Early response to neoadjuvant chemotherapy (NAC) in combination with regional hyperthermia (RHT) to predict long-term survival for adult-type high-risk soft tissue sarcoma (HR-STS): Results of the EORTC-ESHO intergroup phase III study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10054-10054
Author(s):  
Rolf D. Issels ◽  
Eric Kampmann ◽  
Lars Lindner ◽  
Nelli Dieterle ◽  
Ulrich Robert Mansmann ◽  
...  

10054 Background: A randomized phase III completed trial showed that RHT added to NAC was beneficial in terms of local progression-free (LPFS), and disease-free (DFS) survival. Overall survival (OS) was improved in patients (pts) who completed the preoperative induction therapy with RHT (Lancet Oncol 2010). Here we analyzed both the radiographic (RR) and histopathologic (HR) response as early predictors for survival. Methods: 341 pts were randomized to receive 4 cycles of NAC + RHT (169 pts) or NAC alone (172 pts) as induction therapy. RR (CR/PR vs NC/PD) and HR (>75% vs <75% necrosis) were used to define responder vs non-responder. Predictive impact of response on LPFS, DFS, DDFS (distant disease-free survival) and OS was evaluated by intention-to-treat using Kaplan-Meier estimates and the log-rank test. Stratified (surgery before study entry yes/no; extremity vs non-extremity tumors) multivariate analyses were carried out by Cox regression. Results: Early response in pts with measurable disease was performed in 238 pts (103 pts not evaluable because of surgery before study entry). In the NAC+RHT group (114 pts) response rate was 49.1% (56 responders: RR: 18; HR: 22; RR + HR: 16) and substantially higher (p<0.001) compared to the NAC alone group (124 pts) which was 26,6% (33 responders: RR: 7; HR: 17; RR + HR: 9). In the NAC + RHT group, tumor response was associated with improved DFS (HR 0.58 CI 0.36-0.95; p=0.031) and OS (HR 0.50 CI 0.27-0.90; p=0.020) but not LPFS (HR 0.91 CI 0.49-1.71; p=0.78). For responders, OS median time was > 120 months vs 33 months for non-responders. For the entire NAC + RHT group (169 pts, including pts with surgery before study entry) response remained predictive for better OS (HR 0.54 CI 0.32-0.94; p=0.028) and was also associated with better DDFS (HR 0.47 CI 0.27-0.83; p=0.009). Conclusions: Adding RHT to NAC as induction therapy compared to NAC alone leads to significantly higher early response in almost half of the pts classified as responders which translates in better OS and prevention of distant metastases.

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Joachim Geers ◽  
Joris Jaekers ◽  
Halit Topal ◽  
Raymond Aerts ◽  
Cindy Vandoren ◽  
...  

Abstract Background Several clinicopathological predictors of survival after curative surgery for perihilar cholangiocarcinoma (pCCA) have been identified; however, conflicting reports remain. The aim was to analyse clinical and oncological outcomes after curative resection of pCCA and to determine prognostic factors. Methods Eighty-eight consecutive patients with pCCA underwent surgery with curative intent between 1998 and 2017. Survival curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Twenty-one prognostic factors were evaluated using multivariate Cox regression models. Results Postoperative complications were observed in 73 (83%) patients of which 41 (47%) were severe complications (therapy-oriented severity grading system (TOSGS) grade > 2), including a 90-day mortality of 9% (n = 8). Overall survival (OS) and disease-free survival (DFS) rates at 5 and 10 years after surgery were 33% and 19%, and 37% and 30%, respectively. Independent predictors of OS were locoregional lymph node metastasis (LNM) (risk ratio (RR) 2.12, confidence interval (CI) 1.19–3.81, p = 0.011), patient American Society of Anesthesiologists (ASA) physical status classification system > 2 (RR 2.10, CI 1.03–4.26, p = 0.043), and depth of tumour penetration (pT) > 2 (RR 2.58, CI 1.03–6.30, p = 0.043). The presence of locoregional LNM (RR 2.95, CI 1.51–5.90, p = 0.002) and caudate lobe resection (RR 2.19, CI 1.01–5.14, p = 0.048) were found as independent predictors of DFS. Conclusions Curative surgery for pCCA carries high risks with poor long-term survival. Locoregional LNM was the only predictor for both OS and DFS.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. LBA528-LBA528
Author(s):  
H. T. Mouridsen ◽  
A. Keshaviah ◽  
L. Mauriac ◽  
J. Forbes ◽  
R. Paridaens ◽  
...  

LBA528 Background: The Primary Core Analysis (PCA) of BIG 1–98 comparing letrozole (L) to tamoxifen (T) as initial adjuvant endocrine therapy showed that L significantly prolonged disease-free survival (DFS), particularly reducing the risk of relapse in distant sites, compared with T for postmenopausal women with endocrine-responsive breast cancer (BC). The aim of the Second Primary Analysis (SPA) is to compare L and T given in sequence vs. alone. On Mar 15, ‘06, the Data Safety Monitoring Committee (DSMC) will review the results of the 2nd interim analysis of the SPA. We will present safety and efficacy data from this analysis if the DSMC recommends release of the results. Methods: 8028 women were randomized upfront to Tx5 years (yrs) (A), Lx5 (B), Tx2→Lx3 (C), or Lx2→Tx3 (D); 1835 to the 2-arm option of the study (arm A vs. B; Mar ’98 - Mar ‘00) and 6193 to the 4-arm option (arm A vs. B vs. C vs. D; Apr ’99 - May ‘03). The primary endpoint was DFS (time from randomization to first occurrence of invasive BC recurrence, invasive contralateral BC, second non-breast malignancy, or death from any cause). The SPA is comprised of two pair-wise comparisons: arm A vs. C and B vs. D. Only 4-arm patients (pts) alive and disease-free at 2 yrs after study entry (corresponding to the treatment switch for arms C and D) are included. These analyses will determine if the risk of an event beyond 2 yrs is reduced by switching agents. Additional exploratory analyses based on all events and follow-up (FU) for 4-arm pts will be conducted, including the comparison of arm B vs. C. The final SPA is planned for Feb ‘08, after 662 events. In Jan ‘05, the 1st interim efficacy analysis was presented to the DSMC, after 162 events among 3641 pts (excluding those who had an event within 2 yrs or did not yet have at least 2 yrs of FU). The median SPA FU (from 2 yrs after study entry) was 11.1 months. The 2nd interim efficacy analysis will be presented to the DSMC on Mar 15, ‘06 based on data received as of a Dec 21, ‘05. Results: Conclusions: No significant financial relationships to disclose.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4128-4128
Author(s):  
Y. Baraki ◽  
P. N. Kostuik ◽  
B. Merriman ◽  
C. Nieroda ◽  
A. Sardi

4128 Background: Appendiceal tumors represent 2.8% of gastrointestinal tumors and less than 0.5% of gastrointestinal malignancies, but frequently involve intraperitoneal spread. Controversial treatment of disseminated tumor has consisted of extensive debulking surgery, peritonectomy, and intraperitoneal chemotherapy. We evaluated the disease free and overall survival, morbidity and mortality of patients with disseminated appendiceal tumors treated by cytoreductive surgery (CRS) and intraperitoneal hyperthermic chemotherapy (IPHC). Methods: A retrospective review of a prospective database was performed between 1999 and 2005. Thirty-one patients underwent CRS followed by IPHC using mitomycin 40 mg infused over 90 minutes at 40–42°C. Patients were given a Peritoneal Carcinomatosis Index (PCI) score pre and post operatively. Postoperatively, patients were assigned cytoreductive scores, indicating completeness of resection: CC-0 = no residual disease, CC-1 ≤ 0.25 cm, CC-2 = 0.25–2.5 cm, CC-3 ≥ 2.5 cm. Cox proportional-hazards models were used to test the influence of different variables on survival. The models were adjusted for age, grade of differentiation, histology and cytoreductive score. Results: There were 14 females and 17 males with a mean age 50 years (range 33–80). Two-thirds of all patients had a preoperative PCI score of >20. The overall survival at 1 year was 96% (95% CI, 74% to 99%) and at 3 years was 69% (95% CI, 38% to 86%). Disease free survival at 3 years was 30% ( 95% CI, 8% to 56%). There was no mortality from the procedure. Overall morbidity, including Grades 1–5 as described by the CTCAE guidelines, was 48%. A multivariate analysis was performed for grade of differentiation and was not found to be statistically significant. However, log rank test for equality of survivor functions in patients with CC scores of 0 or 1 experience recurrence of disease at a slower rate than patients with scores of 2 or 3 (p < 0.001). Conclusions: Although further study is necessary, Cytoreductive surgery followed by IPHC, where a low PCI score and a CC score of ≤1 is achieved, can lead to increased survival for selected patients having advanced appendiceal cancer with peritoneal dissemination. No significant financial relationships to disclose.


2013 ◽  
Vol 137 (12) ◽  
pp. 1761-1769 ◽  
Author(s):  
Ronghui Xia ◽  
Rongrui Zhou ◽  
Zhen Tian ◽  
Chunye Zhang ◽  
Lizhen Wang ◽  
...  

Context.—Histone methylation and acetylation play important roles in the carcinogenesis and progression of cancer. Objective.—To investigate whether histone modifications influence the prognosis of patients with salivary adenoid cystic carcinoma (ACC). Design.—The expression of histone H3 lysine 9 trimethylation (H3K9me3) and histone H3 lysine 9 acetylation (H3K9Ac) was assessed by immunohistochemistry in 66 specimens of primary ACC. Tests were used to determine the presence of any correlation between H3K9me3 and H3K9Ac levels and clinicopathologic parameters. Log-rank test and Cox proportional hazards regression models were used to analyze the survival data. Results.—H3K9me3 expression was positively correlated with solid pattern tumors (P = .002) and distant metastasis (P = .001). Solid pattern tumors had lower H3K9Ac expression levels than cribriform-tubular pattern tumors (P = .03). Patients whose tumors showed high H3K9me3 expression and a solid pattern had a significantly poorer overall survival (OS) (P &lt; .001 and P &lt; .001, respectively) and disease-free survival (P &lt; .001 and P = .01, respectively). Low H3K9Ac expression was correlated with poor OS (P = .05). The multivariate analysis indicated that high levels of H3K9me3 expression and solid pattern tumors were independent prognostic factors that significantly influenced OS (P = .004 and P = .04, respectively). H3K9me3 expression was identified as the only independent predictor of disease-free survival (P = .006). Conclusions.—Our results suggest that high levels of H3K9me3 expression are predictive of rapid cell proliferation and distant metastasis in ACC. Compared with histologic patterns, H3K9me3 might be a better predictive biomarker for the prognosis of patients with salivary ACC.


2021 ◽  
Author(s):  
Bertrand Baussart ◽  
Chiara Villa ◽  
Anne Jouinot ◽  
Marie-Laure Raffin-Sanson ◽  
Luc Foubert ◽  
...  

Objective: Microprolactinomas are currently treated with dopamine agonists. Outcome information on microprolactinoma patients treated by surgery is limited. This study reports the first large series of consecutive non-invasive microprolactinoma patients treated by pituitary surgery and evaluates the efficiency and safety of this treatment. Design: Follow-up of a cohort of consecutive patients treated by surgery. Methods: Between January 2008 and October 2020, 114 adult patients with pure microprolactinomas were operated on in a single tertiary expert neurosurgical department, using an endoscopic endonasal transsphenoidal approach. Eligible patients were presenting a microprolactinoma with no obvious cavernous invasion on MRI. Prolactin was assayed before and after surgery. Disease-free survival was modeled using Kaplan-Meier representation. A cox regression model was used to predict remission. Results: Median follow-up was 18.2 months (range: 2.8 to 155). In this cohort, 14/114 (12%) patients were not cured by surgery, including 10 early surgical failures, and 4 late relapses occurring 37.4 months (33 to 41.8) after surgery. From Kaplan Meier estimates, 1-year and 5-year disease free survival were 90.9% (95% CI, 85.6%-96.4%) and 81% (95% CI,71.2%-92.1%) respectively. The preoperative prolactinemia was the only significant preoperative predictive factor for remission (P<0.05). No severe complication was reported, with no anterior pituitary deficiency after surgery, one diabetes insipidus, and one postoperative cerebrospinal fluid leakage properly treated by muscle plasty. Conclusions: In well selected microprolactinoma patients, pituitary surgery performed by an expert neurosurgical team is a valid first-line alternative treatment to dopamine agonists.


2018 ◽  
Vol 29 (7) ◽  
pp. 1521-1527 ◽  
Author(s):  
E. Fokas ◽  
R. Fietkau ◽  
A. Hartmann ◽  
W. Hohenberger ◽  
R. Grützmann ◽  
...  

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 246-246
Author(s):  
Marieke Pape ◽  
Pauline A.J. Vissers ◽  
Laurens Beerepoot ◽  
Mark I. Van Berge Henegouwen ◽  
Sjoerd Lagarde ◽  
...  

246 Background: Among patients with potentially curable esophageal cancer (EC) or gastroesophageal junctional cancer (GEJC) treated with curative intent, survival remains poor and around half of these patients have disease recurrence within a few years. This study addresses the need for real-world data on disease-free survival (DFS) and overall survival (OS) in patients with EC or GEJC who underwent potentially curative treatment. Methods: Patients selected from the nationwide Netherlands cancer registry (NCR) had received a primary diagnosis of non-metastatic EC or GEJC (excluding patients with T4b tumors) in 2015 or 2016 and received treatment with curative intent. Curative intent was defined as receiving resection (with or without [neo]adjuvant therapy) or definitive chemoradiotherapy (dCRT) without surgery. DFS and OS were analysed using Kaplan-Meier curves with Log-Rank test from resection date or end of dCRT. A sub-analysis was performed for NCR patients selected to align with the population of the CheckMate-577 phase 3 study of adjuvant nivolumab, i.e. patients with non-cervical stage II/III disease, R0 resection and residual pathological disease after neoadjuvant CRT (nCRT) and surgery. Results: We identified 1916 patients of median age of 67 years and predominantly male (76%). The majority (79%) received surgery and 21% of patients received dCRT. In resected patients, 83% received nCRT, 10% neoadjuvant chemotherapy (with or without adjuvant CRT) and 7% received no (neo)adjuvant treatment. Compared to the resected group, the population receiving dCRT had significantly fewer males (65% vs 78%), a higher median age (72 vs 65 years) and worse performance status. Patients receiving dCRT significantly shorter median DFS (14.2 months) and OS (20.9 months) compared to resected patients (DFS: 26.4 months, p < 0.001; OS: 40.5 months, p < 0.001). The 1- and 3-year DFS probabilities were 68% and 44%, respectively, in resected patients, and 56% and 24%, respectively, in patients receiving dCRT. In patients receiving nCRT followed by surgery, the median DFS and OS were 25.2 and 38.0 months, respectively, and 1- and 3-year DFS probabilities were 67% and 43%, respectively. In the sub-analysis (n = 725) the median DFS and OS were 19.2 and 29.4 months, respectively, and the 1- and 3-year DFS rates were 62% and 36%, respectively. Conclusions: Although patients are treated with curative intent, a considerable amount of patients with non-metastatic EC or GEJC experienced recurrence within two years. Resected patients had a higher DFS and OS compared to patients receiving dCRT.


2020 ◽  
Author(s):  
Hao Zhao ◽  
Xuening Zhang ◽  
Zhan Shi ◽  
Songhe Shi

Abstract Background Tumor microenvironment (TME) and immune checkpoint inhibitors has been shown to promote active immune responses through different mechanisms. We aimed to identify the important prognostic genes and prognostic characteristics related to TME in prostate cancer (PCa).Methods The gene transcriptome profiles and clinical information of PCa patients were obtained from the TCGA database, and the immune, stromal and estimate scores were calculated by the ESTIMATE algorithm. We evaluated the prognostic value of risk score (RS) model based on univariate Cox and LASSO Cox regression models analysis, and established a nomogram to predict disease-free survival (DFS) in PCa patients. The GSE70768 data set was used for external validation. Finally, 22 subsets of tumor-infiltrating immune cells (Tiics) were analyzed using the Cibersort algorithm.Results In this study, the patients with higher immune, stromal, and estimate scores were associated with poorer DFS, higher Gleason score, and higher AJCC T stage. Based on the immune and stromal scores, the Venny diagram screened out 515 cross DEGs. The univariate COX and Lasso Cox regression models were used to select 18 DEGs from 515 DEGs, and constructed a RS model. The DFS of the high-RS group was significantly lower than that of the low-RS group (P<0.001). The AUC of 1-year, 3-year and 5-year DFS rates in RS model were 0.778, 0.754 and 0.750, respectively. In addition, the RS model constructed from 18 genes was found to be more sensitive than Gleason score (1, 3, 5 year AUC= 0.704, 0.677 and 0.682). The nomograms of DFS were established based on RS and Gleason scores. The AUC of the nomograms in the first, third, and fifth years were 0.802, 0.808, and 0.796, respectively. These results have been further validated in GEO. In addition, the proportion of Tregs was higher in high-RS patients (P<0.05), and the expression of five immune checkpoints (CTLA-4, PD-1, LAG-3, TIM-3 and TIGIT) was higher in high-RS patients (P<0.05).Conclusion We identified 18 TME-related genes from the TCGA database, which were significantly related to DFS in PCa patients.


1991 ◽  
Vol 9 (6) ◽  
pp. 941-946 ◽  
Author(s):  
M L McMaster ◽  
J P Greer ◽  
F A Greco ◽  
D H Johnson ◽  
S N Wolff ◽  
...  

Small-noncleaved-cell (SNC) lymphoma is a high-grade, biologically aggressive neoplasm notable for poor response to therapy, high relapse rate, and less than a 20% long-term survival. We treated 20 patients with SNC lymphoma with a novel chemotherapeutic regimen using intensive doses of chemotherapy at frequent intervals in the inpatient setting. All patients were previously untreated. Sixteen patients (80%) had stage IV disease. Most patients (95%) had at least one other characteristic associated with poor prognosis (bulky [greater than 10 cm] disease, multiple extranodal sites, poor performance status), and 85% had two or more characteristics associated with poor prognosis. Seventeen patients (85%) achieved a complete response (CR) to therapy, including all three patients with human immunodeficiency virus (HIV)-associated disease. There have been three relapses, all occurring less than 18 months after treatment, and two of three relapses occurred in patients who were unable to complete therapy. At a median follow-up of 29 months, 13 patients (65%) remain disease-free; the calculated 5-year actuarial disease-free survival is 60%. Toxicity, chiefly myelosuppression, was severe but manageable. There were two treatment-related deaths, both in elderly patients with poor performance status and advanced-stage disease. These data suggest that such a dose-intensive approach improves the response and survival of patients with SNC lymphoma.


2019 ◽  
Vol 29 (9) ◽  
pp. 1355-1360 ◽  
Author(s):  
Giorgio Bogani ◽  
Daniele Vinti ◽  
Ferdinando Murgia ◽  
Valentina Chiappa ◽  
Umberto Leone Roberti Maggiore ◽  
...  

ObjectiveNodal involvement is one of the most important prognostic factors in cervical cancer patients. We aimed to assess the prognostic role in relation to the burden of nodal disease in stage IIICp cervical cancer.MethodsData on all consecutive patients diagnosed with cervical cancer undergoing primary surgery (radical hysterectomy plus lymphadenectomy) or neoadjuvant chemotherapy followed by radical hysterectomy plus lymphadenectomy, between January 1980 and December 2017, were collected in a dedicated database. Exclusion criteria were: (1) consent withdrawal; (2) synchronous malignancies (within 5 years). Survival outcomes were assessed using Kaplan-Meier and Cox models.ResultsOverall, 177 (14.1%) of 1257 patients with cervical cancer were diagnosed with positive lymph nodes. After a median follow-up of 58 (range 4–175) months, 66 (37.3%) and 37 (20.9%) patients developed recurrent disease and died of disease, respectively. Via multivariate analysis, positive para-aortic nodes (HR 2.62, 95% CI 1.12 to 6.11; p=0.025) and the number of positive nodes (HR 1.06, 95% CI 1.02 to 1.11; p=0.002) correlated with worse disease-free survival. Furthermore, the number of positive nodes (HR 1.06, 95% CI 1.01 to 1.12; p=0.021) correlated with worse overall survival. Number of positive nodes (1, 2 or ≥3) strongly correlated with both disease-free survival (p<0.001, log-rank test) and overall survival (p=0.001, log-rank test). Focusing on patients receiving adjuvant radiation and chemotherapy, the number of positive lymph nodes was associated with response to treatment (p<0.001). Median disease-free survival was 100, 42, and 12 months for patients with one, two, or three or more positive lymph node(s), respectively (p<0.001, log-rank test).ConclusionsIn stage IIICp cervical cancer, adjuvant radiation and chemotherapy provides adequate overall survival in patients diagnosed with only one metastatic node, while survival outcomes are poor in patients with two or more metastatic nodes. This highlights the need for innovative treatments in patients with a high burden of lymphatic disease.


Sign in / Sign up

Export Citation Format

Share Document