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  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 4_suppl ( 2019-02-01), p. 671-671
    Abstract: 671 Background: Hepatic resection is the gold standard treatment for pts with liver-limited mCRC with 5- and 10-yrs survival rates reaching up to 60% and 20%. Although multidisciplinary team (MDT) management might ensure a more accurate assessment of pts and a faster referral to surgeons, reports discussing the impact of MDTs on survival are controversial and to date there are no strong evidences supporting routinely MDT discussion. The aim of this study was to evaluate the benefit of MDT management in pts with liver-limited mCRC in our single institution experience. Methods: Clinical records of pts with liver-limited mCRC who underwent radical surgery at Fondazione Policlinico “A. Gemelli” - IRCCS from Jan-2006 to Dec-2016 were retrospectively analyzed. The objective of the analysis was to compare survivals of pts managed within our MDT (MDT cohort) to those of pts referred to surgery from other hospitals without MDT discussion (non-MDT cohort). Primary endpoints were DFS and OS. Differences in baseline characteristics and in post-operative morbidity were evaluated. Results: Of the 619 pts analyzed, 230 were included in the MDT cohort and 389 in the non-MDT cohort. No significant difference between the two groups was found in terms of DFS (12vs11 m; p 0.09) and OS (55vs51 m; p 0.68). Concerning baseline characteristics, in the MDT cohort compared to non-MDT cohort there was a statistically higher number of median metastases (4.5vs2.6; p 〈 0.0001) and a higher rate of synchronous metastases (61.7vs39.3%; p 〈 0.001). Despite pre-operative CT rate was higher in the MDT group (75.8vs70.7%), the median duration of CT before surgery was significantly lower in MDT pts (7 vs 8 cycle; p 〈 0.001). Moreover, post-operative morbidity was significantly lower in the MDT cohort (6.2vs19.2%; p 〈 0.00001). Conclusions: Our study does not demonstrate a survival benefit from MDT management of pts with liver limited mCRC. However, the analysis shows that MDT assessment allows to consider eligible for surgery pts with a more advanced disease. Moreover, MDT discussion seems to reduce the median duration of pre-operative CT with a consequent lower rate of post-operative morbidities. Our data warrant prospective validation.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e15039-e15039
    Abstract: e15039 Background: Unlike liver metastases surgery, the resection of colorectal cancer lung metastasis (CCLM) is not standardized and data are still poor. Therefore, we conducted a retrospective analysis to evaluate the management of CCLM at our Centre. Methods: We retrospectively analyzed patients (pts) with CCLM treated at our Institution from Jan-2007 to Jan-2017. Aim of the study was to evaluate the impact of clinical and pathological features with survival outcomes (DFS and OS). Differences were compared with the use of log-rank test and parameters considered statistically significant ( p value 〈 0.5) at univariate were compared at multivariate analysis. Results: 141 pts were included in the analysis. 87 pts received a preoperative chemotherapy (pCT) and 54 an adjuvant (a)CT. In the whole population median DFS (mDFS) was 24 m (20-24) and median OS (mOS) 54 m (46-82), while 21 m (20-34) and 65 m (45-108) for pts undergoing pCT and 15 m (20-28) and 53 m (38 – 76) for those receiving aCT respectively, without statistically significant differences (p=0.4). Age, gender, PS, disease-free interval (DFI) ( 〉 or 〈 24 months), primary tumor sidedness, mucinous histology, grading, RAS status, timing of lung metastasis (metachronous vs synchronous), number of lesions ( 〉 2), metastasis location (uni vs bilateral) and liver resection were evaluated at univariate and multivariate analysis. DFS was correlated with DFI 〉 24m (p=0.02), timing (p=0.03), number (p 〈 0,0001) of metastasis and metastasis location (p=0.01) whereas OS was associated to DFI (p=0.02), number (p=0.0005), metastasis location (p=0.037) and RAS status (p=0.05) at univariate. At multivariate analysis, number of lesions correlated to DFS (p=0.0006) while DFI (p=0.0034) and RAS status (p=0.05) to OS. Conclusions: Our single Centre retrospective experience suggests an important clinical impact from surgery of CCLM based on mOS of the whole population. These data strengthen the role of a multidisciplinary management to allow pts to achieve surgery whenever possible, regardless of previous liver surgery, metachronous vs synchronous metastasis, DFI and RAS status.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. e15558-e15558
    Abstract: e15558 Background: Approximately 50%-60% of CRC pts develop metastases, usually to liver and lung. When feasible, MR is the only potentially curative option in the multimodal management of mCRC pts. Few studies have compared survival outcomes based on different surgical sites with contrasting data. Hence, we retrospectively analyzed mCRC pts, underwent radical lung and/or liver resection at our Institution, investigating the impact of resection site on overall survival (OS). Methods: mCRC pts underwent radical liver (group 1), lung (group 2) or liver and lung (group 3) resection were included. The following variables were collected: age ( 〉 vs ≤ 65 years); gender (male vs female); primary tumor site (right vs left); synchronous vs metachronous; RAS/BRAF status; number (N) of MR (1, 2 or ≥3); chemotherapy treatment (No treatment vs Post-operative vs Peri-operative/pre-operative treatment) and chemotherapy regimen (5FU monotherapy, Oxaliplatin-based, Irinotecan-based regimen, FOLFOXIRI, Bevacizumab, Anti-EGFR). The association of MR site and OS was evaluated. Univariate and multivariate analyses for OS were performed. Results: A total of 191 mCRC pts underwent radical MR were included in the analysis: 112 (59%) pts in group 1, 38 pts (20 %) in group 2, 41 pts (21 %) in group 3. 145 (76%) pts had a left-sided tumor and 46 (24%) a right-sided tumor. Out of 156 evaluable pts, 73 (47%) pts harbored a RAS mutation, while out of 136 evaluable pts, 4 (3%) pts had a BRAF mutation. Regarding the N of MR, 125 pts (65%) underwent 1 radical MR, 43 (23%) pts 2 MR and 23 (12%) ≥3 MR. In the overall population, median OS was 77.2 months. According to MR site, median OS was 59.4, not reached (NR) and 99.1 months, in group 1, 2 and 3, respectively (p = 0.075). At the multivariate analysis no significant association with OS was shown for MR site, while the N of MR and RAS status were indipendently associated with OS. Median OS was 58.5, 97.7 months and NR in pts underwent 1, 2 and ≥3 MR, respectively (p = 0.02). Median OS was 58.5 and 83.1 months in RAS mutated and RAS wild-type pts, respectively (p = 0.12). Conclusions: Despite the limited number of pts and the retrospective nature of our study, these results confirmed that surgery represents the only option with curative intent for mCRC pts, independently of metastatic site (liver vs lung vs liver and lung). Based on our analysis, a higher number of MR is associated to a better outcome, and this could be explained with an accurate selection of patients that could benefit from multiple radical resections. Thus, a multidisciplinary approach is essential for the management of mCRC pts and surgery should be evaluated case by case and always performed when possible, even several times, independently of site of MR.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 15_suppl ( 2018-05-20), p. e12665-e12665
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 4_suppl ( 2019-02-01), p. 669-669
    Abstract: 669 Background: Nowadays the optimal treatment for mCRC beyond second line is still questioned. During last years, regorafenib and TAS-102 showed to improve survival compared to best supportive care in pts with refractory mCRC. Recently, some retrospective analyses compared the efficacy and safety of regorafenib and TAS-102 reporting no significant differences in survival and response outcomes. In real-world clinical practice, chemotherapy (CT) rechallenge is often considered for refractory mCRC. However, evidences regarding CT rechallenge is limited and no study has previously compared such approach with the recently approved antineoplastic agents in late lines. The aim of this study was to compare the efficacy between CT rechallenge and regorafenib in pts with refractory mCRC. Methods: This is a mono-institutional retrospective study. We compared the efficacy of FOLFOX rechallenge and regorafenib in pts with mCRC refractory to at least 2 lines of standard CT, treated at Fondazione Policlinico Universitario “A. Gemelli”-IRCCS between Jan-10 and Jan-18. The primary endpoint was OS. Secondary endpoints were RR and PFS. Results: One hundred thirty-one pts received regorafenib and 43 FOLFOX rechallenge. OS was significantly higher with FOLFOX rechallenge than it was with regorafenib (13 vs. 6 months; HR 0.67, 95% CI 0.33-0.66; p = 0.0002). PFS was significantly higher in the FOLFOX rechallenge group compared to the regorafenib group (5 vs. 3 months; HR 0.64, 95% CI 0.46-0.89; p = 0.0073). Accordingly, RR was better in pts receiving FOLFOX rechallenge compared to regorafenib (25 vs. 3%; Chi-square p 〈 0.0001). Conclusions: Our study, although retrospective and small-sized, compared for the first time to our knowledge the efficacy of CT rechallenge to regorafenib in refractory mCRC. In our analysis, CT rechallenge with FOLFOX proved to be superior compared to regorafenib, with a survival and response benefit in pretreated mCRC. The survival benefit observed for rechallenge might be explained by the significantly higher tumor shrinkage achieved with CT rechallenge compared to regorafenib. Our results warrant further confirmation in wider and/or prospective analyses.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 6
    In: Journal of Personalized Medicine, MDPI AG, Vol. 11, No. 8 ( 2021-08-20), p. 816-
    Abstract: Background: The aim of this study is to identify miRNAs able to predict the outcomes in breast cancer patients after neoadjuvant chemotherapy (NAC). Patients and methods: We retrospectively analyzed 24 patients receiving NAC and not reaching pathologic complete response (pCR). miRNAs were analyzed using an Illumina Next-Generation-Sequencing (NGS) system. Results: Event-free survival (EFS) and overall survival (OS) were significantly higher in patients with up-regulation of let-7a-5p (EFS p = 0.006; OS p = 0.0001), mirR-100-5p (EFS s p = 0.01; OS p = 0.03), miR-101-3p (EFS p = 0.05; OS p = 0.01), and miR-199a-3p (EFS p = 0.02; OS p = 0.01) in post-NAC samples, independently from breast cancer subtypes. At multivariate analysis, only let-7a-5p was significantly associated with EFS (p = 0.009) and OS (p = 0.0008). Conclusion: Up-regulation of the above miRNAs could represent biomarkers in breast cancer.
    Type of Medium: Online Resource
    ISSN: 2075-4426
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662248-8
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e15589-e15589
    Abstract: e15589 Background: R is an emerging field of research based on the extraction of a large amount of F from biomedical images and on computed analysis algorithms of tumour architecture. Few data regarding mCRC are available, in particular no correlation of baseline RF both with m sites and clinical-pathological characteristics was so far investigated. Methods: Baseline chest-abdomen CT scans of mCRC patients (pts) were retrospectively analysed. RF were extracted from Regions of Interest (ROI) delineated on CT scan from each m sites, including primary tumor, when on site. The association of specific F and disease site (liver, lung, nodes, peritoneum and on-site primary tumor) was investigated. Sites similarity was assessed with Principal Component Analysis, an unsupervised learning technique to identify patterns and clusters. Then RFs were tested individually for correlation with clinical-pathological covariates of interest (gender, CEA level, synchronous disease, RAS/BRAF status, mucinous histology, grading, number of m site, primary tumor site). Wilcoxon-Mann-Whitney test was used for this purpose (significance level set at 0.05). Results: After RF extraction from the different ROIs, the dataset was composed of 433 observations of 236 variables. Observations referred to the number (N) of pts = 89 and the N of ROIs = 18. RF classes were divided in statistical F (grey-level histogram) (N of F = 10); morphological F (N = 14); texture F GLCM (grey level co-occurrence matrix) (N = 100); texture F GLRLM (grey level run length matrix) (N = 66); texture F GLSZM (grey level size zone matrix) (N = 32). Regarding the association of RF with m sites, an homogenous distribution with liver, nodes, peritoneum and primary tumor was detected, while lung metastases showed a different pattern for all the RF classes. A significant correlation of specific RF with clinical-pathologic characteristics was shown, in particular with gender, CEA level, synchronous disease, mucinous histology, RAS/BRAF status. Conclusions: Despite its retrospective nature and the limited number of pts, this is the first experience demonstrating I) a different pattern of RF for lung m versus an homogeneous RF distribution for the other m sites; and II) a significant association of specific RF with few clinical-pathologic characteristics. Our results, if confirmed in a prospective validation set, may represent an hypothesis generator regarding the different behaviour of lung metastases and a possible R signature able to identify different prognostic subgroups of pts.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e16759-e16759
    Abstract: e16759 Background: Three main phase III randomized studies investigated the role of 2nd-line tx in APC pts. The PANCREOX study failed to demonstrate a survival advantage of mFOLFOX vs 5FU/LV. Conversely, the CONKO-003 and NAPOLI-1 trials, demonstrated a significant survival improvement from the combination regimen OFF and 5FU+Nal-IRI, respectively, in comparison to 5FU/LV alone. Recently, final OS analysis from NAPOLI-1 demonstrated an association of specific characteristics (ECOG PS, age, Ca 19.9 baseline level, neutrophil-to-lymphocyte ratio and no liver metastases (m)) with OS 〉 1 year. The main limit of all these studies was due to the period they were carried out: no pts received 1st-line GemNab. Hence, we retrospectively analysed an homogeneous population of APC treated with 1st-line GemNab at our Institution, investigating the impact of 2nd-line tx. Methods: APC pts receiving a 2nd-line tx after 1st-line GemNab were included in the analysis. The following variables were collected: gender; age ( 〉 vs ≤ 55 years and ≥ vs 〈 70 years ); baseline ECOG PS (0-1 vs 2-3); Ca 19.9 baseline level (≥ vs 〈 200); anamnesis of diabetes; site of primary tumor (head/uncinate process vs body/tail); number of m sites (1 vs 〉 1); m sites (liver, peritoneum, lung, nodes); RECIST response and ETS during 1-line GemNab. Univariate and multivariate analyses for PFS and OS were performed. Results: Out of 167 APC pts progressed to 1st-line GemNab, 93 (56%) pts received a 2nd-line tx, specifically 58 pts received an oxa-based regimen, 11 FOLFIRINOX, 8 FOLFIRI and 16 pts received other tx. Median 2nd-line PFS and OS were 3.3 and 5.6 months, respectively. Out of 87 pts evaluable for response, 7 pts achieved a partial response and 27 a stable disease, with a RR and a disease control rate (DCR) of 8% and 39%, respectively. Pts with baseline ECOG PS 0-1 had a significant better outcome in comparison to pts with PS 3-4 (PFS 4.2 vs 1.2 months, p 〈 0.0001; OS 7.2 vs 2.6 months, p = 0.0001). This significant association with survival parameters and ECOG PS was confirmed at the multivariate analysis. Conclusions: Despite the limited number of pts evaluated and the restrospective nature of our analysis, our results are in line with previous evidences, confirming the importance of a 2nd-line combination tx, when feasible, as well in an homogeneous population of APC pts treated with 1st-line GemNab. On the basis of our results, ECOG PS may be considered a prognostic factor and the choice of 2nd-line tx should be guided in primis by the baseline general conditions of APC pts.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 4081-4081
    Abstract: 4081 Background: Radical resection of LM is the only chance of cure for liver-only mCRC pts. Besides the evaluation of technical resectability, several factors must be taken into account for the evaluation of recurrence risk. Among them we should consider the Fong Risk Score and its modified version, including RAS/BRAF status (Brudvik’s score). Tumor sidedness is an important prognostic factor in CRC. The impact of PT site on the outcome of LM resection is still debated. Hence, we retrospectively analysed mCRC pts, underwent to radical LM resection at our Institution, investigating the impact of PT site on DFS and OS. Methods: Liver-only mCRC pts underwent to radical LM resection were included. The association of PT site with DFS and OS was evaluated. The following variables were collected: gender; age (≥ vs 〈 75 years ); ECOG PS; CEA baseline level; PT site; RAS and BRAF status; mucinous histology; grading (G1-2 vs G3); RECIST response during preoperative treatment; resected PT; synchronous vs metachronous; number of LM; bilobar vs unilobar LM; LM diameter ≥ 5 cm; R0 vs R1 resection. Univariate and multivariate analyses for DFS and OS were performed. Results: A total of 463 liver-only mCRC pts underwent to radical LM resection were included. Seventy (15%) pts had a right-sided (r-s) tumor and 393 (85%) pts a left-sided (l-s) tumor. R-s CRC pts more often had RAS/BRAF mutations in comparison to l-s tumors (76% vs 37%; p 〈 0.0001). Median DFS and OS was 13.1 and 41.6 months, respectively, in r-s CRC vs 16.0 (p = 0.65) and 62.2 months (p = 0.033), respectively, in l-s tumors. At the multivariate analysis no significant association with survival parameters was shown for tumor sidedness. At the multivariate analysis, R0 resection was independently associated both with better DFS and OS; RAS/BRAF wt CRC and resected PT were significantly associated with improved OS. Considering all wt CRC pts (N = 237), 14 (6%) pts had r-s tumor and 223 (94%) l-s tumor. No significant association of tumor sidedness with survival was shown (DFS r = 10.0 vs l = 16.0 months, p = 0.62; OS r = 40.3 vs l = 66.2 months, p = 0.12). Conclusions: Our results showed that a significant smaller proportion of r-s CRC underwent to radical LM resection, indirectly confirming its worse prognosis. Among radically resected pts, r-s CRC was associated to a shorter OS (significant) and DFS (not significant) compared to l-s CRC, but it was not confirmed at the multivariate analysis. We can conclude that right PT site should not be considered as a contraindication for radical LM surgery, when feasible.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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  • 10
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e16758-e16758
    Abstract: e16758 Background: GemNab is one of the first-line standard treatment (tx) of APC. To date, no predictive factors, both clinical and molecular, of benefit from this regimen exist. Two retrospective studies showed that early tumor shrinkage (ETS) can predict an improved outcome in APC pts receiving a first-line tx with FOLFIRINOX or GemNab. However, data regarding GemNab, limited to a small population of only 57 pts, seem to not confirm the association of ETS with a better outcome. Hence, we retrospectively analysed an homogeneous population of APC treated with first-line GemNab at our Institution, investigating the impact of several clinical factors, including response and ETS. Methods: APC pts receiving a first-line tx with GemNab were included in the analysis. The association of RECIST response and ETS with PFS and OS was evaluated. The following variables were collected: gender; age ( 〉 vs ≤ 55 years and ≥ vs 〈 70 years ); baseline ECOG PS; Ca 19.9 baseline level (≥ vs 〈 200); anamnesis of diabetes; site of primary tumor (head/uncinate process vs body/tail); locally A vs metastatic (m) PC; synchronous vs metachronous; number of m sites (1 vs 〉 1); m sites (liver, peritoneum, lung, nodes); number of tx lines (1 vs 〉 1). Univariate and multivariate analyses for PFS and OS were performed. Results: A total of 184 APC pts receiving first-line GemNab at our Institution from February 2014 to May 2019 were included in the analysis. RR and ETS were assessed in 174 and 168 pts, respectively. RR was 30%, disease control rate (DCR) 63% and ETS was 24%. Responders had a significant better PFS (12.5 vs 5.7 months, p 〈 0.0001) and OS (25.1 vs 12.1 months, p 〈 0.0001). ETS was significantly associated with improved PFS (12.3 vs 6.2 months, p 〈 0.0001) and OS (24.0 vs 12.8 months, p 〈 0.0001). At the multivariate analysis a significant association with survival parameters was confirmed for RECIST response, but not for ETS. At the multivariate analysis, also metachronous disease and number of tx lines 〉 1 were independently associated with better OS. Conclusions: Despite its retrospective nature, this is one of the largest series of APC pts treated with first-line GemNab investigating the role of RECIST response and ETS in predicting outcome. On the basis of our results, RECIST response may be considered a positive prognostic factor, whereas ETS does not. In conclusion, achieving tumor shrinkage, not necessarily early, significantly delays PC progression and prolongs survival in pts treated with first-line GemNab.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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