Outcomes of post-operative treatment with concurrent systemic therapy and radiotherapy (RT) in intermediate (INT) risk resected oral cavity squamous cell carcinoma (OCSCC): A multi-institutional collaboration.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17567-e17567
Author(s):  
Jessica Lyn Geiger ◽  
Neil McIver Woody ◽  
C. Jillian Tsai ◽  
Ahmed I. Ghanem ◽  
Neal Dunlap ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Surgical Resection ◽  
Disease Free Survival ◽  
Standard Of Care ◽  
Total Sample ◽  
7Th Edition ◽  
Extranodal Extension ◽  
Kaplan Meier ◽  
Improved Outcomes ◽  
Pathologic Features

e17567 Background: Patients (pts) with adverse pathologic factors in resected OCSCC excluding positive surgical margins or extranodal extension represent a group of INT risk disease. Though not standard of care, adjuvant CRT is often used in INT pts. We conducted a multi-institutional study to evaluate factors associated with improved outcomes in INT pts treated with or without chemotherapy. Methods: An IRB-approved collaborative database of patients with primary OCSCC (Stage I-IVB AJCC 7th edition) treated with primary surgical resection between 1/1/2005 and 1/1/2015 with or without adjuvant therapy was established from 6 academic institutions. Pts were categorized by pathologic features and adjuvant therapy. Kaplan Meier curves, log-rank p-values and multivariate analysis (MVA) were used to describe outcomes by treatment including locoregional control (LRC) and disease free survival (DFS). Results: From a total sample size of 1270 patients, 455 INT risk pts were treated with primary surgical resection and adjuvant therapy; 95 received CRT, 274 received RT alone, and 86 received RT without recorded chemotherapy. 49% of pts had perineural invasion (PNI), 24.8% lymphovascular space invasion, 21.5% poorly differentiated histology, 47.3% with pT3/4 disease, and 27.9% with > 2 lymph node positive (LN+). 55.8% of CRT pts were treated with cisplatin. > 2 LN+ was the only significant predictor of LRC (HR 1.49, p= 0.049). PNI and > 2 LN+ were significant predictors of DFS (HR 1.52, p= 0.003 and HR 1.76, p< 0.001). On MVA, after adjusting for > 2 LN+, treatment with cisplatin-RT was borderline significant for LRC (HR 0.52, p= 0.08). 3 year LRC in pts with > 2 LN+ was 84.4% in pts treated with cisplatin-RT compared with 64.9% for RT alone. Conclusions: The addition of cisplatin-based CRT to INT risk pts is controversial but among pts with > 2 LN+ there was a trend toward benefit. This study is limited by small numbers of pts treated with CRT, though these results highlight the need for further investigation in this population to identify INT pts who would benefit from adjuvant therapy intensification.

Effect of body mass index (BMI) on outcomes after surgical resection and adjuvant therapy for pancreatic cancer patients.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 185-185
Author(s):  
M. R. Khawaja ◽  
N. Zyromski ◽  
M. Yu ◽  
H. R. Cardenes ◽  
C. M. Schmidt ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Therapy ◽  
Cancer Patients ◽  
Surgical Resection ◽  
Survival Rates ◽  
Disease Free Survival ◽  
University Hospital ◽  
Rank Test ◽  
Kaplan Meier ◽  
Significant Difference

185 Background: Obesity is one of the factors commonly associated with pancreatic cancer risk, but its prognostic role for survival is debatable. This study aimed to determine the role of BMI in treatment outcomes of pancreatic cancer patients (pts) undergoing surgical resection followed by adjuvant therapy. Methods: We retrospectively reviewed 165 consecutive pts with pancreatic cancer undergoing pancreaticoduodenectomy at Indiana University Hospital between 2004 and 2008. Fifty-three pts who received adjuvant treatment [gemcitabine alone (C-group): n=19; gemcitabine + radiotherapy (CRT-group): n=34] at our institution were included in the analysis. The Kaplan-Meier method was used to estimate the disease-free survival (DFS) and overall survival (OS); log-rank test was used to compare these outcomes between BMI groups (normal 18.5-24.99 kg/m2 vs. overweight/obese ≥ 25 kg/m2). Results: The sample comprised 53 pts (28 males; median age 62 yrs) with a median follow-up of 18.6 months (mos). Thirty pts (56.6%) had their BMIs recorded before the date of surgery, and 23 pts prior to starting adjuvant therapy. Two (3.8%) pts were underweight, 21 (39.6%) had a normal BMI and 30 (56.6%) were overweight/obese. There was no statistically significant difference in the median DFS of obese/overweight and normal BMI pts irrespective of adjuvant therapy (C or CRT) (14.47 vs. 11.80 mos; p= 0.111). Obese/overweight pts had a better median OS [25.2 vs. 14.6 mos; p=0.045 overall (25.7 vs. 16.9 mos; p= 0.143 for the CRT-group and 17.3 vs. 13.4 mos; p= 0.050 for the C-group)], 1-year survival [96.7% vs. 61.9%; p < 0.0001 overall (95% vs. 64.3%; p= 0.001 for the CRT-group, and 90% vs. 57.1%; p=0.016 with C)], and 2-year survival [52.6% vs. 25.4%; p < 0.0001 overall (60.0% vs. 30.0%; p=0.0001 for the CRT-group and 37.5% vs. 14.3%; p=0.0002 for the C-group)] than patients with normal BMI. Conclusions: In our experience, overweight/obese pts undergoing surgery followed by adjuvant therapy have better survival rates than patients with normal BMI. [Table: see text] No significant financial relationships to disclose.

Outcomes of postoperative treatment with concurrent chemoradiotherapy (CRT) in high risk resected oral cavity squamous cell carcinoma (OCSCC): A multi-institutional collaboration.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6080-6080 ◽  
Author(s):  
Jessica Lyn Geiger ◽  
Neil McIver Woody ◽  
C. Jillian Tsai ◽  
Ahmed I. Ghanem ◽  
Neal Dunlap ◽  
...  
Keyword(s):  
High Risk ◽  
Demographic Data ◽  
Disease Free Survival ◽  
Total Sample ◽  
Postoperative Treatment ◽  
High Dose ◽  
P Values ◽  
Administration Schedule ◽  
7Th Edition ◽  
Pathologic Features

6080 Background: Adjuvant CRT with high-dose cisplatin remains standard treatment for OCSCC with high risk pathologic features of positive surgical margins (SM+) and/or extranodal extension (ENE). High-dose cisplatin is associated with significant toxicities, and alternative dosing schedules or treatments are used. We evaluated outcomes associated with different systemic therapies concurrent with RT and the effect of cumulative dosing of cisplatin. Methods: An IRB-approved collaborative database of patients (pts) with primary OCSCC (Stage I-IVB AJCC 7th edition) treated with primary surgical resection between 1/1/2005 and 1/1/2015 with or without adjuvant therapy was established from 6 academic institutions. Pts were categorized by systemic therapy received, and resultant groups compared for demographic data, pathologic features, and outcomes by t-test and Chi-squared tests. Kaplan-Meier curves, log-rank p-values, and multivariate analysis (MVA) for disease free survival (DFS) and freedom from metastatic disease (DM). Results: From a total sample size of 1282 pts, 196 pts were identified with high risk features (SM+, ENE) who were treated with adjuvant CRT. Median age was 56 years, 63.3% of pts were men, 81.1% were Caucasian, 70.9% had significant tobacco history. 35.7% of pts had SM+, 82.7% ENE, 65.3% with perineural invasion (PNI), 49% had lymphovascular space invasion (LVSI). There was a trend associating higher cisplatin dose delivered with improved locoregional control, DM, and overall survival (OS) (p-values 0.131, 0.084, and 0.187, respectively). DFS was significantly better with higher cisplatin dose (HR = 0.95 per 100 mg/m2 increase in cisplatin). Administration schedule of cisplatin (weekly versus high-dose) was not significantly associated with DFS. On MVA, PNI and higher cisplatin dose remained statistically significant for DFS (p < 0.001 and 0.007). Median OS by cisplatin dose was 10.5 ( < 200 mg/m2) vs. 20.8 months ( > / = 200 mg/m2). Conclusions: This multi-institutional analysis demonstrated cumulative cisplatin dose > / = 200 mg/m2 was associated with improved DFS in high risk resected OCSCC pts. It remains unclear by this analysis if cisplatin administration schedule has any prognostic implication. Further study is warranted to elucidate the optimal cisplatin schedule for this population.

scholarly journals Outcomes of Post-Operative Treatment with Concurrent Chemoradiotherapy (CRT) in High-Risk Resected Oral Cavity Squamous Cell Carcinoma (OCSCC): A Multi-Institutional Collaboration

2021 ◽  
Vol 28 (4) ◽  
pp. 2409-2419
Author(s):  
Arslan Babar ◽  
Neil M. Woody ◽  
Ahmed I. Ghanem ◽  
Jillian Tsai ◽  
Neal E. Dunlap ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
High Risk ◽  
Oral Cavity ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Demographic Data ◽  
Disease Free Survival ◽  
Total Sample ◽  
High Dose ◽  
Pathologic Features

Adjuvant chemoradiation (CRT), with high-dose cisplatin remains standard treatment for oral cavity squamous cell carcinoma (OCSCC) with high-risk pathologic features. We evaluated outcomes associated with different cisplatin dosing and schedules, concurrent with radiation (RT), and the effect of cumulative dosing of cisplatin. An IRB-approved collaborative database of patients (pts) with primary OCSCC (Stage I–IVB AJCC 7th edition) treated with primary surgical resection between January 2005 and January 2015, with or without adjuvant therapy, was established from six academic institutions. Patients were categorized by cisplatin dose and schedule, and resultant groups compared for demographic data, pathologic features, and outcomes by statistical analysis to determine disease free survival (DFS) and freedom from metastatic disease (DM). From a total sample size of 1282 pts, 196 pts were identified with high-risk features who were treated with adjuvant CRT. Administration schedule of cisplatin was not significantly associated with DFS. On multivariate (MVA), DFS was significantly better in patients without perineural invasion (PNI) and in those receiving ≥200 mg/m2 cisplatin dose (p < 0.001 and 0.007). Median DFS, by cisplatin dose, was 10.5 (<200 mg/m2) vs. 20.8 months (≥200 mg/m2). Our analysis demonstrated cumulative cisplatin dose ≥200 mg/m2 was associated with improved DFS in high-risk resected OCSCC pts.

Multicenter randomized controlled phase III study of nivolumab alone or in combination with ipilimumab as immunotherapy vs standard follow-up in surgical resectable HNSCC after adjuvant therapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS6095-TPS6095
Author(s):  
Chia-Jung Busch ◽  
Adrian Muenscher ◽  
Christian Stephan Betz ◽  
Volkan Dogan ◽  
Philippe Schafhausen ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Distant Metastasis ◽  
Tumor Antigens ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Late Toxicity ◽  
Standard Of Care ◽  
Phase Iii ◽  
Free Survival ◽  
Treatment Naïve

TPS6095 Background: Surgically treated locally advanced head and neck squamous cell carcinoma (LA HNSCC) often requires postoperative chemoradiation with high risk of acute and late toxicity. Disease-free survival (DFS) after 2 years is approximately 70%. Combining Nivolumab (N), a PD-1inhibitor, and Ipilimumab, a CTLA4 inhibitor, as maintenance therapy may improve DFS due to anti-tumor effects of immunotherapy by enhancing cross-presentation of tumor antigens. The IMSTAR HN study compares neoadjuvant N and N±I 6 months after adjuvant therapy vs the standard therapy as first-line treatment for LA HNSCC. Methods: Eligible pts are ≥18 years old with treatment-naive LA HNSCC (oral cavity, oropharynx p16-, hypopharynx, and larynx), ECOG PS ≤1, and no distant metastasis. 276 pts will be randomized (2:1) into 2 arms and approximately 10 centers in Germany will be involved. Standard of care (arm II) consists of surgical resection followed by risk-adapted adjuvant (chemo)radiation. The experimental arm I receives neoadjuvant N 3mg/kg. After treatment according to standard arm a second randomization will be performed: In arm Ia N 3mg/kg will be given every 2 weeks until progression or up to 6 months. In arm Ib I 1mg/kg will be applied additionally every 6 weeks also until progression or up to 6 months. Primary endpoints is DFS in arms I and II. Secondary endpoints: Local regional control (LRC), distant metastasis free survival (DMFS), overall survival (OS), quality of life (QoL), survival depending on PD-L1 status, comparison of arm Ia vs arm II and Ib vs. II. AEs, graded per CTCAE v4.03, are evaluated for at least 12 months after randomization. The translational program includes investigations concerning immunmodulation, mutational load in general, but also specific mutations in targets involved in immune function and antigen presentation. Recruitment started in August 2018. Clinical trial information: NCT03700905.

scholarly journals Phase 2 Study of Abbreviated 3 Cycles of Rituximab Plus CHOP (Cyclophosphamide, Adriamycin, Vincristine, and Prednisolone) Immunochemotherapy in Patients with Completely Excised Stage I or II CD20+ Diffuse Large B-Cell Lymphoma (CISL 12-09)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4193-4193
Author(s):  
Dok Hyun Yoon ◽  
Byeong Seok Sohn ◽  
Jung Yong Hong ◽  
Sung Yong Oh ◽  
Won-Sik Lee ◽  
...  
Keyword(s):  
Overall Survival ◽  
Disease Progression ◽  
Surgical Resection ◽  
Disease Free Survival ◽  
B Cell Lymphoma ◽  
Stage I ◽  
Chop Chemotherapy ◽  
Free Survival ◽  
Kaplan Meier ◽  
Disease Free

Abstract Introduction: Full cycles of R-CHOP chemotherapy or abbreviated chemotherapy followed by radiotherapy are recommended as standard of care for limited stage (LS) diffuse large B-cell lymphoma (DLBCL). There are occasions when lesions are completely excised during the diagnostic surgical resection. In addition, initial surgical resection of the involved area is often performed in the treatment of intestinal lymphomas with LS disease due to obstructive lesions or perforation risk. As to these patients without residual gross lesions, however, the number of cycles of chemotherapy has not so far been questioned and full cycles of chemotherapy are usually performed. Thus, we aimed to investigate the effectiveness of an abbreviated three courses of R-CHOP chemotherapy in patients with completely excised stage I or II CD20+ DLBCL. Methods: This is a multicenter, single arm, phase 2 study designed to evaluate efficacy and safety of 3 cycles of R-CHOP chemotherapy in low risk LS DLBCL. Key inclusion criteria were as follows: pathologically confirmed CD20 positive DLBCL, age >18 years, stage I or II, and complete resection with no residual lesion after surgical resection. Patients with B symptoms, bulky disease, primary breast, testicular or CNS lymphomas were excluded. R-CHOP chemotherapy started within 6 weeks from surgical resection and was repeated every 3 weeks for 3 cycles. Prophylactic G-CSF was not administered. Radiologic tumor assessment was performed at baseline, every 3 months until 2 years, then every 6 months until 5 years after completion of study treatment. The primary endpoint was 2-year disease-free survival (DFS). Secondary endpoints included overall survival and safety. (ClinicalTrials.gov: NCT01279902.) Results: Twenty-three patients were enrolled between Dec 2010 and May 2013. Of these, one was excluded because of ineligibility and the remaining 22 patients were included in the analysis. The median age at diagnosis was 57 years (range, 29-77 years). Fourteen patients had stage 1 disease and the other eight had stage 2. Preoperative LDH level was available in 11 patients and it was elevated in two of them. Thus, preoperative IPI scores could be calculated in those 11 patients; 0 in 8, 1 in one, and 2 in one patients, respectively. Postoperative IPI scores were 0 in 11, 1 in 10 and 2 in one patients. Primary sites included intestine (n=15), cervical lymph nodes (n=4), stomach (n=1), tonsil (n=1) and spleen (n=1). All the 22 patients completed 3 cycles of R-CHOP chemotherapy as planned. With a median follow-up of 39.5 months (95% CI, 29.9-47.1 months), only one patient showed disease progression and died with the estimated 2-year DFS and OS rates of 95.0%. It was the only one patient with IPI of 2 with elevated LDH and age>60 that showed disease progression at 12.7 months. He had a splenic mass and underwent splenectomy followed by 3 cycles of R-CHOP. He underwent one cycle of salvage R-ESHAP chemotherapy but died of rapid disease progression. No grade 3 or 4 non-hematologic toxicities were observed. Neutropenia was the most common grade 3 or 4 hematologic toxicity which was noted in 8 (36.4%) patients. Three patients experienced G3 febrile neutropenia. Conclusions: Three cycles of abbreviated R-CHOP chemoimmunotherapy is an effective and safe therapeutic approach for patients with localized and completely excised DLBCL especially in those with low-risk IPI. Figure 1 Kaplan-Meier curves of (A) disease-free survival and (B) overall survival. (A) (B) Figure 1. Kaplan-Meier curves of (A) disease-free survival and (B) overall survival. / (A). / (B) Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Disease-Free Survival for Patients with Thin Melanomas according to the American Joint Committee on Cancer 8th Edition

Dermatology ◽  
2019 ◽  
Vol 235 (4) ◽  
pp. 334-339
Author(s):  
◽  
Luisa Elena Gambra Michel ◽  
Jon Uña Gorospe ◽  
Antonio Luis López Figueroa ◽  
Raquel Mullor Nogales ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Staging System ◽  
Tnm Staging ◽  
Wilcoxon Test ◽  
Rank Test ◽  
Free Survival ◽  
7Th Edition ◽  
Kaplan Meier ◽  
Disease Free ◽  
8Th Edition

Background: The recently implemented AJCC 8th edition TNM staging system for malignant melanoma (MM) changed the definition for T1a and T1b tumours. Objectives: To analyse differences in disease-free survival (DFS) among patients with thin MM staged according to both AJCC 7th and 8th editions. Methods: An observational study including 285 patients with cutaneous thin MM (thickness ≤1 mm). Cases were staged as T1a and T1b using both 7th and 8th editions. Neither regional nor visceral diseases were present at diagnosis. DFS curves were generated according to the Kaplan-Meier method. Results: An 8% shift of patients from a T1a towards a T1b stage group was observed after applying the AJCC 8th edition. According to this 8th edition, DFS for T1a patients was significantly longer than for T1b patients (log-rank test; p = 0.005); 5-year DFS for T1a and T1b was 100 and 95%, respectively (Wilcoxon test; p = 0.002). According to the AJCC 7th edition, DFS did not significantly differ for T1a and T1b patients; 5-year DFS for T1a and T1b was 99 and 97%, respectively (p > 0.05). Conclusions: The AJCC 8th edition seems to be a better tool for staging thin melanomas.

Role of adjuvant therapy in resected gallbladder cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 452-452
Author(s):  
Mohamed Abdelrahim Muddathir Hassan ◽  
Nicha Wongjarupong ◽  
Cristobal T. Sanhueza ◽  
Mindy L. Hartgers ◽  
Fatima Hassan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adjuvant Therapy ◽  
Gallbladder Cancer ◽  
Cancer Patients ◽  
Surgical Resection ◽  
Adjuvant Treatment ◽  
Disease Free Survival ◽  
Free Survival ◽  
Disease Free

452 Background: Surgical resection is the only curative treatment for patients with gallbladder cancer, despite surgical advances many patients ultimately develop recurrent disease. Management of resected gallbladder cancer mostly relies on single-arm trials and retrospective observations. The purpose of our study is to assess the role of adjuvant therapy in stage I-III gallbladder cancer patients who have undergone surgical resection. Methods: Clinical data were collected on 251 patients who underwent surgical resection for stage I-III gallbladder cancer and presented to Mayo clinic from January 2000-December 2015. Patients were then classified into adjuvant treatment group and surveillance only group. Overall survival and recurrence were compared between the two groups. Results: 78 (31.1%) patients received adjuvant therapy while 173 patients were observed only. Patients who received adjuvant tended to be younger (63.0[SD 11] vs 66.2 [SD 13.1]), have higher stage, and underwent extended surgery. Most patients received chemoradiotherapy (55) with 5-Fluorouracil (67.3%) and capecitabine (25.5%) as radiosensitizing agents. 21 patients received additional adjuvant chemotherapy. 27% of patients received chemotherapy as the sole adjuvant treatment. The most common chemo regimens included gemcitabine (52.3%) and gemcitabine plus cisplatin combination (23.8%). On multivariate analysis patients > 65 years(HR 1.53 [1.07-2.19], p = 0.02), males (HR 1.7 [1.2-2.4], p = 0.003), positive margins (2.77 [1.69-4.38], p < 0.01), and stage III (HR 1.91 [1.35-2.70], p < 0.01) had worse overall survival. Patients who underwent extended radical resection (HR 0.73 [0.51-1.05], p = 0.09) had better overall survival. Adjuvant therapy had no statistical significant effect on overall survival (HR 1.10 [0.75-1.59], p = 0.63 or disease free survival (HR 1.05 [0.69-1.59], p = 0.81) on overall population. However, in stage IIIB, patients receiving adjuvant therapy had better overall survival (HR 0.51 [0.25-1.01], p = 0.05) and disease free survival (HR 0.45 [0.19-1.09], p = 0.06). Conclusions: In our study, adjuvant treatment, especially chemoradiation therapy, was only beneficial in patients with stage IIIb gallbladder cancer patients.

Surgical Resection and Permanent Brachytherapy for Recurrent Atypical and Malignant Meningioma

Neurosurgery ◽  
2004 ◽  
Vol 54 (1) ◽  
pp. 55-64 ◽  
Author(s):  
Marcus L. Ware ◽  
David A. Larson ◽  
Penny K. Sneed ◽  
William W. Wara ◽  
Michael W. McDermott
Keyword(s):  
Overall Survival ◽  
Surgical Resection ◽  
Surgical Intervention ◽  
Radiation Necrosis ◽  
Disease Free Survival ◽  
Atypical Meningioma ◽  
Malignant Meningioma ◽  
Free Survival ◽  
Kaplan Meier ◽  
Disease Free

Abstract OBJECTIVE Recurrent atypical and malignant meningiomas are difficult to treat successfully. Chemotherapy to date has been unsuccessful, and radiosurgery is limited to smaller tumors. Reoperation alone provides limited tumor control and limited prolonged survival. The addition of brachytherapy at the time of operation is an option. Here, we report the results of our series of patients with recurrent malignant meningioma treated with resection and brachytherapy with permanent low-dose 125I. METHODS The charts of patients in our database with recurrent atypical and malignant meningiomas treated by surgical resection and permanent 125I brachytherapy at the University of California, San Francisco, between 1988 and 2002 were selected for this study. Calculations of disease-free survival and overall survival curves were made by the Kaplan-Meier actuarial method. Univariate analysis between Kaplan-Meier curves was based on the log-rank statistic, with a significance level set at a value of P ≤ 0.05. RESULTS Seventeen patients had recurrent malignant meningioma, and four had recurrent atypical meningioma. The median number of sources implanted after surgical resection was 30 (range, 4–112 sources), with a median total activity of 20 mCi (range, 3.3–85.9 mCi). The median time to progression after brachytherapy was 11.6 months for patients with malignant meningioma and 10.4 months for the combined group. There was a trend toward longer disease-free survival time in patients after gross total resection versus subtotal resection and in patients with tumors located at the convexity and parasagittally versus at the cranial base. These differences did not reach statistical significance. The median overall survival after diagnosis was 9.4 years for patients with atypical meningioma, 6.6 years for those with malignant meningioma, and 8.0 years for all patients combined. Survival from the time of resection and implantation of 125I was 1.6 years for patients with atypical meningioma, 2.4 years for patients with malignant meningioma, and 2.4 years for the combined group. Thirty-three percent of patients had complications requiring surgical intervention. Radiation necrosis occurred in 27% of patients; 13% underwent surgery for radiation necrosis. In addition, 27% had a wound breakdown and required surgical intervention. CONCLUSION The options for patients with recurrent atypical or malignant meningiomas are limited. Our results suggest that for tumors not suitable for radiosurgery, resection followed by permanent brachytherapy should be considered as a potential salvage treatment. However, this approach results in a relatively high complication rate in these heavily treated patients and requires meticulous surgical technique and medical therapies to assist with wound healing after surgery.

Design of a phase II randomized, open-label trial of DN24-02, an autologous cellular immunotherapy targeting HER2/neu, in patients with surgically resected urothelial cancer at high risk of recurrence.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS4673-TPS4673
Author(s):  
Dean F. Bajorin ◽  
Padmanee Sharma ◽  
Robert Brownell Sims ◽  
Andrew Sandler ◽  
Seth P. Lerner
Keyword(s):  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Immune Responses ◽  
Surgical Resection ◽  
Urothelial Cancer ◽  
Disease Recurrence ◽  
Cellular Immunotherapy ◽  
Her2 Expression ◽  
Pathologic Features

TPS4673 Background: Despite surgical resection and the use of (neo)adjuvant chemotherapy, up to 50% of patients with invasive urothelial carcinoma will have disease recurrence and eventually die of metastatic disease. New approaches are needed for these patients. Approximately 50% of patients with high-risk pathologic features have evidence of HER2 expression in the primary tumor or involved lymph nodes. DN24-02 is an autologous cellular immunotherapy targeting HER2, which is based on Dendreon’s Antigen Delivery Cassette technology – the same platform used for sipuleucel-T (an FDA-approved treatment for asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer). Each dose of DN24-02 is manufactured by culture of peripheral blood mononuclear cells obtained by leukapheresis with a recombinant antigen that comprises components of the intra- and extracellular domains of the HER2 antigen linked to GM-CSF. A product similar to DN24-02 has shown evidence of safety and immune response in phase I studies. Objectives: The primary objective is to determine whether DN24-02, given as adjuvant therapy following surgical resection, can prolong survival compared to standard of care (SOC). Secondary objectives are to evaluate disease-free survival, safety, and immune responses to DN24-02. Methods: Eligible patients will have undergone surgical resection of a primary urothelial cancer, with either ≥pT2 or pN+ staging, and HER2 expression ≥1+ by IHC based on pathologic review. Approximately 180 patients will be randomized (1:1) to receive three IV infusions of DN24-02 as adjuvant therapy approximately every 2 weeks, or SOC. Stratification will include 1) neoadjuvant chemotherapy vs surgery alone; and 2) positive (pN+) vs negative lymph node involvement (pN0). Other adjuvant chemotherapy will not be allowed. Patients can be treated per SOC if there is disease recurrence. Patients will be monitored for evidence of recurrence by imaging, and followed for survival. Cellular and serological immune responses will be assessed at baseline and post-DN24-02 therapy.

Institutional retrospective review of presurgical cisplatin-based chemotherapy (chemo) in patients with urothelial carcinoma (UC): Gemcitabine+cisplatin (GC) versus dose-dense methotrexate, vinblastine, doxorubicin, cisplatin (ddMVAC).

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 365-365
Author(s):  
Lauren Christine Harshman ◽  
Susanna J. Jacobus ◽  
Stephanie A. Mullane ◽  
Hope Feldman ◽  
Michelle S. Hirsch ◽  
...  
Keyword(s):  
Cox Regression ◽  
Tumor Resection ◽  
Disease Free Survival ◽  
Standard Of Care ◽  
Logrank Test ◽  
Exact Test ◽  
Kaplan Meier ◽  
Node Positive Disease ◽  
Muscle Invasive ◽  
Dose Dense

365 Background: Neoadjuvant cisplatin-based chemo is the standard of care for muscle invasive UC. ddMVAC and GC are frequently used regimens but have not been directly compared. The choice is often based on physician preference and toxicity profile. We interrogated a pre-existing database of UC patients (pts) for differences in efficacy and toxicity among them. Methods: From 2007-2013, consecutive pts who had received presurgical chemo prior to primary tumor resection for muscle invasive, non-metastatic UC were identified. Tolerability, toxicity and efficacy were evaluated. Rates were calculated by regimen and compared using Fisher’s exact test. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared by regimen using logrank test. Cox regression estimated hazard ratios (HR) in univariate and adjusted models. Results: Of the96 patients eligible for analysis (GC: 40, ddMVAC: 56), 42% of GC pts had ≥cT3 and 23% had cN+ compared to 62% and 39% with ddMVAC. pCR rate was 18% for GC and 27% for ddMVAC (p=0.33). With a median follow-up of 28 mo., 2-yr OS probabilities were 59% [95% CI:(39-74)] on GC and 77%[95%CI:(60-87%)] on ddMVAC (p=0.1). Conclusions: Despite having more clinical ≥T3 and node positive disease at baseline, ddMVAC is at least as active as GC and achieved a numerically higher rate of pCRs/≤pT1 than GC in our cohort. No unexpected toxicities surfaced. Dose delays, discontinuations, and most selected toxicities appeared higher with GC. Neither DFS or OS significantly differed between the two regimens, however, there was a trend to greater benefit with ddMVAC. [Table: see text]

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