scholarly journals Efficacy of Chemotherapy for Malignant Pleural Mesothelioma According to Histology

Author(s):  
Susana Cedres ◽  
Juan David Assaf ◽  
Patricia Iranzo ◽  
Ana Callejo ◽  
Nuria Pardo ◽  
...  

Abstract PurposeCheckMate 743 trial demonstrated survival benefit of immunotherapy in first line in MPM with some differences in the efficacy of chemotherapy according to histology. The objective of this study is to characterize the impact of chemotherapy according to histology in patients diagnosed with MPM at our institution. MethodsClinical records of all MPM patients diagnosed at Vall d´Hebron University Hospital between November 2002 and April 2020 were reviewed. Associations between clinical variables and outcomes were assessed with Cox regression models. Survival data were calculated by the Kaplan-Meier method. Results189 patients were included with 76% of tumors classified as epithelioid subtype. First line chemotherapy was offered to 85% of patients. Median survival in overall population was 21.3 months (95%CI17.2-24.3). We found that patients with epithelioid tumors had better overall survival (OS) and progression free survival (PFS). Median OS of epithelioid patients treated with first line chemotherapy was 26.7 months versus 15.0 months in nonepithelioid patients (HR2.25 CI95% 1.4-3.4; p<0.001). Median PFS for patients with epithelioid tumors treated with chemotherapy was 4.8 months versus 3.6 months in nonepithelioid (HR1.5 CI95% 1.0-2.3; p=0.03). The improvement of outcomes in patients with epithelioid histology was detected in patients treated with cisplatin or carboplatin. Histology was not a predictive factor for the platinum agent sensitivity (p of interaction PFS=0.09, p of interaction OS=0.65). Conclusions In our series, patients with nonepithelioid tumors presented worse prognosis. Although epithelioid tumors exposed to cisplatin had higher PFS, histology was not a clear predictor of chemotherapy efficacy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20563-e20563
Author(s):  
Susana Cedres Perez ◽  
Juan David Assaf Pastrana ◽  
Patricia Iranzo ◽  
Ana Callejo ◽  
Nuria Pardo ◽  
...  

e20563 Background: MPM is a highly aggressive pleural tumor associated with asbestos exposure and with limited survival despite systemic therapy. Histology is a prognostic factor and recently CheckMate 743 trial demonstrated survival benefit of immunotherapy in first line with some differences in the efficacy of chemotherapy according to histology. However, randomized trials who led to the approval of antifolate in mesothelioma did not include analysis of outcomes by histology. The objective of this study is to characterize the impact of chemotherapy according to histology in p with MPM at our institution. Methods: We review 189 MPM p diagnosed at Vall d´Hebron University Hospital between November 2002 and April 2020. Associations between clinical variables and outcome were assessed with Cox regression models and survival data were calculated by the Kaplan-Meier method. Results: Patient’s characteristics: median age 68 years (y) (45-88 y), males: 70%, performance status (PS)1: 69%, asbestos exposure: 75%, epithelioid subtype: 76%. First line chemotherapy was offered to 85% of p (66% cisplatin-pemetrexed and 27% carboplatin-pemetrexed). Median overall survival (OS) in overall population was 21.3 m (95%CI17.2-24.3). Epithelioid histology, PS 0, neutrophil-lymphocyte ratio <5 and treatment with cisplatin vs carboplatin were associated with significant improvements in OS (p<0.001). When we analyzed the survival of patients who received first line chemotherapy according to histology, we found that patients with epithelioid tumors had better PFS and OS. Median PFS for p with epithelioid tumors treated with chemotherapy in first line was 4.8 m versus 3.6 months non-epithelioid (HR1.5 CI95% 1.1-2.3; p=0.03). OS of epithelioid p treated with first line chemotherapy was 26.7 m versus 15.0 m non-epithelioid patients (HR2.25 CI95% 1.4-3.4; p<0.001). We analyzed if the differences in survival according to histology were due to type of systemic treatment received (Table). Conclusions: In our series, p with non-epithelioid tumors presented worse prognosis. We confirmed histology is a prognostic factor with better OS for p with epithelioid tumors. Moreover, we demonstrated better efficacy of chemotherapy in epithelioid tumors, although histology is not a predictive factor for the platinum agent sensitivity (p of interaction PFS=0.09, p of interaction OS= 0.65).[Table: see text]


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 728-728
Author(s):  
Belinda Lee ◽  
Angelyn Anton ◽  
Margaret Lee ◽  
Rachel Wong ◽  
Phillip Parente ◽  
...  

728 Background: BRAF mutated (BRAFm) CRC represents ~10% of all CRC and is associated with significantly poorer prognosis. However, responses to chemotherapy do still occur. Some data suggest that the poor prognosis associated with BRAFm CRC is dominated by substantially poorer second line PFS (PFS2), whereas first line PFS (PFS1) was similar for both BRAFm and BRAF wildtype (BRAFwt) CRC. Using a large multicenter dataset, our study aimed to examine PFS1 and PFS2 in BRAFm versus BRAFwt CRC. Methods: Prospectively collected data from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) database was interrogated. PFS was calculated and compared in patients with BRAFm versus BRAFwt CRC. Median survival was determined by the Kaplan-Meier method and compared using the log rank test. Results: TRACC identified 523 CRC patients with known BRAF mutation status, who received first-line chemotherapy: 53 (10%) were BRAFm, while 470 (90%) were BRAFwt. At the time of data analysis, only 231 (44%) CRC patients had received second-line chemotherapy, of which 21 (9%) were BRAFm and 210 (91%) were BRAFwt. PFS1 analyses demonstrated significantly poorer survival in the BRAFm population (Median 7.8mo versus 11.5mo, HR 1.72, p = 0.0026). PFS2 analyses revealed similar findings for the BRAFm population, albeit non-significant due to smaller numbers (Median 5.5mo versus 7.7mo, HR1.26, p = 0.44). Conclusions: Our study demonstrated that BRAFm CRC was associated with poorer PFS in both first- and second-line settings. Additional analyses will be performed to examine the impact of different treatment strategies and other clinicopathological features.


2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 103-103
Author(s):  
Motoko Arakaki ◽  
Masahiko Aoki ◽  
Hiroshi Imazeki ◽  
Hirokazu Shoji ◽  
Yoshitaka Honma ◽  
...  

103 Background: The continuation of first-line chemotherapy or the maintenance chemotherapy has been selected for advanced gastric cancer patients who have not progressed after 4 to 6 cycles of first-line chemotherapy. However, survival data about those patients remains unclear. We retrospectively assessed the impact of response at 12 weeks on survival for advanced gastric cancer who received first-line chemotherapy. Methods: Eligible patients had unresectable advanced gastric adenocarcinoma and treated for the combination chemotherapy with fluoropyrimidine and platinum from January 2010 to December 2017 in our hospital. Patients with HER2 positive were excluded. Patients were divided into three groups (PR, SD, or PD group) according to response at 12 weeks of first-line chemotherapy, and their overall survival and progression-free survival were assessed. Results: The total number of the subject was 249 whose median overall survival (mOS) and progression-free survival (mPFS) were 13.8 and 5.4 months. Among 152 patients with measurable lesions, 58, 42, and 52 patients achieved PR, SD, and PD at 12 weeks. mOS was 16.7 months in the PR group, 9.8 months in the SD group, and 5.7 months in the PD group. mPFS was 7.1 months in the PR group, 4.5 months in the SD group, and 1.7 months in the PD group. Among 97 patients without measurable lesions, 90 patients achieved nonCR/nonPD at 12 weeks of first-line chemotherapy whose mOS and mPFS were 17.9 months and 9.2 months while those were 9.6 months and 1.9 months in the remaining 7 patients with PD at 12 weeks. Conclusions: There were clear differences in survival among PR, SD, and PD at 12 weeks in patients with measurable lesions while patients without measurable lesions obtaining nonCR/nonPD at 12 weeks showed similar OS and PFS to those with measurable lesion obtaining PR in first-line chemotherapy for advanced gastric cancer. [Table: see text]


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9542-9542
Author(s):  
Yasuhiro Nakamura ◽  
Yukiko Kiniwa ◽  
Hiroshi Kato ◽  
Osamu Yamasaki ◽  
Takeo Maekawa ◽  
...  

9542 Background: Anti-PD-1 antibody monotherapy (PD1) has been commonly used for patients with advanced acral melanoma (AM). However, recent studies have demonstrated the limited clinical efficacy of PD1 in AM compared to non-acral cutaneous melanoma, particularly in nail apparatus melanoma. Although advanced AM patients are strong candidates for first-line anti-PD-1 and anti-CTLA-4 combination therapy (PD1+CTLA4), data on the clinical efficacy of PD1+CTLA4 in AM are lacking. Thus, we aimed to compare the clinical efficacies of PD1+CTLA4 and PD1 in Japanese advanced AM patients. Methods: We retrospectively reviewed the clinical records of advanced AM patients treated with PD1+CTLA4 or PD1 as first-line immunotherapy at 23 Japanese institutions. Clinical response was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Survival was estimated using Kaplan-Meier analysis. Toxicity was assessed according to CTCAE 4.0. Results: A total of 192 patients (median age, 72 years) with advanced AM (palm and sole melanoma, 135; nail apparatus melanoma, 57) were included in the study. PD1+CTLA4 and PD1 were used as first-line immunotherapy in 39 and 153 patients, respectively. The baseline demographics and characteristics were similar between the PD1+CTLA4 and PD1 groups, except for age (median age 67.3 vs. 73.2; P = 0.005). The objective response rate (ORR) in PD1+CTLA4 was significantly higher than that of the PD1 group (38.5% vs. 16.3%; P = 0.047). The median progression-free survival (PFS) and overall survival (OS) in the PD1+CTLA4 group tended to be longer than those of the PD1 group, but the differences were not significant (median PFS 7.3 months vs. 4.5 months; P = 0.19, median OS 43.6 months vs. 18.2 months; P = 0.19). In the subgroup analysis of the palm and sole melanoma cohorts, no significant differences in ORR, PFS, and OS were observed between the PD1+CTLA4 and PD1 groups (ORR 31% vs. 20.8%; P = 0.67, median PFS 5.3 months vs. 5.9 months; P = 0.87, median OS not reached vs. 22.3 months; P = 0.66). Meanwhile, the nail apparatus melanoma cohort in the PD1+CTLA4 group exhibited significantly higher ORR, and longer PFS and OS than the PD1 group (ORR 60% vs 6.1%; P < 0.001; median PFS 19.6 months vs 3.8 months; P = 0.008, median OS 43.6 months vs 13.5 months; P = 0.049). Due to immune-related adverse events in all cohorts, the treatment cessation rate was higher in the PD1+CTLA4 group than the PD1 group (59% vs. 11.8%). Conclusions: PD1+CTLA4 was clinically more efficacious than PD 1 in advanced AM patients. Notably, advanced nail apparatus melanoma patients were strong candidates for first-line PD1+CTLA4.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Takaya Kitano ◽  
Tsutomu Sasaki ◽  
Yasufumi Gon ◽  
Kenichi Todo ◽  
Shuhei Okazaki ◽  
...  

Introduction: Chemotherapy may be a cause of cancer-associated stroke, but whether it increases stroke risk remains uncertain. We aimed to clarify the impact of chemotherapy on stroke risk in cancer patients. Methods: We investigated 27,932 patients enrolled in a hospital-based cancer registry at Osaka University Hospital between 2007 and 2015. The registry collects clinical data, including cancer status (site and stage), on all patients treated for cancer. Of them, 19,006 patients with complete data were included. A validated algorithm was used to identify stroke events within 2 years of cancer diagnosis. Patients were divided based on whether their initial treatment plan included chemotherapy. The association between chemotherapy and stroke was analyzed using the Kaplan-Meier method and stratified Cox regression. Results: Of the 19,006 patients, 5,887 (31%) patients were in the chemotherapy group. Non-targeted chemotherapy was used in 5,371 patients. Stroke occurred in 44 patients (0.75%) in the chemotherapy group and 51 patients (0.39%) in the no-chemotherapy group. Kaplan-Meier curve analysis showed that patients in the chemotherapy group had a higher stroke risk than patients in the no-chemotherapy group (HR 1.84; 95% CI 1.23-2.75; Figure [A]). However, this difference was insignificant after adjustment for cancer status using inverse probability of treatment weighting with propensity scores (HR 1.20; 95% CI 0.76-1.91; Figure [B]). Similarly, in the stratified Cox regression model, chemotherapy was not associated with stroke after adjustment for cancer status (HR 1.26; 95% CI 0.78-2.03). These findings were consistent with analysis wherein the effect of chemotherapy was treated as a time-dependent covariate (HR 1.02; 95% CI 0.55-1.88). Conclusions: In this population, the elevated stroke risk in cancer patients who received chemotherapy was presumably due to advanced cancer stage; chemotherapy was not associated with the increased risk of stroke.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15179-15179
Author(s):  
M. Di Marco ◽  
E. Nobili ◽  
R. Di Cicilia ◽  
G. Brandi ◽  
S. Bertolini ◽  
...  

15179 Background: To date, gemcitabine (GEM) remains the cornerstone of chemotherapy (CHT) for APC. According to GERCOR and GISCAD phase III trials the combination of GEM and oxaliplatin (GEMOX) has proven superior to GEM alone in terms of response rate (RR), time to progression (TTP) and clinical benefit rate (CBR). Methods: We conducted a retrospective analysis on 19 patients (pts) affected with histologically-confirmed APC, in order to determine the impact of GEMOX as first-line chemotherapy in terms of objective responses (OR) and TTP, using the Kaplan-Meier method. Among the 19 pts considered there were 15 males and 4 females (median age at diagnosis of 60.84 yrs; ECOG 0–2). The staging, according to AJCC criteria, was: IIB in 1 case, III in 5 cases and IV in the 13 remaning cases. The only metastatic site was the liver (in 13/19 pts). Ten of the 19 pts underwent surgical treatment prior to CHT: 2 radically resected (R0) subsequently treated with GEMOX after recurrence, 4 with positive margins (R1) and 4 surgically palliated. All pts received GEM 1000 mg/m2/d1 + oxaliplatin 100 mg/m2/d2 every 2 weeks. The median number of cycles was 5.89. Results: Among the 19 pts, 3 had a partial response (PR, 15.69%), 6 had stable disease (SD, 31.57%); no complete response was observed and 10 pts had progressive disease (PD, 52.63%). The overall disease control rate (DCR: PR + SD) was 47.37% while the OR were 15.69%. The median survival observed was 9.03 months (95% C.I. 5.15–12.91) and the median TTP was 6.13 months (95% C.I. 2.81–9.46). The main toxicities were: leucopenia, piastrinopenia, diarrhoea, nausea, fever and peripheral neuropathy; 3 pts discontinued the treatment due to grade 3–4 neurotoxicity. Conclusions: In our experience GEMOX gives an improved control of APC in terms of OR and TTP, with acceptable toxicity. The OS is in accordance to literature as well as the other data. No significant financial relationships to disclose.


2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 547-547
Author(s):  
Cristian Lolli ◽  
Marco Maruzzo ◽  
Lisa Derosa ◽  
Teodoro Sava ◽  
Matteo Santoni ◽  
...  

547 Background: A systemic immune-inflammatory index (SII) based on lymphocyte (L), neutrophil (N), and platelet (P) counts has been recently developed. In this retrospective analysis, we explored its prognostic and predictive value at baseline and changes at week 6 during first-line sunitinib in patients (pts) with metastatic renal cell cancer (mRCC). Methods: We included 335 consecutive pts mRCC treated with first-line sunitinib for which P,N, and L data were available at start of therapy, and 6 weeks thereafter. The SII was defined as follows: SII = P x N/L. The X-tile 3.6.1 software (Yale University, New Haven, CT) was used for bioinformatic analysis of the baseline data to determine the cutoff value of SII. Progression-free survival (PFS), overall survival (OS) and their 95% confidence interval (95% CI) were estimated by Kaplan-Meier method and compared with logrank test. The impact of SII conversion on PFS and OS was evaluated by Cox regression analyses. Results: An optimal cutoff point for the SII of 730 x 109stratified these pts into high (≥ 730) and low SII (<730) groups. Median age was 63 years (range, 27 to 88); histotype clear cell carcinoma was reported in 94% of cases; 29.6%, 59.4% and 11% were classified in the favorable, intermediate and poor Motzer prognostic groups, respectively. The median PFS was 6.2 months (mo) (95% CI=5.5-9.5) in pts with baseline SII ≥730 and 17.7 mo (14.3-21.8) in those with SII <730, P<0.0001. The median OS was 13.7 mo (95% CI=9.6-20.3) in pts with baseline SII ≥730 and 41.8 mo (95% CI=34.5-51.8) in those with baseline SII <730, P<0.0001. Data for SII at baseline and change in SII by week 6 using a cut-off of 730 are shown in the table. Conclusions: The SII is a powerful prognostic and predictive indicator of poor outcome in pts with mRCC. A validation study from prospective data is warranted. [Table: see text]


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16746-e16746
Author(s):  
Arjan Gower ◽  
Gillian Gresham ◽  
Nanor Haladjian ◽  
John Lee ◽  
Camille Ng ◽  
...  

e16746 Background: Ataxia telangiectasia mutated (ATM) protein is a DNA damage repair enzyme and regulates normal cell-cycle mechanisms. Germline ATM mutations are associated with increased risk for developing pancreatic cancer (PC), occurring in approximately 2% of PC patients (pts). The role of germline ATM mutations in PC is not well defined. The objective of this study was to compare survival outcomes in patients with germline ATM mutations compared to somatic ATM mutations in PC. Methods: Tumor genomic profiling was completed in 144 PC patients at a single institution in the US, where pts were included in the analysis if they had either germline ATM mutations or somatic ATM mutations. Clinical outcomes were compared between pts with germline ATM mutations and pts with somatic ATM mutations only. Adjusted Cox regression models were fit to evaluate the impact of ATM mutation on overall survival (OS), calculated from treatment (tx) initiation to death, and progression free survival (PFS) calculated from tx initiation to first progression. Results: From 144 PC pts evaluated, 7 pts (4.9%) had germline ATM mutations, all of whom presented with metastatic disease, and 14 pts (9.7%) with somatic ATM mutations only, of whom 10 presented with metastatic disease and 4 who initially presented with locally advanced PC. The majority of pts (15/21), including all 7 pts with germline ATM mutations and 8 with somatic ATM mutations, were treated with first line gemcitabine and abraxane. Median OS was not reached in patients with germline mutations, and 11 months for patients with somatic mutations. Pts with germline ATM mutations had significantly higher OS (HR: 0.12, 95% CI 0.03-0.62, p = 0.01) and PFS (HR:0.26, 95%CI 0.07-0.91, p = 0.04) compared to patients with somatic ATM mutations only after adjusting for age, sex, and first-line tx. Conclusions: Pts with germline ATM mutations may experience greater survival benefit from tx compared to those with only somatic ATM mutations. Further research into the underlying mechanism is warranted.


2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Minjie Tian ◽  
Wenying Ma ◽  
Yueqiu Chen ◽  
Yue Yu ◽  
Donglin Zhu ◽  
...  

Background: Preclinical models have suggested a role for sex hormones in the development of glioblastoma multiforme (GBM). However, the impact of gender on the survival time of patients with GBM has not been fully understood. The objective of the present study was to clarify the association between gender and survival of patients with GBM by analyzing population-based data. Methods: We searched the Surveillance, Epidemiology, and End-Results database who were diagnosed with GBM between 2000 and 2008 and were treated with surgery. Five-year cancer specific survival data were obtained. Kaplan–Meier methods and multivariable Cox regression models were used to analyze long-term survival outcomes and risk factors. Results: A total of 6586 patients were identified; 61.5% were men and 38.5% were women. The 5-year cancer-specific survival (CSS) rates in the male and female groups were 6.8% and 8.3%, respectively (P=0.002 by univariate and P<0.001 by multivariate analysis). A stratified analysis showed that male patients always had the lowest CSS rate across localized cancer stage and different age subgroups. Conclusions: Gender has prognostic value for determining GBM risk. The role of sex hormones in the development of GBM warrants further investigation.


Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3504
Author(s):  
Silvio Ken Garattini ◽  
Debora Basile ◽  
Marta Bonotto ◽  
Elena Ongaro ◽  
Luca Porcu ◽  
...  

Different de-escalation strategies have been proposed to limit the risk of cumulative toxicity and guarantee quality of life during the treatment trajectory of patients with metastatic colorectal cancer (mCRC). Programmed treatment interruptions, defined as drug holidays (DHs), have been implemented in clinical practice. We evaluated the association between DHs and overall survival (OS). This was a retrospective study, conducted at the University Hospital of Udine and the IRCCS CRO of Aviano. We retrieved records of 608 consecutive patients treated for mCRC from 1 January 2005 to 15 March 2017 and evaluated the impact of different de-escalation strategies (maintenance, DHs, or both) on OS through uni- and multivariate Cox regression analyses. We also looked at attrition rates across treatment lines according to the chosen strategy. In our study, 19.24% of patients received maintenance therapy, 16.12% DHs, and 9.87% both, while 32.07% continued full-intensity first-line treatment up to progression or death. In uni- and multivariate analyses first-line continuous treatment and early discontinuation (treatment for less than 3 months) were associated to worse OS compared to non-continuous strategies (HR, 1.68; 95% CI, 1.22–2.32; p = 0.002 and HR,4.89; 95% CI, 3.33–7.19; p < 0.001, respectively). Attrition rates were 22.8%, 20.61%, and 19.64% for maintenance, DHs, or both, respectively. For continuous therapy and for treatment of less than 3 months it was 21.57% and 49%. De-escalation strategies are safe and effective options. DHs after initial induction chemotherapy may be considered in clinically selected patients with metastatic colorectal cancer.


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