Total neoadjuvant chemo (ctx; TNT) for locally advanced gastric cancer (GC): The Memorial Sloan Kettering Cancer Center experience.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4046-4046 ◽  
Author(s):  
Megan Greally ◽  
Vivian E. Strong ◽  
Sam S. Yoon ◽  
Daniel G. Coit ◽  
Joanne F Chou ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Subtotal Gastrectomy ◽  
Progression Free Survival ◽  
Rank Test ◽  
Cancer Center ◽  
Surgical Morbidity ◽  
Locally Advanced Gastric Cancer ◽  
Kaplan Meier ◽  
Significant Difference

4046 Background: Peri-op chemo (ctx) and surgery is a standard in the treatment of GC, based on the MAGIC (NEJM 2006; 355:11) and FLOT4 (J Clin Oncol 35:4004 [abstr]) studies. However, less than half of patients (pts) completed ctx in the MAGIC and FLOT4 studies, mainly from issues delivering post-op therapy. We assessed safety and feasibility of TNT, where all ctx is given pre-op. Methods: We reviewed GC pts who received TNT or peri-op ctx and had surgery; decision for TNT was by physician preference, based on clinical or radiographic benefit to justify completing ctx pre-op. Pt characteristics were compared using Fisher’s exact and Wilcoxon Rank Sum tests. Post-op length of stay (LOS) was calculated from date of surgery (DOS) to date of discharge and surgical morbidity was determined using the Clavien-Dindo classification. Progression free survival (PFS) and overall survival (OS) were calculated from DOS using Kaplan-Meier methods and compared between groups using the log-rank test. Results: 120 pts were identified, median age 63, 62.5% male, 98% ECOG 0/1. 93 pts (77.5%) received peri-op ctx and 27 (22.5%) received TNT. In peri-op pts, 19%, 43% and 38% received FLOT, platinum/fluropyrimidine (FP) and ECF/EOX respectively. In TNT pts, 56%, 37% and 7% received FLOT, platinum/FP and ECF/EOX respectively. 57% had subtotal gastrectomy. Surgical outcomes were similar between groups; median LOS was 6 and 7 days (p = 0.31) in peri-op and TNT pts respectively. There was no significant difference in Clavien Dindo grade I-II or III-IV morbidity between groups (p = 0.103). There were no deaths. TNT pts received higher proportions of planned treatment than peri-op ctx pts: 90% vs. 60% FP (0.001); 85% vs. 41% platinum ( < 0.001); 100% vs. 9% epirubicin (0.015) and 53% vs. 28% docetaxel (p = 0.169). At median follow-up of 19 months, median PFS and OS were not reached. There was no significant difference in PFS (p = 0.089) or OS (p = 0.59) between groups. Conclusions: TNT appears safe with no increase in post-op LOS or surgical morbidity observed. TNT pts had higher percentage drug delivery, suggesting potential benefit for administering all ctx before surgery. While longer survival follow-up is required, TNT may be considered in pts with locally advanced GC who are candidates for ctx.

Radiotherapy (RT) potentiation with weekly (q1w) or standard every 3 weeks (q3w) cisplatin chemotherapy (CT) for locally advanced head and neck squamous cell carcinoma (HNSCC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6056-6056 ◽  
Author(s):  
Yann Molin ◽  
Emilie Lavergne ◽  
Pascal Pommier ◽  
Severine Racadot ◽  
Xavier Montbarbon ◽  
...  
Keyword(s):  
Cox Model ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Included Study ◽  
Alternative Methods ◽  
Rank Test ◽  
Prognostic Effect ◽  
Kaplan Meier ◽  
Significant Difference

6056 Background: Q3w CT is standard RT potentiation for HNSCC but its toxicity requires to look for new treatment’s modalities. The aim was to explore if q1w CT could be a safe and effective alternative. Methods: Patients (pts) treated by chemoradiation (CT-RT) for a HNSCC were retrospectively included. Study population was first described. Then overall (OS) and progression-free survival since the RT onset were performed. Survival distributions were estimated by Kaplan-Meier method and compared between CT groups using the Log-Rank test. Prognostic effect of CT group was explored using Cox model. Results: 266 pts treated between January 2004 and December 2008 were included: 170 and 96 pts respectively received q1w and q3w CT. At diagnosis, 46% had oropharynx lesions, 20% larynx, 17% hypopharynx and 14% oral cavity. 70% pts experienced surgery, 39% CT induction and a median dose of radiation of 64 Gy without any significant difference between CT groups. However, median age at diagnosis was significantly different between q1w and q3w CT (58 vs 54, p<0.001) as well as alcohol consumption (79% vs 68, p=0.047), stage at diagnosis (30%-60% stage III-IV vs 13% -80%, p=0.003), IMRT use (4% vs 13%, p=0.011) and median weight before RT (66 kg vs71kg, p=0.014). Q3w CT was more toxic than q1w in terms of weight loss (87% vs 75%, p=0.012), renal failure (50% vs 35%, p=0.022), worse CT plan completion (42% vs 66%, p<0.001). Moreover, grade 3/4 toxicities, such as mucositis (34% vs 13%, p<0.001) and dermatitis (7% vs 1%, p=0.012), were more frequent. More pts needed parenteral nutrition (10% vs 2%, p=0.008), analgesics (91% vs 70%, p<0.001), secondary hospitalization (31% vs 8%, p<0.001), RT interruption >= 3 days (8% vs 2%, p=0.037) and had long-term toxicities (24% vs 12%, p=0.014). With a median follow-up of 42 months 95% CI [36.8-48.8], a trend in favour of q3w CT was found:2-years OS of 83% (95% CI [73-90]) vs 74% (95% CI [66-80]), p=0.089. However, after adjustment on prognostic factors CT group was not significantly associated with OS nor with PFS. Conclusions: Q1w RT-CT is safer than q3w and may be as efficient. Follow-up data will be updated to reinforce efficacy results.

Clinical outcome for gastrointestinal cancers with polymerase epsilon mutations treated with immunotherapy.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 828-828
Author(s):  
Limin Zhu ◽  
Funda Meric-Bernstam ◽  
Vijaykumar Holla ◽  
Taebeom Kim ◽  
Kenna Rael Shaw ◽  
...  
Keyword(s):  
Mismatch Repair ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Female Gender ◽  
Rank Test ◽  
Cancer Center ◽  
Kaplan Meier ◽  
Gi Cancers ◽  
Mismatch Repair Status ◽  
Md Anderson

828 Background: Predictive factors for immunotherapy benefit across gastrointestinal (GI) cancers are limited to those with deficient mismatch repair (dMMR). Mutations in DNA polymerase E (POLE) can cause a hypermutated phenotype irrespective of MMR status and may serve as a predictor factor for immunotherapy. Methods: All POLE-mutant GI cancers with tumor mutation burden (TMB) measured at MD Anderson Cancer Center were identified (N = 58) from 2014 to 2019 and those that had received immunotherapy (N = 18) were studied. TMB was measured by genomic profiling assays FoundationOne or STGA 2018. Samples were analyzed using Kaplan-Meier method and compared using log rank test, with a predefined high TMB threshold of 20 muts/mb. Results: Of the 58 POLE-mutant GI tumors a high TMB was present in 50% of the cases. 18 patients (median age 64, female gender 16.7%, median prior lines of therapy 2) with locally advanced (N = 4) or metastatic (N = 14) POLE-mutant GI cancers (13 colorectal, 1 small intestine, 1 esophageal, 1 pancreatic, and 2 gallbladder) were identified. Immunotherapy agents were PD-1/PD-L1 based in 17 and CTLA-4 based in 1. High TMB was present in 11 patients. dMMR was present in 7 patients, all with high TMB. Treatment response was seen in 3 patients (2 CR and 1 PR), all TMB high and dMMR. Progression-free survival (PFS) was significantly longer in those with high TMB (median: 10.1 months vs. 3 months, p = 0.048). Of the 11 pMMR patients median PFS was 9.3 months in high TMB and 3 months in low TMB (p = 0.246). Conclusions: POLE mutations in GI cancers were associated with a high TMB ( > 20muts/mb) in 50% of patients. Within POLE mutant GI cancers a high TMB may identify patients who benefit from immunotherapy irrespective of mismatch repair status.

Outcomes for patients with borderline resectable (BR) and locally advanced (LA) pancreatic cancer (PC) treated with induction FOLFIRINOX (FFX) +/- radiation (RT) followed by surgery compared to induction FFX followed by consolidative RT.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 437-437
Author(s):  
Michael Cecchini ◽  
Joseph Miccio ◽  
Jay Pahade ◽  
Jill Lacy ◽  
Ronald R Salem ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Rank Test ◽  
Vascular Involvement ◽  
Cancer Center ◽  
R0 Resection ◽  
Borderline Resectable ◽  
Term Survival ◽  
Kaplan Meier

437 Background: Induction FFX for PC deemed either BR or LA at diagnosis provides an opportunity to downstage pts with the aim of an R0 surgery. The addition of RT after induction FFX may further downstage. However, there is a paucity of data regarding long-term survival for BR and LA patients successfully downstaged and resected. We performed a retrospective review of BR and LA PC treated with induction FFX +/- RT followed by surgery or consolidative RT at the Yale Cancer Center (YCC) to assess survival in these two cohorts. Methods: Clinical data was abstracted for pts with BR or LA PC who had surgery or received consolidative RT without surgery after induction FFX +/- RT at the YCC from 2010-2018. Surgical pts were re-reviewed by a radiologist to assess vascular involvement (BR vs. LA) using NCCN criteria. PFS and OS for surgery and consolidative RT were analyzed by the Kaplan-Meier method. Survival was compared via the log rank test. Results: 102 pts met inclusion criteria (BR=47, LA=55), 41 pts had surgery [BR=29/47 (62%) LA=12/55 (22%)] and 61 pts had consolidative RT [(BR= 18/47 (38%), LA= 43/55 (78%)] after induction FFX. 18 surgery pts received RT prior to resection and all surgery pts had R0 resection. Median follow up was 25 mo (range 5 – 97). Median PFS with surgery was 22 mo (95% CI 15 – 59) vs 14 mo (95% CI 10.9 – 20.1) with consolidative RT (p<0.001), while OS with surgery was 42 mo (95% CI 25-NR) vs 20 mo (95% CI 17-25) without surgery (p<0.001). For pts with ≥ 2 yr follow up, 12/22 (55%) surgery pts and 17/18 (94%) consolidative RT pts relapsed. For pts with ≥ 3 yr follow up, 6/12 (50%) surgery pts and 10/10 (100%) consolidative RT pts relapsed. 2 yr PFS and OS was 45% (95% CI 28-61) and 74% (95% CI 57 – 86) with surgery versus 15% (95% CI 7-27) and 40% (95% CI 26-53) with consolidative RT. Conclusions: Surgery was associated with a high R0 rate and prolonged PFS and OS compared to consolidative RT in pts with BR and LA PC after FFX +/- RT. However, survival benefit was not statistically significant when selecting only LA pts although numbers are limited.

The Efficacy of Etoposide-Based Therapy in Adult Secondary Hemophagocytic Lymphohistiocytosis

2021 ◽  
pp. 1-9
Author(s):  
Leonard Naymagon ◽  
Douglas Tremblay ◽  
John Mascarenhas
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Proportional Hazards ◽  
Multivariable Analysis ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Kaplan Meier ◽  
Hazard Ratios ◽  
Significant Difference ◽  
The Impact

Data supporting the use of etoposide-based therapy in hemophagocytic lymphohistiocytosis (HLH) arise largely from pediatric studies. There is a lack of comparable data among adult patients with secondary HLH. We conducted a retrospective study to assess the impact of etoposide-based therapy on outcomes in adult secondary HLH. The primary outcome was overall survival. The log-rank test was used to compare Kaplan-Meier distributions of time-to-event outcomes. Multivariable Cox proportional hazards modeling was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Ninety adults with secondary HLH seen between January 1, 2009, and January 6, 2020, were included. Forty-two patients (47%) received etoposide-based therapy, while 48 (53%) received treatment only for their inciting proinflammatory condition. Thirty-three patients in the etoposide group (72%) and 32 in the no-etoposide group (67%) died during follow-up. Median survival in the etoposide and no-etoposide groups was 1.04 and 1.39 months, respectively. There was no significant difference in survival between the etoposide and no-etoposide groups (log-rank <i>p</i> = 0.4146). On multivariable analysis, there was no association between treatment with etoposide and survival (HR for death with etoposide = 1.067, 95% CI: 0.633–1.799, <i>p</i> = 0.8084). Use of etoposide-based therapy was not associated with improvement in outcomes in this large cohort of adult secondary HLH patients.

scholarly journals Cisplatin, Cetuximab, and Radiation in Locally Advanced Head and Neck Squamous Cell Cancer: A Retrospective Review

2015 ◽  
Vol 9 ◽  
pp. CMO.S18682 ◽  
Author(s):  
Prakash Peddi ◽  
Runhua Shi ◽  
Binu Nair ◽  
Fred Ampil ◽  
Glenn M. Mills ◽  
...  
Keyword(s):  
Head And Neck ◽  
Performance Status ◽  
Cell Cancer ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Rank Test ◽  
Advanced Head ◽  
Significant Difference ◽  
Group A ◽  
Group B

Efficacy of cisplatin versus cetuximab with radiation in locally advanced head and neck cancer (LAHNC) was evaluated. A total of 96 patients with newly diagnosed LAHNC treated at our institution between 2006 and 2011 with concurrent radiation and cisplatin (group A, n = 45), cetuximab (group B, n = 24), or started with cisplatin but switched to cetuximab because of toxicity (group C, n = 27) were reviewed. Chi-square test, analysis of variance, and log-rank test were used for analysis. The three groups had similar baseline characteristics, except for median age, T stage, albumin levels, hemoglobin levels, performance status, and comorbidities. A complete response (CR) was seen in 77%, 17%, and 67% of patients ( P < 0.001), respectively. There was no significant difference in median overall survival (OS) between groups A and C. The median OS for groups A and C was not reached (>65 months), even though it was significantly longer than median OS for group B (11.6 months; P ≤ 0.001). The 2-year OS in groups A and C is significantly higher than that in group B (70% for groups A and C, 22% for group B). There is no significant difference in progression-free survival (PFS) between groups A and C. The median PFS for these groups was not reached (>62 months), and is significantly longer than that for group B (4.3 months; P ≤ 0.001). The 2-year PFS of group A (67%) and group C (76%) was significantly longer than that of group B (20%). Cisplatin with radiation appears to be more efficacious even in suboptimal dosing than cetuximab with radiation in LAHNC but the two groups were not well matched.

Gemcitabine (G) plus nab-paclitaxel (nab-P) plus chemoradiation (CRT) in locally advanced pancreatic cancer (LAPC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14714-e14714
Author(s):  
Olugbenga Olanrele Olowokure ◽  
Ivan Dario Bedoya ◽  
Michelle Lynn Mierzwa ◽  
Maria Patricia Torregroza ◽  
Alok kumar Dwivedi ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Categorical Variables ◽  
Rank Test ◽  
Nccn Guidelines ◽  
Prior Therapy ◽  
Significant Difference ◽  
Ecog Ps ◽  
The Impact

e14714 Background: 30-40 % of PC pts present with LAPC. Optimal management remains controversial. Current NCCN guidelines, suggests clinical trial, FOLFIRINOX, G, G based combination therapy, chemo followed by CRT as options in pts with good PS. This single institution retrospective review, evaluated the UC experience of the impact of G+nab-p+/- CRT in LAPC. Methods: From 05/01/09-09/01/11,105 newly registered pts were identifiedusing ICD code 157, 13pts met inclusion criteria: ECOG PS 0-2, histologically proven LAPC, without prior therapy that received G + nab-P, pre or post radiation as part of their treatment. G+nab-p was given as cycles of G=1,000mg/m2 and nab-P=100mg/m2 weekly x3 every 4 weeks with appropriate modifications. CT scans and CA19-9 levels were followed. PFS was estimated from the date of diagnosis to date of progression or death if this occurred first and OS was estimated from date of diagnosis until date of death or loss to follow up. Kaplan Meier survival estimates were obtained with 95% confidence interval (CI). Log rank test was used to compare the PFS according to categorical variables. Results: Median duration of follow up was estimated to be 14.4 months (M) range(R) (5.8-19). CA19-9 data was available for 12 pts, 2 had baseline <1 (R<1-12,861), CA19-9 decrease > 50% from baseline was seen in 9/10. Mean # of G+nab-P cycles administered was 3, R (1-10). 77% received G based CRT with only 1pt receiving this post op. 38% (5/13) underwent resection, 4 post CRT with R0 margins and -ve LN’s and 1 pre CRT with R0 margins but 1/13 LN’s +ve. 11 pts were evaluable for response by RECIST (4PR, 6SD, 1PD). Disease control rate 91%. PFS 92% (CI: 57- 99%) at 6 M and 65% (CI: 31-85%) at 12 M. OS was 85% (CI: 51-96%) at 6M and 77 %(CI: 44-92%) at 12M. At 6M, 100% PFS was observed in resected group, whereas 88% PFS in non-resected group (p=0.12). There was no significant difference in PFS according to gender (p=0.44) and T lesion (p=0.49). Grade III/IV toxicity was mainly hematologic and gastrointestinal. (4/7) 57% received further therapy upon progression. Conclusions: Compared to contemporary G- based trials, the UC experience of G+ nab-P with CRT appears to be associated with improved survival in LAPC and warrants further study.

Long-term cardiopulmonary mortality after radiation for locally advanced esophageal cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 99-99 ◽  
Author(s):  
Abigail Berman Milby ◽  
Andrzej Pawel Wojcieszynski ◽  
Smith Apisarnthanarax ◽  
James M. Metz ◽  
John Peter Plastaras
Keyword(s):  
Esophageal Cancer ◽  
Esophageal Carcinoma ◽  
Background Radiation ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Rank Test ◽  
Trimodality Therapy ◽  
Significant Difference

99 Background: Radiation (RT) is considered an integral component of trimodality therapy for locally-advanced esophageal carcinoma to improve locoregional control and potentially survival. However, the long-term risk of cardiopulmonary mortality (CPM) is not well-understood in this population. Methods: Patients age 20-85 with esophageal carcinoma with T3, T4 or node positive (N+) disease who underwent esophagectomy were identified within 17 Surveillance, Epidemiology, and End Results registries from 1988-2006. Patients with metastatic disease or <6 mo follow up were excluded. CPM was calculated for patients receiving vs not receiving RT and compared by the Kaplan-Meier method. The log-rank test was used for univariate associations and Cox proportional hazards model was used for multivariate analysis (MVA). Results: A total of 4,079 patients met the defined selection criteria of whom 2,408 were treated with RT, and 1,671 were not. Median age was 62.2 yrs (22-84) and follow-up was 22 mos (6-248). There was no significant difference in CPM in patients who received RT versus those who did not (p=0.8). At 10 yr, the majority of deaths were from esophageal cancer (73 with vs 78% without RT) compared to CPM (13.7 with vs 11.6% without RT). On univariate analysis ( table ), age <60, diagnosis era, and histology were significant independent predictors of CPM. On MVA, age <60 (HR 0.36) and diagnosis era (0.63 for 1994-2000 and 0.55 for 2000-2006) remained statistically significant for CPM. Conclusions: RT for esophageal cancer is not associated with an increased long-term risk of CPM in the overall population. Older age and earlier diagnosis era predict for CPM. Although survival in esophageal cancer is dominated by cancer deaths, advances in RT are still needed to prevent excess treatment-related mortality. [Table: see text]

Cisplatin (CDDP) and radiation versus cetuximab (Cx) and radiation in locally advanced head and neck squamous cell cancer (SCHNC): A retrospective review.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e16009-e16009 ◽  
Author(s):  
Prakash Peddi ◽  
Runhua Shi ◽  
Lori Panu ◽  
Fred Ampil ◽  
Cherie-Ann Nathan ◽  
...  
Keyword(s):  
Performance Status ◽  
Cell Cancer ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Complete Response ◽  
Rank Test ◽  
Cancer Center ◽  
Ecog Performance Status ◽  
Chi Square ◽  
Group A

e16009 Background: SCHNC is a common malignancy and approximately 60% of patients present with locally advanced disease. There is paucity of data directly comparing Cx and CDDP with concurrent radiation in locally advanced SCHNC. We retrospectively reviewed charts of patients treated with CDDP and/or Cx along with radiation in locally advanced SCHNC comparing efficacy and outcomes in an academic cancer center. Methods: Ninety-five patients with locally advanced SCHNC were treated with concurrent CDDP (100 mg/m2 day 1, 22, 43) or Cx (400mg/m2 on day -7 and 250mg/m2 weekly) at our institution between January 2006 and June 2011. Forty-four patients were treated with CDDP (group A), 24 with Cx (group B) and 27 were initially started on CDDP but were switched to Cx secondary to toxicity (group C). All patients received concurrent radiation treatments (66-70 Gy, 2.0 Gy/fraction). The selection of CDDP versus Cx was largely based on ECOG performance status (PS) and baseline renal function of the patients. Chi-square test, analysis of variance, and log-rank test was used for analysis. The three groups had similar baseline characteristics except for mean age of 61, 56 and 55 years in group A, B and C respectively; T4 tumors consisted of 44%, 75% and 41% in groups A, B and C respectively. Groups A, B and C had a combined ECOG 0 and I (PS) of 93%, 75% and 92%. Patients with ECOG III PS were excluded. Results: Oropharynx was the most common treated site (38%) followed by Larynx (35%). Complete response (CR) was seen in 77%, 17% and 67% in groups A, B and C respectively (P<0.001). Median progression free survival (PFS) was 16.6, 4.3 and 22.8 in groups A, B and C respectively (P<0.001) and median overall survival (OS) was >35, 11.6 and >32 months in groups A, B and C respectively (P<0.0001). Conclusions: Concurrent CDDP with radiation leads to better response rate PFS and OS as opposed to Cx though many patients treated with CDDP could not complete treatment due to toxicity. Randomized trial comparing the two should be considered.

Comparative study of six cycles versus twelve cycles of adjuvant temozolomide post concurrent chemoradiation in newly diagnosed glioblastoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e13034-e13034
Author(s):  
Menal Bhandari ◽  
Ajeet K Gandhi ◽  
Pramod Kumar Julka ◽  
Chitra Sarkar ◽  
Dayanand Sharma ◽  
...  
Keyword(s):  
Univariate Analysis ◽  
Progression Free Survival ◽  
Extent Of Resection ◽  
Rank Test ◽  
Karnofsky Performance Score ◽  
Free Survival ◽  
Kaplan Meier ◽  
The Impact ◽  
Mib 1

e13034 Background: This study assesses the impact of 6 cycles of adjuvant TMZ (conventional arm) versus 12 cycles (Extended arm) on Progression free survival (PFS), evaluate the toxicity and correlate the outcome with EGFR, P53 and MIB I labelling Index. Methods: Between December 2010 to October 2012, 36 post operative patients of Glioblastoma between age 18-65 years and Karnofsky Performance Score (KPS) ≥ 70 were included. Patients were randomized to receive Radiation with a dose of 60 Gray in 30 fractions over 6 weeks at 2 gray/fraction with concomitant TMZ (75 mg/m2/day) and Adjuvant therapy with either 6 or 12 cycles of TMZ(150 mg/m2 for 5 days, 28 days cycle). Patients were then assessed monthly clinically and imaged with MRI/CT every 3 monthly or when symptomatic. Toxicity was assessed using CTCAE version 3.0. Statistical Analysis was done using SPSS version 17.0.Kaplan Meier method was used for analysis of survival and log rank test was used for assessing the impact of variables on survival. Results: Of 36 patients, 18 patients were treated in each arm. Median age and KPS in both the arms was 47 years and 80 respectively. 44 % patients in the conventional arm and 50% patients in the Extended arm underwent complete surgical resection. 22% patients in the conventional arm and 28% in the extended arm did not complete their intended treatment. Grade ¾ Thrombocytopenia was seen in 16% in the extended arm and 0% in the conventional arm.EGFR, P 53 and MIB 1 >20% was seen in 26%, 45% and 20% patients respectively, overall. Median follow up was 18 months for both the arms (Range 10-23 months).At last follow up,8 patients in each arm had progression. Median PFS was 10 months vs.18.4 months (p 0.47) in conventional and extended arm respectively. On Univariate analysis, patients with KPS ≤ 80 had poorer survival than those >80 (Median PFS 9.5 Months vs. 16.9 Months; p 0.02).Age, extent of resection, EGFR, P53, MIB 1 did not significantly alter survival in the two treatment groups. Conclusions: Our study showed that schedule of extended Temozolomide is well tolerated by patients and tend to have better progression free survival. Further prospective randomized studies are needed to validate the findings of our study.

Association between intratumoral HER2 heterogeneity (IHH) and trastuzumab (T-mab) efficacy in HER2 positive–gastric cancer (GC).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 92-92
Author(s):  
Takeru Wakatsuki ◽  
Noriko Yamamoto ◽  
Keisho Chin ◽  
Mariko Ogura ◽  
Eiji Shinozaki ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Statistical Tests ◽  
Progression Free Survival ◽  
Clinical Impact ◽  
Heterogeneous Group ◽  
Rank Test ◽  
Her2 Positive ◽  
Kaplan Meier ◽  
Significant Difference ◽  
The Difference

92 Background: ToGA study showed superiority of adding T-mab to standard chemotherapy and a positive correlation between HER2 expression levels and the T-mab efficacy. In gastric cancer IHH is frequently recognized but its clinical impact on T-mab efficacy is unclear. Methods: Patients who were treated with T-mab and had surgical specimens available for IHC test were retrospectively examined. When all tumor cells overexpressed HER2 protein by IHC, the tumor was defined as non-HER2-heterogeneous. The others were defined as HER2-heterogeneous. Progression-free survival (PFS) and overall survival (OS) were estimated using by Kaplan-Meier methods and compared by the log-rank test. The level of significance was set to p<0.05 and all statistical tests were two-sided. Results: 23 patients were enrolled. Their median age was 68 years and 83% were male. PS 0, GEJ cancer, intestinal type histology, visceral metastasis (lung or liver), and previous chemotherapy were found in 57%, 35%, 83%, 57%, and 57% of them, respectively. After a median follow-up of 11.3 months, the median OS, PFS, and overall response rate were 14.4 months, 10.8 months, and 62.5%, respectively. All tumors were IHC3+, and 13 were non-HER2-heterogeneous and 10 were HER2-heterogeneous. There was no significant difference in clinicopathological features between the two groups. Median PFS in non-HER2-heterogeneous group (21.9 months) was significantly longer than that in HER2-heterogeneous group (8.6 months), (HR: 0.24 [0.06-0.91], P=0.024). Median OS in non-HER2-heterogeneous group was not reached while that in HER2-heterogeneous group was 12.9 months (HR: 0.29 [0.06-1.42], P=0.102). A higher rate of response to T-mab was seen in non-HER2-heterogeneous group than in HER2-heterogeneous group, though the difference was not statistically significant (75% vs. 50%, p=0.608). Conclusions: IHH might have robust clinical impact on T-mab efficacy for HER2 positive GC. These findings should be validated by independent large cohorts and further molecular correlative analyses are warranted.

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