Normal LDH Levels Research Articles

Clinicopathological analysis and management of primary cardiac sarcomas: A retrospective study from two cancer centers in China.

e23544 Background: Primary cardiac sarcomas (PCS) are rare malignant tumors associated with a poor prognosis. The clinical and pathological features of PCS remain elusive. Methods: We retrospectively collected records of patients with PCS at Peking University Cancer Hospital and Zhejiang Cancer Hospital from 2016 to 2023. Clinicopathological data, treatments, and outcomes were included and analyzed. Results: Between January 2016 and October 2023, a total of 26 patients with primary cardiac sarcoma were included, with the majority of patients being female (57.7%). The median age of the patients was 38.5 years (range: 15-82). Tumors were most frequently located in the right (42.3%) and left (26.9%) atria. The predominant histological subtype was angiosarcoma (46.1%), followed by myxoid fibrosarcoma (15.4%) and intimal sarcoma (11.5%). At baseline, the LDH level was elevated in 42.3% of patients. Metastases were observed in 21 (80.8%) patients, predominantly in lung (61.9%), bone (42.9%) and liver (28.6%). Nineteen patients (73.1%) underwent surgery for the primary tumor, with 8 (42.1%) achieving a complete (R0) resection and 11 (57.9%) achieving a microscopically (R1) or macroscopically (R2) incomplete resection. Sixteen patients (61.5%) received anthracycline-based chemotherapy as their first-line palliative treatment. The median overall survival (OS) for all patients was 19.2 months (95% CI: 16.7-31.2). Patients with normal baseline LDH levels had a significantly longer median OS (25.4 months) compared to patients with elevated LDH levels (11.6 months, P= 0.001). The median OS was 25.4 months for patients who underwent R0 resection, compared to 18.7 months for those who underwent R1/R2 resection, and 6.03 months for those who did not undergo surgery. Patients who received anthracycline-based chemotherapy had a moderately better survival than those who received paclitaxel-based chemotherapy (mOS 19.2 vs.14.8 months, P= 0.13). Conclusions: In patients with PCS, angiosarcoma is the predominant histological subtype, and the most common sites of metastasis are the lung, bone, and liver. Elevated LDH is associated with a poorer prognosis. Complete surgical resection of the cardiac sarcoma after diagnosis may benefit long-term survival. [Table: see text]

Outcome of adjuvant immunotherapy in a real-world nation-wide cohort of patients with melanoma

BackgroundClinical trials have demonstrated promising outcomes for adjuvant immunotherapy in patients with resected melanoma. Real-life data provide valuable insights to support patient guidance and treatment decisions. MethodsObservational population-based study examining a national cohort of patients with resected stage III-IV melanoma referred for adjuvant therapy. Data were extracted from the Danish Metastatic Melanoma Database (DAMMED). ResultsBetween November 2018 and January 2022, 785 patients received adjuvant anti-PD-1. The majority had stage III resected melanoma (87%), normal LDH levels (80%), and performance score 0 (87%). Patients were followed for a median of 25.6 months (95%CI 24−28). The median recurrence-free survival (RFS) and melanoma-specific survival (MSS) were not reached. The RFS was 78% (95%CI 75−81), 66% (63−70), and 59% (55−63); MSS was 97% (95−98), 93% (91−95), and 87% (84−90) at 1-, 2-, and 3-year; respectively. Less than half (42%) of the patients finalized planned therapy, 32% discontinued due to toxicity, and 19% due to melanoma recurrence. Patients discontinuing adjuvant treatment prematurely, without recurrence, had similar outcomes as patients finalizing therapy. In a multivariable analysis, ipilimumab plus nivolumab did not improve outcomes compared to ipilimumab monotherapy as a first-line metastatic treatment after adjuvant anti-PD-1. ConclusionSurvival outcomes in real-world patients with melanoma treated with adjuvant anti-PD-1 align with results from the randomized controlled trials. Patients discontinuing therapy prematurely, for other reasons than recurrence, had similar outcomes as patients finalizing planned treatment. First-line metastatic treatment with ipilimumab and nivolumab post-adjuvant anti-PD-1 did not show improved outcomes compared to ipilimumab/anti-PD-1 monotherapy.

Prognostic factors for overall survival in patients with advanced digestive neuroendocrine carcinoma treated with first-line cisplatin-based chemotherapy: A post-hoc analysis of JCOG1213.

594 Background: Advanced digestive neuroendocrine carcinoma (ADNEC) is a rare and aggressive malignancy without evidence of prognostic factors assessed in prospective studies. We aimed to evaluate prognostic factors in patients with ADNEC receiving first-line cisplatin-based chemotherapy. Methods: This is a post-hoc analysis of JCOG1213, which is a phase 3 randomized trial showing equivalent overall survival (OS) for cisplatin plus etoposide versus cisplatin plus irinotecan as first-line chemotherapy for patients with ADNEC. The primary endpoint of JCOG1213 was OS. For this post-hoc analysis of prognostic factors, patients who had ineligible histology based on the central pathological review or who lacked the necessary clinical data for analysis were excluded. A Cox proportional hazard model was used to assess the effect of independent variables on OS. Priori variables selected on previous reports (performance status (PS), Ki-67 index, and serum LDH level), as well as variables that remained at a level of p-value <0.20 by backward stepwise selection, were incorporated in the final model of OS. Results: Among 170 patients enrolled in JCOG1213, a total of 129 patients with ADNEC were included in this analysis. In multivariable analysis, serum LDH level (> upper normal limit vs. normal) was identified as a significant prognostic factor for OS (HR = 1.721, 95% CI: 1.144–2.589, p = 0.009). Other clinicopathological factors were not found to be significant, including PS (1 vs. 0; HR = 0.784, 95% CI: 0.507–1.214, p = 0.276), Ki-67 (≥ 55% vs. < 55%; HR = 1.475, 95% CI: 0.588–3.698, p = 0.407), liver metastasis (present vs. absent; HR = 1.434, 95% CI: 0.968–2.124, p = 0.072), sex (female vs. male; HR = 1.387, 95% CI: 0.937–2.053, p = 0.102), and serum ALP level (> upper normal limit vs. normal; HR = 0.948, 95% CI: 0.639–1.406, p = 0.789). OS of patients with elevated serum LDH levels was shorter than those with normal serum LDH levels (median: 9.5 months vs. 15.6 months, p = 0.0019). No statistically significant differences were observed between the two groups regarding objective response rate (58.8% vs. 54.1%, p = 0.594) and progression-free survival (median: 4.5 months vs. 5.9 months, p = 0.141). A numerically lower proportion of patients with elevated serum LDH levels received second-line chemotherapy than those with normal serum LDH levels (76.5% vs. 88.3%). Conclusions: Serum LDH level may serve as a prognostic factor in the daily practice of patients with ADNEC and as a risk stratification factor in future randomized clinical trials. Clinical trial information: UMIN000014795 .

Clinical characteristics and survival analysis in patients with isolated pulmonary metastases from colorectal cancer (CRC).

60 Background: Recent studies seem to indicate that patients with metastatic colorectal cancer (mCRC) with exclusive pulmonary metastatic disease have better outcomes than those with other metastatic sites. The aim of this study is to identify differences in clinical and survival characteristics between the two groups in a cohort of a third level hospital. Methods: We retrospectively analyzed a sample of 569 patients with mCRC in a tumor registry from 2015 to 2021, studying clinical and molecular characteristics, as well as overall survival data of patients with isolated pulmonary metastases, versus the rest of patients. Results: Of the total sample analyzed, 61 patients (10.7%) had isolated pulmonary metastases. In these patients, several clinical characteristics were more frequent: primary rectal tumor (52.5% vs 23.4%, p < 0.000), resected primary tumor (95.1% vs 78.9%, p = 0.0026), metachronous metastatic disease (62.3% vs 42%, p = 0.0025) and complete response rate to the first line of treatment (19.3% vs 9.9%, p = 0.026). Furthermore, analytically, these patients were more likely to have normal CEA (75% vs 38.3%, p < 0.000), CA 19.9 (84.3% vs 57.7%, p = 0.0002) and LDH (91.1% vs 66.5%, p = 0.0007) levels. In our cohort, we found no statistically significant differences in tumor mutational status (KRAS, NRAS, BRAF, PI3K and HER2). There were no patients with exclusive pulmonary metastatic disease and microsatellite instability (MSI). 70.3% of patients with isolated pulmonary metastases received lung metastasectomy, and up to 58.3% received a second metastases surgery. We also found a numerical benefit in terms of overall survival (OS) in patients with exclusive metastatic lung disease, although it did not reach statistical signification (median OS 77.3 vs 58.1 months, HR for death 0.70, 95% CI, 0.49 – 1.01, p = 0.083). Conclusions: In our cohort, patients with isolated pulmonary metastases were more likely to have rectal tumors, primary tumor resection, metachronous metastatic disease, higher rate of complete responses and normal CEA, CA 19.9 and LDH levels, with a possible benefit in terms of OS.

Clinical Pathology Characteristics of 221 Pediatric Anaplastic Large Cell Lymphoma-3 Years Follow up and Experience from China Net Childhood Lymphoma(CNCL)

Objective: To investigate the clinical-pathology characteristics, risk factors, necessary for VBL maintenance therapy，through summarize the clinical data of 221 cases of pediatric Anaplastic Large Cell Lymphoma (ALCL), treated with CNCL-ALCL-2017 witch is modify from BFM-ALCL-99 (±vincristine maintenance therapy) in China Net Childhood Lymphoma (CNCL). Methods: Data were collected on 221 children with ALCL enrolled from CNCL at time between April 2017 to March 2023, including: numbers of cases enrolled in each single center, gender and age at the time of initial diagnosis, the first initial symptom, a delay diagnosis, the misdiagnosis disease , the site of involvement, the level of blood uric acid, the level of blood lactate dehydrogenase, the bone marrow and CNS status, tumor complication, complicated with HLH, staging and treatment subgroups, pathological subtypes, CD3 expression in tumor tissue, bone marrow and peripheral blood ALK gene expression at initial diagnosis (qPCR + FISH), and treatment outcomes, treatment strategy(vincristine maintenance or not), time from initial diagnose to relapse, second-line treatment regimen after relapse, and treatment outcomes after relapsed. Statistical analysis was conducted using SPSS 21.0 software. Results: 221 cases were from 22 hospitals in China. Male = 144 cases, female = 71 cases, age range from 1-16 years (median age 8.9 years), duration from initial symptoms onset to diagnosis was 0.3-11 months (median time 1.0 months), delayed diagnosis was present in 51(23%) children (45 children were misdiagnosed with infectious diseases). Pathological subtypes were: common sub type = 150(67.8%), small cell sub type = 19(8.5%), histiocytic variant subtype = 9(4%), ALK negative subtype = 12(5.4%).others = 31(14%). CD3 expression in tumor: negative = 119, positive = 91. ALK positive by qPCR in peripheral blood at the time of the initial diagnosis = 77, ALK positive by qPCR in bone marrow = 78, bulky disease= 21, mediastinal invasion = 84, CNS invasion = 17, skin invasion = 32. tumor related HLH = 25, normal LDH level at initial diagnosis = 133, 1-fold elevated = 45, 2-3-fold elevated = 39, 4-fold elevated = 2, >4-fold elevated = 2, stage I = 5, stage II = 24, stage III = 70, stage IV = 120 , leukemic stage = 2 . Grouping: group A = 1, group B = 21, group C = 191, group D = 8. Vincristine maintenance = 121. Median follow-up time was 35.4 months (0.5-74.9 months), OS at 3 years = 95.1±1.5% (95% CI = 90%-97.3%, Fig. 1), EFS at 3 years = 84.7±4.5% (95% CI = 79%-89.9%, Fig. 2), and there were a total of 23 patients with events, median time was7 months. There were 10 patients died, 5 of them quit to the treatment, median time was 5 months, and 13 patients who had an event but still alive after second line treatment. Univariate results of the 3 years EFS are detailed in Table 1, with statistically significant including (<0.05): tumor related HLH before treatment, LDH levels higher than 4 times normal and MDD positive at the beginning of the disease, and treated without VBL. The event patients are 23 cases ,the detailed in Table 2, which showed that the earlier the event occurs, the higher the mortality rate. Conclusion:Pediatric ALCL in China is mostly found in school-age boys, and it is easy to be diagnosed as infectious diseases at the time of initial diagnosis due to high fever and elevated CRP. 87% of patients were diagnosed as late stage or high-risk group. The application of the CNCL-ALCL-2017 protocol showed a 3-year OS 84.7% and 3-year EFS 95.1%, indicating that the efficacy was significantly better than that of various centers before the multi center cooperation. The overall survival time is significantly better than the event free survival time, indicating that most patients with progression and recurrence still have a chance of re remission after second line treatment. Adverse prognostic factors include a significant increase in LDH levels at initial diagnosis, initial onset of HLH, positive MDD before treatment, and no use of vinblastine maintenance therapy. Recurrent children: The median recurrence time is 7 months, and the prognosis of early progression and recurrence is worse than that of late recurrence. Key words: Anaplastic large cell lymphoma, Pediatric, Clinical-pathology features, Prognosis

Primary tumour category, site of metastasis, and baseline serum S100B and LDH are independent prognostic factors for survival in metastatic melanoma patients treated with anti-PD-1.

Prognostic classification of metastatic melanoma patients treated with anti-PD-1 is of great interest to clinicians. We aimed to determine the anti-PD-1 treatment related prognostic performance of demographics, clinical and histological prognostic markers and baseline serum S100B and LDH levels in advanced melanoma. A total of 200 patients with unresectable metastatic melanoma were included in this retrospective study. 34.5% had stage M1c disease and 11.5% had stage M1d disease at the start of therapy. 30% had pT4b primary melanoma. 55.5% had elevated baseline serum S100B levels and 62.5% had elevated baseline serum LDH levels. We analysed the risk of death using univariate and multivariate Cox proportional-hazards models and the median overall (OS) and progression-free (PFS) survival using the Kaplan-Meier estimator. The median follow-up time from the start of anti-PD-1 treatment in patients who were alive at the end of the study (N=81) was 37 months (range: 6.1-95.9). The multivariate Cox regression analysis showed that M1c stage (vs. M1a, p=0.005) or M1d stage at the start of therapy (vs. M1a, p=0.001), pT4b category (vs. pT1a, p=0.036), elevated baseline serum S100B levels (vs. normal S100B, p=0.008) and elevated LDH levels (vs. normal LDH, p=0.049) were independently associated with poor survival. The combination of M1d stage, elevated baseline serum S100B and LDH levels and pT4b category was associated with a very high risk of death (HR 4.72 [1.81; 12.33]). In the subgroup of patients with pT4b primary melanoma, the median OS of patients with normal serum S100B levels was 37.25 months [95% CI 11.04; 63.46]), while the median OS of patients with elevated serum S100B levels was 8.00 months [95% CI 3.49; 12.51]) (p<0.001); the median OS of patients with normal serum LDH levels was 41.82 months [95% CI 11.33; 72.32]), while the median OS of patients with elevated serum LDH levels was 12.29 months [95% CI 4.35; 20.23]) (p=0.002). Our real-world study indicates that the prognostic role of primary melanoma parameters is preserved in anti-PD-1 treated stage IV patients. Furthermore, there seems to be perspective in combining clinical, histological and serum prognostic markers in a prognostic model.

Imaging response to immune checkpoint inhibitors in patients with advanced melanoma: A retrospective observational cohort study.

e21524 Background: The association of objective imaging response with first line immune checkpoint inhibitor (ICI) therapy regimes in advanced melanoma remains uncharacterized in a real-world context. We compared likelihood of objective response between patients receiving first line anti-programmed cell death protein 1 (anti-PD1) monotherapies (pembrolizumab or nivolumab), or combination nivolumab with the cytotoxic T-cell lymphocyte-antigen 4 inhibitor ipilimumab and outlined the association between objective response and baseline characteristics and survival outcomes. Methods: We conducted a multi-center retrospective cohort analysis of advanced melanoma patients receiving first line ICI therapy from 2013-2020 in Alberta, Canada. Best imaging response was assessed by Response Evaluation Criteria in Solid Tumors, Version 1.1. The primary outcome was likelihood of objective imaging response (complete or partial response) between patients receiving anti-PD1 monotherapy and those receiving combination nivolumab-ipilimumab. Secondary outcomes were the identification of baseline characteristics associated with non-response and the association of imaging response with overall survival (OS) and time to next treatment (TTNT) endpoints. Results: Of the 255 patients included, 49/255 (19.2%) had complete response 112/255 (43.9%) had partial response, 28/255 (11.0%) had stable disease, and 66/255 (25.9%) had progressive disease. Median OS was not evaluable (NE) (95% CI NE-NE) for complete responders, NE (95% CI 52.93 months-NE) for partial responders, 21.30 months (95% CI 15.20 months-NE) for stable disease, and 7.72 months (95% CI 5.77-10.6 months) for progressive disease (log rank p &lt; 0.0001). A robust delineation of TTNT by imaging response was also seen. Likelihood of objective response was similar between patients treated with nivolumab-ipilimumab compared to those receiving anti-PD1 monotherapy (OR 1.87 95% CI 0.85-4.20, p = 0.124). Normal LDH level (OR 2.13; 95% CI 1.01-4.35, p = 0.047), non-mucosal primary site (OR 9.09; 95% CI 2.44-33.33, p &lt; 0.001), and absence of BRAF V600E mutation (OR 3.23; 95% CI 1.39-7.69, p = 0.007) were independently associated with likelihood of objective imaging response in multivariable analysis. Conclusions: In this real-world analysis, we demonstrate no significant difference in likelihood of objective response between patients treated with anti-PD1 monotherapy and combination nivolumab-ipilimumab, and demonstrate that a normal LDH level, non-mucosal primary site, and absence of BRAF V600E mutation are associated with response. Imaging response was also strongly associated with both OS and TTNT irrespective of therapy received. These results may help inform treatment selection, and aid in counseling of advanced melanoma patients treated with first line ICI therapy in a routine clinical practice setting.

A giant congenital ranula: ignorance leading to feeding difficulties

The term “Ranula” originates from the Latin Word Rana which means “underbelly of a frog.” Ranula are epithelial retention cyst or mucus extravasation pseudo cyst arising from the sublingual glands. They are rare in children. A one-year-old female was brought to paediatric surgery emergency OPD by her mother with complaints of swelling arising from oral cavity since birth, gradually increased in size to attain current size. Mother also gives History of difficulty in feeding. Clinical examination revealed a large protruded tongue, with a cystic swelling in the floor of the mouth measuring around 6×4 cm, with elevation of the tongue. Child was further evaluated; ultrasound was suggestive of ranula. Marsupialisation of the cyst was done. Intraoperatively, cyst fluid was aspirated for analysis and cyst wall was opened and excised, lateral margins of cyst were sutured to base of mouth. Cyst fluid analysis revealed elevated amylase and normal LDH levels. The post-operative period was uneventful. The histopathology report showed a pattern consistent with ranula. Child was followed up for a period of 1 year and there was no evidence of recurrence. We report a case of giant congenital ranula. The rarity of this condition in children and its atypical size make this case report unique. We treated the child with marsupialization and there was no recurrence noted. Hereby I would like to state that congenital symptomatic ranulas though rare can be managed with marsupialisation.

Evaluation of Hexokinase 2 and Serum LDH in B-cell Non-Hodgkin’s Lymphoma Patients

Background and Objective: Tumor cells produce energy by glycolysis and Lactate Dehydrogenase and Hexokinase are the key part of glycolysis, The present study aimed to evaluate the expression of Hexokinase 2 and serum LDH in B-cell Non-Hodgkin’s Lymphoma patients Method: A total of 84 B-cell Non-Hodgkin’s Lymphoma Patients were enrolled in the study. HK-2 Marker was studied by Immunohistochemistry and LDH analysis was done by Cobas 6000 analyser method and correlated with Clinico-Pathological Parameters and Diagnostic panel. RESULT:73% of B-cell NHL patients had Abnormal LDH. It was significantly correlated with Multiple Disease site (P=0.002). In correlation with Diagnostic Panel (MIb1, CD10, CD2, MUM1, BCL6, BCL2) a higher trend of Abnormal LDH was seen in BCL-6 positive and BCL-2 negative Patients. 64% of patients had HK-2 expression. In correlation with Clinical parameters, it was significantly correlated with &gt;50 age group, while in correlation with pathological parameters A significant correlation observed with single disease site as compared to multiple disease site (P=0.004), In correlation with Diagnostic panel A higher trend of HK-2 Expression was observed in CD10 Negative and BCL-2 Negative Patients. Further Univariate survival analysis of LDH and HK-2 showed similar Overall survival in Abnormal and normal LDH level patients and HK-2 Positive and negative Patients respectively. Further Intercorrelation of both markers, showed almost similar expression of HK-2 between patients with normal LDH level and abnormal LDH level. CONCLUSION: Abnormal LDH level was closely associated with patients having disease at multiple sites, suggesting its activity to be associated with the advancement of the disease, HK-2 positivity was related with older age group, strengthens the findings of increased altered metabolic activity with older age, They are also associated with BCL-2 negativity that indicates that anti-apoptotic activity of BCL-2 might be responsible for that Though there was no significant correlation of LDH,, HK-2 with overall survival, majority of the patients who were dead had abnormal LDH and half of them showed positive HK-2 expression Briefly our data indicates that LDH and HK-2 can be useful parameter in defining clinical and prognostic aspects in NHL patient but needs further evaluation with larger groups of patients Keywords: NHL, Altered metabolism, Hexokinase, LDH

Total metabolic tumor volume on 18F-fluorodeoxyglucose-positron emission tomography ([18F]-FDG-PET) scan: A potential prognostic factor in extensive-stage small cell lung cancer.

8574 Background: Small-cell lung cancer (SCLC) is a highly aggressive neuroendocrine lung cancer, accounting for 10-15% of all lung cancers, commonly classified in limited stage (LS-SCLC) and extensive stage (ES-SCLC). Despite the introduction of chemoimmunotherapy as new standard first-line therapy for ES-SCLC, the benefit of addition of the programmed-death ligand 1 (PD-L1) inhibitors is limited to a subset of patients, suggesting the importance to identify predictive biomarkers of response. [18F]FDG-PET/CT is commonly used for the staging and therapeutic planning of SCLC patients. Metabolic parameters derived from [18F]FDG-PET could predict patient outcomes by measuring the extension of metabolically active tumor (metabolic tumor volume [MTV]) or its metabolic heterogeneity (total lesion glycolysis [TLG]). Methods: We retrospectively collected patients with pathologically confirmed diagnosis of SCLC, who had undergone an [18F]FDG PET/CT scan within 30 days from the start of first-line treatment for ES-SCLC. Patients with LS-SCLC at diagnosis were included if presenting relapse at pre-treatment scans performed at least 90 days from the end of treatment with radical intent. We calculated metabolic parameters, MTV and TLG, by summing each single lesion’s MTV and TLD respectively. The primary endpoint of the study was overall survival (OS), defined as the time from [18F]FDG PET/CT scan acquisition to death from any cause. Results: A total of 86 SCLC patients ES-SCLC were included. Patients with hyponatremia, hypoalbuminemia and elevated LDH levels were associated with greater number of lesions, greater total MTV, and higher total TLG at [18F]FDG-PET/CT/CT scan. At a median follow-up of 20.9 months, the median OS was 11.1 months. Median survival was longer among patients with Na + ≥135 mEq/L, with normal albumin levels and in those with normal LDH levels and without bone metastases. Patients with low total MTV had longer OS compared with those with high total MTV (11.9 months vs 4.8 months, respectively). High total MTV was independently associated with the risk of death (p &lt; 0.001) but not with the risk of progression. Conclusions: Our preliminary data showed that total MTV could provide prognostic information in patients with ES-SCLC, suggesting a potential role as stratification factor in immunotherapy-based clinical trials.

Sequential treatment with targeted and immune checkpoint inhibitor therapies in patients with BRAF positive metastatic melanoma: Real-world data.

e21539 Background: The use of targeted therapies (TT) and checkpoint inhibitors (IT) significantly prolonged survival in patients with metastatic melanoma, especially in patients with BRAF mutation-positive melanoma. Optimal sequence of therapies use is still a matter of debate. The aim of this study was to evaluate real-life practice and outcomes in melanoma patients treated sequentially. Methods: Consecutive patients with BRAF mutation-positive unresectable or metastatic melanoma started treatment with TT (BRAF and MEK inhibitors) and/or IT (anti-PD1) between 1/Oct/2016 and 31/Dec/2020. Clinical factors including age, gender, ECOG performance status, baseline LDH level, and location of metastases, response to treatment and irAEs occurrence were analyzed. Survival analyses were performed using the Kaplan-Meier method, Log-rank and chi-square tests were used for comparison between groups. Data cut-off was 31/Dec/2021. Results: In total 585 patients were enrolled. 170 (29%) patients were treated with IT and 415 (71%) with TT in the first line. 331 patients (56%) received only one line of treatment – 247/415 (59%) patients only TT and 84/170 (49%) patients received only IT (anti-PD1). Disease progression was found in 175 (71%) patients in the only TT group and in 43 (51%) in the only IT group. 254 patients qualified for sequential treatment 168 (29%) patients received TT then IT (TT-IT), 64 (11%) IT then TT (IT-TT), and 22 (4%) IT-IT (anti-PD-1 then anti-CTLA-4). Patients with brain metastases and elevated LDH were statistically more often treated with first line TT and more patients with normal LDH level received IT-IT therapy. No other statistically significant differences in baseline characteristics was found for IT-TT, TT-IT and IT-IT groups. The estimated median OS (mOS) was not reached in patients treated with only one line of IT treatment, while for TT only it was only 11.8 months. Estimated mOS for patients treated in the first line with IT or TT was significantly different (p = 0.02; HR = 0.74, Cl 95% 0.6-0.9) and reached 25.6 and 15.3 months, respectively; although no statistically significant mOS differences was found in the subgroups without brain metastases (p = 0.56) and with normal LDH (p = 0.36). For sequential treatment groups mOS for IT-TT, TT-IT, and IT-IT was 19.6, 19.9 and 35.9 months, respectively. There was no statistically significant difference in OS between IT-TT and TT-IT treated groups (p = 0.56), and between IT-TT, TT-IT and IT-IT groups (p = 0.19). Conclusions: Patients who were treated with IT in the 1st line had better OS than patients treated TT in the 1st line in real-world data but this may be related to better prognostic factors in the IT group. Selected patients receiving IT in the first line achieve long OS, which is a result of a long-term response to IT. Novel predictive biomarkers factors of IT response should be incorporated in prospective trials.

A novel prognostic index for sporadic Burkitt lymphoma in adult patients: a real-word multicenter study

BackgroundAdult sporadic Burkitt lymphoma (BL) is a rare but highly aggressive subtype of lymphoma which lacks its own unique prognostic model. Systemic inflammatory biomarkers have been confirmed as prognostic markers in several types of malignancy. Our objective was to explore the predictive value of pretreatment inflammatory biomarkers and establish a novel, clinically applicable prognostic index for adult patients with sporadic BL.MethodsWe surveyed retrospectively 336 adult patients with newly diagnosed sporadic BL at 8 Chinese medical centers and divided into training cohort (n = 229) and validation cohort (n = 107). The pretreatment inflammatory biomarkers were calculated for optimal cut-off value. The association between serum biomarkers and overall survival (OS) was analyzed by Kaplan–Meier curves and Cox proportional models. The risk stratification was defined based on normal LDH level, Ann Arbor stage of I and completely resected abdominal lesion or single extra-abdominal mass < 10 cm.Results and conclusionsUnivariate and multivariate analyses revealed that platelets< 254 × 109/L, albumin< 40 g/L, lactate dehydrogenase≥334 U/L independently predicted unfavorable OS. We used these data as the basis for the prognostic index, in which patients were stratified into Group 1 (no or one risk factor), Group 2 (two risk factors), or Group 3 (three risk factors), which were associated with 5-year OS rates of 88.1, 72.4, and 45%, respectively. In the subgroup analysis for high-risk patients, our prognostic model results showed that high-risk patients with no more than one adverse factor presented a 5-year survival rate of 85.9%, but patients with three adverse factors had a 5-year survival rate of 43.0%. Harrell’s concordance index (C-index) of the risk group score was 0.768. Therefore, the new prognostic model could be used to develop risk-adapted treatment approaches for adult sporadic BL.

Effect of MAGE-C1 Gene Expression on Prognosis and Effectiveness of Bortezomib-Containing Courses in Multiple Myeloma

Introduction. The group of genes, encoding cancer-testis antigens is actively studied as a new markers of refractory in some diseases, including multiple myeloma (MM). It is suggested that the MAGE-C1 gene in MM may be considered as an additional marker predicting the effectiveness of therapy.Purpose. Determine of MAGE-C1 gene expression by quantitative real-time polymerase chain reaction (qRT-PCR) in MM patients and assess the correlation of expression with some laboratory parameters and response on bortezomib-containing therapy.Patients and methods. A prospective study from February 2019 to July 2021 included 76 MM patients (43 men and 33 women) aged 35 to 82 years (median 58). The level of MAGE-C1 gene expression by qPCR-PCR in bone marrow samples, enriched with CD138+ cells, was determined for all patients. Quantity of MAGE-C1 expression was calculated with 2ΔCt method relative to housekeeping gene expression. Plasma cell content ranged from 1 to 89% (median 26%), monoclonal paraprotein secretion vary from 2.1 to 82.1 g/l, Bence-Jones protein in urine (from trace values to 12.54 g/day) was determined in 50 patients. High - risk cytogenetic [t(4; 14)(p16; q32), del17p] was documented in 22 patients, bone plasmocytomas - in 36 patients, myeloma nephropathy - in 17. All patients recieved induction with bortezomib - containing courses. Median follow-up duration: 14 months (1-22 months). As a control, similar bone marrow cells of 7 healthy donors were investigated.Results. The average value of MAGE-C1 expression in donors was 0.01 ± 0.007, a range of values vary from 0.0003 to 0.06. Gene expression MAGE-C1 index > 0.06 is accepted as increased expression. High serum lactate dehydrogenase (LDH) level (higher than the upper limit of reference values) was observed in patients with high MAGE-C1 gene expression [median - 0.35], normal LDH-level (≤ 260 U/L) was observed in patients with lower MAGE-C1 gene expression [median - 0.04]; p < 0.0001 (Figure 1). Negative correlation was found between the content of hemoglobin (Hb) and level of MAGE-C1 expression: Hb ≥ 12.0 g/dl was observed in patients with increased MAGE-C1 expression [median - 0.27], and Hb 5.5-11.8 g/dl - in patients with lower expression indices [median 0.1]; p=0,034.Antitumor response was evaluated after induction therapy in 51 patients. In 100% of patients with MAGE-C1 expression of ≤ 0.06 ≥ partial response (PR) was achieved, while in patients with MAGE-C1 expression of 0.07-1.0 ≥ PR was achieved in 84.6% of cases, and in patients with MAGE-C1 expression of > 1.0 - in 58%; p > 0.05. Besides, patients with ≥ PR had a level of MAGE-C1 expression lower than patients with a refractory to bortezomib [median 0.17 vs 1.14]; p = 0.04 (Figure 2).Conclusions. High MAGE-C1 gene expression in MM patients is associated with an increase in LDH, which corresponds to stage III by R-ISS. Probability of achievement of the antitumor response ≥ PR on the bortezomib-containing induction is reliable above at patients with low MAGE-C1 expression while the hyperexpression of this gene is followed by a refractory to a bortezomib therapy. Further study of MAGE-C1 gene expression may promote a personalized approach in the choice of antitumor therapy. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Prognostic value of CD10, BCL6 and MUM1 in diffuse large B-cell lymphoma

Background: Diffuse large B-cell lymphoma (DLBCL) is considered the commonest subtype of non-Hodgkin lymphoma (NHL) in the world. It is a refractory disease with a high mortality rate due to frequent relapses. Several prognostic parameters are now widely studied for risk stratification and achieving a better outcome. Objectives: In this study, we aim to assess the prognostic value of immunohistochemical expression of CD10, BCL6, and MUM1 independently as surrogate markers for cell of origin (COO) classification of DLBCL and their correlation with clinicopathological characters and survival. Patients and methods: This is a retrospective study conducted on 63 cases of DLBCL, NOS. Full-faced sections were constructed and immunostained for CD10, BCL6, and MUM1. Results: CD10 expression was associated with early-stage (P=0.003), normal serum LDH level (P=0.022), absence of B symptoms (P=0.019), low international prognostic index (IPI) and age-adjusted-IPI (P=0.001) and also associated with longer progression free survival (PFS) (P=0.006). BCL6 expression was associated with centroblastic variant (P=0.005), good ECOG performance status (P=0.038) and low IPI (P=0.004) and also associated with better overall survival (OS) (P=0.028) and PFS (P=0.018). MUM1 expression was associated with advanced-stage (P=0.002) while no significant association was detected with other clinicopathological parameters or survival. Conclusion CD10, BCL6, and MUM1 can be used independently as prognostic immunohistochemical markers for DLBCL that may denote the clinical behavior of the disease and further patients' outcomes.

Development of immunity-related adverse events correlates with baseline clinical factors, survival and response to anti-PD-1 treatment in patients with inoperable or metastatic melanoma

Background The relationship between immune related adverse events (irAEs) and efficacy is not definitively proven, and data on the relationship between irAE and treatment efficacy are contradictory. Material and methods Five hundred ninety-three consecutive patients with unresectable or metastatic melanoma treated in the first line with anti-PD-1 (nivolumab or pembrolizumab) between January 2016 and December 2019 were enrolled in the study. Results Statistically significant differences were demonstrated between the group of patients without and with irAE in median OS and PFS (p < .0001 both) and also in OS between the group of patients without irAE and patients with irAE within 3, 6, and 9 months from the start of anti-PD-1 therapy (p = .0121, p = .0014, p < .0001; respectively) and PFS (p = .0369, p = .0052, p = .0001; respectively). A statistically significant relationship was demonstrated between the occurrence of irAE and the location of the primary tumor (skin vs. mucosa vs. unknown; p = .0183), brain metastasis (present vs. absent; p = .0032), other locations (present vs. absent, p = .0032), LDH (normal vs. elevated; p = .0046) and stage according to TNM (p = .0093). Conclusion The occurrence of irAE was associated with longer OS, PFS, and more frequent response to treatment. IrAE occurred statistically significantly more often in patients with mucosa primary tumor, with normal LDH levels, without brain metastases, stages III, M1a, and M1b.

Comparison of the efficacy and toxicity of anti-PD-1 monoclonal antibodies (nivolumab versus pembrolizumab) in treatment of patients with metastatic melanoma.

e21514 Background: Anti-programmed cell death-1 antibodies (anti-PD-1) have become a standard treatment option for melanoma patients. Currently, two anti-PD-1 antibodies are registered in the treatment of melanoma patients: nivolumab and pembrolizumab. Nivolumab is a human monoclonal antibody, while pembrolizumab is a humanized antibody. Unfortunately, there are very few clinical data comparing the efficacy and toxicity of nivolumab and pembrolizumab in routine practice. Methods: Consecutive patients treated in the first line with anti-PD-1 (nivolumab or pembrolizumab) for unresectable or metastatic melanoma in comprehensive cancer centers between 03/2016 and 09/2020 were enrolled in the analysis. Baseline factors (age, gender, primary location of melanoma, BRAF mutation status, ECOG performance status, baseline LDH level, and location of metastases) were evaluated to identify predictors of overall survival (OS). Data on response to treatment and the occurrence of irAEs were collected prospectively during anti-PD-1 treatment. OS were assessed using Kaplan–Meier and Cox models. The Chi-Square statistic was used for testing relationships between categorical variables. Median follow up for nivolumab and pembrolizumab group was 12.6 (range 0.2-52.1) and 10.7 (range 0.03-53.5) months, respectively. Results: Overall, 736 patients were included in the present analysis (443 nivolumab, 293 pembrolizumab). There were no statistically significant differences in baseline factors (age, gender, primary location of melanoma, BRAF mutation status, ECOG performance status, baseline LDH level (normal vs elevated), brain metastasis and TNM stage) between the groups. Median OS for patients treated with nivolumab and pembrolizumab was 22 and was 17.3 months, respectively. There was no statistically significant difference in OS between the nivolumab and pembrolizumab groups (p = 0.12, HR = 1.2, Cl 95% 0.9-1.4). At multivariate analysis normal LDH levels, no brain metastases, and ECOG 0 or 1 were positive prognostic factors for OS both in nivolumab and pembrolizumab groups. In the nivolumab and pembrolizumab groups, 6% and 5% CR (complete response), 33% and 31% PR (partial response), 25% and 24% SD (stable disease), respectively, were observed. There was no statistical difference between the groups in the response to treatment (p = 0.65). There was no statistical difference between the groups in occurrence of the irAEs (p = 0.97) as well as in the type of irAEs. Conclusions: Our analysis in melanoma patients treated in routine practice with nivolumab or pembrolizumab confirmed no statistical differences in OS and treatment responses between these two anti-PD-1 antibodies. There were also no differences in toxicity between the two drugs. The choice of treatment should be based on the preferences of the patient and the physician.

Treatment Following Progression in Metastatic Melanoma: the State of the Art from Scientific Literature to Clinical Need.

In the last few years, the advent of targeted therapy and immunotherapy has improved the management and the prognosis of metastatic melanoma, but the spread of resistance mechanisms can lead to disease progression. The clinical management in this setting can be challenging because the oncologist has to decide what is the best treatment strategy among therapy beyond progression (TBP), therapy change, and the rechallenge approach. This review of the relevant scientific literature is intended to clarify which patients with progressing metastatic melanoma will benefit from continuation of ongoing therapy and which ones will not. The data are based on a total of about 4300 patients coming from the main retrospective studies in the chosen field. The article body is divided into four sections which analyze respectively the targeted therapy beyond progression, the immunotherapy beyond progression, the possible treatment sequences, and finally the rechallenge strategy. Despite the possible approaches of TBP or rechallenge, the patient may not have an optimal response and may need new therapy, which is currently missing. To broaden the pharmacological offer in the fight against melanoma, cancer research is studying new disease targets, like the NRAS, PI3K, and cKIT pathways or combination treatment of targeted therapy plus immunotherapy. Despite the limitations of this work, mainly due to the limited number of studies, their retrospective nature and the lack of comparative studies, the analysis performed allows us to draw some important conclusions: therapy beyond progression, both targeted therapy and immunotherapy, represents a valid treatment option with positive effects on disease control and survival outcomes for patients with low clinical risk, expressed as low disease burden, normal LDH levels, and good performance status; moreover, the prognosis and quality of life of these patients improve when TBP is associated with locoregional treatments. In patients with progressive metastatic melanoma and high clinical risk (high disease burden, high LDH levels, and poor performance status), it is recommended to change therapy, without ever forgetting the possibility of enrolling the patient in a clinical trial. Finally, an efficacious treatment alternative is the rechallenge strategy; this approach consists in a re-treatment with the same drug after a variable interval of discontinuation. Preliminary studies seem to have demonstrated that patients retreated with targeted therapy achieved a greater benefit if they had a low clinical risk and if the drug doublet (BRAF + MEK inhibitors) was used. On the side of immunotherapy, the rechallenge strategy produced a major benefit in patients who prior experienced a severe toxic episode.

Impact of Genetic Polymorphism of Myeloid Differentiation Primary Response Gene 88, Enhancer of Zeste Homolog 2, and B-cell Lymphoma 2 like 11 in Patients with Diffuse Large B Cell Lymphoma Treated with Rituximab, Cyclophosphamide, Doxorubicin, Vincristin

BACKGROUND: Despite the growing landscape of genetic drivers in Diffuse Large B-cell Lymphoma, yet their clinical implication is still unclear and R-CHOP regimen remains a “one size fits all” therapy. We aimed in this study to examine the prevalence of EZH2, BCL211 and MYD 88 genetic polymorphisms in DLBCL patients and correlate the results with various clinical and survival outcomes.&#x0D; METHODS: Genotyping of MYD88 (rs387907272 T/C), EZH2 (rs3757441 C/T), and BCL2L11 (rs3789068 A/G) polymorphisms were conducted using real time polymerase chain reaction analysis in a total of 75 DLBCL patients.&#x0D; RESULTS: Most of our cases carried the wild TT genotype of MYD88 gene (64%), the mutant TT genotype of EZH2 gene (52%) and the wild AA genotype of BCL2L11 gene (48%). Regarding cell of origin, Germinal Centre (GC) phenotype was present in 56% of cases while 44% expressed the Post-GC (PGC) phenotype. Poor response outcome to first line R-CHOP was significantly correlated with the mutated CC genotype of MYD 88 (p=0.02), while better response to R-CHOP was significantly associated with younger age &lt;50 years (p &lt;0.0001), good PS (p=0.046), normal LDH level (p=0.003), earlier stage (p &lt;0.0001), good IPI score (p=0.009), absence of extranodal disease (p &lt;0.0001) and absence of bulky disease (p=0.004). The median PFS and the 2 year OS were significantly higher in younger age, earlier stage, good IPI score, absence of extranodal disease, absence of bulky disease and in GC phenotype.&#x0D; CONCLUSIONS: Our results emphasized that the mutated genotype of MYD 88 gene polymorphism is significantly associated with poor response to R-CHOP therapy.

Study of maternal and perinatal outcomes among women with pregnancy induced hypertension with normal and high serum LDH levels

Study of maternal and perinatal outcomes among women with pregnancy induced hypertension with normal and high serum LDH levels

Karakteristike bolesnika sa sekundarnom eritrocitozom u odnosu na bolesnike sa policitemijom verom

Introduction: Erythrocytosis represents elevated hemoglobin and hematocrit levels above the range of normal values. Primary erythrocytosis - polycythemia vera, is characterized by increased erythrocyte production, due to a disorder at the level of the multipotent stem cell in the bone marrow. On the other hand, secondary erythrocytosis (SE) is the result of bone marrow stimulation by an external factor. Aim: The aim of our study was to determine parameters which are significant in differentiating SE from primary erythrocytosis - polycythemia vera (PV). Materials and methods: This is a retrospective study involving 108 patients with SE and 111 patients with PV, who were diagnosed and treated at the Clinic of Hematology of the Clinical Center of Serbia (CCS), in the period: December 2005 - November 2018.From the patient records, the following data were extracted: demographic characteristics, laboratory parameters, spleen size, total red cell mass, serum erythropoietin (EPO) level, and spontaneous growth of the BFU-E colony. Results: Patients with SE were younger, with a predominance of the male gender and with significantly higher serum EPO values than patients with PV. Patients with PV had significantly higher values of BFU-E, leukocyte and platelet count, spleen size, and LDH level than patients with SE. Total red cell mass analysis did not show a differential diagnostic significance. Conclusion: Findings of normal spleen size, normal leukocyte and platelet count, normal serum LDH level, and elevated EPO, in patients, refer to the diagnosis of secondary erythrocytosis, while the findings of splenomegaly, leukocytosis, thrombocytosis, elevated serum LDH level, decreased EPO, and the presence of spontaneous BFU-E colony speak in favor of the diagnosis of polycythemia vera.