Kaplan-Meier Statistics Research Articles

The impact of pre-treatment smoking status on survival after chemoradiotherapy for locally advanced non-small-cell lung cancer

IntroductionSmoking is a risk factor for the development of lung cancer and reduces life expectancy within the general population. Retrospective studies suggest that non-smokers have better outcomes after treatment for lung cancer. We used a prospective database to investigate relationships between pre-treatment smoking status and survival for a cohort of patients with stage III non-small-cell lung cancer (NSCLC) treated with curative-intent concurrent chemoradiotherapy (CRT). MethodsAll patients treated with CRT for stage III NSCLC at a major metropolitan cancer centre were prospectively registered to a database. A detailed smoking history was routinely obtained at baseline. Kaplan-Meier statistics were used to assess overall survival and progression-free survival in never versus former versus current smokers. ResultsMedian overall survival for 265 eligible patients was 2.21 years (95 % Confidence Interval 1.78, 2.84). It was 5.5 years (95 % CI 2.1, not reached) for 25 never-smokers versus 1.9 years (95 % CI 1.5, 2.7) for 182 former smokers and 2.2 years (95 % CI 1.3, 2.7) for 58 current smokers. Hazard ratio for death was 2.43 (95 % CI 1.32–4.50) for former smokers and 2.75 (95 % CI 1.40, 5.40) for current smokers, p = 0.006. Actionable tumour mutations (EGFR, ALK, ROS1) were present in more never smokers (14/25) than former (9/182) or current (3/58) smokers. TKI use was also higher in never smokers but this was not significantly associated with superior survival (Hazard ratio 0.71, 95 % CI 0.41, 1.26). ConclusionsNever smokers have substantially better overall survival than former or current smokers after undergoing CRT for NSCLC.

Treatment Outcomes of Stereotactic Ablative Body Radiotherapy on Extra-cranial Oligometastatic and Oligoprogressive Breast Cancer: Mature Results from a Single Institution Experience

AimsEvidence shows stereotactic ablative body radiotherapy (SABR) is used as a non-invasive ablative therapy in the treatment of multisite oligometastatic (OM) and oligoprogressive (OP) diseases originating from metastatic breast cancer. This study aims to report the treatment outcomes and to investigate what factors that are prognostic in terms of local control, progression-free survival (PFS) and overall survival (OS) in patients receiving SABR for extracranial OM and OP diseases originating from metastatic breast cancer. Materials and methodsA retrospective review on treatment records of patients with OM and OP from metastatic breast cancer who underwent SABR at a single was carried out. SABR was performed with daily image-guided radiotherapy (IGRT) using a dedicated robotic SABR machine. Local control, PFS and OS were calculated using Kaplan-Meier statistics and the post-treatment toxicity data was scored following the CTCAE v4.0 protocol. Univariate and multivariate Cox regression tests were used in the subgroup analysis of prognostic factors on PFS and OS including patients’ age, types of follow-up imaging (staging CT only vs whole-body MR/PET), metastases status (OM vs OP), primary breast cancer tumour grade, hormone receptors (ER/PR/HER2) status, change of systemic treatments at SABR, number of metastases, SABR treatment sites and doses. Results56 metastatic breast cancer patients (38 patients with OM and 18 patients with OP) were involved in this retrospective review. The median follow-up was 35.6 months (range 4.0–132.9 months). The estimated local control at 1 , 2 and 5 years were 90.9%, 88.7% and 88.7%, respectively. The estimated median PFS was 19.2 months (95%CI 10.3–28.1 months); the PFS at 1, 2 and 5 years were 63.3%, 44.4% and 33.2%. The estimated OS at 1, 2 and 5 years were 98.0%, 91.9% and 74.3%, respectively with the estimated median OS of 105.1 months (95%CI 51.5–158.7 months). The vast majority of patients tolerated the treatment well with the commonest acute side effects as grade 1 fatigue. There were no statistically significant factors found in OS regression analysis. The types of follow-up imaging, metastases status, oestrogen receptor status, and number of metastases for SABR were statistically significant factors (p < 0.05) in the multivariate Cox regression analysis on PFS. ConclusionThere are limited studies published on the efficacy and post-treatment toxicities of metastatic breast cancer OM and OP SABR with adequate length of follow-up. This study confirmed that SABR was a safe, non-invasive treatment option for patients with extracranial OM and OP diseases originated from primary breast cancer in terms of the acceptable post-treatment toxicities.

Predictors of recovery time from severe community-acquired pneumonia among paediatrics patients in selected hospitals in Addis Ababa, Ethiopia: an institution-based retrospective cohort study

ObjectiveSevere community-acquired pneumonia (SCAP) is a significant cause of morbidity worldwide and a major cause of morbidity and mortality in developing countries. Ethiopia ranks 6th out of 15 countries with...

DOP07 Monitoring disease activity by intestinal ultrasound predicts biologic treatment persistence in patients with Inflammatory Bowel Disease

Abstract Background Current biomarker-based monitoring strategies have limited efficacy in predicting risk of biologic treatment failure in inflammatory bowel disease (IBD). Endoscopic assessment identifies patients at risk of disease progression but is expensive and poorly accepted by patients. Therefore, we examined how intestinal ultrasound (IUS) performed as part of a monitoring program to predict treatment persistence to biologics in IBD patients. Methods Data were generated as part of a 1-year prospective, observational, cohort study of patients on biologics comparing tight monitoring to a historic cohort (‘Time It´ study). Data used in the present analysis included Harvey Bradshaw index (HBI), simple clinical colitis activity score (SCCAI), CRP, f-calprotectin (FC), IUS, and ileocolonoscopy all done at inclusion. The following definitions were used: Treatment persistence: no need for dose escalation or switching to another biologic or small molecule; IUS transmural remission (TR): bowel wall thickness ≤3mm in all bowel segments and zero color Doppler activity; endoscopic remission (ER): simple endoscopic score (SES)-CD≤2 or Mayo endoscopic score 0; clinical remission (CR): HBI≤4 or SCCAI≤2; FC remission (FCR): FC≤250; CRP remission (CRPR): CRP≤10 mg/L. Chi-square tests and Kaplan-Meier statistics were used to compare baseline measures in treatment persistent and non-persistent patients. Results Of the 91 patients included in 'Time It’, 77 had IUS performed and 69 ileocolonoscopy. Of the 77 patients, 61% were on maintenance treatment at inclusion and 39% were included during induction (Table 1). COVID-19 restrictions were the main reason for missing IUS or endoscopy. As expected, more patients with ER had 1-year treatment persistence (87% vs. 41%; p&amp;lt;0.001). However, patients with IUS TR also had better treatment persistence (78% vs. 38%; p&amp;lt;0.001). CR or FCR were associated with treatment persistence (p&amp;lt;0.05 and p&amp;lt;0.01, respectively), but not CRPR. Combining TR and FCR performed numerically as well as ER (treatment persistence 85% vs. 41%, p=0.002). Survival analysis of TR showed a mean treatment persistence of 318 days vs. 221 days without TR (p&amp;lt;0.001); corresponding treatment persistence data were 327 days vs. 230 days for combined TR and FCR; and 338 days vs. 226 days for ER (both p&amp;lt;0.001; Figure 1). There was no difference in mean treatment persistence between TR and ER (318 vs. 338 days; p=0.36). Conclusion IUS alone or combined with FCR was comparable to endoscopy to identify patients with high biologic treatment persistence. Being a non-invasive, patient friendly, cost-effective modality, IUS monitoring may improve current disease monitoring programs aiming to increase treatment persistence.

Prognostic value of the CRM status in pancreatic ductal adenocarcinoma: Data from a regional cancer registry.

632 Background: Ductal pancreatic adenocarcinoma (PDAC) still has a dismal prognosis even when deemed resectable. A cancer free resection margin (R0) is associated with a more favourable prognosis than the presence of tumour cells at resection margin (R1). However, the precise definition of the R0 status is still a matter of debate in PDAC. For a more accurate determination of R0 in PDAC the concept of circumferential resection margins (CRM) has been introduced. However, an international standardized nomenclature of CRM is still missing, and the clinical value of the CRM concept is not yet fully established. Here we evaluate whether the CRM status as defined in the national German S3 guideline is an independent prognostic factor in PDAC using data from the regional cancer registry of the State of Baden Württemberg in Germany. Methods: Data from the cancer registry of the State of Baden-Württemberg, Germany were collected, using documented patients diagnosed with invasive ductal adenocarcinoma of the pancreas between 2015 and 2020. The R-status was assessed according to the national German S3 guideline with R0 wide/CRM- when CRM is &gt; 1mm, R0 narrow/CRM+ when CRM is £ 1 mm from the tumour and R1 when tumour cells are found at the resection margin. Progression free survival (PFS) as well as 3-year overall survival (OS) were assessed using Kaplan-Meier statistics and multivariable Cox regression models (adjusted for age, pN stage, primary tumor location and systemic treatment). Results: In total we identified 1098 cases surgically treated for pancreatic cancer and fulfilling the inclusion criteria. 340 patients had an R0 wide/CRM- resection, 410 patients an R0 narrow/CRM+ resection, and 348 patients an R1 resection. The R0 wide/CRM- status was associated with a significantly increased median 3-year OS rate compared to the other two groups (51,5%, 37,4% and 26,7% for R0 wide/CRM-, R0 narrow/CRM+ and R1, respectively). mPFS was also longer in the R0 wide/CRM- group. These findings were robust with regards to grading. 5-FU based adjuvant treatment was mainly mFOLFIRINOX and show better outcome as compared to gemcitabine-based treatments. Conclusions: The present study was performed using real world data reflecting actual clinical settings. The results obtained are in good agreement with data from clinical trials, including the prognostic role of the R- and N- Status as well as the efficacy of adjuvant chemotherapy protocols used.

Prognostic significance of socioeconomic deprivation in patients with colorectal liver metastasis undergoing liver resection: a retrospective cohort study.

To evaluate the effect of socioeconomic deprivation on overall survival (OS) in patients undergoing liver resection for colorectal liver metastasis (CRLM). The STROCSS guideline for observational studies was followed to conduct a single-centre retrospective cohort study. All consecutive patients undergoing resection of CRLM between 2013 and 2021 were considered eligible for inclusion. The Welsh Index of Multiple Deprivation (WIMD) rank was used to determine socioeconomic deprivation status of each patient. Prognostic significance of socioeconomic deprivation was determined by Kaplan-Meier survival statistics and stepwise Cox proportional-hazards regression model. A total of 455 patients were eligible for inclusion; 237 patients were classed as least socioeconomically deprived and 218 patients as most socioeconomically deprived. Kaplan-Meier survival statistics showed that socioeconomic deprivation was associated with significantly lower probability of overall survival (HR: 1.55, 95% CI 1.23-1.95; logrank test: P = 0.0001). The stepwise Cox proportional-hazards regression analysis identified socioeconomic deprivation as predictor of OS (HR: 1.56, P = 0.0003) alongside the following variables: ASA status 1 (HR: 0.43, P = 0.0349), presence of extrahepatic disease (HR: 1.51, P = 0.0075), number of tumours (HR: 1.07, P = 0.0221), size of largest tumour (HR: 1.01, P = 0.0003), extended hemihepatectomy (HR: 3.24, P = 0.0018) and absence of recurrence (HR: 0.55, P < 0.0001). Socioeconomic deprivation reduces the probability of long-term overall survival following liver resection in patients with CRLM. This should be taken into account at different levels of health care planning for management of patients with CRLM including preoperative risk assessment, health care need assessment and allocation of resources.

Biochemical progression free and overall survival among Black men with stage IV prostate cancer in South Africa: Results from a prospective cohort study.

Men of African descent are disproportionately affected by prostate cancer (PCa), and many have metastatic disease at presentation. In South Africa (SA), androgen deprivation therapy (ADT) is the first-line treatment for stage IV PCa. To identify predictors of overall survival (OS) in Black South African men with stage IV PCa treated with ADT. Men diagnosed with prostate cancer (3/22/2016-10/30/2020) at Chris Hani Baragwanath Academic Hospital in Soweto, Johannesburg, were recruited for the Men of African Descent with Cancer of the Prostate study. We included men with newly diagnosed stage IV PCa treated with ADT who had a prostate-specific antigen (PSA) level drawn prior to initiation of ADT and had ≥1 PSA drawn ≥12 weeks after ADT start. We used Kaplan-Meier statistics to estimate OS and Cox regression models to identify predictors of OS. Of the 1097 men diagnosed with prostate cancer, we included 153 men with stage IV PCa who received ADT and met PSA requirements. The median age was 68.0 years (interquartile range 64-73 years). Median OS from time of ADT initiation was 3.39 years (95% confidence interval (CI): 3.14%-noncalculable), while biochemical progression-free survival was 2.36 years (95% CI: 2.03%-3.73%). Biochemical progression (HR 3.52, 95% CI: 1.85%-6.70%), PSA nadir level >4 ng/mL (HR 3.77, 95% CI: 1.86%-7.62%), alkaline phosphatase level at diagnosis >150 IU/dL (HR 3.09, 95% CI: 1.64%-5.83%), and hemoglobin at diagnosis <13.5 g/dL (HR 2.90, 95% CI: 1.28%-6.56%) were associated with worse OS. In this study, we identified factors associated with poor OS among Black South African men with stage IV PCa treated with ADT. These factors may be useful in identifying patients for upfront treatment escalation, including the use of docetaxel chemotherapy or escalation of therapy at the time of biochemical progression. In this study, we found that high alkaline phosphatase level, anemia at diagnosis, and high PSA nadir after initiation of androgen deprivation therapy are associated with worse overall survival among Black South African men treated with androgen deprivation therapy for metastatic prostate cancer.

Bronchial reactivity and asthma at school age after early-life metapneumovirus infection.

The association between early-life lower respiratory tract infection (LRTI) and asthma is well established. Knowledge about bronchial hyperresponsiveness (BHR) and asthma after metapneumovirus (MPV) LRTI is scarce. The aim of this study was to assess BHR and current asthma in school-aged children after hospital admission for early-life LRTI with MPV, and to compare with more well-known viruses, rhinovirus (RV) and respiratory syncytial virus (RSV), and with controls. A cohort consisting of children admitted for LRTI and controls was followed-up at school age with a clinical research assessment and lung function tests, including a methacholine provocation test. Current asthma was defined based on objective variable airway obstruction and clinical symptoms. BHR and asthma were compared according to viral groups. 135 children (median age 9.3 years) were included (16 MPV, 34 RV, 51 RSV, 13 mixed infections and 21 controls). Compared with controls there was increased BHR after MPV and RV LRTI (provocative dose causing a 20% fall in forced expiratory volume in 1 s and dose-response slope; p<0.05). Using Kaplan-Meier statistics, BHR was increased for MPV compared with both controls and RSV (p=0.02 and p=0.01). The proportion of children with current asthma at follow-up was higher in the LRTI children compared with the controls (46% versus 24%; p=0.06). Among children who had undergone MPV and RV infection, 50% fulfilled the asthma criteria compared with 43% in the RSV group (p=0.37). We found increased BHR and a high prevalence of asthma in school-aged children after early-life MPV infection, and findings were similar to RV, and less to RSV, compared with controls.

Magnetocardiography at rest predicts cardiac death in patients with acute chest pain.

Sudden cardiac arrest is a major cause of morbidity and mortality worldwide and remains a major public health problem for which better non-invasive prediction tools are needed. Primary preventive therapies, such as implantable cardioverter defibrillators, are not personalized and not predictive. Most of these devices do not deliver life-saving therapy during their lifetime. The individual relationship between fatal arrhythmias and cardiac function abnormalities in predicting cardiac death risk has rarely been explored. We retrospectively analyzed the measurements at rest for 191 patients with acute chest pain (ACP) magnetocardiographically. Our recently introduced analyses are able to detect inhomogeneities of the depolarization and repolarization. Moreover, electrically silent phenomena-intracellular ionic currents as well as vortex currents-can be measured and quantified. All included ACP patients were recruited in 2009 at Yonsei University Hospital and were followed up until 2022. During half of the follow-up period (6.5 years), 11 patients died. Out of all the included nine clinical, eight magnetocardiographical, and nine newly introduced magnetoionographical parameters we tested in this study, three parameters revealed themselves to be outstanding at predicting death: heart rate-corrected QT (QTc) prolongation, depression of repolarization current IKr + IKs, and serum creatinine (all significant in Cox regression, p < 0.05). They clearly predicted cardiac death over the 6.5 years duration (sensitivity 90.9%, specificity 85.6%, negative predictive accuracy 99.4%). Cardiac death risk was more than ninefold higher in patients with low repolarization reserve and QTc prolongation in comparison with the remaining patients with ACP (p < 0.001). The non-parametric Kaplan-Meier statistics estimated significantly lower survival functions from their lifetime data (p < 0.001). To the best of our knowledge, these are the first data linking magnetocardiographical and magnetoionographical parameters and subsequent significant fatal events in people, suggesting structural and functional components to clinical life-threatening ventricular arrhythmogenesis. The findings support investigation of new prevention strategies and herald those new non-invasive techniques as complementary risk stratification tools.

Timing of Vaccination Impacts Serological Response to COVID-19 Myeloma Patients after BCMA-Targeted CAR T

Whereas COVID-19 mRNA vaccines have shown remarkable efficacy in the prevention of severe disease and mortality in healthy individuals, the effectiveness in cancer patients has been more variable. Patients with multiple myeloma (MM) are at a high risk for severe infection due to disease- or treatment-related immune suppression. Our prior work demonstrated that the immune response to SARS-CoV-2 immunization in MM patients with 2 doses of mRNA vaccine was suboptimal and that a 3rd dose significantly improved neutralization of viral variants. MM patients undergoing treatment targeting BCMA were among those at a higher risk of ineffective immune responses. As BCMA-targeted (CAR T) treatment becomes more widely available, guidance on initiation of vaccination after treatment is needed. To assess the impact of BCMA-targeted CAR T (BCMA CAR T) on the serological immune response to COVID-19, we studied 45 MM patients who received ≥1 dose of a COVID-19 mRNA vaccine after prior BCMA CAR T. We collected demographics, disease/treatment characteristics, and COVID-19 infection/vaccination data via retrospective chart review. We analyzed SARS-CoV-2 spike-binding (anti-spike) IgG level using a validated assay (FDA/EUA approved Kantaro). Cumulative incidence of COVID-19 was analyzed using Kaplan-Meier statistics. All subjects were enrolled to studies approved by the Institutional Review Board at a single US academic hospital. Our cohort consisted of 16 women and 29 men with a median age of 61 years. The patients had received a median 6 lines of treatment and 33/45 (73%) had an ongoing response to BCMA CAR T. Patients received dose 1 at median 567 days after CAR T infusion (range 73-1,374 days). 36 patients (80%) received ≥3 doses and 17 (38%) received ≥4 doses. Across the cohort, anti-spike IgG levels increased from median 8 AU/mL after a single dose to 91, 474 and 612 AU/mL after 2, 3 or 4 mRNA vaccine doses respectively. After 2 doses, 6 patients (of 28 for which the timepoint was available, 21%) had no detectable anti-spike IgG levels, whereas all patients in the cohort had a detectable serological response after ≥3 vaccine doses. We compared the 13 patients (29%) that initiated mRNA vaccination at &amp;lt;12 months (mo) after CAR T infusion (i.e. “early vaccination”) with those who received the first dose after &amp;gt;12 mo. In the early vaccination group, anti-spike IgG levels were significantly lower when measured 0-3 months after 2 vaccine doses (p&amp;lt;0.01). Serological responses were not different when measured after 3 or 4 doses respectively (Fig A). Nevertheless, after 3 vaccine doses, 30% of patients (3/10) in the early vaccination group had anti-spike IgG &amp;lt;100 AU/mL, a level previously shown to be associated with less effective viral neutralization, versus only 5% (1/20) of patients in the group that started vaccination &amp;gt; 12 mo after CAR T. Twenty-four patients (52%) developed a documented COVID-19 infection after vaccination. Of these, 21 (88%) were characterized as mild (i.e. not requiring hospital admission); two patients required hospitalization and recovered, and 1 patient in the early vaccination group passed away from COVID-19. Of note, in the early vaccination group, there was a non-significant trend towards earlier breakthrough infections (Fig B, p=0.16), consistent with the finding of a delayed serological response with suboptimal antibody levels after 2 doses. In this study, all MM patients who initiated mRNA vaccination after prior BCMA CAR T therapy had detectable anti-spike IgG after ≥3 vaccine doses. However, starting vaccination against COVID-19 early (i.e. within 1 year) after CAR T therapy does not result in protective levels of antibody as quickly and to the same extent as when vaccinated &amp;gt;1 year post CAR T infusion. Patients starting vaccination within 12 months need ≥3 doses to achieve comparable serological efficacy to later initiation. A trend towards earlier breakthrough infections suggests that study of neutralizing titers against variants and comprehensive immune phenotyping may be needed to confirm effective immunity in these vulnerable patients. For the first year after CAR T cell therapy, adherence to preventive measures and passive immunization with IVIG with higher titers of anti-spike IgG may be warranted. Analyses comparing this cohort with MM patients receiving other modalities of BCMA-targeted therapy incl. bispecific antibodies are ongoing and will be presented at the meeting.

Risk of Central Nervous System Vs. Systemic Relapse in Patients with Diffuse Large B-Cell Lymphoma Treated with R-CHOP: What Should We Focus on?

Background: Clinical outcome of patients (pts) with diffuse large B-cell lymphoma (DLBCL) has improved during the last two decades. However, a significant proportion of DLBCL pts is still at risk of lymphoma relapse (REL)/progression or death due to progression. DLBCL pts with adverse clinical features, i.e., those with high IPI or CNS IPI scores are at the highest risk of lymphoma REL, systemic (S) or central nervous system (CNS) REL. CNS prophylaxis is questionable based on retrospective analyses. Moreover, the risk of S-REL should be discussed in those pts as well. However, the comparison of the risks of CNS vs S-REL within the different CNS IPI risk groups has not been shown. Methods: Using the prospective observational NiHiL project (NCT03199066), we identified pts ≥ 18 years of age with histologically confirmed DLBCL or high-grade B-cell lymphoma (diagnosed 2011-2021), who received R-CHOP as frontline treatment in 2 centres in Czech Republic. Pts with CNS involvement at diagnosis were excluded. Cumulative incidence of CNS (± S) REL was calculated using Kaplan-Meier statistics treating S-REL and death as competing events. Results: A total of 1242 pts were included; according to CNS IPI score (available in 1225 out of 1242 pts), 344 (28.1%), 539 (44.0%) and 342 (27.9%) pts were categorized as being at low (0-1, LR), intermediate (2-3, IR), and high risk (4-6, HiR) resp. Overall, 308 (24.8%) pts received CNS prophylaxis with either high-dose(HD) Methotrexate (MTX), HD-AraC, intrathecal chemotherapy or combination. By CNS IPI, 150 (43.9%) out of 342 pts with HiR CNS IPI received CNS prophylaxis. CNS prophylaxis was given less frequently in the IR (n 111[20.6%] out of 539 pts) or LR (n 45 [13.1%] out of 344 pts) CNS IPI groups. At a median follow up of 5.3 years (range; 0.1 - 13.3), 307 (24.7%) out of 1242 pts developed lymphoma REL, out of which 45 occurred in CNS (35 isolated CNS REL, 10 simultaneous CNS+S-REL) and 262 lymphoma RELs occurred systemically. CNS prophylaxis had no impact on the incidence of CNS REL in pts with HiR CNS IPI. Median time to CNS (± S) and S-REL was 11.5 months (range; 2.7-116.8) and 11.8 months (range; 0.8 - 144.3), resp. Occurrence of RELs within the first 6, 12 and 24 months after lymphoma diagnosis was as follows: 20%, 53.3% and 80% for CNS (± S) RELs and 21%, 50.4% and 67.2% for S-RELs. In the entire cohort, the 7-year cumulative incidence of CNS (± S) and S-REL were 4.4% and 23.7%, resp. Across all CNS IPI risk groups, there was significantly higher risk of S-REL as compared to CNS (± S) REL. The 7-year cumulative incidence of S-REL vs CNS (± S) REL and the respective HRs were 10.5% vs 1.9%, HR 6.2 (95% CI 3.4-11.2) in the LR-, 25.2% vs 2%, HR 11.7 (95% CI 8.3-16.6) in the IR-, and 35.8% vs. 12.4 %, HR 3.6 (95% CI 2.5-4.9) in the HiR CNS IPI ( Fig1), resp. At the time of analysis, 417 (33.6%) out of 1242 pts were dead. CNS (± S) REL was associated with shorter post-REL overall survival (OS) as compared to S-REL (HR 1.8, p=0.001, median OS 0.38 vs 1.04 years, resp). In the entire cohort, the 7-year cumulative incidence of death due to lymphoma was 19.3% (16.7% and 3.1% due to S-REL and CNS (± S) REL, resp). The 7-year cumulative incidence of death due to R-CHOP-related toxicity, unrelated to lymphoma and unknown causes were 2.5%, 4.2% and 9.8%, resp. In HiR CNS IPI, the 7-year cumulative incidence of death due to lymphoma was 34.9% (28.3% and 9.2% due to S-REL and CNS (± S) REL, resp), while the 7-year cumulative incidence of death due to R-CHOP-related toxicity, unrelated to lymphoma and unknown causes were 5.1%, 5.1% and 14.9%, resp ( Fig2). Conclusion: DLBCL pts are at significantly higher risk of S-REL as compared to CNS (± S) REL overall and across all CNS IPI risk groups. In addition, death due to S-REL is the leading cause of death overall and across all CNS IPI risk groups. However, CNS (± S) REL represents remarkable portion of all lymphoma RELs occurring in the HiR CNS IPI group and non-negligible cause of death in DLBCL. Our results support the conclusion that R-CHOP + HD MTX is not sufficient to reduce the risk of S-REL as well as CNS REL especially in pts with HiR CNS IPI. New 1 st line treatment options able to reduce simultaneously the risk of S-REL as well as CNS REL are needed to improve the outcome of DLBCL pts especially in the subgroup with HiR CNS IPI. Grant support: AZV NU23-03-00127, NU21-03-00411, Charles University Hematology-Oncology Cooperatio Program

NIMG-34. TEMPORAL MUSCLE THICKNESS AS A PROGNOSTIC MARKER IN A REAL-LIFE COHORT OF NEWLY DIAGNOSED MGMT PROMOTER METHYLATED GLIOBLASTOMA PATIENTS: A MULTICENTRIC IMAGING ANALYSIS

Abstract BACKGROUND In cranial MRI assessed temporal muscle thickness (TMT) correlates with lumbar skeletal muscle mass, which serves as surrogate marker of sarcopenia. Prior research has identified TMT as a prognostic marker in glioblastoma. However, incorporation into clinical practice is challenging due to the heterogeneity of previous studies and the absence of established cutoff values. To address this, we conducted a multicenter analysis to validate recently proposed sex-specific cutoff values in a homogeneous real-life cohort of newly diagnosed MGMT promoter-methylated glioblastoma patients uniformly treated with combined CCNU/temozolomide. We implemented a balanced control cohort for comparison. METHODS TMT was measured at baseline using preoperative or early postoperative MRI and in the disease course using the first MRI after completion of radiotherapy. Patients were TMT-based divided into “at risk of sarcopenia” or “normal muscle status”. Kaplan-Meier statistics and multivariable Cox regression analysis were used for correlation with survival. RESULTS In total, n = 126 patients were analyzed (n = 66 received CCNU/temozolomide; n = 60 received temozolomide). Patients with normal muscle mass at baseline (&amp;gt; 6,3 mm for men; &amp;gt; 5,2 mm for women) had significantly prolonged mOS (44.3 versus 16.7 months for CCNU/temozolomide; 29.5 versus 17.4 months for temozolomide) compared to those at risk of sarcopenia. In a multivariable Cox regression analysis, normal muscle mass (HR: 0.39, 95% CI: 0.23-0.66; p = 0.0003) and age at diagnosis of &amp;lt; 50 years (HR: 0.42, 95% CI: 0.22-0.79; p = 0.0067) were significant prognostic markers. Longitudinally, survival was best in patients with lack of TMT decline. CONCLUSIONS This analysis suggests TMT to serve as a prognostic marker in glioblastoma patients treated with CCNU/temozolomide or with temozolomide. However, for TMT assessment to be implemented in a generalizable manner, such as for patient selection for therapeutic measures, further validation in prospective controlled trials is necessary.

NCMP-29. THE NATURAL HISTORY OF NEUROLYMPHOMATOSIS

Abstract Neurolymphomatosis is a rare lymphoid malignancy of the peripheral nervous system. Patients suffer from debilitating neurological deficits due to lymphoma invasion into one or more peripheral nerves and the natural history of this disease is still poorly understood. We performed a PubMed search and extracted data on year of publication, age, gender, type of lymphoma, nerves involved, imaging modalities, treatment received, and survival times. Kaplan-Meier statistics were used to determine outcome parameters over time and compare prognostic factors. Multiple comparisons were done to determine differences among groups. Our search identified 559 patients from 286 articles. Median age was 61 years (range 2-92) from 326 males, 222 females, and 11 with unspecified gender. Median overall survival (OS) was 12.0 months (range 10.0-15.0) for the entire cohort. Most frequent histologies were diffuse large B-cell lymphoma, unspecified T-cell lymphoma, and unspecified B-cell lymphoma, involving the brachial plexus, cranial nerves, and sciatic nerve. None had molecular profiling. There was a progressive lengthening of OS in successive decades, from 0.5 (95%CI 0.0-0.8) to 26.4 (95%CI 18.0-34.8) months from 1951-2022 (r2=0.9432, p&amp;lt; 0.001). Time from first treatment to progression also increased from 2.0 (95%CI N/A) to 28.3 (95%CI 23.1-33.5) months (r2=0.6923, p&amp;lt; 0.001). However, time from symptom onset to diagnosis remained unchanged during this period (r2=0.6206, p=0.277). Patients were most frequently treated with methotrexate-based chemotherapies (n=81), rituximab-based chemotherapies (n=176), and/or radiation (n=79). Only 12 received 3 or more regimens. Primary neurolymphomatosis had a better prognosis than secondary neurolymphomatosis, median OS 15.0 (95%CI 11.0-33.0) vs. 10.0 (95%CI 10.0-10.0) months (p=0.016). No OS difference was noted between B- and T-cell disease (p=0.4393), while patients with low-grade B-cell neurolymphomatosis did better than those with Burkitt's lymphoma (p≤0.001). Outcome for patients with neurolymphomatosis has improved over time. But timely diagnosis remains a major problem that needs improvement.

Oral health in patients with different sites of head and neck squamous cell carcinoma is not different.

Oral health might not only act as risk factor for head and neck squamous cell carcinoma (HNSCC), but might also have a predictive value for the patients' survival. Currently, information on the effect of oral health on survival of patients with different sites of HNSCC is lacking. This single-center retrospective study aimed to compare oral health in patients with different sites of HNSCC and to analyse whether oral health is associated with survival in the different subsets of HNSCC patients. Dental records of HNSCC patients referred for dental assessment prior to radio(chemo)therapy were included. Patient-related parameters (age at time of diagnosis, sex, tobacco exposure, alcohol consumption, HPV status), treatment data (primary treatment, intent), performance status, tumor demographics (anatomical site, TNM staging), and oral health parameters (DMFT, periodontal health, teeth with/without root canal treatment and with/without periodontitis apicalis) were obtained. Oral health parameters were compared between different anatomical sites. Survival of all HNSCC patients and of individual subsets was assessed using Kaplan-Meier statistics, and the effect of tumor demographics, patient-related parameters, and oral health on survival was analysed by cox regression analyses (α = 5%). 371 patients with HNSCC (oral: n = 86, oropharyngeal: n = 174, hypopharyngeal: n = 59, laryngeal: n = 15, other: n = 37) were included. Oral health parameters did not differ between subsets (padj.≥0.199). Five-year cumulative survival of HNSCC patients amounted to 78.6%. Only for HNSCC originating in the oral cavity and oropharynx, survival was associated with the treatment intent (p = 0.015) or performance status (p = 0.007) in the multivariable analyses, respectively. Within the limitations of this study, oral health was not different between different subsets and had no significant effect on survival of HNSCC patients.

The influence of immunodeficiency, disease features, and patient characteristics on survival in plasmablastic lymphoma

AbstractPlasmablastic lymphoma (PBL) is a rare and aggressive non-Hodgkin lymphoma associated with immunodeficiency, characterized by uncertain treatment approaches and an unfavorable prognosis. We conducted a multicenter, international, retrospective cohort study, aiming to characterize the clinical features, risk factors, and outcomes of patients with PBL. Data were collected from 22 institutions across 4 countries regarding patients diagnosed with PBL between 1 January 1999 and 31 December 2020. Survival risk factors were analyzed using both univariate and multivariate regression models. Overall survival (OS) was calculated using Kaplan-Meier statistics. First-line treatment regimens were stratified into standard- and higher-intensity regimens, and based on whether they incorporated a proteasome inhibitor (PI). A total of 281 patients (median age, 55 years) were included. Immunodeficiency of any kind was identified in 144 patients (51%), and 99 patients (35%) had HIV-positive results. The 5-year OS for the entire cohort was 36% (95% confidence interval, 30%-42%). In multivariate analysis, inferior OS was associated with Epstein-Barr virus–negative lymphoma, poor performance status, advanced stage, and bone marrow involvement. In an independent univariate analysis, the international prognostic index was associated with OS outcomes. Neither immunosuppression nor HIV infection, specifically, influenced OS. Among patients treated with curative intent (n = 234), the overall response rate was 72%. Neither the intensity of the treatment regimen nor the inclusion of PIs in first-line therapy was associated with OS. In this large retrospective study of patients with PBL, we identified novel risk factors for survival. PBL remains a challenging disease with poor long-term outcomes.

Long term clinical performance of 'open sandwich' and 'total-etch' Class II composite resin restorations showing proximal deterioration of glass-ionomer cement.

To compare clinical performance of resin composite posterior Class-II restorations placed with etch-and-rinse adhesive or open sandwich technique using glass-ionomer cement. Data on Class II restorations placed by one dentist between 1990 and 2016 were collected from patient files, including caries risk, tooth related variables, applied materials and dates of last check-up visit and restoration placement. Open sandwich restorations were placed before 2001, while after 2001, a total-etch technique using etch-and-rinse 3-step adhesive was used when placing a Class II composite restoration. For statistical analysis, Kaplan-Meier statistics and a multilevel Cox-Regression was conducted (p<0.05). Annual Failures Rates (AFR) were calculated. 675 Class II restorations were placed in 91 patients, 491 total-etch restorations (observation time 2-18y), and 184 open sandwich restorations (observation time 19-29y) showing AFRs at 15 years as 2.9% for total-etch and 9.7% for open sandwich restorations. Secondary caries as failure was equally distributed among the 2 groups and 27% of the failures in the open sandwich group were due to proximal deterioration of glass-ionomer cement. The Cox-regression showed a significant higher risk for failure for the open sandwich technique compared to total-etch class-II composite restorations (HR=2.9; p<0.001). Application of glass-ionomer cement using the open sandwich technique cannot be recommended for class-II restorations as being more complex and showing poorer clinical performance.

Patient-reported lower limb edema after primary radiotherapy for prostate cancer

Background Secondary lymphedema is a known side effect to radiotherapy (RT), but limited information regarding prevalence and risk factors for lower limb edema (LLE) after curative radiotherapy in patients with prostate cancer (PCa) is available. This study provides a descriptive analysis of patient-reported LLE with analysis of risk factors in a cohort of patients with PCa treated with curative RT. Material and methods A total of 302 patients with PCa with prospective registration of patient-reported LLE (EORTC QLQ-PR25 (Question 46)) were included. Analysis of LLE was done with the calculation of prevalence rates and Kaplan-Meier statistics. Risk factors for LLE were analyzed multivariate with Cox regression analysis. Results At a median follow-up of 15 (3–51) months, the overall crude incidence of patients reporting ‘quite a bit’ or ‘a lot’ of LLE was 49 (16.2%) and 21 (7.0%), respectively. The baseline prevalence rate of ‘quite a bit’ and ‘a lot’ of LLE was 5.0% and 0.8%, respectively. During follow-up the prevalence rate for ‘quite a bit’ or ‘a lot’ of LLE increased significantly and remained constant from 6 months where 11.5% (±1.7%) reported ‘quite a bit’ and 2.9% (±0.5%) reported ‘very much’ LLE (p < 0.001), respectively. Significant risk factors (p < 0.10) for LLE in univariate analysis included lymph node irradiation (HR:2.325), baseline Body Mass Index (BMI) (HR:1.100), Charlson Comorbidity Index (HR:1.227), Androgen Deprivation Therapy (HR:2,979), and Performance Status (HR:0.594). Only high BMI (HR:1.091) remained significant in multivariate analysis with a three-fold increase in LLE in patients with BMI ≥ 30 compared to normal weight patients. Conclusion Severe patient-reported LLE after curative RT for PCa is rare. Significantly more patients with a high BMI report ‘quite a bit’ or ‘very much’ LLE compared to patients with a normal BMI. Obese PCa patients could be offered a rehabilitation program for early detection and management of LLE.

Radioactive iodine therapy strategies for distinct types of differentiated thyroid cancer: a propensity score-matched analysis.

The management guidelines of radioactive Iodine (RAI) therapy for distinct types of differentiated thyroid carcinoma (DTC) were the same in clinical practice. However, in distinct types DTC, differences in RAI avidity and response existed and the effect of RAI therapy could not be equated. DTC patients' data in SEER database were extracted to perform retrospective analysis. The differences between case group and control group were compared by chi-square tests. We used Kaplan-Meier statistics and Cox regression analyses to investigate cancer-specific survival (CSS). Propensity score-matched was performed to make 1:1 case-control matching. 105195 patients who receiving total thyroidectomy were identified in SEER database. Compared to papillary thyroid carcinoma (PTC) (52.3%), follicular thyroid carcinoma (FTC) (63.8%) and oncocytic carcinoma of thyroid (OCA) (64.4%) had higher rates of RAI therapy. In the multivariable Cox regression model, RAI therapy was independent prognosis factor in PTC but not in OCA and FTC. In subgroup analysis, RAI therapy could improve prognosis in PTC when gross extrathyroidal extension or lymph node metastases or early survival when distant metastases (DM) were presented. However, OCA and FTC patients with DM rather than regional lesions only could benefit from RAI therapy. High-risk patients receiving RAI therapy showed a better prognosis in PTC but not in OCA and FTC. RAI therapy was an effective treatment for DTC and should be considered individually in PTC, OCA and FTC patients. Our results provided further guideline for treatment selection in DTC.

Surgical repair of external cervical resorption - Prognosis and prognostic factors

Background/purposeExternal cervical resorption (ECR) is an aggressive form of root resorption, which etiology is unclear and its prognosis remains unpredictable. The purpose of this study was to investigate the prognosis and potential prognostic factors of ECR-affected teeth after surgical intervention for external repair with/without root canal treatment. Materials and methodsTreated ECR cases from 2009 to 2019 were collected retrospectively. The survival of the teeth and the status of root resorption were assessed during the follow-up period. Potential prognostic factors were analyzed with log-rank test and Kaplan–Meier statistics. ResultsA total of 42 treated ECR-affected teeth were enrolled. The two-year survival rate was 71.20% [54.16%, 93.59%]. Persistent root resorption was the main complication after treatment. Patients with multiple ECR-affected teeth had greater recurrent potential than patients with solitary ECR-affected teeth. Prolonged calcium hydroxide dressing may contribute to a more favorable clinical outcome. Gender, age, tooth position and the need for root canal treatment did not show statistically significant effect on the prognosis. ConclusionThe current surgical method was able to arrest ECR in most cases. However, the case type (the number of ECR-affected teeth per patient) could highly affect the prognosis of the teeth. Clinicians should consider long-term calcium hydroxide dressing in case of pulp involvement to achieve better results.

THE USE OF 5-AMINOLEVULINIC ACID (5-ALA) IN HIGH-GRADE GLIOMA SURGERY, A SINGLE CANADIAN CENTER EXPERIENCE

Abstract 5-Aminolevulinic acid (5-ALA) is a prodrug used to selectively illuminate high-grade glioma (HGG) tissue intra-operatively, shown to nearly double complete resection rates in a 2006 multicentre, phase III clinical trial. Here, we review the history of the 2020 approval of 5-ALA in Canada and present some of the first preliminary results on resection rates, survival analysis, and adverse effects from a single Canadian center. METHODS: We enrolled 76 patients (median age 61 years, 42 male) with suspected HGG amenable to surgical resection to undergo 5-ALA fluorescence-guided surgery between June 2020 and January 2023. Gross total resection was defined by the absence of enhancing l esions on postoperative MRI. We compared the survival distributions of confirmed HGG cases with complete vs. incomplete resection using a log-rank test and Kaplan-Meier statistics. RESULTS: 52 patients were confirmed as having a HGG (grade III or IV) based on a pathological diagnosis. In 32 of these patients (60.3%) a gross total resection was achieved. 46 patients of the initial cohort had their surgery done for more than 180 days. 47.8% had a survival of 600 or more days. CONCLUSIONS: 5-ALA fluorescence-guided surgery resulted in high complete resection rates, comparable to literature with no notable adverse side effects.