scholarly journals The prognostic value of initial tumor size in patients with Ewing Family of Tumors

2015 ◽  
Vol 12 (2) ◽  
Author(s):  
RAJEEB KUMAR DEO
Keyword(s):  
Tumor Volume ◽  
Bone Marrow Involvement ◽  
Progression Free Survival ◽  
High Volume ◽  
Patient Characteristics ◽  
P Value ◽  
Survival Times ◽  
Initial Tumor ◽  
Oncology Centre ◽  
Ewing Family Of Tumors

<p>Ewing Family of Tumors (EFT) is a high grade embryonal malignancy, common in children and young adults (CYAs). The prognostic factors include initial tumor volume, site, presence of metastasis, and the EWS/FLI 1 mutation. Low volume disease is known to result in higher response rates and longer survival times. In a community oncology centre, longer system intervals results in higher percentage of high volume disease at presentation.</p> <p>In this retrospective observational study, twelve patients with non metastatic EFT were managed on the intensive Ewing Family Tumor (EFT 2001) protocol. The patient characteristics studied were - age, sex, site, number of sites involved, bone marrow involvement and size (volume). Tumor volume was measured in non-metastatic tumors &nbsp;by tri-dimensional volume.</p> <p>Progression free survival (PFS) of patients with initial tumor volume &le;100 cc ranged from 30 months to 74 months (mean 56.4 months) while that for &gt; 100 cc ranged from 19 months to 79 months (mean 40 months) (p value: 0.701). However there was trend towards better survival in patients with initial tumor volume &le;100 cc.</p> <p><strong>Conclusion</strong>: There is a trend towards better PFS in patients with smaller tumor volume at presentation. Thus initial tumor volume is a prognostic factor in Ewing family of tumors.</p><p>&nbsp;</p>

scholarly journals The Prognostic Value of Initial Tumor Size in Patients with Ewing Family of Tumors

2015 ◽  
Vol 12 (2) ◽  
pp. 31-35
Author(s):  
Rajeeb Kumar Deo ◽  
Prakash Chitalkar ◽  
Amit Joshi ◽  
Sushil Ranamagar
Keyword(s):  
Prognostic Value ◽  
Tumor Volume ◽  
Bone Marrow Involvement ◽  
Progression Free Survival ◽  
Patient Characteristics ◽  
P Value ◽  
Free Survival ◽  
Initial Tumor ◽  
Initial Tumor Size ◽  
Ewing Family Of Tumors

Introduction: Ewing Family of Tumors (EFT) is a high grade embryonic malignancy, common in children andyoung adults (CYAs). The prognostic factors include initial tumor volume, site, presence of metastasis, and theEWS/FLI 1 mutation. Low volume disease is known to result in higher response rates and longer survival times.Methods: Twelve patients with non-metastatic EFT were managed with the intensive Ewing Family Tumor(EFT 2001) protocol. The patient characteristics studied were - age, sex, site, number of sites involved,bone marrow involvement and size (volume). Tumor volume was measured in non-metastatic tumors by tridimensionalvolume in MRI scans.Results: Progression free survival (PFS) of patients with initial tumor volume ????100 cc ranged from 30 monthsto 74 months (mean 56.4 months) while that for > 100 cc ranged from 19 months to 79 months (mean 40months) (p value: 0.701). However there was trend towards better survival in patients with initial tumor volume????100 cc.Conclusions: There is a trend towards better PFS in patients with smaller tumor volume at presentation. Thusinitial tumor volume is a prognostic factor in Ewing family of tumors.doi:http://dx.doi.org/10.3126/mjsbh.v12i2.12925 

Molecular profiling of advanced pancreatic ductal adenocarcinoma (PDAC): Role of ctDNA.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 425-425
Author(s):  
Angela Lamarca ◽  
Mairead Geraldine McNamara ◽  
Richard Hubner ◽  
Juan W. Valle
Keyword(s):  
Palliative Therapy ◽  
Progression Free Survival ◽  
Patient Characteristics ◽  
Molecular Profiling ◽  
Ductal Adenocarcinoma ◽  
P Value ◽  
Ctdna Analysis ◽  
Chemotherapy Initiation ◽  
The Impact

425 Background: Molecular profiling of tumour samples and circulating tumour DNA (ctDNA) may inform treatment of advanced cancer; the role of ctDNA to predict progression-free-survival (PFS) and overall survival (OS) in advanced PDAC is not fully understood. Methods: Eligible patients: those diagnosed with advanced PDAC undergoing molecular profiling [tumour (Foundation Medicine CDx/Caris) or ctDNA (FoundationMedicine Liquid (72 cancer-related genes))]. Baseline patient characteristics and molecular profiling outcomes, including mutant allele frequency (MAF) for pathological alterations were extracted. The primary aim was to assess the impact of presence of ctDNA at time of systemic chemotherapy initiation on PFS and OS. Results: Total of 26 samples (ctDNA 18 samples and 8 tumour samples) from 25 patients diagnosed with advanced PDAC underwent molecular profiling. When the whole population was analysed, the rate of sample analysis failure seemed to be higher when tumour tissue was tested (37.5%) compared to ctDNA (5.56%); p-value 0.072. The overall rate of identification of pathological findings was 72.73%, with 18.18% of patients having targetable findings [EGFRmut (1 patient), KRAS G12C mut (1 patient), FGFR2 fusion (1 patient), RNF43 mut (1 patient)]; these findings impacted treatment management in one patient only (RNF43 mutation; Wnt inhibitor). Variants of unknown significance were identified in 63.64% of samples. Patients with ctDNA analysis at time of palliative chemotherapy initiation (16 samples; 15 patients) were analysed [6 female (40.00%), median age 69.57 years (range 51.61-81.49), metastatic disease (66.67%), 80% first-line (80%), 20% second-line]. Pathological mutations were identified in 9/15 (60.00%) of these patients (KRAS mutation identified in 6/9). After median follow-up of 8.33 months from sample acquisition, 80% and 53.33% of patients had progressed and died, respectively. Median estimated PFS and OS were 5.65 months (95% CI 1.59-8.17) and 7.80 months (95% CI 4.13-not reached). Presence (vs absence) of pathological alterations in ctDNA showed a trend towards shorter PFS (2.91 vs 6.51 months; HR 1.38 (95% CI 0.40-4.77)) and OS (6.12 vs 9.72 months; HR 2.03 (95% CI 0.60-6.82)). Conclusions: This pilot study demonstrates the feasibility of ctDNA analysis in patients with advanced PDAC prior to initiation of palliative therapy. The presence of pathological alterations in ctDNA may prognosticate for worse PFS and OS. Larger studies are required to confirm these findings.

THE INFLUENCE OF VOLUMETRIC TUMOR DOUBLING TIME ON SURVIVAL OF PATIENTS WITH INTRACRANIAL TUMORS

2021 ◽  
pp. 39-43
Author(s):  
Yadav Ambica ◽  
Tandon Anupama
Keyword(s):  
Prognostic Factors ◽  
Doubling Time ◽  
Tumor Volume ◽  
Histological Grade ◽  
Tumor Location ◽  
P Value ◽  
Intracranial Tumors ◽  
Excellent Correlation ◽  
Tumor Doubling Time ◽  
Initial Tumor

Objective:To evaluate inuence of volumetric tumor doubling time on survival of patients with intracranial tumors. Study design: 20 patients with intracranial tumor of either sex and any age were included, if two imaging scans were available/could be done in which change in tomor volume was appreciable and the tumor margins were well demarcated. Based on change in tumor volume, tumor doubling time (DT) and predictive survival time (PST) were calculated. Patients were followed up for 6 months or longer for actual survival time (AST). Results: The histological grade was found to have a signicant correlation with DT (P value 0.046) and PST of the tumor (P value 0.038). DT and PSTwere found to be signicantly lower in high grade astrocytomas. Age, gender, tumor location and initial tumor volume were not found to have a signicant correlation with DTand PST. When DTwas compared to PST, excellent correlation was seen which was statistically signicant (Pvalue < 0.001) and suggested a linear relationship. Conclusion: Computed Tomography (CT) & Magnetic Resonance Imaging (MRI) can accurately dene the intracranial tumors and can reliably measure their volume. Calculation of tumor volume, change in tumor volume, DT and PST based on imaging studies is easy and reproducible. DT and PST have an excellent correlation & there is a linear relationship between the two. Histological grade and DT are the signicant prognostic factors while age, gender, tumor location and initial tumor volume are not signicant prognostic factors in patients with brain tumors.

Alemtuzumab Reduces Chronic Graft Versus Host Disease (cGVHD) and Treatment Related Mortality (TRM) after Reduced Intensity Conditioning for AML and MDS.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1076-1076 ◽  
Author(s):  
Koen van Besien ◽  
Marcos de Lima ◽  
Andrew Artz ◽  
Betul Oran ◽  
Wendy Stock ◽  
...  
Keyword(s):  
Chronic Gvhd ◽  
Progression Free Survival ◽  
Patient Characteristics ◽  
Cancer Center ◽  
P Value ◽  
Unrelated Donor ◽  
Post Transplant ◽  
Md Anderson

Abstract In vivo T-cell depletion with alemtuzumab has been used to reduce acute and chronic GVHD. In order to evaluate its overall effect on transplant outcomes in AML and MDS we compared 90 pts who received fludarabine/melphalan/alemtuzumab (FMA) conditioning and post-transplant tacrolimus at the University of Chicago, with 112 who received fludarabine/melphalan (FM) and post-transplant tacrolimus/methotrexate at MD Anderson Cancer Center. Pt and transplant characteristics were well balanced except for a higher proportion of MDS in the FM group. Median age, proportion unrelated donor tx and proportion high/intermediate and low risk by ASBMT criteria were balanced between the groups. With median follow up of 28 months in both groups, one year progression free survival and overall survival are identical. TRM is significantly higher after FM, but relapse is higher in FMA. 19/103 d 28 survivors after FM vs 7/84 after FMA developed gr III–IV acute GVHD (p=0.04). 46/77 d100 survivors after FM developed ext cGVHD vs 7/63 after FMA (p=0.0000). 43 patients remain alive after FM and 27 have ext cGVHD. 41 remain alive after FMA and 1 has ext cGVHD. Alemtuzumab results in a considerable reduction in acute and particularly chronic GVHD. TRM is reduced compared with standard GVHD prophylaxis. Low incidence of chronic GVHD and reduced TRM may be the major benefit of this strategy. Relapse rates are increased, because of reduced GVL effects or because of improved early survival of high risk patients. Other approaches are necessary for improving long term outcomes. Patient Characteristics and Outcome FMA FM P-value N 90 102 Age (range) 54 (22–74) 51 (17–77) 0.6 AML/MDS 13/77 29/83 0.04 MUD/related 42/48 59/63 0.5 High./Intermediate/LowRisk 48/13/28 76/10/26 0.12 Median Follow up mths (range) 28 (3–89) 28 (1–66) 0.07 TRM@ 100 days 13% + 7% 24% + 8% 0.04 TRM@ 1 year 30% + 12% 42% + 10% 0.04 Relapse @ 1 year 40% + 12% 26% + 10% 0.01 PFS @ 2 years 33% + 11% 37% + 9% 0.9 OS @ 2 year 42% + 11% 44% + 9% 0.5 AGVD gr III–IV 7/84 19/103 0.04 Ext cGVHD 7/63 46/77 0.0000 Ext cGVHD in survivors 1/41 27/43 0.0000

Doxil, Vincritine, Reduced Frequency Dexamethasone in Combination with Thalidomide (DVd-T) Is Associated with Higher Overall and Progression Free Survival as Compared to DVd in Patients with Multiple Myeloma (MM).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2557-2557 ◽  
Author(s):  
Khaldoun Almhanna ◽  
Revathi Suppiah ◽  
Rachid Baz ◽  
Mary Ann Karam ◽  
Beth Faiman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow Involvement ◽  
Pegylated Liposomal Doxorubicin ◽  
Progression Free Survival ◽  
Disease Stage ◽  
P Value ◽  
Free Survival ◽  
Number Of Patients

Abstract Background: Although initially responsive to chemotherapy, multiple myeloma ultimately relapses. Replacing Adriamycin with pegylated liposomal doxorubicin in the VAD regimen results in a regimen with better safety profile (less neutropenia, alopecia, fewer hospital and clinic visit). DVd resulted in normalizing the angiogenic process however this did not improve PFS or OS. Thalidomide because of its antiangiogenic, immunomodulatory effects and chemo-sensitizing activity through modulating integrins was added to the DVd regimen. Adding the thalidomide to the DVd regimen resulted in an overall response rate of 89% with a CR/NCR rate of 49 % as compared to 60% and 18 % respectively for the DVd. At this stage it is not clear if the quality of response affects outcome in multiple myeloma patients receiving conventional dose therapy. To better assess the prognostic implication of improved quality responses and to define the role of up front Thalidomide, we compared the DVd to the DVd-T regimen by retrospectively reviewing the two trial data, the follow up for both trials is mature. It is still not clear whether thalidomide is more appropriately used up front or in the management of relapse. Methods: we recruited a total of 68 patients in our DVd trial versus 105 patient in the DVd-T trial. A total of 155 patients in both groups were evaluable for follow-up and response (58 received DVd and 97 received DVd-T). Patients were matched for age, disease prognosticators, disease stage, and bone marrow involvement. The newly diagnosed patients were comparable in both groups except for the b 2 microglobulin which was higher in the DVd-T group as compared to the DVd (3.2 vs. 5.0; respectively. p0.05). In the relapsed/refractory group of patients, all variables were comparable. Results: The median follow up was 5 years for the DVd group and 2 years for the DVd-T group. Median age for the DVd was 62 years, which was similar to the DVd-T. For the DVd vs. the DVd-T group of patients achieving complete and near complete remission was 17% vs. 49.5% respectively with a p value of 0.001. Progression free survival was significantly longer for the DVd-T regimens vs. the DVd (28 vs. 13 months p= 0.0002) Figure 1., and for over all survival the median is not reached for the DVd-T vs. 28 months for he DVd (p=0.006). Conclusion: we conclude that the addition of thalidomide significantly improved the quality of response and this appears to translate in to a PFS and OS benefit. While, recently published SWOG data suggests that the overall survival is determined by the duration of the PFS and not the quality of the response, this discrepancy could be related to the small number of patients in our study or the lack of use of biologic immune modulators among SWOG patients. Figure Figure

Bendamustine and Rituximab Combination In Untreated Indolent Non Follicular B-Cell Non-Hodgkin's Lymphomas. A Phase II Study From The Fondazione Italiana Linfomi (INFL09)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3049-3049 ◽  
Author(s):  
Stefano Luminari ◽  
Maria Cecilia Goldaniga ◽  
Marina Cesaretti ◽  
Lorella Orsucci ◽  
Alessandra Tucci ◽  
...  
Keyword(s):  
Adverse Events ◽  
B Cell ◽  
Response Rate ◽  
Bone Marrow Involvement ◽  
Severe Infection ◽  
Progression Free Survival ◽  
Complete Response ◽  
P Value ◽  
Pathology Report ◽  
Hodgkin's Lymphomas

Abstract Background Indolent non follicular B-Cell Lymphomas (INFL) are a heterogeneous group of lymphomas and include small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphomas (LPL), and marginal zone lymphomas (MZL). Combination chemo-immunotherapy regimens are used in the majority of patients (pts) with advanced stage INFL who require treatment. Bendamustine in combination with anti-CD20 monoclonal antibody therapy has been shown to be highly active and well tolerated. The purpose of this phase 2, multicenter study was to determine the activity and safety of bendamustine in combination with rituximab in first-line treatment of patients with INFL. Methods Untreated patients with SLL, nodal MZL and LPL who met predefined need-for-treatment criteria, had adequate hematologic function and stage II-IV disease, were eligible for study entry. Patients were scheduled to receive 6 cycles BR: bendamustine (90 mg/m2 on days 1 and 2 every 28 days) and 6 rituximab doses (375 mg/m2 on day 8 of cycle 1, and on day 1 of subsequent cycles) + 2 rituximab doses every 2 weeks. The primary endpoint of the study was the complete response rate (CRR) based on 2007 International Working Group criteria (Cheson 2007). The secondary endpoints were the rate of adverse events, the overall response rate (ORR), the progression free survival (PFS) and the overall survival (OS). Sample size was defined at 67 patients evaluable for response assuming a CR rate of 60%, a power of 80% and p value of 5%. Results The study was conducted from February 2011 to march 2012. Seventy-two patients were enrolled, and 3 patients were excluded from the study due to violation of inclusion criteria (1 patient) and due to treatment interruption before completion of cycle one (2 patients). Based on local pathology report 17 patients had SLL, 20 had nodal MZL, and 32 had LPL. Median age was 65 years (45-75) and 65% were male. LDH value was increased in 17% of pts and β2-microglobulin in 67%. B-symptoms were present in 16% of pts, 91% percent had bone marrow involvement and 99% had stage III/IV disease. Fifty-nine out of the 69 patients received at least 6 cycles of bendamustine/rituximab (BR, 85,5%). Based on the intention to treat analysis and on local assessment of response, ORR was 84% including 40 patients in CR in (58%), and 18 in PR (26%); 1 patients had stable disease and 5 patients had lymphoma progression; in 5 patients response was not assessed due to adverse event or early withdrawal. Safety analysis was available for all 69 patients and for 472 cycles. Overall, the combination of BR was well-tolerated. The most common grade 3/4 adverse events were neutropenia (43% of pts), febrile neutropenia (3%), thrombocytopenia (9%), gastrointestinal disorders (3%), and skin reaction (3%). One patient died during treatment due to a severe infection after cycle 2. At time of current analysis after a median follow-up of 15.6 months (range 1 to 25 months), 2 disease progressions and 2 deaths (due to lymphoma) were observed. As a result 1 year PFS was 90% (CI95% 80-95%) and 1 year OS was 95% (CI95% 87-98%). Conclusions Based on this preliminary analysis of the INFL09 study, BR combination is active and well tolerated in patients with previously untreated INFL. The ORR of 85% and CRR of 58% compare favorably with previously reported response rates observed in patients with indolent lymphoma. Disclosures: Federico: MedImmune: Research Funding.

scholarly journals ATIM-03. ANTI-TGFß2 RNA THERAPEUTIC OT-101 INDUCES DURABLE OBJECTIVE RESPONSES IN PATIENTS WITH RECURRENT/REFRACTORY (R/R) GLIOBLASTOMA MULTIFORME (GBM, WHO GRADE 4) OR ANAPLASTIC ASTROCYTOMA (AA, WHO GRADE 3)

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi1-vi2
Author(s):  
Fatih Uckun ◽  
Sanjive Qazi ◽  
Larn Hwang ◽  
David Nam ◽  
Vuong Trieu
Keyword(s):  
T Cell ◽  
Transforming Growth Factor Beta ◽  
Tumor Volume ◽  
Transforming Growth Factor ◽  
Single Agent ◽  
Progression Free Survival ◽  
P Value ◽  
Convection Enhanced Delivery ◽  
Chi Square ◽  
Who Grade

Abstract BACKGROUND High-grade gliomas (HGG) are characterized by a T-cell exhaustion signature and pronounced T-cell hyporesponsiveness of their tumor microenvironment (TME). Transforming growth factor beta 2 (TGF-ß2) has been implicated as a key contributor to the immunosuppressive landscape of the TME in HGG. OT-101 is a first-in-class RNA therapeutic designed to abrogate the immunosuppressive actions of TGF-ß2. Here we report the single-agent activity of OT-101 in adult patients with R/R HGG. METHODS In this phase 2 clinical trial (NCT00431561), OT-101 was administered with an intratumoral catheter using a convection enhanced delivery (CED) system. 77 patients received 4–11 cycles of OT-101 via continuous infusion over 7d. Response determinations were based on central review of MRI scans by an independent review committee according to standard and modified McDonald criteria. Standard statistical methods were applied for the analysis of data. RESULTS The median progression-free survival (PFS) and overall survival (OS) were 86d and 432d, respectively. 26 patients (33.8%) had marked reductions of their tumor volume after receiving OT-101: 19 achieved durable objective responses (CR: 3, PR: 16). The median time for 90% reduction of the baseline tumor volume was 11.7 months (Range: 4.9–57.7 months). The mean log reduction of the tumor volume was 2.2 ± 0.4 (Median = 1.4: Range: 0.4–4.5) logs. 7 had stable disease (SD) lasting > 6 months. The median PFS (1109d [95% CI: 992 - > 1423] vs. 37d [95% CI: 35 – 59] (Log-rank Chi Square = 69.9, P-value < 0.0001) and OS (1280d [95% CI: 1116- > 1743] vs. 240d [95% CI: 169 – 361] (Log-rank Chi Square = 47.0, P-value < 0.0001) of these 26 patients was significantly better than the PFS or OS of the remaining 51 patients. CONCLUSION Anti-TGFß2 RNA therapeutic OT-101 exhibits clinically meaningful single-agent activity and induces durable CR/PR/SD in R/R HGG patients.

Correlation of progression-free survival (PFS) and overall survival (OS) in men with metastatic castration-resistant prostate cancer (CRPC) who failed first-line chemotherapy: Results from the SPARC Trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5150-5150
Author(s):  
S. Halabi ◽  
O. Sartor ◽  
D. Petrylak ◽  
C. N. Sternberg ◽  
J. A. Witjes ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Progression Free Survival ◽  
Statistical Dependence ◽  
P Value ◽  
Castration Resistant Prostate Cancer ◽  
Survival Times ◽  
First Line ◽  
Double Blind ◽  
Line Chemotherapy

5150 Background: It has been shown in chemotherapy naïve patients that PFS is a statistically significant predictor of OS. The main objectives of this analysis were to explore whether PFS at 3-months is a predictor of OS and to investigate the dependence between PFS and OS in CRPC men who failed first line chemotherapy. Methods: Data from SPARC, a multi-national, randomized, double-blind trial, comparing satraplatin + prednisone vs placebo + prednisone in 950 CRPC patients were used. For the purpose of this analysis, the two treatment groups were combined. PFS was defined as the time from date of randomization to date of first progression (bone scan progression, radiographic, soft-tissue progression, symptomatic, or skeletal related events) or death, whichever occurred first. PFS at 3-months was defined as a binary variable in the following manner: if a patient experienced any type of progression at or before 3-months then this was considered as an event. If a patient did not progress at 3 months then he was censored. Landmark analysis of PFS at 3-months predicting OS was performed. In addition, the proportional hazards model was used to assess the significance effect of PFS at 3-months in predicting OS adjusting for the stratification factors. Finally, the association between OS and PFS was investigated using a statistic that estimates Kendall's tau measure of association for bivariate time to event outcomes subject to censoring. Results: 477 (56%) men progressed at 3-months of 853 men who were alive at 3-months. The median survival times were 34.5 weeks (95% CI = 30.8–40.4) and 78.7 weeks (95% CI=70.1–83.2, p-value<0.001) respectively in men who did and did not experience progression at 3-months. Men who had progressed at 3-months were more likely to die than men who did not progress (hazard ratio = 2.16, 95% CI =1.84 -2.55, p-value < 0.001). The dependence between PFS and OS was 0.29 (95% confidence limits = 0.24–0.33, p-value < 0.00001). Conclusions: PFS at 3-months predicts OS. The results of this large retrospective analysis show moderate, but strong statistical dependence between PFS and OS. Future studies are needed to assess the clinical relevance of the distinct components of progression. [Table: see text]

Clinical and FDG-PET markers of immune checkpoint inhibitor (ICI) response in patients with metastatic Merkel cell carcinoma (mMCC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9540-9540
Author(s):  
Alison Weppler ◽  
Prachi Bhave ◽  
Paolo De Ieso ◽  
Jeanette Raleigh ◽  
Athena Hatzimihalis ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Tumor Volume ◽  
Progression Free Survival ◽  
Metabolic Responses ◽  
Prior History ◽  
P Value ◽  
Merkel Cell ◽  
Efficacy And Safety ◽  
Fdg Pet Scan ◽  
History Of

9540 Background: mMCC is a rare, highly aggressive neuroendocrine cancer with a poor prognosis. ICIs have favourable efficacy and safety in clinical trials. We outline single centre experience utilising ICIs in mMCC. Methods: Medical records of patients (pts) with mMCC treated with ICIs from Aug 2015 to Dec 2018 at Peter MacCallum Cancer Centre in Australia were retrospectively analysed. RNA sequencing and immunohistochemistry for PD-L1, CD3 and Merkel cell polyomavirus (MCPyV) on tumor samples were performed. Baseline tumor volumes and responses were assessed with FDG-PET scans using the Hicks criteria. Results: 23 pts with mMCC were treated with ICIs. Pt characteristics are summarised in Table. A median of 8 cycles (range 1 to 47) were administered, with treatment ongoing in 7 pts. Objective responses (OR) were observed in 14 pts (61%); 10 (44%) complete metabolic responses (CMR) and 4 (17%) partial metabolic responses (PMR). Median time to response was 9 weeks (range 4 to 11) and 12-month progression-free survival (PFS) rate was 32%. Increased OR were seen in pts aged less than 75 (OR 8/10, 80% vs 46%), no prior history of chemotherapy (OR 10/14, 71% vs 44%), pts with an immune-related adverse event (irAE) (OR 6/6, 100% vs 47%) and in MCPyV negative pts (OR 9/11, 82% vs 50%). Pts with a CMR had lower mean-tumor volume on baseline FDG-PET scan (CMR: 35.7mL, no CMR: 187.8mL, p value 0.05). 10 pts received radiation (RT) during ICI: 4 pts started RT concurrently (OR 75%, CMR 50%), 3 pts had isolated ICI-resistant lesions successfully treated with RT and 3 pts with multisite progression continued to progress despite RT. 6 pts (26%) had a Grade 1-2 irAE. Conclusions: ICIs showed efficacy and safety consistent with trial data. Younger age, negative MCPyV status, no prior chemotherapy, lower baseline FDG-PET tumor volume and irAEs are potentially associated with better responses. [Table: see text]

Superiority of trimodality therapy to surgery alone in esophageal cancer: Results of CALGB 9781

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4012-4012 ◽  
Author(s):  
J. E. Tepper ◽  
M. Krasna ◽  
D. Niedzwiecki ◽  
D. Hollis ◽  
C. Reed ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Randomized Study ◽  
Progression Free Survival ◽  
Patient Characteristics ◽  
Rank Test ◽  
P Value ◽  
Term Survival ◽  
Trimodality Therapy ◽  
Survival Difference

4012 Background: CALGB 9781 was a prospective randomized Intergroup trial of trimodality therapy versus surgery alone for the treatment of stages 1–3 esophageal cancer. Methods: Five-hundred patients were targeted for enrollment with three years of follow-up planned. The primary endpoint was overall survival. All patents had EGD with biopsy, barium esophagogram and CT. Additional staging by EUS and/or thoracoscopy/laparoscopy was recommended. Patients were randomized to treatment with either surgery alone or cisplatin (100mg/m2) and 5FU (1000 mg/m2/d × 4d) weeks 1 and 5 concurrent with radiation therapy (50.4 Gy- 1.8 Gy/fx over 5.6 weeks) followed by esophagectomy with lymph node dissection. Results: A total of 56 patients were entered on study between October 1997 and March 2000 when the trial was closed due to poor accrual. Thirty patients were randomized to trimodality therapy and 26 to surgery alone. Patient characteristics were similar between groups. Surgical staging was conducted in just over 50% of patients in both groups. The primary toxicities of Gr 3 or greater with preoperative therapy were hematopoietic (54%), and esophagitis/dysphagia (40%). There were 14 and 17 patients with surgical complications on the trimodality and surgery alone arms, respectively, with 2 post-surgical deaths (within 30 days), both on the surgery alone arm. Postoperative hospital stays were 11.5 and 10 days, respectively. Median follow-up is 6 years. An intent- to- treat analysis showed a median survival of 4.5 yrs vs 1.8 yrs in favor of trimodality therapy (log-rank p=0.02). A log rank test with stratifications by N stage, staging approach and histology demonstrated a p-value of 0.005. 5-year survival was 39% (95% CI [21%, 57%]) vs 16% (95% CI [5%, 33%]) in favor of trimodality therapy. Analysis of progression-free survival is underway. Conclusions: This randomized study demonstrates a long-term survival advantage with the use of chemoradiation therapy followed by surgery in the treatment of esophageal cancer. Although accrual was well below that planned, the observed survival difference is statistically significant and suggests that trimodality therapy is an appropriate standard of care for patients with this disease. No significant financial relationships to disclose.

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