Significant Prognostic Factors For Overall Survival Research Articles

Treatment Outcomes in Advanced Biliary Tract Cancers: Single Institution Retrospective Analysis

Abstract Purpose Biliary tract cancers (BTCs), particularly gallbladder cancers (GBCs), are prevalent in India. Yet there are limited data on treatment outcomes. To bridge this gap, we performed an analysis of advanced BTC treatment outcomes at our institute, seeking to offer insights into real-world scenario. Materials and Methods This is a retrospective study comprising advanced BTC patients treated at our institute from January 2015 to March 2023. We assessed demographics, treatment approaches, progression-free survival (PFS), overall survival (OS), and associated toxicities. Results Of the 411 patients analyzed, the majority were GBC (67.3%, n = 277), while the rest were cholangiocarcinoma (CCA) (32.6%, n = 134). The median age of study population was 56 years. Palliative chemotherapy was administered in 85% (n = 349) of all patients. Gemcitabine–cisplatin doublet was the most commonly used chemotherapy regimen (80.2%, n = 280). Platinum doublets yielded higher response rates compared with single-agent/nonplatinum chemotherapy (60 vs. 30%, n = 133). The median PFS was 4 months. The median OS was 8 months with platinum doublets and 5 months with single-agent/nonplatinum chemotherapy (hazard ratio [HR]: 0.60, 95% confidence interval: [CI] 0.43–0.84, p = 0.0001). OS was no different based on the type of platinum agent used. Patients receiving multiple lines of treatment lived longer compared with those who received single line only (14 vs. 6 months, respectively, HR: 0.36, 95% CI: 0.28–0.45, p < 0.0001). Significant prognostic factors for OS were treatment with chemotherapy, platinum doublets, platinum exposure in first line, and treatment beyond first line. Grade 3 or 4 adverse effects seen were anemia (13.9%, n = 36), vomiting (4.2%, n = 11), diarrhea (3.4%, n = 9), thrombocytopenia (3.4%, n = 9), and febrile neutropenia (3.1%, n = 8). Conclusion This analysis confirms that chemotherapy is beneficial for advanced BTC. Platinum-based doublets are more effective than single agents. There is no significant difference between cisplatin and oxaliplatin. Patients who received multiple lines of treatment had better OS.

Gustave Roussy Immune score as a prognostic biomarker in patients with platinum-refractory metastatic urothelial carcinoma treated with pembrolizumab: YUSHIMA study.

This study aimed to investigate the prognostic value of the Gustave Roussy Immune score (GRIm-score) in platinum-refractory metastatic urothelial carcinoma (UC) treated with pembrolizumab. This multicenter retrospective study (YUSHIMA study) evaluated 331 patients with metastatic UC treated with pembrolizumab after platinum-based chemotherapy between January 2018 and June 2023 at 13 institutions. We collected pretreatment variables, including the GRIm-score based on serum albumin, lactate dehydrogenase, and neutrophil-to-lymphocyte ratio. The patients were divided into low and high GRIm-score groups. Prognostic factors for overall survival (OS) and progression-free survival (PFS) were determined using the multivariate Cox proportional hazard model. During the median follow-up period of 7.3months, 278 (84%) patients showed disease progression, and 223 (67%) died from any cause. Multivariate analysis revealed that the high GRIm-score group was an independent and significant adverse prognostic factor of both OS and PFS (hazard ratio, 1.65 and 1.82, respectively; both p < 0.001) along with Eastern Cooperative Oncology Group Performance Status of ≥ 2 (both p < 0.001), presence of visceral metastasis (both p < 0.001), and hemoglobin of < 9.2g/dL (p = 0.030 and p = 0.038). C-reactive protein of > 42mg/L was a significant prognostic factor for OS (p = 0.001). The GRIm-score is an independent prognostic marker for survival outcomes in patients with platinum-refractory metastatic UC treated with pembrolizumab.

Five-year survival outcomes from the PIT-1 trial: Pemetrexed-cisplatin plus bevacizumab or concurrent thoracic radiation therapy followed by surgery in stage IIIA (N2) nonsquamous non-small cell lung cancer.

8064 Background: Personized Induction Therapy-1 (PIT-1) is a multicenter, randomized phase II selection design trial of pemetrexed-cisplatin plus bevacizumab (BEV arm) or concurrent thoracic radiation therapy (TRT arm) followed by surgery in patients with stage IIIA (N2) nonsquamous non-small cell lung cancer (NSCLC). The TRT arm was chosen as the investigational induction treatment strategy for a future phase III study based on the results of a numerically higher 2-year progression-free survival (PFS, primary endpoint) in the TRT arm and fatal postoperative complications observed only in the BEV arm. We report updated, exploratory analyses of survival, approximately 5 years after the last patient was randomly assigned. Methods: Patients with stage IIIA (N2) nonsquamous NSCLC were randomly assigned (1:1) induction therapy consisting of pemetrexed and cisplatin plus bevacizumab (n = 44) or concurrent TRT (n = 44) followed by surgery. Among them, 38 patients in the BEV arm and 37 patients in the TRT arm underwent surgery. Five-year overall survival (OS), 5-year PFS, and patterns of postoperative recurrence were compared between arms. Prognostic factors of OS were analyzed in surgically resected patients using Cox’s proportional hazard model. Results: The median follow-up was 66.4 months. In 82 treated patients, the 5-year OS and PFS rates were 63.5% (95% CI: 46.9-76.1) and 26.2% (95% CI: 14.1-40.0) in the BEV arm (n = 42), and 57.2% (95% CI: 40.5-70.8) and 27.5% (95% CI: 14.9-41.7) in the TRT arm (n = 40), respectively. There were no statistical differences in OS ( P = 0.572) and PFS ( P = 0.356). In 75 surgically resected patients, pathological nodal down stage was the only significant prognostic factor of OS ( P = 0.014). Age, sex, smoking status, clinical T stage, clinical N stage based on a computed tomography scan, preoperative serum CEA and CYFRA level, EGFR mutation status, pathological complete response, and major pathological response did not have a significant prognostic impact on OS. The patterns of postoperative recurrence were different between arms: locoregional only, in four (11%) and one (3%); distant metastasis only, in 16 (42%) and 21 (57%); and both, in five (13%) and four (11%) in the BEV and TRT arms, respectively. The recurrence rate of ipsilateral hilar or mediastinal lymph nodes (the irradiation field) was significantly lower in the TRT arm (3%) than in the BEV arm (21%, P= 0.01). Conclusions: Five-year survival outcomes were not different between the BEV and TRT arms. The TRT arm demonstrated sufficient local control, but insufficient control of distant metastasis so this is an important issue that requires improvement in the future. Clinical trial information: s031180402.

Induction Immunochemotherapy Yields a Higher Conversion Rate and Better Overall Survival than Chemotherapy in Initially Unresectable Esophageal Squamous Cell Carcinoma.

This study compared the surgical conversion rate and overall survival (OS) between induction chemotherapy (iC) and induction immunochemotherapy (iIC) for patients with initially unresectable esophageal squamous cell carcinoma (iuESCC). In this multicenter, retrospective cohort study, patients from four high-volume institutions with unresectable diseases were included. The primary endpoints were the conversion surgery rate and OS. A multivariate Cox regression analysis was used to identify the independent significant prognostic factors associated with OS. The stabilized inverse probability of treatment weighting was applied to confirm the survival comparison between the iIC and iC cohorts. A total of 309 patients (150 in the iIC cohort and 159 in the iC cohort) were included. A significantly higher conversion surgical rate was observed in the iIC cohort (iIC vs. iC: 127/150, 84.7% vs. 79/159, 49.7%, P < 0.001). The pathological complete response rates were 22.0% and 5.1% in the iIC and the iC cohorts, respectively (P = 0.001). A significant difference in the OS was observed between the iIC (not reached) and iC cohorts (median 95% CI 36.3 [range 27.2-45.5]). The stabilized inverse probability of treatment weighting yielded similar results. Regimen (iIC vs. iC, HR 0.215, 95% CI 0.102-0.454, P < 0.001) and operation (yes vs. no, HR 0.262, 95% CI 0.161-0.427, P < 0.001) were the significant prognostic factors for OS. Immunochemotherapy plus conversion surgery in the induction setting may be a better treatment option to achieve high pathological responses and improve OS in iuESCC patients.

The outcome of relapsed childhood acute lymphoblastic leukemia after allogeneic hematopoietic stem-cell transplantations: A single-center experience.

In children with high-risk childhood acute leukemia who undergo allogeneic hematopoietic stem-cell transplantation (allo-HSCT), relapse is still the leading cause of treatment failure. The prognosis is poor, yet prospective studies have only limited data on risk factors and outcomes. We aimed to understand the outcomes and prognostic factors for patients with acute lymphoblastic leukemia (ALL) who relapsed following allo-HSCT. We analyzed retrospectively 46 children with childhood acute lymphoblastic leukemia who had relapsed after receiving their first alloHSCT. All these patients received salvage chemotherapy which consisted of fludarabine, cytarabine, and idarubicin before performing a second alloHSCT. The median follow-up of the 46 patients after the first transplantation was 366 days. The median time from first allo-HSCT to relapse was 278.4±238.4 days. Forty-six patients received salvage chemotherapy before the second alloHSCT, and CR was achieved in 32 of 46 patients. However, only 17 (37%) of 46 patients received a second allo-HSCT, and 15 of 46 patients died from disease progression, infections, and bleeding. Twelve patients are still alive after the second allo-HSCT. Two-year overall survival (OS) was 38.9%. Local therapy was given to 10 (21.8%) patients, either as part of systemic therapy or alone. In multivariate analyses, the time of relapse and curative salvage therapy with a second allo-HSCT were identified as significant prognostic factors for OS. Children with leukemia who had relapsed after the first allo-HSCT received salvage chemotherapy. Our statistical analysis showed that the second HSCT could be beneficial for outcomes if patients relapsed beyond 180 days of the first allo-HSCT.

Nomogram-based prognostic tool for stage IIIB/IV non-small cell lung cancer patients undergoing traditional Chinese medicine treatment

ObjectiveGiven the significant impact of long-term traditional Chinese medicine (TCM) treatment on the prognosis of patients with non-small cell lung cancer (NSCLC), we aimed to develop nomograms, with or without consideration of TCM treatment duration, to accurately predict the overall survival (OS) of patients with stage IIIB/IV NSCLC treated with TCM. MethodsNomograms were developed from a training cohort comprised of 292 patients diagnosed with NSCLC, using univariate and multivariate Cox regression analyses to screen for various prognostic factors with and without TCM treatment. The nomograms were evaluated using the concordance index (C-index), calibration curve, and decision curve analysis (DCA), after which they were validated, using the bootstrap self-sampling method for internal validation, and a validation cohort comprised of 175 patients for external validation. Bootstrap validation is a resampling technique that involves randomly selecting and replacing data from the original dataset to make statistical inferences, thereby circumventing the issue of sample reduction that can arise from cross-validation. ResultsWe identified seven significant prognostic factors for OS. For nomogram A (excluding TCM treatment time), the C-indexes (95 % confidence interval [CI]) were 0.674 (0.635–0.712) and 0.660 (0.596–0.724) for the training and validation cohorts, respectively. For nomogram B (including TCM treatment time), the C-indices (95 % CI) were 0.846 (0.822–0.870) and 0.783 (0.730–0.894), for the training and validation cohorts, respectively, indicating that nomogram B was superior to nomogram A. Both the calibration curves and DCA results exhibited favorable clinical concordance and usefulness. ConclusionThe nomogram B yielded precise prognostic predictions for patients with advanced NSCLC treated with TCM.

Prognostic impact of muscle mass loss in elderly patients with oesophageal cancer receiving neoadjuvant chemoradiation therapy.

We aimed to identify the impact of muscle mass on locally advanced oesophageal cancer (LAEC) in elderly patients receiving neoadjuvant chemoradiation therapy (NACRT). We reviewed the medical records of 345 patients diagnosed with LAEC who underwent NACRT and surgery. Physical variables, including height, weight, skeletal muscle mass, and laboratory values, were obtained before and after NACRT. Body mass index (BMI, kg/m2), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) were calculated as height/(weight)2, ANC/ALC, platelet count/ALC, and (10×albumin+0.05×ALC), respectively. The cutoff for low muscle mass was 43.0cm2/m2 for BMI below 25kg/m2 and 53.0cm2/m2 for BMI 25kg/m2 or higher. The skeletal muscle index (SMI) was defined as skeletal muscle area/(height)2 (cm2/m2). The ΔSMI (%/50days) was defined as (SMI after NACRT-SMI before NACRT)/interval (days)×50 (days) to compare changes over the same period. The excessive muscle loss (EML) group was defined as patients with ΔSMI ≤-10% following NACRT. An elderly patient was defined as aged ≥65years. The primary outcome measure was overall survival (OS). During a median follow-up of 32.8months (range, 2.0-176.2), 192 patients died, with a median OS of 50.2months. Elderly patients did not show inferior OS (young vs. elderly, 57.7% vs. 54.0% at 3years, P=0.247). 71.0% and 87.2% of all patients had low muscle mass before and after NACRT, respectively, which was not associated with OS (P=0.270 and P=0.509, respectively). Inflammatory (NLR and PLR) and nutritional index (PNI) values or their changes did not correlate with OS. However, the EML group had worse OS (41.6% vs. 63.2% at 3years, P<0.0001). In the multivariate analysis, EML was also a significant prognostic factor for OS. In the subgroup analysis by age, EML was a strong prognostic factor for OS in the elderly group. The 3-year OS was 36.8% in the EML group and 64.9% in the non-EML group (P<0.0001) in elderly patients, and 47.4% and 62.1% (P=0.063) in the young patients. In multivariate analysis of each subgroup, EML remained prognostic only in the elderly group (P=0.008). EML may be strongly associated with a deteriorated OS in elderly patients undergoing NACRT, followed by surgery for LAEC. The strategies for decreasing muscle loss in these patients should be investigated.

Clinical characteristics and prognostic factors of male breast cancer in China.

This study aimed to explore the clinical characteristics of male breast cancer (MBC) patients and the factors influencing their prognosis. We conducted a retrospective case series analysis of 117 MBC cases who were treated at Zhejiang Cancer Hospital from 2009 to 2022. Cox proportional hazard model was used to identify prognostic factors of MBC. Nomogram was constructed based on these factors, which was further evaluated by C-index and calibration curves. A total of 115 MBC cases were finally included in our analyses, with median diagnosis age of 59 years. Of these cases, 80.0% were estrogen receptor (ER) positive, 79.2% were progesterone receptor (PR) positive, 48.7% were human epidermal growth factor receptor 2 (HER2) negative, and 42.6% had Ki67 levels higher than 15%. 108 (93.9%) cases underwent radical mastectomy, while only 3 (2.6%) received breast-conserving surgery. The Logrank test suggested that lymphocyte-to-monocyte ratio (LMR) was negatively associated with both overall survival (OS) and disease-free survival (DFS) of MBC, while platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) were only positively associated with OS (all P-values < 0.05). Multivariate regression analysis showed that age (HR 1.08, 95% CI 1.03-1.13) was significant prognostic factors for OS. Meanwhile, age (HR 1.06, 95% CI 1.02-1.10), histological differentiation grade (poorly differentiated/undifferentiated vs. well-differentiated: HR 2.55, 95% CI 1.05-6.17), and TNM stage (IV vs. I: HR 31.59, 95% CI 6.01-165.93) were also significant prognostic factors for DFS. Nomograms were developed for DFS, with C-indexes of 0.782, indicating good predictive performance. Increased age, bigger tumor size, higher TNM stage, and lower histological differentiation grade were associated with poor MBC prognosis, and LMR, PLR, and NLR might be potential predictors for MBC prognosis.

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 &lt;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 (&gt; 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. &lt; 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 (&gt; 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 .

Prognostic impact of the number and total tumor burden of secondary cerebral lesions in patients with resected brain metastases of non-small cell lung cancers.

Systemic therapeutic advancements have improved the prognosis of cancer patients, leading to surgery more frequently being carried out for patients with multiple brain metastases (BM). The underlying evidence for the strategy is currently lacking. This study aimed to evaluate the prognostic significance of the number of BM and total tumor burden (TTB) on the overall survival (OS) of patients with resected BM of non-small cell lung cancer (NSCLC) in a modern series. In this monocentric retrospective series, patients who underwent resection of BM of NSCLC between 2015 and 2021 were included. Demographic, clinical, and histological parameters were collected, and formal radiological volumetric analyses were performed. Prognostic biomarkers for cerebral progression-free survival (C-PFS) and OS were analyzed with univariate and multivariate Cox proportional hazards analysis. One hundred eighty-four patients were included in the study. Among these, 108 patients (58.7%) presented with a single brain metastasis, 36 patients (19.6%) with 2 BM, 22 patients (11.9%) with 3 BM, and 18 patients (9.8%) with more than 3 BM (maximum 15 BM). The mean ± SD (range) preoperative tumor burden was 23.1 ± 25.3 (1.1-145.3) cm3. The mean residual tumor burden after surgery was 0.3 ± 0.8 (0.0-6.3) cm3. By the time of the analysis, 128 patients (69.6%) had died. The median follow-up duration was 49.0 months (95% CI 39.6-63.6). The median OS was 19.2 months (95% CI 13.2-24.0), and the survival rates at 6 months, 1 year, and 2 years were 76% (95% CI 69%-82%), 61% (95% CI 53%-67%), and 43% (95% CI 35%-50%), respectively. The median C-PFS was 8.4 months (95% CI 7.2-12.0). In the Cox multivariate regression model, younger age (< 65 years), single brain metastasis, adjuvant brain radiation therapy, adjuvant use of targeted therapy, and TTB < 7 cm3 were all independent predictors of longer OS. In this era of modern systemic treatments for cancer, the number of BM and total cerebral tumor burden remain significant prognostic factors of OS. However, resection should be considered as an option even in those patients with multiple BM in order to enhance patient clinical status, enable further local and systemic treatment delivery, and improve their survival and quality of life.

Percutaneous ultrasound-guided radiofrequency ablation for patients with liver metastases from gastrointestinal stromal tumors

Objectives This study aimed to analyze the survival outcomes and prognostic factors of radiofrequency ablation (RFA) for liver metastases from gastrointestinal stromal tumors (GISTs). Methods Between March 2011 and November 2022, 34 patients (16 males; age range, 25–72 [median age, 52.5] years) who underwent RFA for liver metastasis from GISTs were included. The mean maximum diameter of metastatic lesions was 2.4 ± 1.0 (range, 1.1–5.2) cm. Survival curves were constructed using the Kaplan–Meier method and compared using the log-rank test. Multivariate analyses were performed using a Cox proportional hazards model. Results For 79 lesions among 34 patients, all targeted lesions were completely ablated. The mean hepatic progression-free survival (HPFS) period was 28.4 ± 3.8 (range, 1.0–45.7) months. The 1-, 3-, and 5-year HPFS rates were 67.2%, 60.5%, and 20.2%, respectively. Based on the univariate analysis, the number of metastatic tumors and tyrosine kinase inhibitors(TKI) therapy before RFA were prognostic factors for HPFS. Multivariate analysis showed that pre-RFA TKI therapy was associated with a better HPFS(p = 0.030). The mean overall survival (OS) period was 100.5 ± 14.1 (range, 3.8–159.5) months and the 1-, 3-, and 5-year survival rates were 96.9%, 77.1%, and 58.7%, respectively. Both univariate and multivariate analysis indicated that extrahepatic metastasis before RFA (p = 0.044) was a significant prognostic factor for OS. Conclusions Liver metastases from GIST exhibit relatively mild biological behavior. RFA is safe and effective, particularly in patients without pre-RFA extrahepatic metastases. Patients received targeted therapy before RFA can obtain an extended HPFS.

Prognostic Factors Influencing Survival in Ovarian Cancer Patients: A 10-Year Retrospective Study.

To analyze the factors associated with overall survival (OS) and progression-free survival (PFS) in patients with ovarian cancer in Cyprus. We retrospectively analyzed data from patients with histologically confirmed epithelial ovarian cancer (EOC) and primary peritoneal cancer (PPC). A total of 106 women diagnosed with ovarian cancer were included, with a median age at diagnosis of 58 years. The Kaplan-Meier survival analysis showed a median OS of 41 months (95% C.I = 36.9, 45.1), and the FIGO stage (p < 0.001), type of surgery (p < 0.001) and performance status (p < 0.001) were identified as statistically significant prognostic factors for OS. PFS analysis revealed the FIGO stage (p = 0.006) and the performance status (p < 0.001) as significant prognostic factors. Additionally, a Cox regression analysis for median OS was performed for patients with high-grade serous carcinoma, identifying the performance status, FIGO stage, and type of surgery as prognostic factors in univariate analysis. However, in the subsequent multivariate analysis, the performance status and the FIGO stage were confirmed to be the only statistically significant prognostic factors for OS (p < 0.05). This study confirms that the FIGO stage, performance status, and surgery type were considered as prognostic factors for OS in ovarian cancer.

Incidence, Management and Outcome of Post-Transplant Lymphoproliferative Disease after 5797 Solid-Organ Transplants over a 30-Year Period in a Single Hospital

Introduction: Post-transplant lymphoproliferative disorders (PTLD) are heterogenous lymphoproliferative disorders that develop because of immunosuppression in transplant recipients. Epstein-Barr Virus (EBV) infection is a major risk factor for the development of PTLD. Its management generally involves a reduction in immunosuppression and initial treatment with rituximab monotherapy (RM). Aim: To present the epidemiology, management, and outcomes of PTLD in a large unicentric Spanish cohort of solid organ transplant (SOT) recipient who were transplanted over a 30-year period. Methods: This is a retrospective study of 5797 SOT recipients who had their first transplant between 1992 and 2021 at Hospital Universitario 12 de Octubre. For each type of transplant, we calculated the incidence rate of PTLD. OS (Overall survival) was analyzed using the Kaplan-Meier model and the log-rank test Prognostic impact of the main clinical, analytical variables and prognostic indexes were analyzed. Results: With a median follow-up of 16.4 years, 105 of 5797 SOT developed a monomorphic or Hodking-like PTLD (1.8%). The incidence was: 10% multivisceral transplantation (MVT), 2.8% heart, 2.3% liver, 2.2% lung, 1.4% kidney and 1.3% simultaneous kidney-pancreas (SPK). Median age at transplant was 48.3 (1-89) years. 12 were pediatric recipients' (1 lung, 1 kidney, 10 liver). 72% were men. Histochemical stains for Epstein-Barr virus (EBV) were performed in 75 of 105 diagnoses. EBER-positive histology was observed in the majority of patients (n = 44/77, 57%). Median time from transplantation to PTLD was 6.7 (0-16.4) years (21% in the 1st year post-transplant). In EBER-positive the onset was earlier (3.2 vs 9.2 years; p: .004) with 36% arising the 1st year post-transplant. 5-years cumulative incidence was 10% in MTV compared to 0.18%-1.6% in the rest. With a median follow-up of 6.9 years; median OS was 79.5 months, with no difference between type of organ transplanted, era of transplant, EBER histology or time from transplant to PTLD. Using logistic regression, age, beta-2-microglobulin (B2M), as well as the IPI, modified R-IPI, NCCN-IPI and GELTAMO-IPI prognostic indices were found to be significant prognostic factors for OS ( Table 1). Interestingly, the highest OS stratification was observed with the modified R-IPI, showing a median OS not reached in the low-risk group, versus 38 months at high risk and 3.2 months at very high risk (p&amp;lt;0.001). Immunosuppression (IS) was switched as the 1st therapeutic aptitude in 57% of the patients. Median OS was not reached in patients with IS switch (n=41) (plateau at 10 years; estimated OS 56%) vs. 15.3m for patients without IS switch (n=39) (P: .004) ( Figure 1). IS was reduced in 80%. It also reached OS impact (P: .05). There were 89 monomorphic patients who were treated as follows: RM (n=22), R-Chemotherapy (n=37), chemotherapy (n=6), no treatment (n=7), unknown (n=16). Of the 22 RM patients, 9 (41%) achieved complete remission (CR) with RM and required no further treatment. In the R-Chemotherapy (n=37) group (70% R-CHOP), 26 (70%) reached CR. There was no significant difference in OS between the two groups. 8/22 (36%) died in the RM group (2/22 (9%) due progressive disease (PD), 2/22 (9%) died pre-remission of non-PTLD causes and 4/37 (18%) died in remission of unrelated causes). In the R-Chemo group 8/37 (48%) patients dead (4/37 (10%) patients died of PD, 6/37 (16%) died pre-remission of non-PTLD causes and 8/37 (22%) died in remission of unrelated causes). Conclusion: With this SOT cohort from a center with long experience we demonstrated an incidence of PTLD of 1.8%. EBV positive PTLD emerged sooner but OS was similar to those EBV negative. Stablished prognostic indices in DLBCL such as IPI, NCCN-IPI, and modified R-IPI were also applicable in PTLD. The modified R-IPI showed the best separation between the groups. Switch or reduction of the IS is an essential point to improve its prognosis. Our data suggest that first-line RM is an interesting option to consider. Strategies to tailor treatment with the least possible toxicity are necessary in these vulnerable patients. Additionally, our results suggest the utility of modified R-IPI in the clinical practice of PTLD and may serve as a basis for the development of specific prognostic models for this entity.

Measurable Residual Disease As Assessed By Flow Cytometry As Predictor of Survival in Pediatric AML Patients

Introduction Pediatric acute myeloid leukemia (pedAML) is a heterogeneous group of hematological malignancies classified according to morphology, immunophenotyping, and genomics. The optimal adjustment of therapy based on level of response is not well defined. Aim: Herein, we present the results of a retrospective study aiming to analyze the prognostic value of measurable residual disease (MRD) as determined by flow cytometry (FC-MRD) in pediatric AML. Patients and Methods All pediatric and adolescent patients (aged 0-18 years old) with AML treated in our unit between 1/2013-6/2023 were included in this study. French American British (FAB) morphological classification, immune-phenotype analysis, and molecular characterization were performed on diagnosis, and all patients were treated according to AML-BFM protocols. Final risk classification was based on evaluation of response and on genetic abnormalities at diagnosis. MRD was assessed by FC-MRD after Induction 1 and 2, and, either after course 5 or before hematopoietic stem cell transplantation (HSCT). Complete Remission (CR) was defined as regenerative or normocellular bone marrow with &amp;lt;5% blasts; in peripheral blood ≥1.0x10 9/L neutrophil granulocytes and ≥80x10 9/L thrombocytes or Remission with partial regeneration ( CRp: regenerative or normocellular bone marrow with &amp;lt;5% blasts; in the blood: ≥1.0x10 9/L leukocytes, ≥0.5x10 9/L, neutrophil granulocytes and ≥50x10 9/L, self-sustained platelets), lasting at least 4weeks; no extramedullary disease. Overall survival (OS) was defined as the time interval from the treatment initiation date to the date of death due to any cause. Progressive free survival (PFS) was defined as the time interval from the response date to the date of disease relapse or death due to any cause. The probabilities of OS and PFS were estimated with the Kaplan-Meier method. Results Overall, there were 52 patients (median age at diagnosis:7 years, 37males/15 females) diagnosed with AML, of whom: 40 patients with de novo AML, 5 patients with therapy- or myelodysplasia-related AML and 7 patients with mixed-lineage leukemia. Cytogenetics were considered favorable for 16 (31.0%), intermediate for 4 (7.6%), and adverse for 32 (61.4%) patients. Standard-risk patients (n=16) received only chemotherapy, whereas all high-risk patients, and intermediate-risk patients with available matched donors, underwent HSCT should they have reached remission. Forty-four patients (84.6%) achieved complete response (CR). Among these patients, 43 patients (97.7%) achieved CR after 1 course of induction, and 1 patient (2.3%) required at least 2 courses. Twenty-four patients (46.1%) underwent HSCT during either their first (20/24) or second (4/24) CR. Overall, 12 patients (23.07%) died, 4 patients due to resistant disease, 3 patients due to relapse, 2 patients due to serious complications upon diagnosis, 1 patient due to infection and 2 patients due to transplant-related complications. With a median follow-up time of 3.7 years (range 0.1-11.1years), the five-year OS and PFS of the entire cohort was 74.0% and 70.0%, respectively. The level of FC-MRD was a significant prognostic factor for OS and PFS. More specifically, achievement of FC-MRD &amp;lt; 0.1% at all time points was associated with a significant improvement in PFS and OS. (figure 1). FC-MRD ≥ 0.1% after course 5 or before HSCT was the only independent adverse prognostic factor that was statistically significant for both progression-free (P=0.001) and overall survival (P&amp;lt;0.001) (figure1). Conclusions We investigated the association between FC-MRD and survival in Greek pediatric patients with AML. In our cohort, achieving an MRD status &amp;lt;0.1% according to FC is associated with significant improvement in the outcome of pediatric patients with AML.

Role of Adjuvant Radiotherapy in Patients with Cervical Cancer Undergoing Radical Hysterectomy.

The benefit of adjuvant radiotherapy (RT) after radical hysterectomy in patients with cervical cancer remains controversial. The aim of this study was to determine adjuvant RT's impact on survival in accordance with Sedlis criteria. Patients with early-stage cervical cancer undergoing radical hysterectomy between 2005 and 2022 at a single tertiary care institution were included. A multivariate analysis was performed to determinate if RT was an independent prognostic factor for recurrence or death. We also analysed whether there was a statistically significant difference in overall survival (OS) between patients who met only one or two Sedlis criteria, depending on whether they received adjuvant RT or not. 121 patients were included in this retrospective study, of whom 48 (39.7%) received adjuvant RT due to the presence of unfavourable pathological findings. In multivariate analysis, RT was not found to be a statistically significant prognostic factor for OS (p = 0.584) or disease-free survival (DFS) (p = 0.559). When comparing patients who met one or two Sedlis criteria, there were no statistically significant differences in OS between RT and no adjuvant treatment in either group. Since the selection of patients with cervical cancer eligible for surgery is becoming more accurate, adjuvant RT might not be necessary for patients with intermediate risk factors.

Long-Term Outcomes in a Phase II Study of Hypofractionated IGRT 60Gy/ 20F in Patients with Isolated Lymph Node Recurrence after Surgery for Esophageal Carcinoma

In oligo metastases in lymph node recurrence after surgery for esophageal cancer, since SBRT (BED>100 Gy10) to mediastinal and abdominal lymph node lesions was not an option due to toxicities in the organs at risk (OAR) such as vessels and gastrointestinal tract, we performed a prospective cohort study of hypofractionated IGRT for isolated lesions. The primary end-points of this study are disease specific survival (DSS) and late treatment toxicities. From 2011 to 2021, 60 Gy/20F/4-4.5wks (78 Gy10) hypofractionated IGRT was performed in a total ITT population of 70 patients after radical surgery (67 cases) and ESD (3 cases), who were diagnosed by CT/PET-CT as having solitary lymph node recurrence (62 cases) or up to 2 adjacent nodes (8 cases). The mean time from surgery to recurrence was 17.9 months (SD 18.1) with a mean age of 67.5 years (SD 9.3), and male to female ratio was 62:8. Pathological results showed that 63 patients (90%) had squamous cell carcinoma. The mean maximum diameter of lesions was 2.5 cm (SD; 1.1 cm). And 51 cases (73%) were treated with CRT concurrently using 5FU plus CDDP (FP), and the rest were treated with RT alone. Lymph node location was lower neck or upper mediastinum in 42 cases, middle and lower mediastinum in 16 cases, and abdomen in 12 cases, respectively. Treatment planning was performed by taking 4DCT fusing PET or MRI images. The Kaplan-Meier method and the Cox proportional hazards regression model were used for overall survival (OS), DSS, and progression free survival (PFS). The mean observation period was 38 months. Primary efficacy was CR in 45 cases (64%), but CR was maintained only in 29 cases (41%). Twenty-two of the 70 patients were relapse-free. OS were 53% and 34% at 2 and 5 years, DSS were 56% and 38% at 2 and 5 years, and PFS were 40% and 39% at 2 and 5 years, respectively. The site of first recurrence was the same or adjacent lymph nodes in 33 cases (47%) and distant metastases in 9 cases (13%). Number of tumors (1 vs. 2), age, and CRT were not significant prognostic factors for OS, DSS, or PFS. In a multivariate analysis, the time from surgery to recurrence ≥12 months was the only significant prognostic factor for PFS (p = 0.018, HR0.50). The same multivariate analysis showed that the only significant prognostic factor for DSS was the location of the recurrent lymph node in the neck and upper mediastinal regions (p = 0.009, HR 0.59). The only late adverse events of Grade 2 or higher were Grade 2 pleural effusion (little and transient) in 6 cases and Grade 2 radiation pneumonitis in 1 case. No acute adverse events were observed other than hematologic toxicity due to FP administration. In locally advanced esophageal cancer, a relatively reliable regional lymph node dissection is often performed, so there is still a chance to aim for cure in cases of solitary recurrence. We found that if the lesion is solitary, localized RT of about 60 Gy/20F/4-4.5 weeks with IGRT can achieve a long-term survival in 40% of patients without any significant adverse events.

Choosing Wisely between Radiotherapy Dose-Fractionation Schedules: The Molecular Graded Prognostic Assessment (molGPA) for Elderly Glioblastoma (eGBM-molGPA)

This study aimed to develop a graded prognostic assessment (GPA) model integrating genomic characteristics in patients with elderly glioblastoma (eGBM), and compare the efficacy between conventionally fractionated radiotherapy (CFRT) vs. hypofractionated radiotherapy (HFRT) in each risk group. Patients aged ≥65 years who underwent surgical resection followed by radiotherapy (RT) with or without temozolomide (TMZ) for newly diagnosed IDH-wildtype eGBM between 2006 and 2021 were included in this multicenter cohort study. Patients who were planned for a ≥6-week or ≤4-week radiotherapy were regarded as being treated with CFRT or HFRT, respectively. Based on the prognostic factors significantly identified through multivariate analysis for overall survival (OS), we developed the molecular GPA for eGBM (eGBM-molGPA) and assigned 0.0, 0.5, and 1.0 points in proportion to the corresponding hazard ratio (HR) of each factor. Then, the survival outcomes by treatment groups were evaluated according to the eGBM-molGPA scores. A total of 334 and 239 patients who underwent CFRT and HFRT were included, respectively, and 86% of patients were treated with TMZ-based chemoradiation. With a median follow-up of 17.4 months for survivors, the median OS was 18.7 months for CFRT plus TMZ group, 15.1 months for HFRT plus TMZ group, and 10.4 months for RT alone group, respectively (all p<0.001). In the multivariate analysis, Karnofsky performance scale, surgical extent, TMZ, and the methylation status of the MGMT promoter were identified as strong prognostic factors for OS, with an estimated HR of greater than 1.5 (all p<0.001). Additionally, subventricular zone involvement, temporalis muscle thickness, RT regimen, and the mutation status of TERT promoter and TP53 gene were found to be significant prognostic factors for OS, with an estimated HR of less than 1.5. The eGBM-molGPA was established based on these prognostic factors (Table 1) and patients were allocated to three risk groups, which included high risk (total score of 3.0-4.5), intermediate risk (1.5-2.5), and low risk (0.0-1.0). Patients treated with CFRT plus TMZ had significantly improved OS compared to those treated with HFRT plus TMZ or RT alone in the low and intermediate risk groups (p<0.001). However, in the high-risk group, there was no significant difference in OS between treatment options (p = 0.770). CFRT plus TMZ can be a more effective strategy for selected eGBM patients compared to HFRT. For high-risk patients, a protracted treatment schedule might not be beneficial. The novel eGBM-molGPA can be used as a clinical tool for choosing wisely among treatment options. Further prospective studies are warranted to establish optimal RT guidelines for eGBM patients.

Platelet count and MCHC as independent prognostic markers for feline mammary carcinomas

Mammary neoplasms are common in felines species and represent a significant disease for its unfavorable prognosis. Changes in the blood count and serum biochemical profile of these patients have potential as non-invasive prognostic markers prior to mastectomy, however, they are poorly described in literature. In this study univariate and multivariate analyses were performed using these factors to determine the effect of each parameter on the one-year survival time after the surgical procedure in these animals. The median overall survival (OS) and the disease-free survival (DFS) were 365 and 242 days, respectively. In univariate analysis, values within the reference range of monocyte, platelet and creatinine counts were identified as significant prognostic factors for OS and only creatinine was significant for DFS (P < 0.05). In the multivariate analysis, platelets and mean corpuscular hemoglobin concentration (MCHC) remained independent prognostic factors for OS. The results presented suggest that monocytes, platelets and creatinine may be important non-invasive pre-surgical prognostic markers, and that platelet count and MCHC are independent prognostic markers for feline mammary carcinomas (FMC). The correlation between such alterations is of important relevance for veterinary oncology, and prospective studies are needed to validate their clinical use and that platelet count and MCHC are independent prognostic markers for FMC. The results found in this study can also be studied in human medicine, regarding blood markers in human breast cancer (HBC).

The Prognostic Value of Sequential 18 F-FDG PET/CT Metabolic Parameters in Outcomes of Upper-Third Esophageal Squamous Cell Carcinoma Patients Treated with Definitive Chemoradiotherapy.

Objective The aim of this study is to determine prognostic values of sequential 18 F-FDG PET/CT metabolic parameters in locally advanced esophageal squamous cell carcinoma (ESCC) patients treated with definitive chemoradiotherapy. Materials and Methods Forty locally advanced ESCC patients treated with definitive chemoradiotherapy (dCRT) who received pre-treatment 18 F-FDG PET/CT (PET1) and 3-months post-treatment 18 F-FDG PET/CT (PET2) were enrolled in the prospective study. 18 F-FDG PET parameters of the primary tumor including maximum and mean standardized uptake values (SUVmax, SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were calculated on PET delineated primary tumor. Using Kaplan-Meier curves to estimated overall survival (OS), progression-free survival (PFS), and local-regional control (LRC). Cox regression analysis was performed to find significant prognostic factors for survival. Results With a median follow-up of 13.5 months, the 4-year OS, PFS, and LRC rates were 67.3%, 52.6%, and 53.4% respectively. Patients with MTV 2 > 5.7 had lower OS, PFS, and LRC rates than the lower MTV 2 group (p < 0.05). Univariate Cox regression analysis showed that MTV2 was a significant prognostic factor for OS, PFS, and LRC (p < 0.05). Conclusion MTV parameter of sequential 18 F-FDG PET/CT could be used as a prognostic factor for OS, PFS, and LRC in locally advanced ESCC patients treated with dCRT.

High grade tumor budding is associated with poor survival in pathologic stage I lung adenocarcinoma

AimTumor budding is a significant prognostic parameter that has been related to aggressive behavior in early-stage tumors of various origins. The aim of this study was to evaluate the clinicopathological significance of tumor budding in pathologic stage (pStage) I lung adenocarcinomas. MethodsThis study comprised 107 patients who underwent curative resection for pStage I lung adenocarcinomas at our hospital between December 2010 and January 2016. We examined tumor budding on routine hematoxylin and eosin (H&E) slides from resected specimens. Tumors were categorized into two groups based on the degree of tumor budding: low grade (grade 0–1) and high grade (grade 2–3). We evaluated the relationship between tumor budding and overall survival (OS), disease-free survival (DFS) and clinicopathological parameters. ResultsThere is a significant difference (p = 0.002) between the 5-year DFS rates of the high-grade and the low-grade tumor budding group, which were 70 % and 90 %, respectively. High-grade tumor budding positive patients from the same pathological stage (p < 0.001; HR = 2.93 [1.51–5.68]) and clinical stage (p = 0.002) had poorer cumulative survival rates than low grade tumor budding positive patients. High grade tumor budding was positively associated with spread through air spaces (STAS) (p < 0 0.001), lymphovascular invasion (LVI) (p < 0.001), tumor necrosis (p < 0.001), high SUVmax value (SUVmax>3.0) (p < 0.001), and tumor size >20 mm (p = 0.024). High-grade tumor budding was significant prognostic factor of OS (p < 0.006) and DFS (p < 0.001) on univariate Cox regression hazard model analysis. However, it did not show significance in the multivariate analysis (p > 0.05). ConclusionsHigh-grade tumor budding is an independent prognostic factor and associated with adverse clinicopathological features and poor survival rates. We proposed that high-grade tumor budding should be recognized as a new prognostic parameter and will be beneficial in predicting the clinical course in pStage I lung adenocarcinomas.