Eastern Cooperative Oncology Group Score Research Articles

Adverse drug reactions to the three doses of the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) mRNA-1273 vaccine in a cohort of cancer patients under active treatment of a tertiary hospital in Madrid, Spain

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines efficacy and safety have been tested in phase 3 studies in which cancer patients were not included or were underrepresented. Methods: The objective of this study is to evaluate the safety profile of the mRNA-1273 vaccine across cancer patients and its relationship to patients' demographics. We selected from our records all 18-years or older solid cancer patients under active treatment vaccinated with the complete three-dose schedule mRNA-1273 vaccine whose adverse drug reactions (ADRs) after each dose were recorded. Medical records were reviewed retrospectively to collect data between April 19, 2021, and December 31, 2021. Patients with documented previous infection by SARS-Cov-2 were excluded. Results: A total of 93 patients met the inclusion criteria. Local ADRs were reported more frequently after the first and second dose than after the third (41.9%, 43% and 31.1% of the patients respectively), while systemic ADRs followed the opposite pattern (16.1%, 34.4% and 52.6% of the patients respectively). We found a statistically significant association between sex and systemic adverse reactions after the third dose, p < 0.001 and between systemic adverse reactions after the second dose and systemic adverse reactions after the third dose, p = 0.001 A significant linear trend, p = 0.012, with a higher Eastern Cooperative Oncology Group (ECOG) score associated with a lower proportion of patients suffering from systemic side effects was found. Women had 5.79 times higher odds to exhibit systemic ADRs after the third dose (p=0.01) compared to males. Increasing age was associated with a decreased likelihood of exhibiting ADRs (p=0.016). Conclusion:The mRNA-1273 vaccine shows a tolerable safety profile. The likelihood of ADRs appears to be associated with gender and age. Its association with ECOG scores is less evident. Further studies are needed to elucidate this data in cancer patients.

Comprehensive assessment of quality of life in patients during neoadjuvant chemotherapy

Relevance. Advances in cancer treatment over the past decades have improved long-term patient survival, but increased the incidence of chemotherapy-associated cardiotoxicity (CTA). The study of quality of life (QOL) indicators is becoming an important and integral subject of management for patients receiving high doses of anticancer therapy. In particular, CTA carries a high burden on the healthcare system and the habitual lifestyle of patients due to a decrease in the functional ability of the body. Due to the increase in the life expectancy of patients with oncological diseases, the issues of maintaining a high QoL are becoming increasingly important. The aim of the study was to conduct a comprehensive assessment of QoL in patients during neoadjuvant chemotherapy. Materials and methods. The study included 72 patients with breast cancer who underwent a comprehensive assessment of the cardiovascular system at the National Medical Research Centre for Cardiovascular Surgery n. a. A. N. Bakoulev as a continuous cardiac monitoring during neoadjuvant chemotherapy. To assess the QoL, all patients filled out a standardized questionnaire SF-36, EQ-5D-5L, as well as indicators according to the international Karnovsky and ECOG (Eastern Cooperative Oncology Group) scales. The possible relationship between various indicators of the questionnaire with internationally validated scales, as well as data on the clinical status of patients, were studied. Results. Significant deterioration in the quality of life of patients receiving neoadjuvant chemotherapy was observed in all analyzed parameters: SF-36, Karnovsky scale, ECOG and EQ 5D-5L decreased sharply, the prevalence of general weakness, shortness of breath and decreased exercise tolerance increased. According to the SF-36, initially low rates were observed in a large number of patients, respectively, 80 and 82 %, at the intermediate and final stages, almost all patients showed a deterioration in condition compared to the outcome (p = 0.0002–0.0001). Predictors of a pronounced negative deviation of QoL indicators are the presence of initial reduced ECOG and Karnovsky scores, as well as the presence of an initial decrease in exercise tolerance, the presence of weakness and shortness of breath. Conclusion. In the course of continuous cardiac monitoring, we demonstrated a deterioration in all QoL indicators, according to questionnaires and validated international scales during neoadjuvant chemotherapy. The predictors of a pronounced decrease in QoL indicators are the presence of initial reduced ECOG and Karnovsky scale, as well as the presence of an initial decrease in exercise tolerance, the presence of weakness and shortness of breath. The Karnovsky scale and ECOG can be adapted for an objective assessment of QoL indicators during neoadjuvant chemotherapy.

A Comparison Between Neoadjuvant Chemotherapy and Neoadjuvant Chemoradiotherapy in Treating Esophageal Carcinoma: A Study at a Tertiary Care Cancer Center in Suburban India.

Background and objectiveEsophageal carcinoma remains a disease associated with high mortality rates among patients even after receiving treatment. Management with surgery alone offers a five-year survival of only 20%. Hence adjuvant and neoadjuvant therapies were instituted to treat this condition along with surgery. Neoadjuvant chemoradiotherapy (NACRT) followed by surgery is currently the standard of care. Neoadjuvant chemotherapy (NACT) is also recommended by some authors as a method of adequate care. There is a scarcity of studies in the literature comparing NACRT with NACT. In light of this, we employed the criteria of pathological response as a primary endpoint to compare the effectiveness of NACT and NACRT in treating esophageal carcinoma.Materials and methodsA total of 50 patients with esophageal cancer having Eastern Cooperative Oncology Group (ECOG) scores 0-2 with cancer stages cT2-T4a, cN0-N1, and cM0 were enrolled. The patients were further classified into two groups of 25 each. While one group received chemotherapy using inj. paclitaxel and carboplatin (NACT group), the other was managed with inj paclitaxel and carboplatin as well as 42 Gy of fractionated irradiation (NACRT group). Six weeks after the last dose of radiation or three weeks after chemotherapy, they were evaluated and offered transthoracic esophagectomy (TTE).ResultsSquamous cell carcinoma was found in 39 (78%) cases and 11 (22%) cases had adenocarcinoma. Pathologically complete or near-complete responses were seen in 42% of patients in the NACRT group and 22% in the NACT group.ConclusionWhile NACT and NACRT are both effective therapies for esophageal cancers, NACRT offers better tumor regression compared to NACT. Given the higher rates of complete or near-complete response in the NACRT group, NACRT is likely to offer higher overall survival rates than NACT.

The Application of Nimotuzumab Combined With Definitive Chemoradiotherapy Toward the Treatment of Locally Advanced Cervical Esophageal Carcinoma: A Retrospective Study.

ObjectiveTo evaluate the safety and effectiveness of nimotuzumab in combination with chemoradiotherapy for locally advanced cervical esophageal squamous cell carcinoma.MethodsRetrospective analysis was conducted from September 2012 to February 2017 among 50 locoregional-advanced cervical esophageal carcinoma (CEC) patients who received concurrent chemoradiotherapy (CRT) combined with or without nimotuzumab at Ningbo Medical Center Lihuili Hospital. Intensity-modulated radiotherapy (IMRT) was administrated on all patients. All patients were divided into two groups, of which 26 (Group A) received 200 mg (22 of 50) or 400 mg (4 of 50) of nimotuzumab per week with CRT and 24 (Group B) received definitive CRT.ResultsThe median follow-up time was 23 months. The median overall survival (OS) and progression-free survival (PFS) were 40.6 and 21.1 months for all, respectively. The 1-, 2-, and 3-year OS rates on the whole were 79.6%, 62.1%, and 47.8%. There was no statistical difference in overall response rate and disease control rate between the two groups. Patients treated with nimotuzumab (group A) had better PFS than the definitive CRT group (group B) (P < 0.05). However, the median OS was 41.4 months in group A and 32.4 months in group B, respectively (P = 0.517). Multivariate analysis showed that PFS among those with lower Eastern Cooperative Oncology Group (ECOG) score (HR = 5.11; P < 0.01), stage II (HR = 9.52; P < 0.01) and the application of nimotuzumab combined with CRT (HR = 0.16; P < 0.01) was much longer. Furthermore, ECOG, stage, C-reactive protein (CRP) baseline, and histological grade can also be used as independent predictors of OS. Grade >3 adverse reactions were not observed. The most common adverse event related to nimotuzumab was mild fever and the occurrence rate was 19% (5 of 26). The incidence of anemia was 65.4% in group A and 87.5% in group B (P < 0.05).ConclusionsFor locoregional-advanced CEC, nimotuzumab combined with IMRT and concomitant chemotherapy was tolerated and effective. In addition, patients with a normal pretherapeutic serum CRP level (CRP < 10 mg/L) can achieve better OS.

Real-world KINDLE-Latin America subset data on treatment patterns and clinical outcomes in patients with stage III non-small-cell lung cancer.

Stage III non-small-cell lung cancer (NSCLC) management is challenging given the heterogeneous nature of the disease. The LATAM subset of the real-world, global KINDLE study reported the treatment patterns and clinical outcomes for LATAM from the pre-immuno-oncology era. The study was conducted in seven countries (Argentina, Chile, Colombia, Dominican Republic, Mexico, Peru and Uruguay) in stage III NSCLC (American Joint Committee on Cancer, 7th edition) diagnosed between January 2013 and December 2017. Retrospective data from patients' medical records (index date to the end of follow-up) were collected. Summary statistics, Kaplan-Meier survival estimates and a two-sided 95% confidence interval (CI) were provided. Cox proportional hazard model was used for univariate and multi-variate analyses. A total of 231 patients was enrolled, the median age was 65.0 years (range 21.0-89.0), 60.6% were males, 76.6% had smoking history, 64.0% had adenocarcinoma and 28.7% underwent curative resection. Multiple treatment regimens (>25) were used; chemotherapy alone was the most common (24.8%). The overall median progression-free survival (mPFS) and median overall survival (mOS) were 14.8months (95% CI, 12.1-18.6) and 48.6months (95% CI, 34.7 to not calculable). Significantly better mPFS and mOS were observed for stage IIIA with curative surgery and resectable tumours and stage IIIB with an Eastern Cooperative Oncology Group score of 0/1, female gender, resectable tumours, adenocarcinoma and curative surgery (p < 0.05). Results show diversity in treatment practices and the corresponding clinical outcomes in stage III NSCLC. There is a need to streamline treatment selection and sequencing to decrease relapse rates after initial therapy.

A generational comparison for unfavorable cancer of unknown primary in a single institute over 20 years.

The prognosis of unfavorable cancer of unknown primary is extremely poor. This is the first report to compared the treatment results between generations of CUP and examined prognostic factors. This retrospective single-center cohort study enrolled 68 patients with newly diagnosed unfavorable cancer of unknown primary at Taipei Veteran General Hospital from 2017 to 2020 as study cohort and 167 patients from 2000 to 2009 as historical cohort. The median overall survival was 4.3 months in the study cohort (95% CI, 2.7-6.2 months) and 4.5 months in the historical cohort (95% CI, 3.0-5.5 months; p = 0.858). Eleven patients in the study cohort received immunotherapy. The disease control rates were 45%. Multivariate analysis showed that an Eastern Cooperative Oncology Group score > 1 and a C-reactive protein level > 1 correlated with poor survival. A new prognostic stratification model was constructed by using Eastern Cooperative Oncology Group score and C-reactive protein values. The good-, intermediate-, and poor-risk groups had distinct median overall survival of 18.3, 7.0 and 1.2 months, respectively (area under the curve, 0.817; p < 0.001). The outcome of unfavorable cancer of unknown primary has not changed much over the last 20 years. The application of a new prognostic stratification model can further stratify unfavorable cancer of unknown primary.

The role of LENT and PROMISE scores in predicting survival in malignant pleural effusion.

Background:Malignant pleural effusion (MPE) is a condition, that can be seen in 15% of patients diagnosed with cancer. Because of the short overall survival, it is important to identify the appropriate treatment. In addition to the palliation of secondary symptoms due to MPE, it should also be decided in which cases a more aggressive treatment is to be followed. The purpose of the study was to evaluate the performance of LENT and clinical PROMISE scores in predicting survival in patients with MPEMethods:Age, sex, smoking history, Eastern Cooperative Oncology Group (ECOG) score, cancer type, history of chemotherapy/radiotherapy, laboratory values, and pleural fluid lactate dehydrogenase were recorded. The LENT and the PROMISE scores were calculated and risk categories were determined. During the follow-up, blood tests and tomography controls were performed on the patients as routine. The overall survival was calculated as the period from the date of diagnosis of MPE to death or until December 31, 2019Results:A total of 169 patients were included. The median age was 65 (26–86). In the single-variable analysis, there was a significant increase in mortality risk in the poor performance score and if the LENT risk group progressed from the low-to medium-/high-risk group or PROMISE categories A to B, A to C or A to D. In multivariate analysis, mortality risk in 1, 3, 6, and 12 months increased significantly in poor performance score, in PROMISE category B, C, and D. In high LENT risk-group, an increased mortality risk was shown in only 12 months of survivalConclusions:Our data show that poor performance score (ECOG 3-4), PROMISE category B, C, and D significantly increase mortality risk and the LENT score is inadequate in predicting survival.

Prevalence of constipation in patients undergoing chemotherapy and the effect of constipation on quality of life.

This study was conducted as a descriptive and cross-sectional study to determine the prevalence of constipation and the impact of constipation on quality of life in patients receiving outpatient chemotherapy. The data of the study were collected from 252 patients who applied to the outpatient chemotherapy unit of a university hospital between January 2021 and March 2021. The data were collected using the "Patient Information Form," "Eastern Cooperative Oncology Group (ECOG) Performance Status Scale," "Constipation Severity Scale (CSS)," "Patient Assessment of Constipation Quality of Life Questionnaire (PAC-QOL)," and "The Bristol Stool Form Scale" through face-to-face interview technique. In the analysis of data, numbers, percentile distributions, minimum and maximum values, mean values, and standard deviations, as well as t-test, were used in the comparison of paired groups in normally distributed measurements, while the analysis of variance (ANOVA) was used in the comparison of more than two groups. The constipation prevalence of the patients included in the study was 31.7% and the mean constipation severity score was 30.48 ± 13.87. It was found that the quality of life of the patients due to constipation was (71.79 ± 18.74) impacted adversely on a moderate level. A significant difference was found between sex, educational status, use of antiemetic and antiulcer medication, presence of hemorrhoid disease, ECOG score, appetite, and mean CSS and PAC-QOL scores (p < 0.05). Constipation occurs in one-third of cancer patients receiving ambulatory chemotherapy. The severity of constipation in patients is at a moderate level and it impacts the quality of life moderately.

A predictive model based on liquid biopsy for non-small cell lung cancer to assess patient’s prognosis: Development and application

Background and objectiveImproving ability to predict the prognosis of patients with progressive lung cancer is an important task in the era of precision medicine. Here, a predictive model based on liquid biopsy for non-small cell lung cancer (NSCLC) was established to improve prognosis prediction in patients with progressive NSCLC. MethodsClinical data and blood samples of 500 eligible patients were collected and screened from the electronic case database and blood sample center of Hwa Mei Hospital, University of Chinese Academy of Sciences and Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences. Patients were randomly assigned to training set (300 cases) and validation set (200 cases) in a ratio of 3:2 by random number method. Baseline levels of the two datasets were compared. Progression-free survival (PFS) analysis was performed on the training set using Kaplan-Meier method. The independent prognostic factors affecting patients’ PFS were determined by multivariate Cox regression analysis. The prognosis predictive model of patients was constructed by using the nomogram. Calibration curve and C-index were used to evaluate the accuracy of the prognosis predictive model in both internal and external validations. ResultsIn training set, the age distribution of patients was 59.00 (46.00, 71.00) years, including 137 (45.7 %) females and 163 (54.3 %) males, 198 cases (66.0 %) with Eastern Cooperative Oncology Group (ECOG) score 0–1, and 102 cases (34.0 %) with ECOG score 2. In verification set, the age distribution of patients was 60.00 (48.25, 73.00) years, including 92 females (46.0 %) and 108 males (54.0 %), 130 cases (65.0%) with ECOG score 0–1, and 70 cases (35.0 %) with ECOG score 2. Patients in training set showed PFS differences stratified by gene mutation type (p < 0.0001), differentiation degree (p < 0.0001), circulating tumor cell (CTC) content (p = 0.00026), and brain metastasis (p < 0.0001). Besides, multivariate Cox regression analysis indicated that gene mutation type, differentiation degree, CTC content (p = 0.002), and brain metastasis (p = 0.005) are independent prognostic factors for PFS. These factors were included in the nomogram parameters, and both internally validated calibration curve (C-index = 0.672) and externally validated calibration curve (C-index = 0.657), showing good predictive performance of the model. ConclusionThe predictive model has a good predictive ability for prognosis of patients with progressive NSCLC. Notably, the differentiation degree and CTC content are both impact factors for PFS of patients, and the performance of these indicators in predicting the survival of patients with progressive NSCLC needs to be clarified in the future.

Vacuum sealing drainage combined with naso-intestinal and gastric decompression tubes for the treatment of esophagogastrostomy neck fistula

ObjectiveTo evaluate the clinical results of the vacuum sealing drainage (VSD) combined with a naso-intestinal nutritional tube (NIT) and a gastric decompression tube (GDT) for the treatment of esophagogastrostomy neck fistula (ENF).MethodsFrom January 2018 to October 2020, twenty patients (13 men and 7 women, ages 46–72) with ENF secondary to esophagogastrostomy were treated with VSD combined with NIT and GDT. Technical and clinical success rates, the incidence of early/late complications, the time of fistula closure (TFC) and therapy-related indicators were analyzed. The Karnofsky score and Eastern Cooperative Oncology Group (ECOG) score were compared before and after triple treatment.ResultsTechnical and clinical success rates were 100% and 85%, respectively. Early complications occurred in 5/20 (25%) patients, and late complications occurred in 8/20 (40%) patients. The median TFC was 18 days (range 10–23). All therapy-related indicators were normalized posttreatment. The Karnofsky score and ECOG score after treatment were significantly different compared with pretreatment scores (p < 0.001).ConclusionVSD combined with NIT and GDT is a safe and effective strategy for ENF, while severe strictures warrant further research.

Radical Nephroureterectomy Tetrafecta: A Proposal Reporting Surgical Strategy Quality at Surgery

BackgroundStandardized methods for reporting surgical quality have been described for all the major urological procedures apart from radical nephroureterectomy (RNU). ObjectiveTo propose a tetrafecta criterion for assessing the quality of RNU based on a consensus panel within the Young Association of Urology (YAU) Urothelial Group, and to test the impact of this tetrafecta in a multicenter, large contemporary cohort of patients treated with RNU for upper tract urothelial carcinoma (UTUC). Design, setting, and participantsThis was a retrospective analysis of 1765 patients with UTUC treated between 2000 and 2021. Outcome measurements and statistical analysisWe interviewed the YAU Urothelial Group to propose and score a list of items to be included in the “RNU-fecta.” A ranking was generated for the criteria with the highest sum score. These criteria were applied to a large multicenter cohort of patients. Kaplan-Meier curves were built to evaluate differences in overall survival (OS) rates between groups, and a multivariable logistic regression model was used to find the predictors of achieving the RNU tetrafecta. Results and limitationsThe criteria with the highest score included three surgical items such as negative soft tissue surgical margins, bladder cuff excision, lymph node dissection according to guideline recommendations, and one oncological item defined by the absence of any recurrence in ≤12 mo. These items formed the RNU tetrafecta. Within a median follow-up of 30 mo, 52.6% of patients achieved the RNU tetrafecta. The 5-yr OS rates were significantly higher for patients achieving tetrafecta than for their counterparts (76% vs 51%). Younger age, lower body mass index, and robotic approach were found to be independent predictors of tetrafecta achievement. Conversely, a higher Eastern Cooperative Oncology Group score, higher clinical stage, and bladder cancer history were inversely associated with tetrafecta. ConclusionsHerein, we present a “tetrafecta” composite endpoint that may serve as a potential tool to assess the overall quality of the RNU procedure. Pending external validation, this tool could allow a comparison between surgical series and may be useful for assessing the learning curve of the procedure as well as for evaluating the impact of new technologies in the field. Patient summaryIn this study, a tetrafecta criterion was developed for assessing the surgical quality of radical nephroureterectomy in patients with upper tract urothelial carcinoma. Patients who achieved tetrafecta had higher 5-yr overall survival rates than those who did not.

The effect of demographic features on survival in patients with gastric cancer

Aim: This study aimed to investigate the relationship between some demographic and clinical factors and survival in patients with gastric cancer. Materials and Methods: We retrospectively evaluated the records of 252 gastric cancer patients followed up in the medical oncology department between 01.01.2016 and 10.01.2020. Gastric lymphoma, gastrointestinal stromal tumor, and neuroendocrine tumor were excluded. Factors evaluated in the study included age, sex, urban/non-urban residence, admitting complaints, smoking history, Eastern Cooperative Oncology Group (ECOG) score, stage at diagnosis, histological subtype, surgical history, tumor location, grade, diameter and macroscopic view of tumor, metastatic lymph node ratio, chemotherapy regimens, febrile neutropenia, post-chemotherapy radiological reports, chemoradiotherapy (CRT) history and survival after diagnosis. Results: Mean overall survival (OS) time was significantly shorter in patients with weight loss (p&amp;lt;0.001), high ECOG score (p&amp;lt;0.001), radiological progression (p&amp;lt;0.001), advanced cancer stage (p&amp;lt;0.001) and tumor grade (p=0.024). Mean OS was longer in patients who received chemotherapy compared to those who did not at stage 4 (p&amp;lt;0.001). Mean OS was significantly longer in patients who underwent gastrectomy and received adjuvant CRT compared to those who did not (p&amp;lt;0.001). Mean OS was shorter in patients with a metastatic lymph node ratio over 30% (p&amp;lt;0.001) and those with tumor diameter larger than 3 cm (p=0.02). Conclusion: In this study, survival time was associated with advanced stage, ECOG score, weight loss, radiological progression, high tumor grade, history of gastrectomy and adjuvant CRT, metastatic lymph node ratio &amp;gt;30%, tumor diameter &amp;gt;3 cm and presence of palliative chemotherapy in terminal patients.

Does the Combined Use of Aspirin and Immunotherapy Result in Better Outcomes in Non-Small Cell Lung Cancer Than Immunotherapy Alone?

Introduction: Immunotherapy works by stimulating the immune system against cancer cells. Resistance to immunotherapy represents a significant challenge in the field of medical oncology. The mechanisms by which cancer cells evade immunotherapy are not well understood. Prior research suggested overexpression of prostaglandin E-2 (PGE-2) by cancer cells, which bind to EP-2 and EP-4 receptors on the tumor-specific cytotoxic T-lymphocytes (CTLs) and suppress their anticancer role. This immunosuppressive effect is involved in evading the programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade of immunotherapy, which fuels cancer cell growth and recurrence. Studies found that combining PGE-2 blockade and a PD-1 signaling inhibitor helped promote the anticancer immunity cells. If confirmed in a clinical setting, the above in vitro findings could be of great clinical significance.Methods: Given that aspirin (ASA) blocks PGE-2 production, this work aimed to evaluate whether ASA use with immunotherapy results in better outcomes than immunotherapy alone. We performed a retrospective chart review of 500 non-small cell lung cancer (NSCLC) patients aged 21 years or older treated with PD-1 and/or PD-L1 directed immunotherapy at St. Luke’s University Health Network between July 2015 and July 2021. Relevant patient, disease, and treatment-related variables were collected, including ASA use (≥ 81 mg daily) and the type of immunotherapy. Bivariate analyses were conducted to determine which variables to include in a multivariable model. The four primary outcomes included survival at 18-months, both after diagnosis and starting immunotherapy, achieving complete remission (CR), and having a progressive disease (PD), as defined by RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Secondary outcomes included therapy-related toxicities and complications in the different treatment groups. Results: After bivariate analysis, no statistical significance was found for a difference in 18-month survival between ASA and non-ASA groups (50.3% vs 49.7%, p-value = 0.79). ASA with PD-L1 inhibitor showed a trend towards a higher likelihood of achieving CR [adjusted odds ratio (AOR) 1.85] with a p-value close to statistical significance (0.06). However, ASA with PD-L1 showed high statistical significance as an independent variable associated with a decreased likelihood of having PD (AOR 0.44, p < 0.001). These findings suggest that NSCLC patients receiving PD-L1 inhibitors could benefit more from daily ASA than patients treated with PD-1 inhibitors. Our study emphasizes using the Eastern Cooperative Oncology Group (ECOG) scoring of the performance status (PS) in NSCLC patients. Poorer PS was associated with lower survival, decreased likelihood of CR, and more PD. Other variables associated with worse outcomes were advanced cancer stage at diagnosis and male gender. Low-PD-L1 expression in NSCLC was associated with an increased likelihood of survival; this could be of clinical significance, especially with previous studies suggesting better outcomes of using ASA in PD-L1 low tumors. Conclusion: These findings suggest that daily ASA use with PD-L1 inhibitors is associated with more favorable outcomes in NSCLC. More studies are needed to investigate further the potential benefits vs. risks of using ASA with different immunotherapies and the other possible variables affecting treatment outcomes.

Sequential Geriatric Assessment in Older Patients with Colorectal Cancer during Chemotherapy: Subgroup Analysis of a Prospective, Multicenter Study EpiReal 75

Introduction: Colorectal cancer (CRC) is a disease of older patients, but evidence-based guidelines for chemotherapy in older patients are scarce. Geriatric assessment (GA) evaluates a patient’s functional status (FS) and helps in decision-making when choosing chemotherapy for older patients. However, the change of FS during chemotherapy is rarely studied as GA is mostly performed once instead of sequentially. Methods: We performed a subgroup analysis of a prospective, multicenter study EpiReal 75. Patients aged ≥75 years with gastrointestinal malignancy prior to initiation of chemotherapy or receiving palliative chemotherapy were screened. We defined geriatric core assessments including the Eastern Cooperative Oncology Group score, Barthel’s activities of daily living (ADL) scale, Lawton’s instrumental activities of daily living (IADL) scale, and G-8 questionnaire, which were performed at baseline and repeated every 3 months. Quality of life (QoL) assessed by QLQ-C30 questionnaire was also re-evaluated every 3 months. We defined any deterioration in any of the geriatric parameters as unstable in the corresponding function. Results: 28 patients with CRC were enrolled between April 2014 and December 2018. 20 patients were evaluable for statistical analysis with a mean age of 78.5 years (range, 75–88). Most patients received chemotherapy in palliative setting. During 3 months of chemotherapy, 25% of patients became more dependent as measured by ADL or IADL. During a median follow-up of 15 months, patients with unstable ADL or IADL had a significantly shorter overall survival (OS) than those with stable ADL or IADL (p_logrank = 0.0055 and 0.0253, respectively), without a significant difference in progression-free survival (PFS). Also, unstable IADL correlated with a deterioration in aspects of QoL such as role functioning and emotional functioning (p = 0.0189 and 0.0239, respectively). 20% of patients experienced treatment-related grade 3 adverse events (AEs), no grade 4–5 AEs occurred. Conclusion: Sequential GA revealed changes in FS in older patients with CRC receiving chemotherapy. A deterioration of FS during chemotherapy did not influence PFS but had a negative impact on OS and QoL. It is therefore important to maintain FS in older patients with cancer, and regular performance of geriatric core assessments should be encouraged in the clinical practice.

Comparison of Pneumonitis Rates and Severity in Patients With Lung Cancer Treated by Immunotherapy, Radiotherapy, and Immunoradiotherapy.

IntroductionRadiation pneumonitis (RP) is a common dose-limiting toxicity of radiotherapy to the chest in lung cancer patients. Similarly, the revolutionary use of immune checkpoint inhibitors (ICIs) to treat lung cancer can be complicated by immune-related adverse events (irAEs), particularly checkpoint inhibitor pneumonitis (CIP). Our study aimed to assess the effect of immunotherapy, with and without radiotherapy, on pneumonitis and other outcomes.MethodsWe performed a retrospective chart review of 680 lung cancer patients treated with either radiotherapy, immunotherapy, or both at St. Luke's University Health Network to determine the incidence rates of pneumonitis. Then, a more extensive review of 346 patients was completed, 181 of whom had pneumonitis, to investigate risk factors and outcomes.ResultsAll-grade pneumonitis incidence was 26.6% while more severe pneumonitis (grade 3 or higher) was 13%. Receiving programmed cell death-1 (PD-1) or ligand-1 (PD-L1) inhibitors, having squamous cell carcinoma (SCC), and having poorer performance status were independently and significantly associated with increased risk of pneumonitis, with AOR (adjusted odds ratios) of 8.32, 4.10, 2.91, and 1.71, respectively. Among those who had pneumonitis, more severe cases (grade 3 or higher) were related to immunotherapy, either alone (58.32%) or with radiation (55.7%), compared to radiation therapy alone (36.2%).Poorer performance status (defined as a higher Eastern Cooperative Oncology Group (ECOG) score) was the only covariate we found to be significantly and independently associated with reduced odds of 18-months survival. More of the patients treated with both lung radiation and immunotherapy had progressive disease (53.8%) compared to those treated with only radiation (30.4%) or immunotherapy (36.7). Progressive disease occurred more in patients with pneumonitis grade 3 or higher (48.3%) than those with no or low-grade pneumonitis (27.2%).ConclusionReceiving PD-L1 and PD-1 inhibitors, either with or without radiotherapy, was associated with a higher risk of more severe pneumonitis (PD-L1 > PD-1) than radiotherapy alone. Given its high incidence and complications, more about therapy-induced pneumonitis is yet to be studied. Learning more about pneumonitis' risk factors and complications is of great clinical importance, as it may result in better treatment planning and improved outcomes. Future studies are needed to investigate the suggested association between symptomatic pneumonitis and poorer response to treatment and whether SCC increases the risk of higher-grade pneumonitis.

Progression-Free Survival and Local Control After SABR for up to 5 Oligometastases: An Analysis From the Population-Based Phase 2 SABR-5 Trial

Despite increasing utilization of SABR for oligometastatic cancer, prospective outcomes are lacking. The purpose of this study was to determine progression-free survival (PFS), local control (LC), and prognostic factors from the population-based phase 2 SABR-5 trial. The SABR-5 trial was a single-arm phase 2 study with the primary endpoint of toxicity, conducted at the 6 regional cancer centers across British Columbia (BC), Canada, during which time SABR for oligometastases was only offered on trial. Patients with up to 5 oligometastases (total or not controlled by prior treatment and including induced oligometastatic disease) underwent SABR to all lesions. Patients were 18 years of age or older, had an Eastern Cooperative Oncology Group score of 0 to 2, and had life expectancy ≥ 6 months. The secondary outcomes of PFS and LC are presented here. Between November 2016 and July 2020, 381 patients underwent SABR on trial. Median follow-up was 27 months (interquartile range, 18-36). Median PFS was 15 months (95% confidence interval [CI], 12-18). LC at 1 and 3 years were 93% (95% CI, 91-95) and 87% (95% CI, 84-90), respectively. On multivariable analysis, increasing tumor diameter (hazard ratio [HR], 1.09; P < .001), declining performance status (HR, 2.13; P < .001), disease-free interval <18 months (HR, 1.52; P=.003), 4 or more metastases at SABR (HR, 1.48; P=.048), initiation or change in systemic treatment (HR, 0.50; P < .001), and oligoprogression (HR, 1.56; P=.008) were significant independent predictors of PFS. Tumor diameter (sub-hazard ratio [SHR], 1.28; P < .001), colorectal histology (SHR, 4.33; P=.002), and "other" histology (SHR, 3.90; P < .001) were associated with worse LC. In this population-based cohort including patients with genuine oligometastatic, oligoprogressive, and induced oligometastatic disease, the median PFS was 15 months and LC at 3 years was 87%. This supports ongoing efforts to randomize patients in phase 3 trials, even outside the original 1 to 5 metachronous oligometastatic paradigm.

Short-term efficacy of furmonertinib in treatment of NSCLC patients with EGFR exon20 insertion.

e21063 Background: EGFR is a key driver gene of lung cancer, in which exon 20 insertion (Ex20ins) mutation accounts for about 1-5%. However, the first- and second-generation EGFR-TKI had poor efficacy on patients with Ex20ins mutation (ORR = 6.9%, mPFS = 1.9 months, mOS = 12.9 months, DCR = 44.8%). Our study retrospectively observed the short-term efficacy and safety of furmonertinib in Chinese NSCLC patients with EGFR Ex20ins mutation. Methods: The study retrospectively collected 15 NSCLC patients with EGFR Ex20ins mutant who were treated in two medical institutions in Changzhou City, Jiangsu Province from April 2021 to December 2021. All patients received targeted therapy with furmonertinib. The last follow-up time was December 30, 2021. All patients received 160 mg furmonertinib orally until disease progression, drug intolerance, patient refusal or death. EGFR Ex20ins mutation was confirmed by ARMS or next generation sequencing (NGS). The patient's gender, age, score of Eastern Cooperative Oncology Group (ECOG), smoking history, pathological type, tumor stage, gene status and other basic clinical characteristics and adverse events (AES) were collected. The clinical efficacy was evaluated according to RECIST version 1.1, and the adverse events were evaluated according to the NCI-CTCAE version 5.0. SPSS 25.0 software was used to record and analyze the data. Results: All 15 patients had received ≥2 lines of therapy. The median age was 62 (25-80) years old, and there were 8 male patients (53.3%). Most patients had no smoking history (13 cases, 86.7%). ECOG score was mostly 1 (13 cases, 86.7%). In 15 patients, we found 10 different EGFR Ex20ins variants, among which p.A767_V769dup (n = 3) and p.A767_V769dup (n = 4) were more common. By the end of follow-up, 15 patients had completed at least one efficacy evaluation, and all had different degrees of tumor regression. No patient reached CR, 8 patients had PR and 7 patients had SD. This preliminary efficacy data showed that the overall ORR was 53.5% and DCR was 100%. No grade 3 or above adverse events were observed. The 3-months PFS rate was 100%. Conclusions: The results of this study in ≥2 lines patients treated with twice the conventional dose had a good curative effect (compared with 3 times of conventional dosage in FAVOUR study), which provided more treatment options for NSCLC patients in multiple lines of treatment and could alleviate part of their economic pressure, but the PFS and OS data still need further follow-up and verification of a larger sample size. The overall findings suggested that furmonertinib is a third generation EGFR-TKI with good efficacy and acceptable safety. Given the heterogeneity of EGFR Ex20ins mutation, the efficacy of targeted therapy may vary in different mutation types and requires further investigation.

Pazopanib in metastatic soft tissue sarcoma (STS): Results of a multi-institutional observational study.

e23542 Background: Soft tissue sarcomas (STS) are a heterogenous group of tumors which have limited therapeutic options and poor prognosis in advanced/metastatic settings. Herein, we present the clinical outcomes of metastatic STS patients treated with pazopanib (PAZ) in real-life. Methods: We retrospectively collected data about adult patients treated with PAZ for metastatic STS in Turkey. We described the clinical characteristics and tumor responses, and estimated the progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier method. The Cox proportional hazards regression model (HR, 95%CI) was used for evaluation of prognostic factors for PFS. Results: 507 patients (median age: 52 [range: 18-87]; 56.8% female) were included in the analysis. Extremities were the most common primary tumor sites (n:202; 39.8%) followed by abdomen (n:116; 22.9%) and pelvic cavity (n:102;20.1%) where 98% of STSs arose in uterus (n:100). The leading histologic subtypes were leiomyosarcoma (n:192; 37.9%), synovial sarcoma (n:58; 11.4%) and undifferentiated pleomorphic sarcoma (n:48; 9.5%). Of the reported tumor grades (n = 350), 61.4% (n:215) were grade 3. The most common metastatic sites were lungs (52.7%) and liver (20.3%). Doxorubicin plus ifosfamide (45.9%) was the preferred front-line regimen and PAZ was the treatment of choice in second (59.8%) and third-line (61.8%) settings. The median follow-up under PAZ treatment was 5.03 (0.10-84.67) months. Objective response and disease control rates were 31.4% and 42.2%, respectively. Overall, 183 (36.1%) patients were alive at last follow up, 123 of which (67.2%) did not show progression. The median PFS and OS for the study group and the most commonly observed types of STS are shown in Table. Favorable prognostic factors for PFS were low-intermediate tumor grade (HR[95% CI] for grade I and 2 vs 3:1.371[1.016-1.849]; p = 0.039) and ECOG (Eastern Cooperative Oncology Group) score (HR[95% CI] for ECOG score &lt; 2 vs ≥2: 2.698[1.923-3.787]; p = 0.0001). Weakness/asthenia (10.8%), impaired liver function tests (4.7%) and diarrhea (3.6%) were the most common adverse events, no grade 4 or 5 events were observed. Conclusions: This large scale real-life study confirms that PAZ, with its positive impact on clinical outcomes and acceptable tolerability and safety profile is a valuable treatment option for metastatic STS.[Table: see text]

Efficacy and safety of orelabrutinib in diffuse large B-cell lymphoma: A real-world analysis.

e19556 Background: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease. Recently, based on in-depth genomic analysis, new taxonomies for DLBCL have been proposed. Genetic subtype MCD is predominantly enriched with B-cell receptor-dependent NF-κB activation and well responded to Bruton’s tyrosine kinase (BTK) inhibitors. Ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) proved the efficacy in patients with MCD DLBCL in PHOENIX study. Orelabrutinib is a novel BTK inhibitor with excellent target selectivity. This study aimed to evaluate the efficacy and safety of orelabrutinib-containing regimens for the treatment of patients with MCD DLBCL in a real-world setting. Methods: Eligible patients with pathologically confirmed MCD DLBCL, regardless previous treatment, were included from 6 centers between January and December 2021. All patients received orelabrutinib-containing regimens and underwent at least one treatment response evaluation. Patients with known CNS lymphoma and primary mediastinal lymphoma were excluded. The primary endpoint was complete response rate (CRR) assessed by investigator using PET-CT per the 2014 Lugano Response Criteria for Non-Hodgkin Lymphoma. Safety was assessed by adverse events (AEs) referring to Common Terminology Criteria for AEs version 5.0. Results: Fourteen patients (10 males) were included. The median age was 66 (range 45-77) years, and 35.71% (5/14) documented ≥2 extranodal involved sites. Most patients had an Eastern Cooperative Oncology Group score of 0-1 (9/14, 64.29%), Ann Arbor Stage III-IV disease (11/14, 78.57%), elevated lactate dehydrogenase (9/14, 64.29%), and International Prognostic Index score ≥3 (8/14, 57.14%). All patients received orelabrutinib 150 mg once daily. Among them, 8 (57.14%) were treated with R-CHOP or rituximab plus etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (R-EPOCH) as first-line therapy, and 6 (42.86%) with rituximab plus ifosfamide, carboplatin and etoposide (R-ICE), R-CHOP or rituximab with lenalidomide as second-line therapy. The CRR for the first-line and second-line therapy were 75.00% and 66.67%, respectively. The most common AEs were hematologic (platelet count decrease, white blood count decrease or lymphocyte count decrease), and non-hematologic AE was infection (urinary or respiratory). Reported AEs were generally manageable and resolved soon after supportive treatment. AEs associated with off-target activities such as atrial fibrillation, diarrhea, and major hemorrhage were not reported. Conclusions: Orelabrutinib-containing regimens demonstrated encouraging efficacy and well-tolerated safety profile among patients with MCD DLBCL. A large-scale prospective clinical study is on registration, which would offer a new potential therapeutic option for patients with MCD DLBCL.

Trial in progress update on ENGOT-cx8/GOG-3024/innovaTV 205: Addition of a new cohort with first-line (1L) tisotumab vedotin (TV) + pembrolizumab (pembro) + carboplatin (carbo) ± bevacizumab (bev) in recurrent/metastatic cervical cancer (r/mCC).

TPS5603 Background: Despite the use of platinum-taxane doublets ± bev in eligible patients (pts), overall survival (OS) outcomes for pts with r/mCC remain poor. With the US approval of pembro + chemotherapy ± bev in the 1L setting for r/mCC with ≥1% of programmed death ligand 1–positive cells in the tumor, an unmet need remains for pts who do not meet this threshold and for pts who progress or are intolerant to standard treatment (tx). TV is a tissue factor–directed antibody–drug conjugate that has been granted accelerated approval in the United States for the tx of adults with r/mCC with disease progression on or after chemotherapy. To develop more effective treatments, we investigated TV in combination with agents with known activity in cervical cancer. We conducted a 2-part, multicohort phase 1b/2 trial, ENGOT-cx8/GOG-3024/innovaTV 205 (NCT03786081), to evaluate TV in combination with bev, pembro, or carbo. The phase 1b dose-escalation phase of innovaTV 205 established the recommended phase 2 dose (RP2D) and the feasibility of these doublet combinations (Monk et al, IGCS 2021). Moreover, we recently reported encouraging antitumor activity from the dose-expansion cohort of TV + carbo (1L; confirmed objective response rate [ORR], 55%; median duration of response [DOR], 8.3 mo) and TV + pembro (second-line; confirmed ORR, 38%; median DOR, 13.8 mo) (Vergote et al, ESMO 2021). The current report describes the design of a new, ongoing dose expansion cohort in the innovaTV 205 study to evaluate the combinations of TV, pembro, and carbo ± bev. Methods: A new cohort has been added to the innovaTV 205 study, comprising adult pts with recurrent or stage IVB squamous, adenosquamous, or adenocarcinoma of the cervix with no prior systemic therapy and an Eastern Cooperative Oncology Group score of 0 or 1. Pts will be treated with the RP2D of TV (2.0 mg/kg) + carbo (AUC 5 mg/mL), pembro (200 mg), and bev (15 mg/kg) every 3 weeks or with TV + carbo (AUC 5 mg/mL) and pembro (200 mg). To assess the regimen’s initial tolerability, there will be a dose-limiting toxicity evaluation period that will consist of completion of 1 tx cycle of 21 days for 6 pts enrolled to receive the quadruplet combination. The primary endpoint of this dose expansion phase is confirmed ORR per RECIST v1.1; secondary endpoints include DOR, time to response, progression-free survival, OS, and safety. Enrollment is ongoing in the United States and Europe, with additional sites planned globally. Clinical trial information: NCT03786081.