group compared to 15% in the control group (confidence interval = 95%, χ 2 = 173.97, P = 0.001). The relationship between Vitamin D concentration and Karnofsky scale categories was statistically significant ( r = 0.752, P = 0.01). Interpretation and Conclusions: Vitamin D deficiency is associated with TB and a decrease in functional capacity in the region of Bundelkhand, highlighting the vital role of Vitamin D for TB patients.

Minimally invasive interventions on celiac plexus in patients with persistent abdominal pain caused by pancreatic cancer

Background. Chronic abdominal pain is common in 50 % of patients with intra-abdominal malignancies and has a huge impact on quality of their lives. As the number and doses of systemic analgesics increase, so does the frequency of side effects that can further worsen functional status, which is important for this cohort of patients who have a five-year survival rate of only 8 %. The purpose of the study: to assess the efficacy and safety of computed tomography-guided celiac plexus neurolysis as a method of reducing persistent, severe pain in patients with pancreatic cancer that affects their functional status. Materials and methods. The analysis of the results of 17 interventional procedures on the celiac plexus in 16 participants was conducted, sympatholysis was performed twice in one patient. Inclusion criteria: pancreatic cancer with persistent pharmacoresistant neuropathic abdominal pain for ≥ 3 months, which did not respond to medications, including opioids, anti-inflammatory drugs, and other conservative methods of treatment. Age of patients was 39 to 72 years (mean of 62.6 ± 8.2 years), 10 (62.5 %) research participants were male and 6 (37.5 %) were female. Results. Interventions were successfully performed for all patients on the first attempt. There were no cases of perforations of hollow organs, damage to blood vessels, pleural sinuses, or other structures of the abdominal and thoracic cavities. No neurological complications were recorded, and no one required blood transfusion. All study patients had a significant reduction in pain on the visual analogue scale compared to baseline, both one week after the procedure, from 9.7 ± 0.6 to 4.7 ± 1.4 (P < 0.001), and in six months, from 9.7 ± 0.6 to 4.1 ± 1.4 (P < 0.001). The average Karnofsky Performance Status Scale score compared to the data before the procedure, one week after increased from 64.7 ± 7.9 to 78.2 ± 6.4 (P < 0.001). A significant improvement in functional status was maintained up to three months — 71.2 ± 6.9 (P < 0.001). However, in six months, this indicator was 63.5 ± 6.0 (Р = 0.668), which may be related not only to the intensity of the pain syndrome, but also to other complications of the underlying disease (ascites, cachexia, tumor growth, palliative surgical interventions, etc.). Conclusions. Computed tomography-guided celiac plexus neurolysis is a safe and effective procedure for patients with abdominal pain caused by inoperable pancreatic cancer. Sympatholysis provides a long-term significant reduction in pain syndrome according to the visual analogue scale after 1, 3, 6 months (Р < 0.001) and increases the functional status of patients according to the Karnofsky Performance Status Scale in 1 (Р < 0.001), 3 months (Р = 0.023). Celiac plexus neurolysis should be considered as part of a multidisciplinary approach to the comprehensive treatment of upper abdominal pain associated with cancer in the early stages of the disease.

Outcomes and influencing factors of dental implants in fibula, iliac crest, and scapula free flaps: a retrospective case–control study

PurposeReconstruction with vascularized bone grafts after ablative surgery and subsequent dental rehabilitation with implants is often challenging; however, it helps improve the patient’s quality of life. This retrospective case–control study aimed to determine the implant survival/success rates in different vascularized bone grafts and potential risk factors.MethodsOnly patients who received implants in free vascularized bone grafts between 2012 and 2020 were included. The free flap donor sites were the fibula, iliac crest, and scapula. The prosthetic restoration had to be completed, and the observation period had to be over one year after implantation. Implant success was defined according to the Health Scale for Dental Implants criteria.ResultsSixty-two patients with 227 implants were included. The implant survival rate was 86.3% after an average of 48.7 months. The causes of implant loss were peri-implantitis (n = 24), insufficient osseointegration (n = 1), removal due to tumor recurrence (n = 1), and osteoradionecrosis (n = 5). Of all implants, 52.4% were classified as successful, 19.8% as compromised, and 27.8% as failed. Removal of osteosynthesis material prior to or concurrent with implant placement resulted in significantly better implant success than material not removed (p = 0.035). Localization of the graft in the mandibular region was associated with a significantly better implant survival (p = 0.034) and success (p = 0.002), also a higher Karnofsky Performance Status Scale score with better implant survival (p = 0.014).ConclusionImplants placed in vascularized grafts showed acceptable survival rates despite the potential risk factors often present in these patient groups. However, peri-implantitis remains a challenge.Graphical abstract

Mirtazapine as Appetite Stimulant in Patients With Non–Small Cell Lung Cancer and Anorexia

Currently there is no standard therapy to improve cancer-related anorexia, hampering survival. Mirtazapine has been suggested as a feasible option in this context. To assess the effect of mirtazapine on appetite and energy consumption in patients with advanced non-small cell lung cancer (NSCLC). This randomized, double-blind, placebo-controlled clinical trial including adults was performed in a tertiary cancer care center from August 2018 to May 2022 with a follow-up of 8 weeks. Overall, 134 patients were screened; 114 were assessed for eligibility and 28 were excluded. Patients were randomized in a 1:1 ratio to receive mirtazapine, 15 mg, or placebo for 2 weeks followed by a dose escalation to 30 mg until week 8 or placebo. Both groups received nutritional assessment and dietary advice. Appetite was assessed by the Anorexia Cachexia Scale and energy intake. Dietary parameters were evaluated at baseline, 4 weeks, and 8 weeks, with a 24-hour dietary recall, and energy quantification based on the Mexican system of nutritional equivalents. A total of 86 patients met the inclusion criteria and were randomized to the placebo (n = 43) or the mirtazapine group (n = 43). The mean (SD) age was 63.5 (11.2) years, 41 were women (57.7%) and had adenocarcinoma, Eastern Cooperative Oncology Group performance status scale score of 1, stage IV NSCLC, and were receiving first-line treatment. Baseline characteristics were similar between groups. There was no difference in appetite scores in patients who received mirtazapine or placebo after 4 and 8 weeks. After 4 weeks, mirtazapine significantly increased energy intake (379.3 kcal; 95% CI, 1382.6-576.1; P < .001) including proteins (22.5 g; 95% CI, 11.5-33.4; P = .001), carbohydrates (43.4 g; 95% CI, 13.1-73.8; P = .006), and fats (13.2 g; 95% CI, 6.0-20.4; P = .006). Fats intake was significantly higher in patients in the mirtazapine group (14.5 g vs 0.7 g; P = .02) after 8 weeks. The mirtazapine group significantly decreased the proportion of patients with sarcopenia (82.8% vs 57.1%, P = .03) at 8 weeks. Patients on mirtazapine tolerated the treatment well, but reported a higher perception of nightmares at 2 weeks based on a 10 cm VAS score (0 [25th-75th percentile, 0-1] vs 0 [25th-75th percentile, 0-0] in the control group; P = .009) but this finding was nonsignificant after 4 and 8 weeks. In this randomized clinical trial of patients with advanced NSCLC, there was no difference in appetite scores in all patients who received mirtazapine or placebo, but the mirtazapine group had a significant increase in energy intake through the 4- and 8-week follow-up, mainly in fat intake, which is a better and crucial source of energy. The addition of mirtazapine in the treatment of patients with advanced NSCLC and anorexia may help these patients achieve their energy requirements and improve health-related quality of life, specifically emotional and cognitive functioning. ClinicalTrials.gov Identifier: NCT04748523.

Application of traditional Chinese medicine acupoint needle embedding combined with emotional nursing in patients with gynecological malignant tumors.

Few relevant literature reports on applying acupoint press-needle embedding combined with emotional nursing in patients with a gynecological malignant tumor. To explore the effect of traditional Chinese medicine acupoint needle embedding combined with emotional nursing on chemotherapy-related nausea and vomiting (CINV), cancer-related fatigue (CRF) and psychological state in patients with gynecological malignant tumors. Retrospective analysis of the clinical information of 84 patients with gynecological malignant tumors treated in our hospital from August 2020 to December 2022 Led to the development of an observation group (n = 42) and a control group (n = 42) based on various nursing approaches. Ondansetron hydrochloride injection was administered to the individuals in the control group. However, the observation group received emotional nursing based on the control group and acupoint press-needle embedding of traditional Chinese medicine. Patients in both groups received the chemotherapy regimen of paclitaxel liposome + carbo-platin/ cisplatin. For four weeks, both groups intervened. The CINV grade, quality of life, CRF, psychological status and sleep quality scores of the two groups before and after intervention were compared. After intervention, the degree of CINV in the observation group was significantly better than that in the control group. After intervention, the scores of each dimension and total score of FLIE scale were significantly higher than those in the control group. After intervention, the scores of each dimension and total score of Piper Fatigue Scale were significantly lower than those in the control group (P < 0.05). After intervention, the scores of avoidance and yield dimensions in the observation group were significantly lower than those in the control group, and the scores of confrontation dimension were significantly higher than those in the control group (P < 0.05). After intervention, the sleep quality score of the observation group was significantly lower than that of the control group, and the Karnofsky Performance Status scale score was significantly higher than that of the control group (P < 0.05). The acupuncture point needle embedding of traditional Chinese medicine combined with emotional nursing can further reduce the incidence of chemotherapy-related nausea and vomiting in patients with gynecological malignant tumors, improve the quality of life and the degree of CRF, alleviate the bad psychological state, adopt a positive way to face the disease and treatment, and improve the quality of sleep and quality of life.

Postoperative Limb Function and QOL in Elderly Patients With Malignant Bone Tumor/Soft Tissue Sarcoma.

Malignant bone tumors (MBT) and soft tissue sarcomas (STS) require wide excision. Although the number of elderly patients is increasing, wide excision may decrease limb function and quality of life (QOL) for elderly patients. However, no detailed evaluation of the functional prognosis or QOL of elderly patients with sarcoma has been reported. This study evaluated postoperative limb function and QOL in elderly patients with MBT and STS. This retrospective study included 67 patients aged >70 years with MBT or STS who underwent surgery at a single institution. The Toronto Extremity Salvage Score (TESS), EuroQoL 5-dimension 5-level (EQ-5D-5L) questionnaire, Musculoskeletal Tumor Society (MSTS) score, and psoas muscle index (PMI) were evaluated. We also assessed factors associated with the postoperative TESS and EQ-5D-5L index. Detailed examination of the MSTS items perioperatively revealed significant decline in manual dexterity/walking ability and support but significant improvement in pain and emotional acceptance. The mean PMI decreased significantly from 4.7 to 4.23 perioperatively. The postoperative mean TESS and EQ-5D-5L index was 76.9 and 0.74, respectively. Patients with good performance status and clinical frailty scale scores preoperatively had better postoperative TESS and EQ-5D-5L scores. The current study strongly suggests the possibility of maintaining postoperative limb function, satisfaction, and QOL in patients with MBT and STS by choosing patients in good condition and the appropriate procedure that the patient desires. However, perioperative progression of sarcopenia should be noted.

Pembrolizumab Added to Ifosfamide, Carboplatin, and Etoposide Chemotherapy for Relapsed or Refractory Classic Hodgkin Lymphoma

To our knowledge, this is the first clinical trial designed to investigate concurrent treatment with a checkpoint inhibitor and conventional chemotherapy in relapsed or refractory classic Hodgkin lymphoma in patients destined for an autologous stem cell transplant. To evaluate the complete response rate as assessed by 18F-fluorodeoxyglucose-positron emission tomography with computed tomography (FDG-PET/CT) after salvage therapy for patients with relapsed or refractory classic Hodgkin lymphoma. A single-group, phase 2, multi-institutional nonrandomized clinical trial to evaluate the addition of pembrolizumab to ifosfamide, carboplatin, and etoposide (ICE) chemotherapy was conducted from April 20, 2017, to October 29, 2020, at 5 US sites. The 42 patients were aged 18 years or older, with an Eastern Cooperative Oncology Group Performance Status Scale score of 0 or 1 and biopsy-proven relapsed or refractory classic Hodgkin lymphoma after 1 or 2 prior lines of chemotherapy. Patients were required to be appropriate candidates for transplant, with measurable lesions detected by FDG-PET/CT. Two cycles of pembrolizumab (200 mg intravenously on day 1) with ICE chemotherapy every 21 days, followed by stem cell mobilization and collection, and then 1 cycle of pembrolizumab monotherapy followed by FDG-PET/CT response assessment. The primary end point was complete response rate detected by FDG-PET/CT, defined as a Deauville score of 3 or lower. Patients with a complete response proceeded to an autologous stem cell transplant. Secondary end points included progression-free survival, overall survival, stem cell mobilization, and neutrophil and platelet engraftment. Adverse events were monitored to assess safety. Forty-two patients were enrolled, with 37 evaluable for the primary end point. The median age was 34 years (range, 19-70 years), 25 patients were female (68%), 6 were African American (16%), and 26 were White (70%). The complete response rate for the 37 patients assessed by FDG-PET/CT imaging was 86.5% (95% CI, 71.2%-95.5%); the overall response rate was 97.3% (36 patients), with 10.8% partial responses (4 patients). New areas of FDG-PET positivity in 2 patients were biopsied, showing noncaseating granuloma in 1 case and a reactive lymph node in a second. Progression-free survival and overall survival 2-year estimates were 87.2% (32 patients; 95% CI, 77.3%-98.3%) and 95.1% (95% CI, 88.8%-100%), respectively. The addition of pembrolizumab to ICE chemotherapy did not negatively affect stem cell mobilization or collection or engraftment, similar to prior experience in this patient population and setting. Results suggest that the addition of pembrolizumab to ICE chemotherapy was well tolerated and highly effective in comparison with prior reports of chemotherapy-only regimens, supporting further investigation in patients with relapsed or refractory classic Hodgkin lymphoma eligible for an autologous stem cell transplant. ClinicalTrials.gov Identifier: NCT03077828.

Influence of humanized nursing on patients with intracranial aneurysm subarachnoid hemorrhage undergoing interventional embolization

ObjectiveTo investigate the effect of nursing intervention on patients with intracranial aneurysm subarachnoid hemorrhage who underwent interventional embolization. MethodsAccording to the random number table method, 80 patients with subarachnoid hemorrhage caused by intracranial aneurysm who received interventional embolization in our hospital from September 2018 to May 2021 were randomly divided into a control group of 40 cases and an observation group of 40 cases. 40 cases, the two groups were implemented routine nursing and humanized nursing. ResultsCompared with before nursing, the anxiety score, depression score, compliance rate, complication rate and PSQI score of the observation group were significantly lower than those of the control group after nursing (P < 0.05); Karnofsky Performance Status Scale score, Activity of daily living scale of the observation group and quality of life scores were significantly higher than those in the control group (P < 0.05). ConclusionHumanized nursing can effectively improve the psychological state of patients with subarachnoid hemorrhage caused by intracranial aneurysm during the perioperative period of interventional embolization, enhance their compliance with treatment, reduce complications, and make patients more satisfied with nursing services.

Association between Karnofsky performance status and outcomes in cancer patients on home parenteral nutrition

The selection of appropriate criteria is essential to accurately identify cancer patients eligible for home parenteral nutrition (HPN). In this study, the association between Karnofsky Performance Status (KPS) Scale scores and outcomes in cancer patients on HPN was evaluated. Retrospective-observational-longitudinal-analytical study of a database of adult cancer patients on HPN. The variables analyzed were sex, age, cancer diagnosis, cancer location (digestive tract and genitourinary), nutritional status, including initial weight (IW), at the start of HPN), usual weight (UW) and IW/UW ratio, and body mass index (BMI) at the start of HPN. Performance status was assessed with the KPS scale. Type of catheter used, number of days on HPN and clinical progression of cancer patients were also studied. Data of 41 cancer patients (60.8% female) were evaluated. Mean age at the start of HPN was 60.45 years. Cancer location was digestive tract (n=36; 87.8%); gynecologic (n=4; 9.7%), urinary tract (n=1; 2.4%). Median IW was 55kg (45; 64) and BMI was 20 (17.58; 22.84). The IW/UW ratio was-15kg (-20;-10). The catheters used were peripherally inserted central catheter (n=30; 73.2%), tunneled (n=9; 22%) and port (n=2; 4.8%). The median duration of HPN was 72 days (30; 159). The KPS results showed that 16 cancer patients (39%) had KPS scores ≤50, 17 (41.5%) requiring HPN were discharged and 24 (58.5%) died. The association between disease progression and KPS scores ≤50 was significant (p=0.025; OR (95% CI): 5.28 (1.07; 36.18). The KPS scale is a reliable tool to identify cancer patients eligible for HPN. Cancer patients with ≤50 scores had a five-fold increased risk of death than patients with >50 scores.

Orthopedic therapeutic surgery for bone metastasis of liver cancer: Clinical efficacy and prognostic factors.

In this study, the objectives were to investigate the clinical efficacy of orthopedic therapeutic surgery (OTS) in patients with bone metastasis of liver cancer and explore the prognostic factors. The electronic medical records of patients with bone metastasis of liver cancer in the Third Affiliated Hospital of Naval Medical University from September 2016 to August 2021 were retrospectively collected. A total of 53 patients were included. Patients were assigned to the OTS (n = 35) or the control group (n = 18) based on receiving orthopedic therapeutic surgery or conservative treatment. The pre/posttreatment Karnofsky Performance Status scale (KPS) and numeric rating scale (NRS) scores were compared. Univariate and multivariate Cox regression analyses were used to explore the prognostic factors affecting survival after bone metastasis. Logistic regression analyses were adopted to discover potential factors that contributed to greater KPS score improvement. The axial bone accounted for 69.8% of all bone metastases. The proportion of multiple bone metastases was 52.8%. After surgery, the median KPS score of the OTS group increased from 60 to 80 (p < 0.001), and the median increase in the OTS group was higher than that of the control group (p = 0.033). The median NRS score of the OTS group declined from 6 to 2 after surgery (p < 0.001), and the median decline in the OTS group was higher (p = 0.001). The median survival was 10 months in the OTS group vs. 6 months in the control group (p < 0.001). Higher pretreatment KPS scores, undergoing liver primary lesion surgery, and undergoing orthopedic therapeutic surgery were protective factors of survival. Undergoing orthopedic therapeutic surgery greatly improved the KPS score. Orthopedic therapeutic surgery for bone metastasis of liver cancer provides benefits to the quality of life. Patients who have their primary liver lesions removed, undergo orthopedic therapeutic surgery, and have a better physical condition before treatment tend to have longer survival.

Karnofsky performance status and visual analogue scale scores are simple indicators for quality of life in long-term AYA survivors who received allogeneic hematopoietic stem cells transplantation in childhood

The purpose of this study was to investigate Karnofsky performance status (KPS) scores and visual analogue scale (VAS) scores to explain which domains in the standardized self-reported quality of life (QOL) are instrumental for long-term hematopoietic stem cell transplantation (HSCT) survivors. We conducted a nationwide cross-sectional questionnaire study on 221 survivors with allogeneic-HSCT in 28 pediatric centers. Patient-reported QOL was assessed at a single time point using the 36-item Short-Form Survey (SF-36), the Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), and VAS scores. KPS scores were significantly correlated with both physical and role component summary scores of the SF-36, while the VAS provided by the patient (VASpt) was significantly correlated with the mental component summary score of the SF-36 and many subscales of the FACT-BMT. The VAS provided by the participants' attending physician (VASdoc) was correlated well with KPS scores. A VASpt score more than 40% lower than KPS scores suggested mental health problems. In conclusion, KPS scores might be considered as an indicator for physical and role/social components and VASpt score as an indicator for mental components and HSCT-specific QOL.

Pembrolizumab (pembro) plus axitinib (axi) versus sunitinib as first-line therapy for advanced clear cell renal cell carcinoma (ccRCC): Analysis of progression after first subsequent therapy in KEYNOTE-426.

4513 Background: The randomized, open-label, phase 3 KEYNOTE-426 study (NCT02853331) met its primary and key secondary end points of improved OS, PFS, and ORR with pembro + axi versus sunitinib as first-line treatment for patients with advanced ccRCC. Extended follow-up (42.8-mo median follow-up) continued to show the superior efficacy of pembro + axi versus sunitinib in this patient population. We describe the results of PFS2 for all randomly assigned patients and across IMDC risk categories. Methods: Treatment-naive patients with advanced ccRCC, Karnofsky Performance Status Scale score ≥70% and measurable disease per RECIST v1.1 were randomly assigned 1:1 to receive pembro 200 mg IV every 3 weeks for up to 35 doses (̃2 y) + axi 5 mg orally twice daily or sunitinib 50 mg orally once daily on a 4-wk on/2-wk off schedule. The end point of this exploratory analysis was PFS2, defined as time from randomization to progression after first subsequent therapy or any-cause death. The Kaplan-Meier method was used to estimate PFS2 and hazard ratios were estimated using a Cox regression model. Results: Of 861 patients, 432 were assigned to receive pembro + axi; 429, to sunitinib. Median time from randomization to the database cutoff date (January 11, 2021) was 42.8 mo (range, 35.6-50.6). Overall, 47.2% of patients (204/432) in the pembro + axi arm and 65.5% of patients (281/429) in the sunitinib arm received ≥1 line of subsequent anticancer therapy. For patients who received subsequent therapy, anti–PD-1/PD-L1 agents were the first subsequent treatment for 11.3% of patients (23/204) in the pembro + axi arm and 54.8% of patients (154/281) in the sunitinib arm. In the pembro + axi arm, 82.8% of patients (169/204) received a VEGF/VEGFR inhibitor as first subsequent therapy, as did 43.4% (122/281) in the sunitinib arm. PFS2 results are displayed in the Table. Conclusions: In this exploratory analysis, PFS2 was longer for patients randomized to pembro + axi compared to sunitinib. Results were consistent across IMDC risk groups. These data support use of pembro + axi for the first-line treatment of patients with advanced ccRCC. Clinical trial information: NCT02853331. [Table: see text]

The Effect of Race in the Palliative Treatment of Bone Metastases

PurposePrior studies demonstrated that single and multiple-fraction radiation therapy (RT) provide comparable pain relief in palliative-care patients. In addition, unconscious racial biases may affect practice patterns in oncology. In this study, we examined the effect of race on the duration of RT for palliative treatment of bone metastases. Methods and MaterialsThis is a retrospective study of 707 patients treated for bone metastases between 2013 and 2020 (1348 treatments). Patient race, demographics, RT dose, number of fractions, use of stereotactic radiosurgery (SRS), and performance score were collected. A short-course was defined as a single fraction, whereas a long-course was defined as more than one fraction. SRS cases were analyzed separately. ResultsOf all nonradiosurgery RT treatments delivered, 28.9% were single fraction and 71.1% were multiple fraction. In total, 76% of the patients were White and 24% were non-White. With regard to race, the number of White patients receiving short- and long-course RT was 256 (27.9%) and 663 (72.1%), respectively. The number of non-White patients receiving short- and long-course RT was 97 (31.9%) and 207 (68.1%), respectively. There was no difference in treatment duration based on patient race (P = .20). The use of SRS did not vary based on race (P = .79). There was no statistically significant difference in Karnofsky Performance Status Scale score between White and non-White patients (P = .44). ConclusionsAnalysis of patient and physician characteristics revealed that race did not influence treatment decisions such as duration of palliative RT regimen or use of SRS. Although palliative-care regimens must be individualized for each patient, such investigations can identify potential biases in treatment decisions.

416 An open-label phase 2 study of 2 doses of the hypoxia-inducible factor (HIF)–2α inhibitor belzutifan for the treatment of advanced clear cell renal cell carcinoma after progression on systemic therapy

BackgroundAccumulation and aberrant stabilization of transcription factor HIF-2α drives the expression of genes associated with progression of clear cell renal cell carcinoma (ccRCC). Belzutifan, a first-in-class HIF-2α inhibitor, has demonstrated promising antitumor activity with a favorable safety profile in patients with heavily pretreated ccRCC. The efficacy and safety of 2 doses of belzutifan in patients with advanced ccRCC who experienced progression after systemic therapy will be evaluated in this randomized, open-label, multicenter, phase 2 trial (NCT04489771).MethodsApproximately 150 adults will be randomly assigned 1:1 to receive oral belzutifan 120 mg once daily or 200 mg once daily. Patients with locally advanced or metastatic ccRCC (per RECIST v1.1) who experienced progression on or after 1 line of anti–PD-1/PD-L1 therapy as monotherapy or combined with other agents, with the immediately preceding line of treatment an anti–PD-1/PD-L1 therapy, will be enrolled. Progression is defined as received ≥2 doses of an anti–PD-1/PD-L1 agent and having demonstrated radiographic disease progression (per investigator). Other key eligibility criteria: ≤3 prior systemic regimens and a Karnofsky Performance Status Scale score ≥70%. Patients who previously received belzutifan or another HIF-2α inhibitor; require supplemental oxygen; have a baseline hemoglobin level &lt;10 g/dL; have a history of HIV, hepatitis B, or hepatitis C infection; or have active central nervous system metastases are excluded. Patients will be stratified by International mRCC Database Consortium prognostic scores (0, 1 or 2, or 3–6) and by number of prior tyrosine kinase inhibitor–containing therapies (0, 1, or 2 or 3). Treatment will continue until progression, unacceptable toxicity, or withdrawal of consent. Computed tomography or magnetic resonance imaging will be performed at baseline, every 8 weeks through week 49, and every 12 weeks thereafter. Adverse events will be monitored throughout the study and for 30 days after treatment (90 days for serious adverse events). The primary end point is objective response rate per RECIST v1.1 by blinded independent central review (BICR). Secondary end points are progression-free survival, duration of response, and clinical benefit rate per RECIST v1.1 by BICR, overall survival, pharmacokinetics, and safety. The study will enroll patients in at least 9 countries (Australia, Belgium, Greece, Ireland, Israel, Netherlands, Russia, the United Kingdom, and the United States) and is recruiting.AcknowledgementsMedical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp &amp; Dohme Corp., a subsidiary of Merck &amp; Co., Inc., Kenilworth, NJ, USA. Funding for this research was provided by Merck Sharp &amp; Dohme Corp., a subsidiary of Merck &amp; Co., Inc., Kenilworth, NJ, USA.Trial RegistrationClinicaltrials.gov, NCT04489771Ethics ApprovalThe study and the protocol were approved by the Institutional Review Board or ethics committee at each site.

417 Phase 3 study of pembrolizumab + belzutifan + lenvatinib or pembrolizumab/quavonlimab + lenvatinib versus pembrolizumab + lenvatinib as first-line treatment for advanced renal cell carcinoma

BackgroundPembrolizumab + vascular endothelial growth factor (VEGF) inhibitor lenvatinib demonstrated antitumor activity as first-line treatment for advanced clear cell renal cell carcinoma (ccRCC) in phase 3 trial KEYNOTE-581/CLEAR (NCT02811861). Hypoxia-inducible factor 2α (HIF-2α) inhibitor belzutifan (MK-6482) showed antitumor activity in ccRCC, and a coformulation of pembrolizumab and CTLA-4 inhibitor quavonlimab (MK-1308A) showed antitumor activity in non–small cell lung cancer. HIF-2α or CTLA-4 inhibition with PD-1 and VEGF inhibition backbone combination may provide additional benefit as first-line treatment in ccRCC. This open-label, randomized, phase 3 study (NCT04736706) will be conducted to compare novel combination therapies pembrolizumab + belzutifan + lenvatinib (arm A) and MK-1308A + lenvatinib (arm B) with pembrolizumab + lenvatinib (arm C).MethodsApproximately 1431 adults with metastatic ccRCC, measurable disease per RECIST v1.1, and Karnofsky Performance Status Scale score ≥70% who had not previously undergone systemic therapy for advanced ccRCC will be enrolled. Patients will be randomly assigned 1:1:1 to arm A (belzutifan 120 mg + lenvatinib 20 mg oral once daily + pembrolizumab 400 mg IV every 6 weeks), arm B (MK-1308A [quavonlimab 25 mg + pembrolizumab 400 mg] IV every 6 weeks and lenvatinib 20 mg oral once daily), or arm C (pembrolizumab 400 mg IV every 6 weeks + lenvatinib 20 mg oral once daily). Treatment will continue until documented disease progression, withdrawal of consent, or other discontinuation event; patients will receive pembrolizumab and MK-1308A for up to 18 cycles (approximately 2 years). Patients will be stratified by International mRCC Database Consortium (IMDC) score (favorable vs intermediate vs poor), region of the world (North America vs Western Europe vs rest of the world), and sarcomatoid features (yes vs no). Response will be assessed by CT or MRI per RECIST v1.1 by blinded independent central review (BICR) at week 12 from randomization, every 6 weeks through week 78, and every 12 weeks thereafter. Adverse events and serious adverse events will be monitored throughout the study and for 90 days after treatment. Dual primary end points are progression-free survival per RECIST v1.1 by BICR and overall survival. Primary end points will be assessed in arm A compared with arm C and in arm B compared with arm C for patients with IMDC intermediate/poor status and in all patients regardless of IMDC status. Secondary end points are objective response rate and duration of response per RECIST v1.1 by BICR, patient-reported outcomes, and safety.AcknowledgementsMedical writing and/or editorial assistance was provided by Matthew Grzywacz, PhD, of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp &amp; Dohme Corp., a subsidiary of Merck &amp; Co., Inc., Kenilworth, NJ, USA, and Eisai Inc., Woodcliff Lake, NJ, USA. Funding for this research was provided by Merck Sharp &amp; Dohme Corp., a subsidiary of Merck &amp; Co., Inc., Kenilworth, NJ, USA,Eisai Inc., Woodcliff Lake, NJ, USA.Trial RegistrationClinicaltrials.gov, NCT04736706Ethics ApprovalThe study and the protocol were approved by the Institutional Review Board or ethics committee at each site.

Cement-Augmented Carbon Fiber–Reinforced Pedicle Screw Instrumentation for Spinal Metastases: Safety and Efficacy

To investigate the complication rates and long-term implant failure rates in a monocentric study of a consecutive cohort of patients with thoracolumbar spinal metastases after posterior instrumentation with a fenestrated carbon fiber-reinforced poly-ether-ether-ketone (CFRP) pedicle screw system. We retrospectively reviewed demographics, Karnofsky Performance Status Scale scores, complications, and implant failure rates. Between June 2016 and November 2019, 51 consecutive patients underwent cement-augmented CFRP pedicle screw instrumentation at our institution. Mean age was 68 years (standard deviation 10.5), the median preoperative Karnofsky Performance Status Scale of 80 increased to 90 postoperatively (P= 0.471). Most common primary entities were breast (25.5%), lung (15.7%), and prostate (13.7%) cancers. Of 428 placed screws, 293 (68.5%) were augmented with polymethylmethacrylate, a mean 6 per patient (standard deviation ±2). Screws were inserted via a minimally invasive system technique in 54.9% of cases. In total, 11.8% of patients had immediate postoperative sequelae related to the cement. Pulmonary cement embolisms were noted in 3 patients, 2 had paravertebral extravasation, and 1 had an embolism into a segmental artery. Of these 6, 2 patients with pulmonary embolisms reported related symptoms. Follow-up was available for 80.4%. After a mean 9.8 months, screw loosening was noted in 11.8% of cases on computed tomography, although it was asymptomatic in all but 1 patient. Screw pull-out did not occur. Neither cement-related (P= 0.353) nor general complication rates (P= 0.507) differed significantly between open and minimally invasive system techniques. Percutaneous cement-augmented CFRP pedicle screw instrumentation facilitates artifact-reduced postoperative imaging, while maintaining a risk profile and implant failure rates comparable to conventional metallic instrumentation.

Post-Transplantation Cyclophosphamide and Short-Term Methotrexate for Tolerance Induction in HLA-Haploidentical Transplantation for Severe Aplastic Anemia

Background. Haploidentical related donors (HIDs) are attractive donors for patients with severe aplastic anemia (SAA) because they are readily available for nearly all the patients. Bone marrow transplant (BMT) using post-transplant cyclophosphamide (PTCy) has been shown effective to cross the immune barriers between the recipients and their HIDs. Short-term low dose of methotrexate (ST-MTX) has long been adopted either alone or combined with calcineurin inhibitors to get across the immune barrier in hematopoietic stem cell transplant (HSCT).Aim of the study. We presented the outcome of 15 patients with SAA who underwent haploidentical transplant (HIT) using T-cell-replete peripheral graft and combination of PTCy with ST-MTX.Patients and grafts. We analyzed the medical records of 15 patients with SAA between Jan 2015 and July 2017. The transplants were either upfront (8/15) or rescue treatment (7/15). The median age of the patients was 16 (range 5-39) years and 66.7% (10/15) were male. All the patients received granulocyte colony-stimulating factor (G-CSF) mobilized peripheral graft from haploidentical related donors. The median mononuclear cells (MNCs) was 12.4 × 108 cells/kg recipient ideal body weight (IBW) with the range of (7.0-22.0) × 108 cells/kg, the CD34+ cell was 7.5 × 106 cells/kg with the range of (5-23) × 106 cells/kg and the CD3+ cells was 2.7 × 108 cells/kg with the range of (1.8-5.0) × 108 cells/kg.Conditioning regimen and GvHD prophylaxis. We used a TBI-free transplantation platform named FBC+PTCy/ST-MTX. Fludarabine was administered at 40 mg/m2 IV daily for 5 days. Busulfan was delivered in a total dose of 6.4mg/kg. Cyclophosphamide was given 14.5 mg/kg daily for 2 days. PTCy was administered at 60mg/kg/day IV on days +3 and +4 post-transplant. Low doses of MTX were delivered on days +1, +2 and +5 post-transplant at 15mg/m2, 10mg/m2 and 10mg/m2. Cyclosporine was given from day +6 through day +180 with the target through level 150~180ng/ml and then was tapered until 12 months post transplant. Mycophenolate mofetil (MMF) was given from day +6 to +35 days for the first 3 patients and then was eliminated for the following patients.Results.Neither primary nor secondary graft failure (GF) was seen in this study. Neutrophil engrafted at 15 days (range, 13-18 days). Platelets engrafted at 19 days (range, 14-36 days) and recovered over 100 × 109/L at 38 days (range, 14-77 days). The time to total lymphocytes recovery over 0.5 × 109/L for 3 consecutive days was 34 days (range, 25-72 days). The accumulated engraftment of neutrophil and platelets were both 100% at +40 days. (Figure 1-A, B.)The cumulative incidence of aGvHD at 100 days was 20.0%(3/15). Two patients had grade I skin aGvHD and the other one had grade II skin aGvHD. No grade III-IV aGvHD was seen. 12 patients were evaluable for the incidence of cGvHD and none of them developed moderate or sever cGvHD with a median of 150 (102-806) days post transplant. (Figure 1-C, D.) During the follow-up, one patients had skin cGvHD and received systemic therapy with corticoid. The treatment was discontinued after 8 months post transplant. All 3 patients, who survived beyond 12 months post transplant at the end of our follow-up, were off immunosuppress.With a median follow-up of 230 days (range 41-806 days), all the patients are alive. They are transfusion independent with karnofsky performance status scale (KPS) scores 100.Conclusion.This study shows that haploidentical related transplant can be successfully applied using T-cell-repleted peripheral grafts. ST-MTX may facilitate PTCy to achieve a stable engraftment with a minimal risk of GvHD in HIT for patients with SAA. Our approach should expand the donor pool for patients with SAA. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Dose and Volume De-Escalation for Human Papillomavirus–Positive Oropharyngeal Cancer is Associated with Favorable Posttreatment Functional Outcomes

To report functional outcomes for patients with human papillomavirus-positive oropharyngeal cancer treated on a phase 2 protocol of risk- and induction chemotherapy response-adapted dose and volume de-escalated radiation therapy (RT)/chemoradiation (CRT). Patients were stratified as low risk (LR) or high risk (HR) according to T/N-stage and smoking history. Induction chemotherapy was followed by radiographic response assessment. LR patients with ≥50% response received 50 Gy RT (RT50), whereas LR patients with 30% to 50% response or HR patients with ≥50% response received 45 Gy CRT (CRT45). All other patients received 75 Gy CRT (CRT75) with RT limited to the first echelon of uninvolved nodes. Pre- and post-RT/CRT modified barium swallow studies were performed. Percutaneous endoscopic gastrostomy (PEG) tube placement, body mass index (BMI), and narcotic use were recorded. Statistical comparisons used linear or logistic regression, the Mann-Whitney U test, the χ2 test, or Fisher's exact test as appropriate. Twenty-eight LR and 34 HR patients were enrolled; 49 completed RT50/CRT45 and 11 completed CRT75. PEG-tube dependency at the end of RT/CRT and 3 months post-RT/CRT significantly differed according to risk and treatment groups (all P < .05). Treatment intensity was independently associated with 3-month PEG status while adjusting for risk group (P = .002). The CRT75 group had a median -8.42% change from baseline BMI at 1 year post-RT/CRT versus -2.54% for the RT50/CRT45 group (P = .01). At the end of RT/CRT, CRT75 patients were less likely to tolerate a normal diet, more likely to have swallowing performance status scale scores ≥4, more likely to have Rosenbek's penetration-aspiration scores ≥7, more likely to have developed trismus, and more likely to require narcotics >2 months (all P < .05). Induction chemotherapy followed by risk- and response-adapted dose and volume de-escalated RT/CRT is associated with clinically meaningful functional outcomes including (1) improved swallowing function, (2) higher BMI, and (3) shorter narcotic use for patients receiving de-escalation.

Evaluation of the Prognosis of Neuroglioma Based on Dynamic Magnetic Resonance Enhancement

This paper explores the diagnostic value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for the prognosis of glioma, and judges the relevant factors affecting the prognosis of glioma. This paper used a Cox proportional hazards model to retrospectively analyze clinical data of 81 patients with complete neuroglioma from the same neurosurgery medical team from January 2012 to November 2018, including DCE-MRI data. To determine the prognostic factors, P < 0.05 was used as the statistical standard, and the survival curve of statistically significant factors was drawn by Kaplan-Meier method. The Cox proportional hazard model analysis showed the preoperative Karnofsky Performance Status Scale (KPS) score, age, tumor pathologic grade, postoperative radiotherapy, temozolomide use, and Ki-67 expression had an impact on the prognosis of patients with neuroglioma. Multivariate analysis and DCE-MRI data showed that age, tumor grade, preoperative KPS score, postoperative radiotherapy, and Ki-67 expression were prognostic factors for patients with glioma. The older the age, the higher the pathologic grade, the higher the Ki-67 expression level, and the lower the KPS score before surgery, the worse the prognosis. Postoperative radiotherapy and appropriate temozolomide chemotherapy will help improve the prognosis of patients with neuroglioma.

Adjuvant therapy of moxibustion combined with Wenyang Lishui formula for peritoneal effusion of ovarian malignant tumors

To observe the clinical efficacy of adjuvant therapy of moxibustion combined with Wenyang Lishui formula for peritoneal effusion of ovarian malignant tumors. Sixty patients with peritoneal effusion of ovarian malignant tumors were randomly divided into an observation group and a control group, 30 cases in each group. The patients in the control group were treated with intravenous infusion of paclitaxel liposome at the first day and cisplatin at the 2nd to 4th day, 21 days as a course of treatment, and 4 courses were given. Based on the treatment of the control group, the patients in the observation group were treated by moxibustion combined with Wenyang Lishui formula. Moxibustion was applied at Mingmen (GV 4), Pishu (BL 20), Shenshu (BL 23), Shenque (CV 8), Guanyuan (CV 4), Zigong (EX-CA 1), Zhongwan (CV 12), Shuifen (CV 9), Qihai (CV 6) and Zhongji (CV 3), each acupoint for 30 min, once a day for 12 weeks. Wenyang Lishui formula was taken twice orally, one dose a day, 2 weeks as a course of treatment, and 6 courses were given. The levels of , , and / in peripheral blood were measured before and after 12-week treatment in the two groups. The changes of peritoneal effusion volume and Karnofsky performance status scale (KPS) score before and after treatment were compared between the two groups, and the clinical efficacy of the two groups was evaluated. The symptom improvement rate was 96.7% (29/30) and overall effective rate was 86.7% (26/30) in the observation group, which were significantly superior to those in the control group [80.0% (24/30) and 56.7% (17/30), P<0.05]. After treatment, the levels of , and / in peripheral blood were significantly increased in the observation group (P<0.01), there was no significant difference in the control group before and after treatment (P>0.05), and the increase in the observation group was significantly higher than that in the control group (P<0.05). After treatment, the volume of peritoneal effusion in the two groups was decreased (P<0.01), and the reduced volume in the observation group was higher than that in the control group (P<0.05). After treatment, KPS scores were increased significantly in both two groups (P<0.01), and the increase in the observation group was higher than that in the control group (P<0.05). The incidence rate of adverse reactions in the observation group was lower than that in the control group [23.3% (7/30) vs 53.3% (16/30), P<0.05]. Moxibustion combined with Wenyang Lishui formula could effectively improve the immune function, reduce the volume of peritoneal effusion, improve the symptom improvement rate, overall effective rate and the quality of life, and reduce the incidence of adverse reactions in chemotherapy of patients with peritoneal effusion of ovarian malignant tumors.