Actuarial Disease-free Survival Research Articles

Treatment Outcomes and Toxicity Profiles with PORTEC-3 Trial Regimen in South Asian Cohort of High-Risk Endometrial Cancer Patients: A Single-Center Ambispective Analysis

Objectives Adjuvant chemoradiation followed by chemotherapy is the current standard of care in high-risk endometrial cancer after the PORTEC-3 trial. There is a lack of data on this treatment regimen in the South Asian patient cohort. The present study aims to assess toxicity profiles and outcomes in this cohort of patients. Materials and Methods High-risk endometrial cancer patients planned for adjuvant chemoradiation followed by chemotherapy were included. Toxicity was graded using the Radiation Therapy Oncology Group and Common Terminology Criteria for Adverse Events criteria. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Survival curves were compared using the log-rank test. Cox regression analysis was done to find out the predictors of DFS. Results This study included 58 patients treated from October 2016 to August 2022. Median age was 61 years (interquartile range [IQR] 56–66), with Fédération Internationale de Gynécologie et d'Obstétrique Stages I = 26 (44.8%), II = 5 (8.6%), and III = 27 (46.6%). p53 positivity was seen in 38 (65.5%) patients. Intensity-modulated radiotherapy was used in 44 (79.3%) patients. There was no treatment discontinuation during chemoradiation. Acute Grade 2 and above toxicity during chemoradiation were diarrhea in 10 (17.2%) and hematological in 2 (3.4%). For the planned adjuvant chemotherapy in 55 patients, 51 (92.7%) completed four cycles. Grade 2 or above neuropathy was seen in 11 (20%), with 5 (9%) having persisting neuropathy at 1-year follow-up. At a median follow-up of 31 months, 15 (25.8%) patients recurred; distant = 13 and isolated para-aortic = 2. The median time to recurrence was 16 months (IQR 12–22), with 80% (12 out of 15) of recurrence within the first 2 years of follow-up. The actuarial 5-year DFS and OS were 63.8 and 76.5%, respectively. In univariate analysis, p53 positivity and lymphovascular space invasion were predictors for DFS, with p-values 0.031 and 0.027, respectively. There was no significant predictor identified in multivariate analysis. Conclusion There is good tolerance and compliance to adjuvant chemoradiation and chemotherapy in this South Asian cohort of patients with high-risk endometrial cancer, with no toxicity-related treatment breaks during radiation. The majority of the recurrences were seen at distant sites and within the first 2 years of follow-up. These findings are in line with the outcomes of the PORTEC-3 trial.

Stereotactic radiotherapy for liver oligometastases: a pooled analysis following the estro/eortc consensus recommendations.

A large pooled analysis of liver oligometastases, classified accordingly to the ESTRO/EORTC recommendations, treated by stereotactic radiotherapy (SBRT) and Radiosurgery (SRS) was carried out. The clinical and dosimetric data of patients who underwent SBRT/SRS for liver metastases were analysed in terms of efficacy and toxicity profile. In particular, the Local Control (LC), the Distant Metastases Free Survival (DMFS), the Disease-Free Survival (DFS), the Overall Survival (OS), and the Next Systemic Therapy Free Survival (NEST-FS) rates were analysed. 113 patients (M/F: 49/64), accounting for a total of 150 hepatic lesions (March 2006-February 2023) in two Italian radiotherapy Institutions were evaluated. Median age was 67years old (36-92) and 48 (42.5%) patients had at least one comorbidity. The majority of the lesions were induced (30.7%) or repeated oligoprogressive (12.7%) metastases. 98 lesions were treated with more than one daily fraction (mainly 50Gy in 5 fractions), while 52 were radiosurgery treatments (mainly 32Gy). The treatment response at 3-4months was evaluable in 147 lesions: complete response was 32.0%, partial response 17.0%, and stable disease 32.0%. Actuarial LC, DMFS, DFS, OS, and NEST-FS at 1 year were 75.8%, 37.7%, 34.9%, 78.7%, and 59.4% respectively; while actuarial LC, DMFS, DFS, OS, and NEST-FS at 2 years were 52.1%, 24.9%, 21.9%, 51.3%, and 36.8%, respectively. The achievement of complete response, synchronous oligometastases, and no treatment interruptions correlated with a more favorable outcomes. As per the toxicity profile, we registered only two acute and one late toxicity cases higher than grade 2. Stereotactic treatment for liver metastases seems to be a safe and promising option in terms of local control. The best results in term of outcomes have been obtained in patients with complete response, synchronous oligometastases, favorable histology, and no treatment interruptions.

Relapse Hodgkin lymphoma autologous stem cell transplant long term follow up.

e19031 Background: Autologous Stem Cell Transplantation (ABMT) is a standard treatment approach for patients with relapsed Hodgkin’s Lymphoma (HL). We wish to report long term (>10 year) outcomes for patient’s with HL treated with ABMT at our institution. Methods: We treated 35 patients over a 30 year time period (1992-2022). Of these 35 patients, there were 19 males and 16 females with a median age of 41 years (range 21-70 years) and a median performance status of 1 (0-1). The preparative regimen was carmustine, etoposide, and melphalam (CEM, 1992-2005) and BCNU, etoposide, cytarabine and melphalan (BEAM, 2006 to present). Bretuximab was added to BEAM in 2018 as post-transplant consolidation therapy in 13 patients. All patients underwent mobilized peripheral blood stem collections with high dose filgrastim, and starting in 2008 were mobilized with both filgrastim and plexiform. The required stem cell product was at a minimum of 2 million CD34+ cells per kilogram of body weight. Results: Fifteen patients received CEEM and 9/15 (60%) achieved a complete response (CR). Twenty patients received BEAM and 16/20 (80%) achieved a CR, p=0.27 (Fisher’s exact test). The median time to hematological recovery was 12 days (range 8-21). Treatment related complications included: S. epidermis sepsis (3 patients), E. coli sepsis (3 patients), and esophageal perforation that lead to death in 1 patient. With a median follow up 13 years (range 1-23 years), the actual 10 year disease free survival (DFS) is 52% and overall survival (OS) is 64%. The actuarial DFS and OS at 15 years are 52% and 64% respectively. Six patients are in continuous CR for greater than 20 years. Long term complications at greater than 15 years include: cardiomyopathy (5 patients), breast cancer (1 patient), and liposarcoma (1 patient). Conclusions: Patients with relapsed HL can achieve long term curative outcomes when treated with ABMT with most frequent long term complication being cardiomyopathy.

Multicenter Registry of Adenomas of the Pituitary and Related Disorders: Initial Description of Cushing Disease Cohort, Surgical Outcomes, and Surgeon Characteristics.

To address the lack of a multicenter pituitary surgery research consortium in the United States, we established the Registry of Adenomas of the Pituitary and Related Disorders (RAPID). The goals of RAPID are to examine surgical outcomes, improve patient care, disseminate best practices, and facilitate multicenter surgery research at scale. Our initial focus is Cushing disease (CD). This study aims to describe the current RAPID patient cohort, explore surgical outcomes, and lay the foundation for future studies addressing the limitations of previous studies. Prospectively and retrospectively obtained data from participating sites were aggregated using a cloud-based registry and analyzed retrospectively. Standard preoperative variables and outcome measures included length of stay, unplanned readmission, and remission. By July 2023, 528 patients with CD had been treated by 26 neurosurgeons with varying levels of experience at 9 academic pituitary centers. No surgeon treated more than 81 of 528 (15.3%) patients. The mean ± SD patient age was 43.8 ± 13.9 years, and most patients were female (82.2%, 433/527). The mean tumor diameter was 0.8 ± 2.7 cm. Most patients (76.6%, 354/462) had no prior treatment. The most common pathology was corticotroph tumor (76.8%, 381/496). The mean length of stay was 3.8 ± 2.5 days. The most common discharge destination was home (97.2%, 513/528). Two patients (0.4%, 2/528) died perioperatively. A total of 57 patients (11.0%, 57/519) required an unplanned hospital readmission within 90 days of surgery. The median actuarial disease-free survival after index surgery was 8.5 years. This study examined an evolving multicenter collaboration on patient outcomes after surgery for CD. Our results provide novel insights on surgical outcomes not possible in prior single-center studies or with national administrative data sets. This collaboration will power future studies to better advance the standard of care for patients with CD.

Long Term Disease Free Survival and Survival of Patients with Relapsed Hodgkin's Lymphoma Treated with Autologous Stem Cell Transplantation

CONCLUSION Autologous Stem Cell Transplantation (ABMT) is a standard treatment approach for patients with relapsed Hodgkin's Lymphoma (HL). We wish to report long term (>10 year) outcomes for patient's with HL treated with ABMT at our institution. We treated 35 patients over a 30 year time period (1992-2022) Of these 35 patients, there were 19 males and 16 females with a median age of 41 years (range 21-70 years) and a median performance status of 1 (0-1). The preparative regimen was carmustine, etoposide, and melphalan (CEM,1992-2005) and BCNU, etoposide, cytarabine, and melphalan (BEAM, 2006 to present). Brentuximab was added was added to BEAM in 2018 as post-transplant consolidation therapy in 13 patients. All patients underwent mobilized peripheral blood stem cell collections with high dose filgrastim and since 2008 filgrastim and plexiform. The required stem cell product was at a minimum 2 million CD34+ cells per kilogram of body weight. Fifteen patients received CEM and 9/15 (60%) achieved a complete response (CR). Twenty patients received BEAM and 16/20 (80%) achieved a CR, p=0.27 (Fisher's exact test). The median time to hematologic recovery was 12 days (range 8-21). Treatment related complications included: S. Epidermis sepsis (3 patients), E. coli sepsis (3 patients) and esophageal perforation that lead to death (1 patient). With a median follow up of 13 years (range 1-23 years).The actual 10 year disease free survival (DFS) is 52% and overall survival (OS) is 64%. The actuarial DFS and OS at 15 years are 52% and 64% respectively. Six patients are in continuous CR for greater than 20 years. Long term complications at greater than 15 years include: cardiomyopathy (5 patients), breast cancer (1 patient), liposarcoma (1patient). Patients with relapsed HL can achieve long term curative outcomes when treated with ABMT. The most frequent long term complication is cardiomyopathy.

Simultaneous Integrated Boost for Dose Escalation in Node-Positive Cervical Cancer: 5-Year Experience in a Single Institution.

This study retrospectively evaluates clinical outcomes of dose escalation to involved nodes using volumetric modulated arc therapy (VMAT) with simultaneous integrated boost (SIB) for node-positive locally advanced cervical cancer (LACC) at a single institution. Consecutive patients with node-positive LACC (FIGO2018 IIIC1-IVA) who received definitive chemoradiotherapy by VMAT 45 Gy in 25 fractions with SIB to 55-57.5 Gy, followed by magnetic resonance image-guided adaptive brachytherapy (IGABT) between 2018 and 2022 were identified. A standardized strategy regarding nodal boost delivery and elective para-aortic (PAO) irradiation was employed. Primary endpoints were involved nodal control (INC) and regional nodal control (RNC). Secondary endpoints were pelvic control (PC), locoregional control (LRC), disease-free survival (DFS), overall survival (OS), failure pattern, and radiotherapy-related toxicities. A total of 234 involved nodes (182 pelvic and 52 PAO) in 54 patients, with a median of 3 involved nodes per patient (range 1-16), were analyzed. After a median follow-up of 19.6 months, excellent INC was achieved, with four (2%) boost-volume failures occurring in three patients. The 2-year actuarial RNC, PC, LRC, DFS, and OS were 93%, 87%, 87%, 78%, and 85%, respectively. Adenocarcinoma histology was associated with worse RNC (p = 0.02) and OS (p = 0.04), whereas the primary tumor maximum standardized uptake value (SUVmax) was associated with worse PC (p = 0.04) and LRC (p = 0.046) on univariate analysis. The incidence of grade ≥3 acute and late radiotherapy-related toxicity were 2% and 4%, respectively. Treatment of node-positive LACC with VMAT with SIB allows safe and effective dose escalation. The 5-year local experience demonstrated excellent treatment outcomes without additional toxicity.

Outcomes of Locally Advanced Rectal Cancer Patients Treated with Total Neoadjuvant Treatment: A Meta-Anaysis of Randomized Controlled Trials

Background & AimsDetermining outcomes using the total neoadjuvant therapy (TNT) in patients with local advanced rectal cancer is important for stratifying patients according to expected outcomes in future studies in the era of treatment combination. The present meta-analysis estimated the pathological complete response, disease-free survival, and overall survival probabilities of rectal cancer patients and identified predictors of outcomes. MethodsStudies reporting pathological complete response rate and time-dependent outcomes (progression or death) after total neoadjuvant treatment of locally advanced rectal cancer (LARC) were identified in MEDLINE through January 2022. Three independent observers extracted data on patient populations and outcomes and combined the data using a distribution-free summary survival curve. The primary outcomes were actuarial probabilities of recurrence and survival. ResultsFourteen RCTs, including 18 TNT arms, met the inclusion criteria. The pooled estimate of pathological complete response (pCR) probability was 23.6%, with moderate heterogeneity between studies. The pooled estimates of actuarial disease-free survival rate were 70.6% at 3 years and 65.4% at 5 years. The pooled estimates of actuarial survival rates were 93% at 3 years and 81.6% at 5 years. In both these outcomes, heterogeneity between studies was highly significant. ConclusionThis meta-analysis showed that Total Neoadjuvant Therapy is an optimal approach for LARC patients. The results provide a useful benchmark for future comparisons of the benefits of combinations of other drug families as target therapies or immunotherapies.

Local Recurrence and Disease-Free Survival After Transanal Total Mesorectal Excision: Results From the International TaTME Registry.

The oncologic safety of transanal total mesorectal excision (TaTME) for rectal cancer has recently been questioned, with high local recurrence (LR) rates reported in Dutch and Norwegian experiences. The objective of this study was to evaluate the oncologic safety of TaTME in a large cohort of patients with primary rectal cancer, primarily in terms of LR, disease-free survival (DFS), and overall survival (OS). This was a prospective international registry cohort study, including all patients who underwent TaTME for primary rectal adenocarcinoma from February 2010 through December 2018. The main endpoints were 2-year LR rate, pattern of LR, and independent risk factors for LR. Secondary endpoints included 2-year DFS and OS rates. Kaplan-Meier survival analysis was used to calculate actuarial LR, DFS, and OS rates. A total of 2,803 patients receiving primary TaTME were included, predominantly men (71%) with a median age of 65 years (interquartile ratio, 57-73 years). After a median follow-up of 24 months (interquartile ratio, 12-38 months), the 2-year LR rate was 4.8% (95% CI, 3.8%-5.8%) with a unifocal LR pattern in 99 of 103 patients (96%). Independent risk factors for LR were male sex, threatened resection margin on baseline MRI, pathologic stage III cancer, and a positive circumferential resection margin on final histopathology. The 2-year DFS and OS rates were 77% (95% CI, 75%-79%) and 92% (95% CI, 91%-93%), respectively. This largest TaTME cohort to date supports the oncologic safety of the TaTME technique for rectal cancer in patients treated in units that contributed to an international registry, with an acceptable 2-year LR rate and a predominantly unifocal LR pattern.

Does Pathological Stage and Nodal Involvement Influence Long Term Oncological Outcomes after CROSS Regimen for Adenocarcinoma of the Esophagogastric Junction? A Multicenter Retrospective Analysis.

Simple SummaryChemoradiotherapy according to CROSS regimen is the standard of care for locally advanced esophageal cancer. The studies conducted on this topic have demonstrated the benefits of this type of treatment particularly for squamocellular cancers. Its application for adenocarcinoma has evidenced different results and few studies have investigated its role for adenocarcinomas of esophagogastric junction. Our intent is to evaluate the relation between pathological (yp) stage after CROSS regimen followed by surgery for adenocarcinoma of cardia and overall (OS) and disease-free survival (DFS) in a retrospectively analyzed group of patients. Sites of relapse after surgery were also analyzed. Our results evidenced no differences in term of OS and DFS according to different pathological response after chemoradiotherapy and surgery. Further analyses could be performed to identify the histological and molecular characteristics of these tumors and predict the efficacy of systemic therapy identifying patients who can most benefit from this type of treatment.Background:After the results reported by the “Chemoradiotherapy for esophageal Cancer Followed by Surgery Study” (CROSS) trial, neo-adjuvant chemoradiotherapy became the standard treatment for locally advanced cancers of esophagus and gastroesophageal junction (GEJ). Excellent results were reported for squamocellular carcinomas (SCCs). Since the advent of the CROSS regimen, the results of surgery for esophageal adenocarcinomas (EAC) have cast some doubts about its efficacy on overall survival (OS) even in the presence of local response. This study evaluated the relation between pathological (yp) stage after CROSS regimen followed by surgery for adenocarcinoma of cardia and overall (OS) and disease-free survival (DFS). Sites of relapse after surgery were also analyzed. Methods: Patients submitted to the CROSS regimen for locally advanced EAC of the cardia followed by transthoracic esophagectomy were analyzed. Actuarial OS and DFS were analyzed and stratified according to yp stage. The site of relapse, distal and local, was also analyzed. Results: The study included 132 patients. The 50-month OS and DFS were 45% and 6.7%, respectively. No differences emerged analyzing OS according to yp stage. Time to relapse was significantly longer for yp Stage I and II, and for yp N0, compared with yp N+. Recurrence occurred in 48 cases (36.3%) with a 9 months median time to relapse. Local and distal relapse were 10 (7.5%) and 38 (28.7%) cases, respectively (p ≦ 0.001). Conclusions: Pathological stage after CROSS regimen does not relate to OS and DFS. Time to recurrence is significantly longer for yp Stages I and II and ypN0. Chemoradiotherapy in a neoadjuvant setting may influence the site of relapse, significantly reducing local recurrences.

Full donor chimerism after allogeneic hematopoietic stem cells transplant for myelofibrosis: The role of the conditioning regimen.

The aim of this retrospective study was to assess the rate of full donor chimerism (F-DC) in patients with myelofibrosis, prepared for an allogeneic stem cell transplant, with one or two alkylating agents. We analyzed 120 patients with myelofibrosis, for whom chimerism data were available on day +30. There were two groups: 42 patients were conditioned with one alkylating agent (ONE-ALK), either thiotepa or busulfan or melphalan, in combination with fludarabine, whereas 78 patients were prepared with two alkylating agents, thiotepa busulfan and fludarabine (TBF). Patients receiving TBF were older (57 vs 52 years), were less frequently splenectomized pre-HSCT (31% vs 59%), had more frequently intermediate-2/high DIPSS scores (90% vs 74%), were grafted more frequently from alternative donors (83% vs 33%) and received more frequently ruxolitinib pre-HSCT (26% vs 7%). The proportion of patients with F-DC on day +30, in the TBF vs the ONE-ALK group, was respectively 87% vs 45% (P < .001). The 5-year cumulative incidence of relapse was 9% in the TBF group, vs 43% for the ONE-ALK group (P < .001). The 5-year actuarial disease-free survival was 63% for TBF and 38% for the ONE-ALK group (P = .004). In conclusion, early full donor chimerism is a prerequisite for long term control of disease in patients with myelofibrosis, undergoing an allogeneic HSCT. The combination of two alkylating agents in the conditioning regimen, provides a higher chance of achieving full donor chimerism on day+30, and thus a higher chance of long term disease free survival.

Baseline Lymphocyte Counts Do Not Predict Oncologic Outcomes and Survival in Patients Receiving Short Course Total Neoadjuvant Therapy for Rectal Cancer

Total neoadjuvant therapy (TNT) is increasingly utilized for patients with locally advanced rectal cancer. Prior studies have suggested that markers of systemic inflammation at baseline may predict treatment outcomes for patients receiving neoadjuvant long-course chemoradiation (LC-CRT). However, this has not been evaluated in patients receiving TNT with short-course radiation (SC-RT). We evaluated the prognostic value of baseline neutrophil-to-lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and monocyte to lymphocyte ratio (MLR) in rectal cancer patients receiving SC-TNT. Between 2010 and 2019, we identified 186 patients with rectal cancer who received SC-TNT at our institution. Of these, 141 patients had a pre-treatment complete blood counts available within 2 months prior to initiating therapy. All patients received neoadjuvant SC- RT 25 Gy/5 Fx to the pelvis followed by chemotherapy followed by delayed surgery +/- adjuvant chemotherapy based on pathologic features. Primary clinical outcomes of interest were pathologic complete response (pCR), loco-regional control (LRC), distant control (DC), disease-free survival (DFS), and overall survival (OS). Cox regression analysis was performed to determine potential associations between NLR, PLR, and MLR with clinical outcomes. NLR, PLR, and MLR were analyzed as both continuous and dichotomized variables. Multiple cutoff values were evaluated based on cohort mean, cohort median, and previously published values. Statistical analyses were performed using SPSS version 26. P <0.05 was considered statistically significant. The median baseline NLR was 2.5 (interquartile range 1.36). The median baseline PLR was 142.73 (interquartile range 82.11). The median baseline MLR was 2.56 (interquartile range 2.26). Median follow-up was 2.44 years (range 0.11 – 9.59 years). pCR was achieved in 34 patients (24.1%). Three-year actuarial LRC, DC, DFS, and OS were 93%, 84.2%, 78.9%, and 87.7%, respectively. NLR as a continuous variable was significantly associated with LRC, DFS, and OS on univariate analysis but not multivariate analysis. There was no other association found between NLR, PLR, or MLR with any other clinical outcomes of interest when analyzed as either continuous or dichotomous variables. In our SC-TNT cohort, baseline NLR, PLR, and MLR did not predict tumor response, oncologic outcomes, or overall survival in rectal cancer patients. Our data contrasts prior studies for LC-CRT, possibly due to differences in neutrophil or lymphocyte depletion with hypo-fractionated RT. Further studies are warranted to compare post-RT immune markers between LC-CRT and SC-RT. As hypo-fractionated RT use increases, identification and validation of biomarkers in rectal cancer patients undergoing neoadjuvant SCRT will become increasingly important.

Novel biomarker for hepatocellular carcinoma: high tumoral PLK-4 expression is associated with better prognosis in patients without microvascular invasion

BackgroundHepatocellular carcinoma (HCC) recurrence after liver resection (LR) adversely affects prognosis but is difficult to predict. Aberrant expression of Polo-Like Kinase 4 (PLK-4) is implicated in several adult malignancies. We sought to evaluate the prognostic value of PLK-4 expression in HCC after curative-intent LR. MethodsPatients undergoing LR for HCC between July-2015 and November-2017 at our centre were retrospectively identified. PLK-4 expression was measured in tumour and adjacent non-tumour liver tissue using quantitative RT-PCR. Disease-free survival (DFS) was evaluated by Kaplan–Meier and Cox proportional hazard models. ResultsA total of 145 patients were identified. Patients were divided according to PLK-4 expression (high: n = 58, low: n = 87) by generating a receiver operating characteristic curve for recurrence with an area under the curve of 0.72 (95% CI: 0.6–0.8). Recurrence and death rates were similar between groups. In patients without mVI, low PLK-4 expression was associated with worse actuarial DFS (low 1-, 3-, 5-year 83%, 60%, 47% vs. high 91%, 81%, 81%; p = 0.02). In patients without mVI, high PLK-4 expression was an independent predictor of survival (HR 0.3, 95% CI: 0.1–1.0; p = 0.04). ConclusionPLK-4 represents a biomarker for good prognosis in patients with HCC who do not have mVI. This could aid clinical decision making for adjuvant clinical trials.

P192 CROSS REGIMEN FOR ADENOCARCINOMA OF THE ESOPHAGUS AND CARDIA: DOES PATHOLOGICAL RESPONSE INFLUENCE OVERALL AND DISEASE FREE SURVIVAL? MULTICENTER RETROSPECTIVE ANALYSIS

Abstract Aim Primary aim is to evaluate the relationship between pathological response after CROSS regimen for locally advanced esophageal adenocarcinomas and overall and disease-free survival. Secondary endpoint is to analyze the principal sites of relapse after surgery in this group of patients. Background &amp; Methods The CROSS trial showed an improvement of overall survival after neoadjuvant chemoradiation and subsequent surgical resection compared to surgery alone for patients with esophageal cancer, representing the benchmark [1]. Patients submitted to CROSS regimen for adenocarcinoma of the esophagus and cardia followed by esophagectomy with a transthoracic extended lymphadenectomy were analyzed. The patients were treated in 4 centers part of Italian Group for the Study of Esophageal Diseases (SISME). Actuarial Overall survival (OS) and actuarial disease-free survival (DFS) were analyzed and stratified according to yp Stage (1 – stage I and II; 2 – stage IIIA and IIIB and 3 - stage IVA) as described in the 8th edition of TNM. Kaplan-Meier method was used to estimate overall and progression-free survival, with the log-rank test to ascertain significance (p&lt;0.05). Median and range were used. Statistical analysis was done with SPSS version 21.0. Results 132 patients, from January 2014 to February 2019, were analyzed. Median age was 63 years (range 42-82). The site of the neoplasm was the distal esoghagus-EGJ in 127 cases and the middle esophagus in 5. Ivor Lewis was the procedure adopted. Fifty-month OS and DFS were respectively 42% and 6.7% respectively. No difference emerged when overall survival was analyzed according to yp Stages. Time to relapse is significantly longer for ypStage I and II. Recurrence occurred in 48 cases (36.3%) with 9 months as median time to relapse. Local and distal relapse were 10 (paratracheal nodes) and 38 respectively (7.5% and 28.7%, p&lt;0.001). Conclusion Pathological response after CROSS regimen doesn’t relate to OS and DFS. Time to recurrence is significantly longer for yp Stage 1 e 2 rather than other ypStages. Chemoradiotherapy in a neoadjuvant setting may influence the site of relapse.

Full Donor Chimerism after Allografts for Myelofibrosis: The Role of Conditioning Regimen

Background : The conditioning regimen for patients with myelolfibrosis undergoing an allogeneic HSCT is usually composed of a combination of fludarabine (FLU) with one alkylating agent, busulkfan (BU), thiotepa (THIO) or melphalan. In a recent prospective randomized study comparing BU-FLU versus THIO-FLU, the proportion of patients with full donor chimerism at 6 months, was respectively 63% and 65% (Patriarca et al, BBMT 2019). Aim of the study. Assess the rate of full donor chimerism in patients with myelofibrosis, after conditioning with one or two alkylating agents. Methods. We analyzed 113 patients with myelofibrosis, for whom chimerism data were available on day +30 . There were two groups: 35 patients were conditioned with either thiotepa-cyclophosphamide , thiotepa-fludarabine or busulfan-fludarabine (ONE-ALK), whereas 78 patients were prepared with thiotepa, busulfan, fludarabine (TBF). Patients receiving TBF were older (57 vs 52 years, p=0.008), were less frequently splenectomized pre-HSCT (30% vs 54%, p=0.03), had more frequently intermediate-2/high DIPSS scores (89% vs 74%, p=0.04) , and had comparable transfusion burden pre-HSCT (p=0.7). Chimerism was assessed via STR (PowerFlex-Promega) Results. The proportion of patients with full donor chimerism on day +30 in the TBF vs the ONE-ALK group was 87% vs 51% (p=0.00002); on day +60 these figures were 93% vs 13% (p&lt;0.0001) and on day +90 , the figures were 90% vs 21% (p&lt;0.00001). Full donor chimerism on day+30 was achieved in 81% of patients with DIPSS int1 (n=16), 74% of patients with int2 DIPSS, and 70% of patients with high risk DIPSS (p=0.6). Acute GvHD grade II-IV occurred in 27% vs 37% of patients in the two groups (p=0.7), and moderate severe chronic GvHD in 20% and 21% (p=0.8). The 5 year cumulative incidence of relapse was 8% in the TBF group, versus 50% for the ONE-ALK group (p&lt;0.0001), whereas the CI of TRM was 25% vs 11% (p=0.1). The 5 year actuarial disease free survival (DFS) was respectively 65% for TBF and 38% for the ONE-ALK group (p=0.004). Complete chimerism day+30. When looking at whether patients had (n=84) or not (n=29) full donor chimerism on day +30, the CI of relapse was respectively 44% vs 15% (p=0.002), the CI of TRM 18% vs 15% (p=0.5), and the 5 year DFS 65% vs 32% (p=0.001). Conclusions. Early full donor chimerism is a prerequisite for long term control of disease in patients with myelofibrosis undergoing an allogeneic HSCT. The combination of 2 alkylating agents in the conditioning regimen, provides a significantly higher chance of achieving full donor chimerism on day+30, and thus long term disease control. Figure Disclosures Angelucci: Vertex Pharmaceuticals Incorporated, and CRISPR Therapeutics: Other: Partecipation in DMC; Roche: Other: Local advisory board; Jazz Pharmaceuticals: Other: Local advisory board; BlueBirdBio: Other: Local advisory board; Novartis: Honoraria, Other: Chair Steering Committee TELESTO protocol; Celgene: Honoraria, Other: Partecipation in DMC.

Duodenal Adenocarcinoma: Surgical Results of 27 Patients Treated at a Single Center

IntroductionDuodenal adenocarcinoma is a rare malignancy. Given the rarity of the disease, there is limited data related to resection results. The objective is to analyze results at our hospital after the curative resection of duodenal adenocarcinoma (DA). Material and methodsThe variables were retrospectively collected from patients operated on between 1990 and 2017 at our hospital. ResultsA total of 27 patients were treated. Twenty-three patients (85%) underwent pancreaticoduodenectomy, and 4 patients (15%) with tumors located in the third and fourth portions of the duodenum underwent segmental duodenal resection. The overall postoperative morbidity was 63% (17 patients). Postoperative mortality was 7% (2 patients); however, postoperative mortality related to surgery was 4% (1 patient). All patients had negative resection margins. A median of 18 lymph nodes (range, 0–38) were retrieved and evaluated, with a median of 1 involved node (range, 0–8). Median follow up was 23 (9–69.7) months. Actuarial overall survival was 62.2 (25.2–99.1) months. Actuarial disease-free survival was 49 (0–133) months. ConclusionsThe surgical treatment of duodenal adenocarcinoma is associated with a high morbidity, although it achieves considerable survival. Depending on the tumor location and if there is no pancreatic infiltration, segmental duodenal resection with negative margins is an alternative to cephalic pancreaticoduodenectomy.

Retreatment for Local Recurrence of Prostatic Carcinoma After Prior Therapeutic Irradiation: Efficacy and Toxicity of HDR-Like SBRT

We evaluated the use of high dose-rate-like stereotactic body radiation therapy (SBRT) retreatment for biopsy-proven local persistence in prostate postradiation therapy, evaluating efficacy and toxicity. From 2009 to 2018, 50 patients with biopsy-proven recurrent prostate cancer >2 years after prior treatment were retreated with a high dose-rate-like dose of 3400 cGy over 5 fractions. Previous radiation therapy dose measured 75.6 Gy (64.8-81.0) and median salvage interval was 8.1 years (32-241 mo.). Eighty-three percent of patients had Gleason score 7 or higher disease at retreatment. Those with preexisting toxicity >grade 1 from their prior course were excluded. The planning target volume was comprised of the clinical target volume (prostate + any contiguous extension only) with no additional expansion. Toxicity assessment used CTCAE v.3.0 criteria. Median follow-up was 44 months (3-110). Median pre-SBRT salvage baseline prostate specific antigen (PSA) of 3.97 ng/mL decreased to 0.6 ng/mL and 0.16 ng/mL at 1 and 5 years in nonrelapsed patients, respectively. Actuarial 5-year biochemical disease-free survival (DFS) measured 60%, with corresponding 5-year actuarial local, distant, and salvage androgen deprivation therapy free rates of 94%, 89%, and 69%, respectively. Actuarial 5-year biochemical DFS measured 78% if PSA at salvage was <6.92 ng/mL versus 12% with ≥6.92 ng/mL (P = .0001). Toxicity was primarily in the GU domain, with an 8% 5-year actuarial rate of grade 3+, 3% when limited to salvage of "conventional external beam only" local relapse. No gastrointestinal (GI) toxicity >grade 1 occurred. Of the 30% sexually potent at the time of salvage, 82% subsequently lost potency. SBRT salvage of local prostate recurrence in previously irradiated patients appears clinically feasible in this challenging group. It demonstrates favorable PSA and DFS response, typically deferring the need for salvage androgen deprivation therapy or other treatment by over 5 years, with low GU and GI toxicity.

Adenocarcinoma duodenal: resultados del tratamiento quirúrgico de una serie unicéntrica de 27 pacientes

IntroductionDuodenal adenocarcinoma is a rare malignancy. Given the rarity of the disease, there is limited data related to resection results. The objective is to analyze results at our hospital after the curative resection of duodenal adenocarcinoma (DA). MethodsThe variables were retrospectively collected from patients operated on between 1990 and 2017 at our hospital. ResultsA total of 27 patients were treated. Twenty-three patients (85%) underwent pancreaticoduodenectomy, and 4 patients (15%) with tumors located in the third and fourth portions of the duodenum underwent segmental duodenal resection. The overall postoperative morbidity was 67% (18 patients). Postoperative mortality was 7% (2 patients); however, postoperative mortality related to surgery was 4% (1 patient). All patients had negative resection margins. A median of 18 lymph nodes (range, 0-38) were retrieved and evaluated, with a median of 1 involved node (range, 0-8). Median follow up was 23 (9-69.7) months. Actuarial overall survival was 62.2 (25.2-99.1) months. Actuarial disease-free survival was 49 (0-133) months. ConclusionsThe surgical treatment of duodenal adenocarcinoma is associated with a high morbidity, although it achieves considerable survival. Depending on the tumor location and if there is no pancreatic infiltration, segmental duodenal resection with negative margins is an alternative to cephalic pancreaticoduodenectomy.

Conditional disease-free survival after curative-intent liver resection for neuroendocrine liver metastasis.

Neuroendocrine liver metastases (NELM) are typically associated with high recurrence rates following surgical resection. Conditional disease-free survival (CDFS) estimates may be more clinically relevant compared to actuarial survival estimates. CDFS was assessed using a multi-institutional cohort of patients. Cox proportional hazards models were used to evaluate factors associated with disease-free survival (DFS). Three-year CDFS (CDFS3) estimates at "x" year after surgery were calculated as CDFS3 = DFS(x + 3)/DFS(x). A total of 521 patients met the inclusion criteria. While actuarial 3-year DFS gradually decreased from 49% at 1 year to 39% at 5 years, CDFS3 increased over time. CDFS3 at 5 years was estimated as 89% vs actuarial 8-year DFS of 39% (P < .001). The probability of remaining disease-free at 5 years after resection increased as patients remained disease-free. For example, the probability of being disease-free for an additional 3 years was 66.3% and 88.8% for patients who lived 2 and 5 years, respectively. Overall, CDFS3 in each subgroup increased postoperatively as years elapsed, however, the impact of each prognostic factor on CDFS3 changed over time. CDFS of patients who underwent resection of NELM exponentially improved as patients survived additional years without recurrence. CDFS provides more accurate prognostic measures compared with traditional DFS measures.

Prognostic Role of Platelets-to-Lymphocytes Ratio and Neutrophils-to-Lymphocytes Ratio in Breast Cancer Patients

Breast cancer (BC) is the most common cancer in women. Several prognostic and predictive factors are usefully considered in clinical practice, but ongoing efforts are made by the scientific community to identify new biomarkers for prognostic models’ improvement and better tailoring of therapeutic choice. Factors associated with inflammation, which is a hallmark of cancer, represent an important object of study. Among these factors, Neutrophils to lymphocytes ratio (NLR) and Platelets to lymphocytes ratio (PLR) are the most analyzed and are associated with prognosis in many solid tumors. The aim of this study is to verify the prognostic role of NLR and PLR in patients affected by localized BC who underwent radiotherapy (RT). Between December 2007 and June 2012, 370 consecutive BC patients treated with adjuvant RT were analyzed. PLR and NLR were calculated as the absolute platelet count divided by the absolute lymphocyte count, and absolute neutrophil count divided by absolute lymphocyte count in a blood sample obtained soon before the start of the RT, respectively. Using receiver operating characteristic analysis PLR and NLR were dichotomized and the cut-off values were 180 (namely, h-PLR≥180, l-PLR<180) and 3.17 (namely, h-NLR≥3.17, l-NLR<3.17), respectively. The end points of the study were local control (LC), disease free survival (DFS), overall survival (OS) and distant metastasis free survival (DMFS). The relationship among NLR, PLR and other clinico-pathological features was studied by chi-square. The end points were calculated using the Kaplan-Meier method and compared by the log-rank test. Multivariable analysis was performed using Logistic Regression. At a median follow-up time of 77 months (range 5-129), 345 patients were alive. Eighteen patients died for disease progression, while 7 deaths were non-cancer related. There were 58 (15.7%) relapses of disease. Actuarial 5-year DFS and OS in h-NLR vs l-NLR were 62% vs 81% (p<0.001) and 85% vs 92% (p=0.010) respectively; similar result was found for PLR (68% vs 82%, p=0.002; 87% vs 93%, p=0.002). Both ratios resulted significantly associated with DMFS (PLR p=0.007, NLR p=0.002), while it was not observed for LC (PLR p= 0.2, NLR p=0.7). In logistic regression that included high Ki67, stage, NLR, PLR, age and chemotherapy (the last two only for DFS and DMFS), NLR was identified as an independent prognostic factor of poor outcome for OS, DFS and DMFS (p<0.05). Multivariate analysis also showed that advanced stage negatively affected DFS and DMFS (p<0.05). Finally, X2- test revealed a significant correlation between NLR and Ki67, Her2 overexpression, stage, and chemotherapy. NLR is a low-cost, reproducible marker available in all patients, its high value is associated with poor prognosis in BC, and it could be used to improve the management of these patients.

Salvage radiation therapy for localized recurrent ovarian cancer.

To evaluate clinical outcomes for patients with localized recurrent ovarian cancer treated with salvage radiotherapy. In a retrospective single institutional analysis, we identified 40 patients who received salvage radiotherapy for localized ovarian cancer recurrence from January 1995 to June 2011. Recurrent disease was categorized as: pelvic peritoneal (45%, 18), extraperitoneal/nodal (35%, 14), or vaginal (20%, eight). Actuarial disease-free and overall survival estimates were calculated by Kaplan-Meier and prognostic factors evaluated by the Cox proportional hazards model. Median follow-up was 42 months. Median patient age was 54 years (range, 27-78). Histologic subtypes were: serous (58%, 23), endometrioid (15%, six), clear cell (13%, five), mucinous (8%, three), and other (8%, three). At the time of salvage radiotherapy, surgical cytoreduction was performed in 60% (24) and 68% (27) had platinum-sensitive disease. Most patients (63%, 25) received salvage radiotherapy at the time of first recurrence. Relapse after salvage radiotherapy occurred in 29 patients at a median time of 16 months and was outside the radiotherapy field in 62%. 18 At 3 years, disease-free and overall survival rates were 18% and 80%, respectively. On multivariate analysis, non-serous histology (hazards ratio 0.3, 95% CI 0.1-0.7) and platinum-sensitivity (hazards ratio 0.2, 95% CI 0.1-0.5) were associated with lower relapse risk. Platinum-sensitivity was also associated with overall survival (hazards ratio 0.4, 95% CI 0.1-1.0). Four patients (10%) were long-term survivors without recurrence 5 years after salvage radiotherapy. Of the five patients with clear cell histology, none experienced relapse at the time of last follow-up. Patients with non-serous and/or platinum-sensitive ovarian cancer had the greatest benefit from salvage radiotherapy for localized recurrent disease. Although relapse was common, radiotherapy prolonged recurrence for > 1 year in most patients and four were long-term survivors.