Radiographic tumor response in pediatric patients with newly diagnosed localized (LOC) or metastatic (MET) Ewing’s sarcoma (EWS) following neoadjuvant chemotherapy

20008 Background: Standard treatment for EWS includes vincristine, doxorubicin, cyclophosphamide (VDC) alternating with ifosfamide and etoposide (IE). Using this therapy, overall survival is 70% in patients with LOC EWS and 30% in patients with MET EWS. We compared the radiographic response to VDC and IE in patients with LOC or MET EWS. Methods: We conducted a randomized trial comparing pegfilgrastim to filgrastim in patients treated with VDC (cycles 1, 2, 5, 9, 11, 13) and IE (cycles 3, 4, 6–8, 10, 12, 14). Local control with radiation or surgery was initiated after cycle 5. We assessed radiographic response after VDC (C1,2) and IE (C3,4) using 1-dimensional (RECIST) and 2-dimensional (WHO) criteria. Measurements were performed using MEDx. Results: Twenty-one patients with EWS, median age 20y (6–25y), were enrolled; 16 were evaluable for this analysis. Primary tumors were in extremity (n=5) or central axis (n=11). Eight patients had MET disease (pulmonary only, n=4). Median (range) decrease in tumor size by WHO after C4 was 61% (40–92%) for LOC and 83% (47–94%) for MET. Decrease by treatment is presented in the table . Overall responses after 4 cycles for LOC patients were 5 PR, 3 SD using RECIST, and 6 PR, 2 SD using WHO. For MET patients, overall responses were the same using RECIST and WHO, 7 PR, and 1SD. Conclusion: Patients with MET EWS responded as well as those with LOC EWS after 4 cycles of neoadjuvant chemotherapy. Similar overall response was demonstrated using RECIST or WHO. Tumor response after VDC was greater than after IE, possibly due to sequence of administration, but patients had continued tumor response with IE. [Table: see text] No significant financial relationships to disclose.

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P5-11-05: Measurement of Neoadjuvant Chemotherapy Tumor Response in Locally Advanced Breast Cancer by Three Methodologies. Correlation with Overall Survival.

10.1158/0008-5472.sabcs11-p5-11-05 ◽

2011 ◽

Author(s):

JA Garcia-Saenz ◽

A Romero ◽

Garcia-Asenjo JA Lopez ◽

JM Roman ◽

A Moreno ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Neoadjuvant Chemotherapy ◽

Advanced Breast Cancer ◽

Tumor Response ◽

Locally Advanced Breast Cancer ◽

Locally Advanced ◽

Advanced Breast

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Tumor Response Ratio Predicts Overall Survival in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy

Annals of Surgical Oncology ◽

10.1245/s10434-014-3922-0 ◽

2014 ◽

Vol 21 (10) ◽

pp. 3317-3323 ◽

Cited By ~ 8

Author(s):

Marian Miller ◽

Rebecca A. Ottesen ◽

Joyce C. Niland ◽

Laura Kruper ◽

Steven L. Chen ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Neoadjuvant Chemotherapy ◽

Cancer Patients ◽

Tumor Response ◽

Response Ratio ◽

Breast Cancer Patients

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Next generation sequencing of urothelial bladder cancer: Memorial Sloan Kettering Cancer Center experience in 454 patients.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.469 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 469-469

Author(s):

Sumit Isharwal ◽

Francois Audenet ◽

Esther N. Drill ◽

Irina Ostrovnaya ◽

Eugene J. Pietzak ◽

...

Keyword(s):

Cell Cycle ◽

Overall Survival ◽

Neoadjuvant Chemotherapy ◽

Tumor Stage ◽

Urothelial Bladder Cancer ◽

Primary Tumors ◽

Free Survival ◽

Urothelial Bladder ◽

Cell Cycle Pathway ◽

Generation Sequencing

469 Background: Genomic characterization of urothelial bladder cancer (UBC) may help to identify alterations associated with tumor stage, novel therapeutic targets and biomarkers to predict outcomes. Methods: 454 UBC patients were sequenced using next generation sequencing assay (MSK−IMPACT). 264 patients (123 NMIBC, 112 MIBC and 29 metastatic) were chemotherapy naïve primary tumors. Results: Patients whose primary tumors harbored TP53, RB1, TP53/MDM2, and cell cycle pathway alterations more frequently presented with advanced disease whereas those with tumors containing FGFR3, and RTK/RAS/RAF pathway alterations generally presented with NMIBC (all FDR < 0.001). TP53, RB1, TP53/MDM2, and cell cycle pathway alterations were associated with worse overall and metastasis free survival whereas FGFR3 alterations were associated with more favorable overall and metastasis free survival (all FDR < 0.05). RTK/RAS/RAF pathway alterations were associated with more favorable metastasis free survival (FDR = 0.01). MIBC with no DDR alterations, DDR alterations of unknown significance and DDR deleterious alterations had pathologic downstaging rates of 37%, 48% and 81% with platinum-based neoadjuvant chemotherapy (p = 0.013). Patients with ERCC2 mutations had significantly higher pathologic downstaging with platinum-based neoadjuvant chemotherapy compared to patients without ERCC2 mutations (p = 0.025). MIBC with DDR alterations had better overall survival with neoadjuvant chemotherapy compared to MIBC without DDR alterations (p = 0.04). Of note, MIBC cases with and without DDR alterations have similar overall survival in the absence of neoadjuvant chemotherapy (p = 0.78). Conclusions: TP53, RB1 and FGFR3 alterations as well as TP53/MDM2, cell cycle and RTK/RAS/RAF pathway alterations showed an association with tumor stage and patient outcomes. MIBC with DDR alterations had higher pathological downstaging as well as better overall survival compared to MIBC without DDR alterations with platinum−based neoadjuvant chemotherapy. In absence of neoadjuvant chemotherapy, MIBC with and without DDR alterations have similar patient outcomes.

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Advances in therapies for non-Hodgkin lymphoma in children

Hematology ◽

10.1182/asheducation-2015.1.522 ◽

2015 ◽

Vol 2015 (1) ◽

pp. 522-528 ◽

Cited By ~ 5

Author(s):

Rachel Kobos ◽

William Terry

Keyword(s):

Overall Survival ◽

Hodgkin Lymphoma ◽

Pediatric Patients ◽

Cell Lymphoma ◽

Large Cell ◽

Newly Diagnosed ◽

Limited Data ◽

Non Hodgkin Lymphoma ◽

Short And Long Term

Pediatric patients with newly diagnosed, non-Hodgkin Lymphoma (NHL) have an excellent overall survival. However, therapy regimens are associated with acute toxicity and late effects. Furthermore, patients with relapsed or refractory disease have relatively few options with proven clinical benefit. Both histologic and molecular differences exist between adult and pediatric NHL preventing simple translation of adult NHL successes into improvements in pediatric NHL treatment. This review summarizes the introduction of targeted therapies into frontline treatments for patients with anaplastic large-cell lymphoma and CD20–positive tumors, with the goal of improving overall survival while limiting both short- and long-term toxicities. In addition, newer approaches that have limited data in children but may have a significant role in how we treat pediatric NHL in the future are reviewed, which include CD19 directed therapy, Notch inhibition, the tri-functional antibody, FBTA05, and EZH2 inhibition.

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Prognostic value of response assessed by RECIST and WHO criteria to neoadjuvant chemotherapy in locally advanced gastric cancer patients

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e15647 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e15647-e15647

Author(s):

S. R. Park ◽

J. S. Lee ◽

Y. W. Kim ◽

I. J. Choi ◽

K. W. Ryu ◽

...

Keyword(s):

Gastric Cancer ◽

Neoadjuvant Chemotherapy ◽

Advanced Gastric Cancer ◽

Tumor Size ◽

Tumor Response ◽

Locally Advanced ◽

R0 Resection ◽

Who Criteria ◽

Locally Advanced Gastric Cancer ◽

Response To Neoadjuvant Chemotherapy

e15647 Background: In metastatic gastric cancer, the response to chemotherapy is assessed by RECIST or WHO criteria according to the change of tumor size. There are no data, however, on the usefulness of those criteria in evaluating tumor response in the setting of neoadjuvant chemotherapy. The aim of this study was to evaluate the relationship between tumor response to neoadjuvant chemotherapy-as assessed by RECIST and WHO criteria-and clinical outcome in locally advanced gastric cancer (LAGC) patients. Methods: This study recruited LAGC patients who, from January 2003 through November 2005, entered the neoadjuvant arm of prospective randomized phase II trials comparing neoadjuvant chemotherapy to adjuvant chemotherapy. LAGC was defined as stage III or IV (M0) disease based on computed tomography (CT) according to the Japanese Classification of Gastric Carcinoma. Patients with measurable lesions received 3 cycles of neoadjuvant chemotherapy consisting of docetaxel (36 mg/m2) and cisplatin (40 mg/m2) on days 1 and 8 every 3 weeks, followed by surgery. Results: After chemotherapy, 40 (95%) patients underwent surgery and the remaining 2 patients showed new distant metastasis on CT scan. Thirty-five (83%) patients had curative R0 resection. Twenty-eight (67%) patients had a clinical response to neoadjuvant chemotherapy according to RECIST/WHO criteria. Although R0 resection rate (93% vs 64%, P = 0.03), median relapse-free survival (RFS) (43.2 vs 7.5 months, P = 0.14), and overall survival (OS) (not reached vs 27.0 months, P = 0.10) were better in responders than non-responders, they did not differ significantly in the subgroup that subsequently underwent surgery. When we redefined the decrease in tumor size judged as a response by RECIST (≥60% rather than ≥30%) and WHO (≥75% rather than ≥50%) criteria, response correlated significantly with both RFS (P = 0.03) and OS (P = 0.02). Conclusions: In the neoadjuvant setting, which frequently involves smaller measurable lesions than the metastatic setting, larger changes in tumor size than those specified by RECIST and WHO criteria are needed to predict postoperative outcome. No significant financial relationships to disclose.

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Triple Negative Breast Cancer Patients Treated with Radiation Therapy: Improvement in Survival and Local Control With Adjuvant Chemotherapy Compared To Neoadjuvant Chemotherapy – A Hypothesis Generating Report

10.21203/rs.3.rs-638570/v1 ◽

2021 ◽

Author(s):

Mary Roselin Nittala ◽

Satyaseelan Packianathan ◽

Gary L. Shultz ◽

Paul Roberts ◽

Eswar K. Mundra ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

African American ◽

Adjuvant Chemotherapy ◽

Neoadjuvant Chemotherapy ◽

African American Women ◽

Local Control ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Disease Free Survival

Abstract Background Triple negative breast cancer (TNBC) (estrogen receptor (ER) – negative, progesterone receptor (PR) - negative, and human epidermal growth factor receptor 2 (HER2) -negative) is an aggressive subtype of breast cancer that is more common in younger women, carries a poorer prognosis and has a greater metastatic potential than receptor positive subtypes. Radiation therapy’s ability to improve outcomes, especially the overall survival is controversial, more so among African American patients. The objective of this study is to evaluate local control and survival rates of TNBC patients treated with radiotherapy (RT) in our institution with a sizeable cohort of African American women. Methods This is a retrospective analysis of 67 TNBCs (2007–2017) at an academic state institution who underwent a lumpectomy and /or mastectomy (surgery) followed by adjuvant irradiation to a median total dose of 50 Gy (range 40.5–50.40 Gy). Chemotherapy was administered in a neoadjuvant (32) or adjuvant setting (35). For all 67 TNBCs, local control (LC), overall survival (OS), and disease-free survival (DFS) were estimated using the Kaplan-Meier method. The significance of survival variables was analyzed using the Cox univariate and multivariate proportional hazards model. A p-value of less than 0.05 was considered statistically significant. The SPSS 24.0 software was used for data analysis. Results The baseline characteristics of all 67 TNBCs were measured with median follow up of 58 months (range 10–142 months). Patients were stratified into two groups (neoadjuvant chemotherapy-RT (32) vs. adjuvant chemotherapy-RT (35)). The five-year rates for LC, DFS and OS were 14.8 % vs. 47.9 % (p = 0.002), 24.2% vs. 53.1 % (p = 0.015), and 65.1% vs. 92.2% (0.002) respectively. On Cox multivariate analysis, patients who received adjuvant chemotherapy were associated with statistically improved significant LC (p = 0.002) and OS (p = 0.002). The variables included were: BMI (p = 0.050), distance travelled (p = 0.027), 8th AJCC TNM staging (p = 0.018) and tumor grade (p = 0.022). Conclusion In this hypothesis-generating report, among TNBC patients undergoing RT, adjuvant chemotherapy appears to be better than neoadjuvant chemotherapy in determining the clinical outcomes.

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Advances in therapies for non-Hodgkin lymphoma in children

Hematology ◽

10.1182/asheducation.v2015.1.522.3916185 ◽

2015 ◽

Vol 2015 (1) ◽

pp. 522-528 ◽

Cited By ~ 1

Author(s):

Rachel Kobos ◽

William Terry

Keyword(s):

Overall Survival ◽

Hodgkin Lymphoma ◽

Pediatric Patients ◽

Cell Lymphoma ◽

Large Cell ◽

Newly Diagnosed ◽

Limited Data ◽

Non Hodgkin Lymphoma ◽

Short And Long Term

Abstract Pediatric patients with newly diagnosed, non-Hodgkin Lymphoma (NHL) have an excellent overall survival. However, therapy regimens are associated with acute toxicity and late effects. Furthermore, patients with relapsed or refractory disease have relatively few options with proven clinical benefit. Both histologic and molecular differences exist between adult and pediatric NHL preventing simple translation of adult NHL successes into improvements in pediatric NHL treatment. This review summarizes the introduction of targeted therapies into frontline treatments for patients with anaplastic large-cell lymphoma and CD20–positive tumors, with the goal of improving overall survival while limiting both short- and long-term toxicities. In addition, newer approaches that have limited data in children but may have a significant role in how we treat pediatric NHL in the future are reviewed, which include CD19 directed therapy, Notch inhibition, the tri-functional antibody, FBTA05, and EZH2 inhibition.

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Does stereotactic body radiation therapy have a role in oligoprogressive metastatic colorectal cancer?

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.755 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 755-755

Author(s):

Will Jin ◽

Aidan M. Burke ◽

Abdul Rashid ◽

John Marshall ◽

Keith Robert Unger

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Radiation Therapy ◽

Metastatic Colorectal Cancer ◽

Local Control ◽

Stereotactic Body Radiation Therapy ◽

Primary Tumors ◽

Progression Of Disease ◽

Delay Progression

755 Background: Patients with metastatic colorectal cancer undergoing systemic therapy may enter an oligoprogressive state. Traditionally, local ablative therapy (LAT) has been limited to symptom palliation. We hypothesize that LAT for oligoprogressive lesions with stereotactic body radiation therapy (SBRT) is a feasible alternative to surgical interventions and may delay progression of disease. Methods: An IRB-approved retrospective review of patients with oligoprogressive, metastatic colorectal cancer who were treated with SBRT at Georgetown University Hospital from 2012-2016 was performed. Results: 40 patients with 41 metastatic lesions of the lung (n = 11), liver (n = 10), lymph nodes (n = 8), soft tissue (n = 6), and bone (n = 6) were reviewed. Median follow-up, overall survival, and freedom from distant progression were 10.6, 17.3, and 6.4 months, respectively. Crude one year local control and overall survival were 82.9% and 75%, respectively. First site of progression was distally in 63.4% of patients. Patients treated with SBRT in the liver were significantly more likely to locally progress than other treated sites (13.18 vs. 39.81 months, p = 0.007). On univariate analysis, non-lymph node treated tumors (p = 0.046), larger CEA change at 6 month follow-up (p = 0.048), and right sided primary tumors (p = 0.004) were associated with local failure within 1 year. On multivariate analysis, only right sided primary tumors were significantly more likely to locally progress (p = 0.009). Conclusions: Patients with oligoprogressive colorectal cancer can be effectively treated with SBRT to achieve acceptable rates of local control and potentially delay progression of disease.

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Comparison of different systemic therapeutic regimes in resectable high-risk soft tissue sarcoma: Results of a network meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.11549 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 11549-11549

Author(s):

Jan Haussmann ◽

Wilfried Budach ◽

Edwin Boelke ◽

Balint Tamaskovics ◽

Freddy Joel Djiepmo Njanang ◽

...

Keyword(s):

Overall Survival ◽

High Risk ◽

Soft Tissue ◽

Neoadjuvant Chemotherapy ◽

Soft Tissue Sarcoma ◽

Literature Search ◽

Standard Treatment ◽

Meta Analysis ◽

Tumor Control ◽

Regional Hyperthermia

11549 Background: The treatment of high-risk soft tissue sarcoma of the trunk or the extremities consists of surgical resection with risk-adapted radiation therapy. Further treatment options which can significantly improve local and systemic tumor control including chemotherapy are not well established. Due to the heterogeneity of disease different systemic approaches as well as their application during different time points have been attempted. Methods: We conducted a literature search for randomized clinical trials in the treatment of localized, resectable high-risk soft tissue sarcoma comparing different treatment modalities according to the PRISMA guidelines. We extracted published hazard ratios and number of events for the endpoints of overall and disease-free survival (OS; DFS) as well as local and distant recurrence-free interval (LRFI; DRFI). The different modalities were compared in a network meta-analysis against the defined standard treatment surgery ± radiotherapy using the inverse-variance heterogeneity model (ivhet) with the help of the Microsoft Excel add-in Meta-XL V5.3. Results: The literature search identified 25 studies including 3489 patients. The network analysis showed that adjuvant chemotherapy (adjCTx) results in a significant improvement in overall survival (HR = 0.86; CI-95%: 0.75-0.97; p = 0.017) compared to the standard treatment of surgery ± radiatherapy alone. Combined treatment with regional hyperthermia and neoadjuvant chemotherapy (HTx+nadjCTx) also improves OS (HR = 0.45; CI-95%: 0.20-1.00; p = 0.049). Preoperative chemotherapy alone (nadjCTx) as well as perioperative chemotherapy (periopCTx) resulted both in non-statistically significant improvements in OS (HR = 0.61; CI-95%: 0.29-1.29; p = 0.195) and (HR = 0.48; CI-95%: 0.15-1.55; p = 0.218). Histology-tailored neoadjuvant chemotherapy (tNaCTx) also showed no effect on overall survival (HR = 1.08; CI-95%: 0.45-2.61; p = 0.868). The analysis of DFS, LRFI and DRFI disclosed a similar pattern between the different treatment regimens. Conclusions: The addition of cytotoxic chemotherapy in resectable high-risk soft tissue sarcomas provides a measurable benefit in overall survival. Shifting of systemic therapy to the neoadjuvant setting and combination with regional hyperthermia might be favored. Predictive clinical and molecular markers are needed to evaluate and limit potentional risks prospectively going forward.

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