Defining the role of neoadjuvant systemic therapy in high-risk retroperitoneal sarcoma: A multi-institutional TARPSWG study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 11513-11513 ◽  
Author(s):  
William W. Tseng ◽  
Francesco Barretta ◽  
Lorenzo Conti ◽  
Giovanni Grignani ◽  
Francesco Tolomeo ◽  
...  
Keyword(s):  
High Risk ◽  
Systemic Therapy ◽  
Statistical Significance ◽  
Objective Response ◽  
Logistic Models ◽  
Major Complication ◽  
Retroperitoneal Sarcoma ◽  
Recurrence Rates ◽  
Pleomorphic Sarcoma ◽  
Neoadjuvant Systemic Therapy

11513 Background: Surgery is the mainstay of treatment for patients with retroperitoneal sarcoma (RPS), but this can be challenging, and recurrence rates are high. Novel treatment approaches are needed. In this study, we sought to 1) determine the frequency and potential predictors of radiologic tumor response and 2) assess clinical outcomes in patients with primary high risk RPS who were treated at sarcoma referral centers with neoadjuvant systemic therapy followed by surgery. Methods: Clinicopathologic data was retrospectively collected for eligible patients treated from 2008-2018 at 13 institutions within the Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG). For each patient, preoperative objective response (RECIST1.1) was reported by each institution. Univariable and multivariable logistic models were performed to determine predictors of response. Kaplan-Meier plots were constructed for overall survival (OS) and cumulative incidences of local recurrence (LR) and distant metastasis (DM). Results: In total, 158 RPS patients were included in this study. A median of 3 cycles (IQ range 2-4) of neoadjuvant systemic therapy were given. No complete responses were observed. Partial response (PR) was seen in 37 patients (23%), stable disease (SD) in 88 (56%) and progressive disease (PD) in 33 (21%). Subtype-specific differences were seen including PR in 5 out of 11 (45%) patients with undifferentiated pleomorphic sarcoma. Overall, higher number of cycles given was positively associated with PR (p = 0.005). No other factors including receipt of neoadjuvant radiation therapy were predictive of PR. All patients underwent complete (R0/R1) resection with a major complication (Clavien-Dindo ≥3) rate of 23%. Differences in OS were observed based on preoperative response type (p = 0.005). In grade 3 dedifferentiated liposarcoma, patients who received adriamycin-ifosfamide versus another regimen had decreased LR and improved OS. In leiomyosarcoma, patients who received adriamycin-DTIC versus another regimen had a higher PR rate (37% vs. 16%), decreased LR, DM and improved OS. Limited by low numbers, these subtype-specific data did not reach statistical significance. Conclusions: In patients with high risk RPS, response to neoadjuvant systemic therapy is overall modest and may be regarded as an indicator of disease biology to predict survival after surgery. Subtype-specific regimens should be further validated and incorporated into prospective trials of neoadjuvant systemic therapy in RPS (e.g. STRASS2).

Neoadjuvant Systemic Therapy for High-Risk Melanoma Patients

2020 ◽  
pp. 767-793
Author(s):  
Emily Z. Keung ◽  
Rodabe N. Amaria ◽  
Vernon K. Sondak ◽  
Merrick I. Ross ◽  
John M. Kirkwood ◽  
...  
Keyword(s):  
High Risk ◽  
Systemic Therapy ◽  
High Risk Melanoma ◽  
Risk Melanoma ◽  
Neoadjuvant Systemic Therapy ◽  
Melanoma Patients

Neoadjuvant Systemic Therapy for High-Risk Melanoma Patients

2018 ◽  
pp. 1-27
Author(s):  
Emily Z. Keung ◽  
Rodabe N. Amaria ◽  
Vernon K. Sondak ◽  
Merrick I. Ross ◽  
John M. Kirkwood ◽  
...  
Keyword(s):  
High Risk ◽  
Systemic Therapy ◽  
High Risk Melanoma ◽  
Risk Melanoma ◽  
Neoadjuvant Systemic Therapy ◽  
Melanoma Patients

Effect of neoadjuvant systemic therapy prior to radical prostatectomy in high-risk prostate cancer on surgical morbidity: Contemporary results utilizing the Clavien System.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 66-66
Author(s):  
Stephen Bentley Williams ◽  
John W. Davis ◽  
Mary F. Achim ◽  
Amado J. Zurita ◽  
Surena F. Matin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Radical Prostatectomy ◽  
Systemic Therapy ◽  
Preoperative Hemoglobin ◽  
High Risk Prostate Cancer ◽  
Estimated Blood Loss ◽  
Neoadjuvant Systemic Therapy ◽  
Risk Prostate Cancer ◽  
Grade 3

66 Background: There is limited evidence definingthe morbidity of radical prostatectomy (RP) with curative intent for patients with high risk prostate cancer. Multimodality treatment for men with high risk prostate cancer using neoadjuvant systemic therapy followed by surgery is being increasingly explored. Methods: We analyzed 215 consecutive patients with high risk and very high risk prostate cancer who underwent robotic or open RP with extended pelvic lymph node dissection previously untreated or received neoadjuvant systemic therapy between 2006 and 2010 at a single tertiary care academic center. Univariable and multivariable logistic regression analyses were used to identify predictors of complications. Results: Baseline characteristics were similar between patients who underwent neoadjuvant systemic therapy followed by RP versus RP alone except for PSA (PSA< or equal to 4 ng/ml: 75.4% vs. 15.5%, p<0.001) and preoperative hemoglobin (13.8 g/dl vs. 14.4 g/dl, p=0.003), respectively. Twenty nine percent of patients (63 of 215 patients) experienced a complication of any grade ≤90 d after surgery 6% experienced Grade ≥3, with no significant difference between either cohort (p=0.50). On multivariate analysis, estimated blood loss [Odds Ratio (OR) 1.10; 95% CI, 1.0 to 1.2, p=0.03), length of stay (OR 1.75; 95% CI, 1.3 to 2.4, p=0.001) and preoperative hemoglobin (OR 0.71; 95% CI, 0.53 to 0.94, p=0.02) were independent predictors of the occurrence of any grade complication. Considering grade 3 or 4 complications, procedure time (OR 2.20; 95% CI 1.0 to 4.8, p=0.05) and estimated blood loss (OR 1.39; 95% CI, 0.98 to 1.96, p=0.06) were significant predictors of major complications. Conclusions: Postoperative morbidity in patients with high risk prostate cancer following RP with or without the use of neoadjuvant systemic therapy is comparable to contemporary RP series of low to intermediate risk disease reporting outcomes in a similar fashion. Use of neoadjuvant systemic therapy prior to RP was safe and did not appear to increase the risk of having a perioperative complication.

scholarly journals MRI-Based Radiomics Analysis for the Pretreatment Prediction of Pathologic Complete Tumor Response to Neoadjuvant Systemic Therapy in Breast Cancer Patients: A Multicenter Study

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2447
Author(s):  
Renée W. Y. Granzier ◽  
Abdalla Ibrahim ◽  
Sergey P. Primakov ◽  
Sanaz Samiei ◽  
Thiemo J. A. van Nijnatten ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Systemic Therapy ◽  
Tumor Response ◽  
Added Value ◽  
Breast Cancer Patients ◽  
Neoadjuvant Systemic Therapy ◽  
Clinical Models ◽  
Combined Models ◽  
Complete Tumor

This retrospective study investigated the value of pretreatment contrast-enhanced Magnetic Resonance Imaging (MRI)-based radiomics for the prediction of pathologic complete tumor response to neoadjuvant systemic therapy in breast cancer patients. A total of 292 breast cancer patients, with 320 tumors, who were treated with neo-adjuvant systemic therapy and underwent a pretreatment MRI exam were enrolled. As the data were collected in two different hospitals with five different MRI scanners and varying acquisition protocols, three different strategies to split training and validation datasets were used. Radiomics, clinical, and combined models were developed using random forest classifiers in each strategy. The analysis of radiomics features had no added value in predicting pathologic complete tumor response to neoadjuvant systemic therapy in breast cancer patients compared with the clinical models, nor did the combined models perform significantly better than the clinical models. Further, the radiomics features selected for the models and their performance differed with and within the different strategies. Due to previous and current work, we tentatively attribute the lack of improvement in clinical models following the addition of radiomics to the effects of variations in acquisition and reconstruction parameters. The lack of reproducibility data (i.e., test-retest or similar) meant that this effect could not be analyzed. These results indicate the need for reproducibility studies to preselect reproducible features in order to properly assess the potential of radiomics.

scholarly journals RTID-05. INDIGO: A GLOBAL, RANDOMIZED, DOUBLE-BLIND, PHASE 3 STUDY OF VORASIDENIB (AG-881) VS PLACEBO IN PATIENTS WITH RESIDUAL/RECURRENT GRADE II GLIOMA WITH AN ISOCITRATE DEHYDROGENASE 1/2 (IDH1/2) MUTATION

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii194-ii194
Author(s):  
Ingo Mellinghoff ◽  
Martin van den Bent ◽  
Jennifer Clarke ◽  
Elizabeth Maher ◽  
Katherine Peters ◽  
...  
Keyword(s):  
High Risk ◽  
Dose Escalation ◽  
Objective Response ◽  
Data Monitoring Committee ◽  
Progression Free Survival ◽  
High Risk Population ◽  
Low Grade ◽  
Who Grade ◽  
Free Survival ◽  
Grade Ii

Abstract BACKGROUND Low-grade gliomas (LGGs; WHO grade II) are incurable and ultimately progress to high-grade gliomas. The current treatment options are surgery followed by observation (“watch and wait”) for patients with lower risk for disease progression or postoperative chemoradiotherapy (high-risk population). There are no approved targeted therapies. IDH1 and IDH2 mutations (mIDH1/2) occur in approximately 80% and 4% of LGGs, respectively, and promote tumorigenesis via neomorphic production of D-2-hydroxyglutarate. Vorasidenib, an oral, potent, reversible, brain-penetrant pan-inhibitor of mIDH1/2, was evaluated in 76 patients with glioma in two phase 1 studies (dose escalation and perioperative) and was associated with a favorable safety profile at daily doses below 100 mg. Preliminary clinical activity was observed in non-enhancing glioma patients in both studies, with an objective response rate (ORR) of 18.2% and median progression-free survival of 31.4 months in the dose escalation study. METHODS Approximately 366 patients will be randomized 1:1 to vorasidenib (50 mg QD) or matched placebo and stratified by 1p19q status (intact vs co-deleted). Key eligibility criteria: age ≥ 12 years; grade II oligodendroglioma or astrocytoma (per WHO 2016 criteria) not in need of immediate treatment and without high-risk features; centrally confirmed mIDH1/2 status; ≥ 1 surgery for glioma with most recent ≥ 1 year but ≤ 5 years before randomization, and no other anticancer therapy; Karnofsky performance status ≥ 80%; and centrally confirmed measurable, non-enhancing disease evaluable by magnetic resonance imaging. Crossover from placebo to the vorasidenib arm is permitted upon centrally confirmed radiographic progression per RANO-LGG criteria. Primary endpoint: progression-free survival assessed by independent review. Secondary endpoints: safety and tolerability, tumor growth rate assessed by volume, ORR, overall survival, and quality of life. Clinical data will be reviewed regularly by an independent data monitoring committee. The study is currently enrolling patients in the US, with additional countries planned (NCT04164901).

scholarly journals Gemcitabine-Containing Chemotherapy for the Treatment of Metastatic Myxofibrosarcoma Refractory to Doxorubicin: A Case Series

2021 ◽  
Vol 28 (1) ◽  
pp. 813-817
Author(s):  
Arielle Elkrief ◽  
Suzanne Kazandjian ◽  
Thierry Alcindor
Keyword(s):  
Overall Survival ◽  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Objective Response ◽  
Case Series ◽  
Progression Free Survival ◽  
Distant Metastases ◽  
First Line ◽  
Pleomorphic Sarcoma ◽  
Line Setting

Background: Myxofibrosarcoma is a type of soft-tissue sarcoma that is associated with high rates of local recurrence and distant metastases. The first-line treatment for metastatic soft-tissue sarcoma has conventionally been doxorubicin-based. Recent evidence suggests that myxofibrosarcoma may be molecularly similar to undifferentiated pleomorphic sarcoma (UPS), which is particularly sensitive to gemcitabine-based therapy. The goal of this study was to evaluate the activity of gemcitabine-containing regimens for the treatment of metastatic myxofibrosarcoma refractory to doxorubicin. Material and Methods: We retrospectively evaluated seven consecutive cases of metastatic myxofibrosarcoma at our institution treated with gemcitabine-based therapy in the second-line setting, after progression on doxorubicin. Baseline clinical and baseline characteristics were collected. Primary endpoints were objective response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results: After progression on first-line doxorubicin, a partial, or complete radiological response was observed in four of seven patients who received gemcitabine-based chemotherapy. With a median follow-up of 14 months, median progression-free and overall survival were 8.5 months and 11.4 months, respectively. Conclusions: Gemcitabine-based chemotherapy was associated with encouraging response rates in this cohort, similar to those seen in UPS. Both entities could be studied together for novel gemcitabine-based regimens.

Systemic Therapy for Head and Neck Skin Cancers

FACE ◽  
2021 ◽  
pp. 273250162110138
Author(s):  
Rebecca Knackstedt ◽  
Peter Taub ◽  
Gary Rogers ◽  
Brian Gastman
Keyword(s):  
Radiation Therapy ◽  
High Risk ◽  
Head And Neck ◽  
Systemic Therapy ◽  
Malignant Tumors ◽  
Curative Therapy ◽  
Recurrent Tumors ◽  
Skin Cancers ◽  
Systemic Therapies ◽  
Melanoma Skin

The mainstay of curative therapy for head and neck skin cancers relies upon surgery and/or radiation therapy. However, for some aggressive, non-resectable or recurrent tumors, systemic therapy is necessary. Recent emerging classes of drugs have shown to improve survival for high-risk, recurrent, and unresectable variants of these tumors. The goal of this paper is to review options for systemic therapies for head and neck skin cancers including melanoma, non-melanoma skin cancers and other rare and non-malignant tumors.

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