Kolorektales Karzinom: Resektable Metastasen resezieren!

2021 ◽  
pp. 138-139
Author(s):  
Hans-Rudolf Raab
Keyword(s):  
Lung Metastases ◽  
Cox Model ◽  
Logistic Models ◽  
Ratio Test ◽  
Conversion Therapy ◽  
Elevated Alkaline Phosphatase ◽  
Retrospective Assessment ◽  
Depth Of Response ◽  
Best Response ◽  
Resection Of Metastases

<b>Background:</b> Tumor assessments after first-line therapy of RAS wild-type mCRC with cetuximab (cet) versus bevacizumab (bev) in combination with FOLFIRI were evaluated for factors influencing resectability, conversion to resectability, and survival after best response. <b>Methods:</b> Conversion to resectability was defined as conversion of initially unresectable to resectable disease at best response as determined by retrospective assessment. Univariate and multivariate logistic models were fitted with resectability at best response as response variable. A Cox model comparing the survival from best response was used to measure the influence of treatment, resectability at best response, and resection. Interaction of resection and treatment arm on survival was tested by likelihood ratio test. <b>Results:</b> Overall, 270 patients were evaluable (127 cet-arm, 143 bev-arm). Lung metastases (odds ratio [OR] 0.35, 95% confidence response [CI] 0.19–0.63), BRAF mutation (OR 0.33, 95% CI 0.12–0.82), and elevated alkaline phosphatase (OR 0.42, 95% CI 0.18–0.9) before randomization were associated with less chance of successful conversion and were integrated into a nomogram. Early tumor shrinkage (OR 1.86, 95% CI 1.06–3.3; p 0.034) and depth of response (OR 1.02, 95% CI 1.01–1.03; p &#x3c; 0.001) were associated with successful conversion therapy. Resection of metastases improved post-best-response survival (hazard ratio 0.53, 95% CI 0.29–0.97; p = 0.039), predominantely in cet-treated patients (interaction test, p = 0.02). <b>Conclusions:</b> Conversion to resectability is significantly associated with baseline characteristics that can be used in a nomogram to predict conversion. Moreover, early efficacy parameters (ETS and DpR) are associated with successful conversion therapy. In FIRE-3, resection of metastases was associated with improved post-best response survival, this effect originated predominantly from the cetuximab-based study arm.

Patterns and management of progression on first-line ipilimumab combined with anti-PD-1 (IPI+PD1) in metastatic melanoma (MM) patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9533-9533
Author(s):  
Ines Pires Da Silva ◽  
Judith M. Versluis ◽  
Tasnia Ahmed ◽  
Douglas Buckner Johnson ◽  
Jennifer Soon ◽  
...  
Keyword(s):  
Lung Metastases ◽  
Acquired Resistance ◽  
Progression Free Survival ◽  
Initial Response ◽  
Best Supportive Care ◽  
First Line ◽  
Disease Characteristics ◽  
Best Response ◽  
Investigational Drugs ◽  
Ecog Ps

9533 Background: First line IPI+PD1 induces long-term response in 36% of MM patients (pts); however, the majority of pts will progress and may require further treatment, which is yet to be established. We studied the patterns of progressive disease (PD) on 1st line IPI+PD1, and the management and outcomes in MM pts. Methods: Demographics, disease characteristics, nature of PD, subsequent treatments and outcomes were examined in MM pts with PD on 1st line IPI+PD1. Multivariable analyses (MVA) identified factors associated with patterns of PD: innate resistance (IR) = PD as best response or stable disease (SD) < 6 mo; acquired resistance (AR) = PD after initial response or SD ≥ 6 mo. Results: 310 MM pts from 14 melanoma centres were included; 208 (67%) had PD during and 102 (33%) after ceasing IPI+PD1. Overall med. progression-free survival (mPFS) was 2.8 mo (CI 95% 2.7 – 3.0); 187 pts (60%) had IR (mPFS 2.2 [2.1 – 2.5]), 112 pts (36%) had AR (mPFS 8.5 [7.2 – 10.2]) and 11 pts (4%) had pseudoprogression, i.e. PD followed by response without changing treatment (mPFS 2.7 mo [1.4 – NA]). On MVA, pts with ECOG PS ≥ 1 were more likely to have IR vs AR; and within IR pts, those with head & neck primary melanomas and lung metastases were more likely to have PD < 1.5 mo. Most pts with IR (68%) had PD in multiple sites, while 61% AR pts had PD in a single site. Brain was most common site of single organ PD; 49% of IR and 41% of AR. Med. follow-up from PD was 32.7 mo (28.1 – 36.8). After PD, 61 pts (20%) had best supportive care (26% of IR and 11% of AR pts). 259 pts (80%) received further treatment: 39% IR pts had systemic treatment (ST) only and 27% had ST + local; 31% AR pts had ST only and 39% had ST + local. Of 200 pts (65%) who had ST(+/-local), 54% had 1 line of ST and 46% had ≥ 2; 1st line ST (ST1) was BRAF/MEKi in 36% of pts, PD1 in 32%, IPI+PD1 in 7%, investigational drugs in 11%, chemotherapy in 9% and others in 5%. ORR in IR pts was lower than in AR pts for every type of ST1 (see Table). Med. OS from PD was 11.4 mo (CI 95% 9.6 – 16.1); IR 6.4 mo (CI 95% 5.6 – 10.2) and AR 26.1 mo (CI 95% 17.1 – NA). Conclusions: These data suggest longer OS from PD for AR vs IR pts independent of ST type. BRAF/MEKi, rechallenge with PD1+/-IPI and investigational drugs showed activity after PD on IPI+PD1, while chemotherapy has no role in this context.[Table: see text]

A global test for competing risks survival analysis

2020 ◽  
Vol 29 (12) ◽  
pp. 3666-3683
Author(s):  
Dominic Edelmann ◽  
Maral Saadati ◽  
Hein Putter ◽  
Jelle Goeman
Keyword(s):  
Survival Analysis ◽  
Likelihood Ratio ◽  
Likelihood Ratio Test ◽  
Competing Risks ◽  
Cox Model ◽  
Wald Test ◽  
Ratio Test ◽  
Type I ◽  
Multistate Models ◽  
Global Test

Standard tests for the Cox model, such as the likelihood ratio test or the Wald test, do not perform well in situations, where the number of covariates is substantially higher than the number of observed events. This issue is perpetuated in competing risks settings, where the number of observed occurrences for each event type is usually rather small. Yet, appropriate testing methodology for competing risks survival analysis with few events per variable is missing. In this article, we show how to extend the global test for survival by Goeman et al. to competing risks and multistate models[Per journal style, abstracts should not have reference citations. Therefore, can you kindly delete this reference citation.]. Conducting detailed simulation studies, we show that both for type I error control and for power, the novel test outperforms the likelihood ratio test and the Wald test based on the cause-specific hazards model in settings where the number of events is small compared to the number of covariates. The benefit of the global tests for competing risks survival analysis and multistate models is further demonstrated in real data examples of cancer patients from the European Society for Blood and Marrow Transplantation.

Comparison of progression-free survival (PFS) and tumor response as endpoints for predicting overall survival (OS) in untreated extensive-stage small cell lung cancer (ED-SCLC): Findings based on North Central Cancer Treatment Group (NCCTG) trials

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8085-8085
Author(s):  
N. R. Foster ◽  
Y. Qi ◽  
J. E. Krook ◽  
J. W. Kugler ◽  
S. A. Kuross ◽  
...  
Keyword(s):  
Tumor Response ◽  
Logistic Models ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Prognostic Impact ◽  
Cox Models ◽  
Landmark Analysis ◽  
Best Response ◽  
Primary Endpoints ◽  
Extensive Stage

8085 Background: Historically, tumor response has been the primary endpoint in phase II (P2) trials in ED-SCLC. We investigated the suitability of alternate PFS based endpoints to predict OS as early evidence of efficacy in the P2 setting. Methods: Individual patient (pt) data from 942 pts from 11 previously untreated ED-SCLC P2 and phase III (P3) platinum- or paclitaxel-based treatment trials were pooled. Best response (BR), response confirmed (RC), objective status at 16 weeks (RR16), and PFS rate at 5 and 6 months were considered. Percent agreement (PA) and kappa (k) for PFS5, PFS6, BR, RC, and RR16 with OS at 12 months (OS12) was calculated on a per-pt basis and predictive utility was assessed using the area under the receiver operating characteristic (A- ROC) curve in logistic models. Cox models were used to assess the prognostic impact of the endpoints on subsequent survival, using landmark analysis. Results: The median OS and PFS were 9.6 m and 5.5 m, respectively. PFS5 and PFS6 had the highest PA, k, and A-ROC values, and were predictive of subsequent survival in the landmark analysis (p <0.0001; c-statistics ≥ 0.60). While RR16 and BR were significantly associated with subsequent survival (p<0.0001, c-statistics of 0.61 and 0.57, respectively) the PA, k, and A-ROC values were lower. Conclusions: PFS rate at 5 and 6 months is more predictive of 12-month OS and subsequent survival than tumor response in untreated ED-SCLC. PFS based endpoints should be routinely used as primary endpoints in P2 trials within ED-SCLC. [Table: see text] No significant financial relationships to disclose.

A genomic classifier independently prognostic of prostate cancer death in a high-risk surgical cohort.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 60-60
Author(s):  
Matthew R. Cooperberg ◽  
Anamaria Crisan ◽  
Anirban Pradip Mitra ◽  
Mercedeh Ghadessi ◽  
Christine Buerki ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Cox Model ◽  
Ratio Test ◽  
Net Benefit ◽  
Prognostic Information ◽  
Full Data ◽  
Combined Model ◽  
Prostate Cancer Death ◽  
Cox Analysis

60 Background: Biomarkers may improve ascertainment of progression risk after radical prostatectomy (RP). We compared two validated post-RP classifiers: the Decipher genomic classifier (GC) and CAPRA-S (based on standard clinicopathologic parameters), to predict prostate cancer-specific mortality (CSM) in a contemporary cohort of RP patients. Methods: From a cohort of 1,010 RP patients treated from 2000-06, a case-cohort design was used to analyze a subset of 219 men with one or more high risk features and available paraffin-embedded tissue. Median follow-up was 6 years. The GC, derived from expression levels of 22 biomarkers and dichotomized to denote low- and high-risk, and CAPRA-S, calculated from preoperative PSA and pathologic grade and staging variables, scores were determined. The scores were evaluated individually and in combination using concordance index, decision curve, (DC), re-classification, and Cox analyses for prediction of CSM. Results: 212 men had full data available to calculate the CAPRA-S; 27 experienced CSM. The c-index for GC (0.78) and CAPRA-S (0.76) were similar, although GC showed improved calibration and higher net-benefit on DC analysis. In 103 patients with high-risk CAPRA-S scores (≥6), GC scores were likewise high-risk for 49, among whom 19 had CSM events. The other 54 men were reclassified as low-risk by GC; among these only 1 CSM event was observed. In multivariable Cox analysis both GC and CAPRA-S were independently prognostic of CSM, with hazard ratios of 1.62 (p<0.001) and 1.22 (p=0.01), respectively for unit score increases. A combined model defined based on the Cox model as (0.20*CAPRA-S + 5.68*GC) was more accurate than either score alone (p<0.001 by likelihood ratio test). DC analysis indicated greater net benefit for the combined model than for either score alone. Conclusions: In men treated with RP at high risk of recurrence based on clinical and pathologic variables, both GC and CAPRA-S were significant predictors of CSM. Notably, GC was able to 'down-risk' >50% of men stratified to high risk based on CAPRA-S alone. Thus the GC provides independent prognostic information, and a model integrating GC and CAPRA-S may further improve the prediction of lethal prostate cancer.

Imatinib Mesylate in Patients With Adenoid Cystic Cancers of the Salivary Glands Expressing c-kit: A Princess Margaret Hospital Phase II Consortium Study

2005 ◽  
Vol 23 (3) ◽  
pp. 585-590 ◽  
Author(s):  
Sébastien J. Hotte ◽  
Eric W. Winquist ◽  
Elizabeth Lamont ◽  
Mary MacKenzie ◽  
Everett Vokes ◽  
...  
Keyword(s):  
Phase Ii ◽  
Tyrosine Kinases ◽  
Group Performance ◽  
Lung Metastases ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Evaluation Criteria ◽  
Growth Factor Receptor ◽  
Adenoid Cystic ◽  
Best Response

Purpose This study aimed to assess the antitumor activity of imatinib in adenoid cystic carcinoma (ACC) of the salivary gland expressing c-kit. A high level of c-kit expression has been identified in more than 90% of ACCs. Imatinib specifically inhibits autophosphorylation of the bcr-abl, platelet-derived growth factor receptor beta, and c-kit tyrosine kinases. Patients and Methods In a single-arm, two-stage, phase II clinical trial, adult patients with unresectable or metastatic ACC measurable by Response Evaluation Criteria in Solid Tumors Group criteria and expressing c-kit by immunohistochemistry were treated with imatinib 400 mg orally bid. Response was assessed every 8 weeks. Results Sixteen patients have been enrolled onto the study; 10 were female. Median age was 47 years (range, 31 to 69 years). Median Eastern Cooperative Oncology Group performance status was 1 (range, 0 to 2). Fourteen patients had lung metastases, 14 had prior radiotherapy, and six had prior chemotherapy. Toxicities occurring in at least 50% of patients included fatigue, nausea, vomiting, diarrhea, anorexia, edema, dyspnea, and/or headache, usually of mild to moderate severity. In 15 patients assessable for response, no objective responses have been observed. Nine patients had stable disease as best response. Six patients had progressive disease after two cycles. Conclusion Because of the lack of activity, the study has been stopped after the first stage and additional evaluation of imatinib in this population is not warranted. Overexpression of wild-type c-kit was not sufficient for clinical benefit from imatinib in ACC. Accrual to this study was rapid for a relatively rare cancer, encouraging additional efforts to identify more effective systemic therapy for these patients.

scholarly journals Depth of Response in Waldenstrom Macroglobulinemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4141-4141
Author(s):  
Jonas Paludo ◽  
Jithma Prasad Abeykoon ◽  
Morie A. Gertz ◽  
Prashant Kapoor ◽  
Aneel Paulus ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Response To Therapy ◽  
Response Criteria ◽  
Advisory Committees ◽  
Free Survival ◽  
Depth Of Response ◽  
Best Response ◽  
The Impact ◽  
Disease Free

Abstract Introduction Recent advances in the understanding of the WM pathobiology led to the expansion of our therapeutic options in this disease. A number of targeted drugs are either available or under investigation and are poised to change the chemo-immunotherapy paradigm in the treatment of WM. Now more than ever, an individualized treatment approach for patients with WM is possible, where patient characteristics and preferences can be matched by different treatment goals and side effect profiles. While deep responses have been associated with longer disease-free survival in other hematologic malignancies, data on patients with WM are sparse. We report the impact of depth of response in disease-free and overall survival (OS) in WM. Methods WM patients consecutively seen at Mayo Clinic between 01/1998 and 12/2016 were reviewed for response to therapy and disease burden. The best response achieved after the treatment of interest (TOI) was classified using the IWWM-7 Response Criteria. The included TOI were: BR, DRC, BDR and high-dose chemotherapy followed by ASCT. All time-to-event analyses were performed from the TOI initiation date using the Kaplan-Meier method and the log-rank test. A landmark analysis from the date-of-best response was also performed for OS to prevent immortal-time bias. Univariate and multivariate analyses of progression-free survival (PFS) and time-to-next therapy (TTNT) were performed using the Cox regression method. Results A total of 181 patients had disease response assessed after the TOI. Baseline characteristics at time of diagnosis are summarized in table 1. The median follow up from TOI was 3.8 years (95% CI: 3-4), the majority of patients received TOI as salvage therapy [n=112 (63%); median 2nd line (rage 1-11)]. Best response rates with the corresponding 5-year PFS and TTNT are summarized in table 2. The median OS from TOI was longer in patients who achieved at least a PR [median 7.2 years (95% CI: 5-NR) vs 3.7 years (95% CI: 1.6-NR), p=0.01]. A trend towards a longer OS was also seen with deeper responses (PR or better) achieved with frontline therapy [median 5.8 years (95% CI: 5.8-NR) vs 3.4 years (95% CI: 1.6-NR), p=0.24]. Figure 1 shows the correlation between deeper responses with PFS and TTNT. Among patients achieving a PR or VGPR, those with a normal FLC ratio post TOI demonstrated a longer PFS and TTNT [PFS: median NR (95% CI: 3.4-NR) vs 4.9 years (95% CI: 2.8-8.7), p=0.01; TTNT: median NR (95% CI: 3.5-NR) vs 5.2 years (95% CI: 4.2-9.4), p=0.04], figure 2. In a multivariate analysis including normal FLC ratio, normal IgM level and minimal BM involvement (<5%) post TOI, normal FLC ratio remained an independent prognostic factor for longer PFS and TTNT. Similar trends were seen when considering treatment naïve and relapsed/refractory patients independently (data not shown). Discussion Our results not only suggest an association between depth of response with PFS and TTNT, but also with OS in patients with WM. A normal FLC ratio (not part of the IWWM-7 response criteria) seems to predict a longer disease-free interval in patients achieving a PR or VGPR. Disclosures Gertz: Ionis: Honoraria; Apellis: Consultancy; annexon: Consultancy; Prothena: Honoraria; janssen: Consultancy; Physicians Education Resource: Consultancy; Alnylam: Honoraria; Teva: Consultancy; spectrum: Consultancy, Honoraria; Medscape: Consultancy; celgene: Consultancy; Research to Practice: Consultancy; Amgen: Consultancy; Abbvie: Consultancy. Kapoor:Takeda: Research Funding; Celgene: Research Funding. Ailawadhi:Amgen: Consultancy; Janssen: Consultancy; Takeda: Consultancy; Pharmacyclics: Research Funding; Celgene: Consultancy. Reeder:Affimed: Research Funding. Witzig:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Dispenzieri:Celgene, Takeda, Prothena, Jannsen, Pfizer, Alnylam, GSK: Research Funding. Lacy:Celgene: Research Funding. Kumar:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Ansell:Seattle Genetics: Research Funding; Celldex: Research Funding; Bristol-Myers Squibb: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Pfizer: Research Funding; Takeda: Research Funding; Merck & Co: Research Funding; Affimed: Research Funding; Regeneron: Research Funding.

scholarly journals A Comparative Study of Cox Regression vs. Log-Logistic Regression (with and without its frailty) in Estimating Survival Time of Patients with Colorectal Cancer

2017 ◽  
Vol 6 (1) ◽  
pp. 35-43
Author(s):  
A.H. Hashemian ◽  
M. Garshasbi ◽  
M.A. Pourhoseingholi ◽  
S. Eskandari
Keyword(s):  
Colorectal Cancer ◽  
Survival Time ◽  
Logistic Model ◽  
Cox Regression ◽  
Cox Model ◽  
Logistic Models ◽  
Individual Characteristics ◽  
Parametric Models ◽  
Biomedical Sciences ◽  
Non Parametric

Colorectal cancer is common and lethal disease with different incidence rate in different parts of the world which is taken into account as the third cause of cancer-related deaths. In the present study, using non-parametric Cox model and parametric Log-logistic model, factors influencing survival of patients with colorectal cancer were evaluated and the models efficiency were compared to provide the best model. This study is conducted on medical records of 1,127 patients with colorectal cancer referred to Taleghani Medical and Training Center of Tehran between 2001 - 2007 and were definitely diagnosed with cancer, pathologically. Semi-parametric Cox model and parametric log-logistic model were fitted. Akaike’s criterion of Cox Snell graph was used to compare the models. To take into account non-measured individual characteristics, frailty was added to Cox and log-logistic models. All calculations were carried out using STATA software version 12 and SPSS version 20.0, at the 0.05 level of significance. From a total of 1,127 patients studied in this research, there were 690 men and 437 women. According to non-parametric Kaplan-Meier method, chances of surviving for 1, 3, 5 and 7 years were 91.16, 73.20, 61.00, and 54.94, respectively. Addition of frailty parameter did not change the model outcome. The results of fitting classified Cox and log-logistic models showed that body mass index (BMI), tumor grade, tumor size, and spread to lymph nodes, were the factors affecting survival time. Based on comparisons, and according to Cox Snell residuals, Cox and log-logistic models had almost identical results; however, because of the benefits of parametric models, in surveying survival time of patients with colorectal cancer, log-logistic can be replaced, as a parametric model, with Cox model.Journal of Medical and Biomedical Sciences (2017) 6(1), 35-43Keywords: Colorectal cancer, Cox regression, Log-logistic model, Cox Snell residual

Chemosensitivity and stratification by a five monoclonal antibody IHC test in the NSABP B20 trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 529-529 ◽  
Author(s):  
D. T. Ross ◽  
C. Kim ◽  
G. Tang ◽  
O. M. Mejia ◽  
R. A. Beck ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Statistical Power ◽  
Risk Group ◽  
Cox Model ◽  
Small Sample ◽  
Tissue Array ◽  
Rank Test ◽  
P Value ◽  
Ratio Test ◽  
Significant Difference

529 Background: We previously reported the association between a five monoclonal antibody test staining p53, NDRG1, SLC7A5, CEACAM5 and HTF9C and recurrence-free interval (RFI) in 711 ER+ N- breast cancer patients from Tamoxifen (Tam) arm of the NSABP trials B14 and B20 (SABCS 2006). In this study, we examined interaction between the test and chemotherapy in the B20 trial. Subjects and Methods: Tissue array sections from B20 paraffin blocks were stained using standard IHC protocols (N=457). Pre-defined scoring rules and cut- points were applied. RFI was defined as time from entry to any local, regional or distant recurrence. Log-rank test was applied to assess the effect of chemotherapy for each risk stratum pre-defined by this IHC test. Interaction between risk strata and treatment was assessed by the likelihood ratio test in a Cox model with age and clinical tumor size adjusted. Results: The IHC test identified high and low risk groups that both showed significant improvement upon treatment with cytotoxic chemotherapy. The moderate risk group was poorly populated and showed no significant difference between chemo-treated and Tam-only patients. Conclusion: It appears that five monoclonal antibodies may be able to identify groups of ER+, node negative patients who have greater absolute benefit from adjuvant Chemo compared to un-stratified patient populations. However, the formal test for interaction between Chemo and the risk group was not significant (p- value=0.127). This may be due to small sample size and a lack of statistical power. The results suggest that this test deserves further evaluation as a method for identifying subsets of patients who may receive more benefit from Chemo. [Table: see text] No significant financial relationships to disclose.

Long-term outcomes of surgical resection of lung metastases from colorectal cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 655-655
Author(s):  
Ryota Mori ◽  
Yoshinori Kagawa ◽  
Yoshiro Yukawa ◽  
Keisuke Toya ◽  
Kouki Takase ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Primary Tumor ◽  
Lung Metastases ◽  
Lung Resection ◽  
Overall Survival Rate ◽  
Long Term Outcomes ◽  
Resection Of Metastases ◽  
Serum Cea

655 Background: The lungs are one of the most frequent sites of metastases from colorectal cancer(CRC). Surgical resection has been widely performed on patients with pulmonary metastases from CRC with favorable outcomes. Surgical treatment is considered an effective option, but the surgical indications of lung resection have institutional bias. In our hospital, we aggressively perform surgery for lung metastases when the primary tumor and other metastases are controlled and all lung metastases are resectable. In this study, the aim is to investigate the long-term outcomes of resections of lung metastases from CRC in our institute. Methods: Between April 2009 and November 2017, patients who underwent lung resections for metastases from CRC with curative intent in our hospital were investigated retrospectively. Kaplan-Meier survival curves, log-rank tests, chi-squared test and T-test were used to analyze the survival rates and the factors predicting recurrence. Results: Sixty-seven patients underwent lung resection of metastases from CRC. The median follow-up period was 25.3 (6-60) months. Five-year disease free survival was 33.6 % and 5-year overall survival was 63.9%. Because of pulmonary recurrence, second surgery was performed in 16 patients and a third surgery in three patients. 5-year overall survival rate after first lung resection in patients who underwent repeated lung resection was 49.2%. There was no significant difference between the number of patients with pulmonary recurrence and those with no recurrence after lung resection (p = 0.38). Twenty-one patients had experienced prior liver resection; the 5-year overall survival rate after lung resection in these patients was 57.9 %. Factors predicting recurrence were vascular invasion (v ≥ 2) of primary tumor (p = 0.02), pre-operative serum CEA (p = 0.03) and CA-19-9 (p = 0.04). Conclusions: The outcome of lung resection of metastases from CRC in our hospital was satisfactory. Aggressive lung resection for cases even after liver resection and repeated pulmonary recurrence may improve long-term outcomes.Vascular invasion of primary tumor and the pre-operative serum CEA and CA 19-9 level can be predictive markers for recurrence.

Evaluating the role of immune-checkpoint inhibitor (ICI) combinations in patients (pts) with unselected “cold” tumors enrolled in early clinical trials (CT).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2597-2597
Author(s):  
Omar Saavedra Santa Gadea ◽  
Alberto Hernando-Calvo ◽  
Roger Berche ◽  
Maria Vieito ◽  
Irene Brana ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Ovarian Cancer ◽  
Clinical Trials ◽  
Cox Model ◽  
Prognostic Score ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
Olfactory Neuroblastoma ◽  
Kaplan Meier ◽  
Best Response

2597 Background: In order to improve the expected response rate (ORR) of less than 10% in cold tumors, several ICI combinations are being evaluated in clinical trials. However, most of these trials don’t require any biomarker and pts are included based solely in histology. We aimed to assess the benefit of ICI combinations in pts with unselected cold tumors included in early CT. Methods: ICI naïve pts with cold tumors treated from 2015 to 2021 with ICI combinations in early CT at VHIO were reviewed. Clinico-pathological data and anti-tumor activity were extracted from a prospective database. ORR was defined as per RECIST v1.1 and clinical benefit rate (CBR) as complete/partial response (CR/PR) + stable disease (SD) for ≥ 4 months (m). Kaplan Meier estimates of progression-free survival (PFS) and overall survival (OS) were calculated and a Cox model according to LIPI (Lung Immune Prognostic Index = baseline LDH and derived neutrophil to lymphocyte ratio) was constructed. Immune-related adverse events (irAE) were classified as per CTCAE v.4.03. Hyperprogressive disease (HPD) was evaluated using RECIST v1.1 (Matos et al, 2020). Results: Out of 97 pts, median age was 62y, 61% had ECOG 0 and 29.8% had LIPI 0 (good prognostic score). Most pts had microsatellite stable (MSS) colorectal cancer (60.8%) or ovarian cancer (14.4%). Regimens included anti-PD1/L1 + another ICI in 69% (most commonly anti-LAG3 [26,8%] and CD40 agonist [20.9%]), anti-PD1/L1 + other molecule in 21.7% (most commonly SHP2 inhibitor [33.3%] and anti p53-HDM2 [28.5%]) and bispecific antibodies in 9.3% (anti-PD1/L1 + anti-LAG3 or CD137 agonist). No patient achieved a response. CBR was 15.3% (11 pts with MSS colorectal cancer, 2 ovarian cancer, 1 olfactory neuroblastoma, 1 paraganglioma). 33 pts (34%) presented irAE, 15 pts (15.5%) had irAE ≥ G2, 4 pts (4.1%) had G3 irAE (dry mouth, hypertransaminasemia, myocarditis and neutrophils count decreased) and 1 patient (1%) had G4 hyperglicemia. 58 pts (59.7%) had progressive disease (PD) as best response, 19 of these pts (32.7%) presented irAE. Overall, 20 pts (20.6%) met definition of HPD, representing 34.4% of pts with PD as best response. Median PFS for overall and CBR population were 1.9 m (CI95% 1.7-2.0) and 5.9 m (5.4-NR), respectively. Median OS for overall population was 7.6 m (5.9-9.5), with a trend for improved OS if LIPI good score vs. others (12.6 m vs. 6.2 m, hazard ratio 1.9, (CI 95% 1.1-3.3), p = 0.02). Among hyperprogressors, median OS was 5.33 m (3.39 - NR) and significantly worse LIPI scores (intermediate [1] or poor [2]) were observed as compared to pts with CBR (75% vs 53.3% p = 0.001). Conclusions: ICI combinations demonstrated very limited activity in pts with unselected cold tumors. However, the risk for irAE and HPD remain substantial. Further drug-biomarker co-development strategies are urgently needed to increase the risk benefit ratio for these pts.

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