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  • 1
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    Management of Early-onset Metastatic Colorectal Cancer (ERMIONE): A single institution analysis.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 3593-3593
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 3593-3593
    Abstract: 3593 Background: Despite rising incidence and mortality reported worldwide for CRC diagnosed in pts aged 〈 50 yrs, currently early onset metastatic CRC (EOmCRC) are treated as their older counterparts. We aimed to investigate how this specific subgroup is treated in real world. Methods: This an observational, retrospective, monocentric study aiming to describe features, management and prognosis of EOmCRC. Pts with EOmCRC treated at our Institution between Apr2002 and Dec2022 were included. Applying a descriptive method, counts and percentages were reported for categorical variables, while median and range for continuous variables. PFS and OS were estimated with the Kaplan-Meier method. A multivariate Cox regression analysis was performed. Results: 172 pts were included, of those 60.5% were female and 66% had an ECOG PS of 0. Median age at diagnosis was 43 yrs (range 12-49 yrs). Metastatic disease was mainly synchronous (72.1%), while only 12.2% and 15.7% were stage II and III at diagnosis and developed metachronous metastases. Primary tumor was left-sided in 70.1%. Metastatic site was most frequently liver (67.4%), followed by peritoneum (41.3%), lungs (33.7%), ovary (23.2%) and bones (9.9%). Disease was mostly widespread, while only 30.2% had a single metastatic site. MMR status was available for 87.2% of pts, being proficient in 90% and deficient in 10%. RAS/BRAF status was available for 95.3% of cases, of those 47.5% was RAS/BRAF wt, 48.2% was RAS mt and 4.3% was BRAF mt. 42.4% of cases had a family history positive for cancer. Germline pathogenic or likely pathogenic variants were identified in 6.4% of cases, of those 63.6% involved MMR genes and 18.2% involved HRD genes. Median number of lines of treatment received was 2 (range 1–6). Most frequent first line regimen was a doublet CT (69.8%), followed by a triplet CT (23.8%) and immunotherapy (4.1%), CT regimens were associated to bevacizumab in 45.3% of cases and to antiEGFRs in 29.1% of cases. Throughout the whole continuum of care 8.7% of pts received immunotherapy and 21.5% received treatment within a clinical trial. 70.3% of pts received surgery and/or local ablative treatments (LATs) with radical intent (52.9% surgery, 12.2 both, 4.6% LATs). At a median FU of 38.6 m, mPFS for first line was 13.5 m (95%CI 12.1-15.0 m) and mOS was 41.5 m (95%CI 33.9 - 44.1 m). Median OS was significantly longer for pts who received surgery and/or LATs compared to those who did not (43.4 vs 23.6 m, p 〈 .0001). At multivariate analysis, besides surgery and/or LATs (p= .0007), BRAF status (p= .0165) and ECOG PS (p= .0209) independently correlated with OS. Conclusions: We confirmed that EOmCRC is more frequently diagnosed as synchronous disease, due to delayed diagnosis. Despite the small population and the retrospective nature, we showed that combining surgery and/or LATs to systemic therapy is associated with increased OS in EOmCRC. These evidence warrant further validation in prospective setting.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.3593
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 2
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    Efficacy of anti-EGFR-based treatment (tx) in second-line and beyond according to tumor location (TL) in RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC) patients (pts): A mono-institutional retrospective analysis.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. e15038-e15038
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. e15038-e15038
    Abstract: e15038 Background: Right- (R) and left-sided (L) mCRCs exhibit different clinical and molecular features. Several retrospective analyses showed that the survival benefit of anti-EGFR-based tx is limited to RAS/BRAF wt L-sided mCRC pts, with a larger effect in the first-line setting. Few data are available concerning the anti-EGFR efficacy according to TL in 2nd and following lines. Methods: Pts affected by RAS/BRAF wt mCRC treated at our Institution with anti-EGFR-based tx in 2nd and following lines were retrospectively collected. The objective of the analysis was to compare tx activity and efficacy according to TL. Primary endpoint was overall survival (OS); secondary endpoints were progression free survival (PFS) and response rate (RR). Results: A total of 47 RAS/BRAF wt mCRC pts treated with an anti-EGFR-based tx in 2nd and following lines were identified. Of those, 32 (68%) were L-sided and 15 (32%) R-sided, respectively. Pts (age, gender, PS ECOG) and tumor (number of metastatic sites) characteristics and number of tx lines were well balanced between the two 21 pts received anti-EGFR alone, 26 pts anti-EGFR plus CT. mOS was 22.3 in L-sided and 7.3 months in R-sided group (HR 2.3, 95%CI 1.02-5.14, p = 0.04). At multivariate analysis TL and PS ECOG independently correlated with OS ( p = 0.02 and p =0.0089). mPFS was 8.4 and 3.9 months in pts with L-sided and R-sided tumor, respectively (HR 1.3; 95%CI 0.64-2.80, p =0.43). RR was higher in L-sided compared to R-sided tumor (37.5 vs 13.3) ( p= 0.09). Conclusions: Our analysis, although limited by the small sample and by its retrospective nature, indicates a better OS in L-sided compared to R-sided tumors treated with anti-EGFR-based tx in 2nd and following lines. A prospective validation is warranted.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.e15038
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
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  • 3
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    Chemotherapy rechallenge or reintroduction (CTr/r), regofenib (REG) and TAS-102 for metastatic pretreated colorectal cancer (mCRC) patients (pts): A propensity score analysis of treatment beyond second-line (PROSERpINA Study).
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. 3556-3556
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 3556-3556
    Abstract: 3556 Background: The optimal treatment for mCRC beyond 2nd line is still questioned. Recently, REG and TAS-102 showed to improve survival compared to BSC. While in real-world practice CTr/r is often considered in this setting, supporting evidences are limited. In absence of studies comparing all these strategies, we aimed to compare the prognostic performance of CTr/r, REG and TAS-102 in mCRC treated beyond 2nd line. Methods: mCRC pts progressing after at least 2 lines of CT, treated with CTr/r, REG or TAS-102 between Jan-10 and Jan-19 were considered eligible. The primary endpoint was OS; secondary endpoints were PFS and RR. Cox’s proportional hazard models for survivals were estimated. A propensity score (PS) adjustment for baseline characteristics was further accomplished for survival analysis. Results: The clinical data of 341 pts (CTr/r 133, REG 150, TAS-102 58) were retrospectively collected. At multivariate analysis type of treatment, ECOG PS, number of metastatic sites and treatment line independently correlated with OS ( p 〈 .001, p .001, p 〈 .001 and p .029, respectively). The mOS was 18.5 (95% CI, 14.3–22.7), 6 (95% CI, 5.6–9.5) and 7.6 months (95%CI, 5.6–9.5), for CTr/r, REG and TAS-102 group, respectively (log-rank p 〈 .0001). mOS was significantly longer for pts receiving CTr/r than for those treated with REG/TAS-102 (15.8 vs 7.1 months; adjusted HR 1.96, 95% CI 1.44-2.66; p 〈 .0001) at the PS analysis, adjusted for ECOG PS, number of metastatic sites and treatment line; 2-yrs OS was 34% and 11.6% for CTr/r and REG/TAS-102, respectively. PFS was significantly longer for pts receiving CTr/r than for those treated with REG/TAS-102 (5.5 vs 3.9 months; HR 1.45, 95% CI 1.11-1.91; p .006) at the PS analysis. Accordingly, RR was higher in pts receiving CTr/r compared to REG/TAS-102 (29.0 vs 1.5%; Chi-square p 〈 .00001). Conclusions: Our analysis, although underpowered, generates the hypothesis of a superiority of CTr/r in comparison to REG or TAS-102, in both efficacy and activity. Given the retrospective nature of our analysis, and the potential role of selection bias in treatment assignment, a prospective validation is mandatory.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.3556
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
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  • 4
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    The impact of the multidisciplinary team (MDT) in the management of colorectal cancer (CRC).
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. e13641-e13641
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e13641-e13641
    Abstract: e13641 Background: The management of CRC is complex, particularly in metastatic disease, where it is crucial the definition of disease burden, the assessment of radiological response and the identification of the right timing for potential radical surgery or loco-regional treatments. A correct CRC evaluation and the subsequent choice of the most appropriate treatment strategy, need, therefore, a MDT involving surgeons, oncologists, radiologists, radiation oncologists, endoscopists, gastroenterologists and pathologists. Based on such considerations, we investigated the impact of the MDT meeting in the management of CRC at our Institution. Methods: We retrospectively evaluated all the cases discussed at our MDT meeting between September 2019 and September 2021. We collected data, both pre- and post-MDT meeting, regarding radiology evaluation (disease control vs progression), surgical assessment (yes vs no) and radiotherapy evaluation (yes vs no). Primary endpoint was the overall rate of discrepancy in evaluation between pre- and post-MDT meeting. Results: Between September 2019 and September 2021, 696 cases were presented at our MDT meeting. The median age was 65 years (24-86), 391 (56%) patients were male and 553 (79%) patients had metastatic disease at diagnosis. After MDT meeting, a total of 214 decisions were modified, for an overall discrepancy rate of 31%. In particular, among 377 cases discussed for radiology evaluation, 110 decisions (29%) were modified after a central imaging review: 80 cases initially evaluated as progressed disease before MDT meeting were defined stable after MDT meeting, for a discrepancy rate of 73%. Regarding the 246 cases discussed for surgical assessment on primary tumor and/or metastatic sites, treatment strategy changed in 86 cases (35%). More specifically, 16 cases (19%), evaluated unresectable before MDT meeting, were then considered resectable after MDT meeting. Finally, among the 71 cases discussed for radiotherapy evaluation, treatment strategy changed in 18 cases (25%). Conclusions: Our analysis demonstrates a significant rate of discrepancy in radiology and/or surgical evaluation between pre- and post-MDT meeting. Our results show that a MDT allows a considerable modification in CRC management, maximizing the treatment strategy, in particular avoiding unnecessary changes in therapy and allowing surgery where possible.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.e13641
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 5
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    Focus on RAS codon 61 mutations in metastatic colorectal cancer (mCRC): A retrospective analysis.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. e15598-e15598
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e15598-e15598
    Abstract: e15598 Background: Nowadays, RAS mutational status remains a key determinant in mCRC patients’ therapeutic algorithm. Mutations involving codon 61 are rare, accounting for 1-4%, but have been recently identified with high frequency in ctDNA of pts with mCRC with secondary resistance to anti-EGFR mAbs, with a prevalence of 50% in the Chronos trial. Despite the growing clinical relevance of these mutations, evidence on clinicopathological features and prognosis of mCRC harboring codon 61 RAS mutations is limited and relies on small retrospective studies. In 2014, a cohort study on 19 codon 61 KRAS mutated (mt) mCRC reported clinicopathological and molecular features similar to KRAS codon 12 and 13 mt mCRC. Methods: This is an observational, retrospective, monocentric study, aiming to investigate and describe clinical phenotype and prognostic performance of codon 61 KRAS or NRAS mt mCRC. Pts with codon 61 RAS mt mCRC, treated at Fondazione Policlinico Gemelli between January 2013 and December 2021 were enrolled. Additional datasets of codon 61 RAS wt mCRC (non-codon 61 RAS mt, BRAF V600E mt and RAS/BRAF wt) treated at our Center during the same time period were used as comparators. Differences between groups for categorical variables were compared using Chi Square test. Endpoint for prognostic assessment was OS, estimated with the Kaplan-Meier method and compared using log-rank test. Statistical significance was set at p = .05. Results: 50 pts with codon 61 mt RAS mCRC were included. The comparator dataset included 648 pts with codon 61 RAS wt mCRC. Interestingly, 54% of codon 61 RAS mt cohort developed peritoneal and/or ovary metastases during their disease history. Metastatic involvement of peritoneum or ovary was significantly more frequent in codon 61 RAS mt mCRC compared to codon 61 RAS wt mCRC (54 vs 28.5%, p= . 000163), significance was retained when comparing codon 61 RAS mt to non codon 61 RAS mt (54 vs 35.6%, p= .012495), BRAF V600E mt (54 vs 25%, p= .001286) and RAS/BRAF wt (54 vs 20.5%, p 〈 .00001) cohorts. At a median FU of 96.2 m, mOS for codon 61 RAS mt was significantly shorter compared to RAS/BRAF wt (26.9 vs 36.0 m, HR 0.56, p= .0006) while no significant difference was observed compared to non codon 61 RAS mt (26.9 vs 30.2 m, p = .0993) and BRAF V600E mt (26.9 vs 22.6 m, p = .9124). Conclusions: We showed a statistically significant correlation between codon 61 RAS mutations and metastatic involvement of peritoneum and ovary. This is the first evidence of an impact of RAS mutational status on metastatization pattern. In addition, our data showed a negative prognostic impact of codon 61 RAS mt compared to RAS/BRAF wt mCRC, while no difference was observed compared to other non codon 61 RAS mt and BRAF mt. These evidence warrant further validation in wider and prospective setting.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.e15598
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 6
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    Efficacy of third-line anti-EGFR-based treatment versus regorafenib or trifluridine/tipiracil according to primary tumor site in RAS/BRAF wild-type metastatic colorectal cancer patients
    Frontiers Media SA ; 2023
    In:  Frontiers in Oncology Vol. 13 ( 2023-2-21)
    Details
    In: Frontiers in Oncology, Frontiers Media SA, Vol. 13 ( 2023-2-21)
    Abstract: Right- (R) and left-sided (L) metastatic colorectal cancer (mCRC) exhibit different clinical and molecular features. Several retrospective analyses showed that survival benefit of anti-EGFR-based therapy is limited to RAS/BRAF wt L-sided mCRC patients. Few data are available about third-line anti-EGFR efficacy according to primary tumor site. Methods RAS/BRAF wt patients mCRC treated with third-line anti-EGFR-based therapy versus regorafenib or trifluridine/tipiracil (R/T) were retrospectively collected. The objective of the analysis was to compare treatment efficacy according to tumor site. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), response rate (RR) and toxicity. Results A total of 76 RAS/BRAF wt mCRC patients, treated with third-line anti-EGFR-based therapy or R/T, were enrolled. Of those, 19 (25%) patients had a R-sided tumor (9 patients received anti-EGFR treatment and 10 patients R/T) and 57 (75%) patients had a L-sided tumor (30 patients received anti-EGFR treatment and 27 patients R/T). A significant PFS [7.2 vs 3.6 months, HR 0.43 (95% CI 0.2-0.76), p= 0.004] and OS benefit [14.9 vs 10.9 months, HR 0.52 (95% CI 0.28-0.98), p= 0.045] in favor of anti-EGFR therapy vs R/T was observed in the L-sided tumor group. No difference in PFS and OS was observed in the R-sided tumor group. A significant interaction according to primary tumor site and third-line regimen was observed for PFS (p= 0.05). RR was significantly higher in L-sided patients treated with anti-EGFR vs R/T (43% vs. 0%; p & lt;0.0001), no difference was observed in R-sided patients. At the multivariate analysis, third-line regimen was independently associated with PFS in L-sided patients. Conclusions Our results demonstrated a different benefit from third-line anti-EGFR-based therapy according to primary tumor site, confirming the role of L-sided tumor in predicting benefit from third-line anti-EGFR vs R/T. At the same time, no difference was observed in R-sided tumor.
    Type of Medium: Online Resource
    ISSN: 2234-943X
    URL: Article
    DOI: 10.3389/fonc.2023.1125013
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
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  • 7
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    Clinical, Pathological and Prognostic Features of Rare BRAF Mutations in Metastatic Colorectal Cancer (mCRC): A Bi-Institutional Retrospective Analysis (REBUS Study)
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 9 ( 2021-04-27), p. 2098-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 9 ( 2021-04-27), p. 2098-
    Abstract: Recently, retrospective analysis began to shed light on metastatic colorectal cancers (mCRCs) harboring rare BRAF non-V600 mutations, documenting a distinct phenotype and a favorable prognosis. This study aimed to confirm features and prognosis of rare BRAF non-V600 mCRCs compared to BRAF V600E and BRAF wild-type mCRCs treated at two Italian Institutions. Overall, 537 cases were retrospectively evaluated: 221 RAS/BRAF wild-type, 261 RAS mutated, 46 BRAF V600E and 9 BRAF non-V600. Compared to BRAF V600E mCRC, BRAF non-V600 mCRC were more frequently left-sided, had a lower tumor burden and displayed a lower grade and an MMR proficient/MSS status. In addition, non-V600 mCRC patients underwent more frequently to resection of metastases with radical intent. Median overall survival (mOS) was significantly longer in the non-V600 compared to the V600E group. At multivariate analysis, only age 〈 65 years and ECOG PS 0 were identified as independent predictors of better OS. BRAF V600E mCRCs showed a statistically significant worse mOS when compared to BRAF wild-type mCRCs, whereas no significant difference was observed between BRAF non-V600 and BRAF wild-type mCRCs. Our study corroborates available evidence concerning incidence, clinicopathologic characteristics and prognosis of BRAF-mutated mCRCs.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13092098
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 8
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    Efficacy of third-line anti-EGFR-based treatment (tx) versus (vs) Regorafenib/TAS-102 (R/T) according to primary tumor site in RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC) patients (pts).
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 4082-4082
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 4082-4082
    Abstract: 4082 Background: Right- (R) and left-sided (L) mCRCs exhibit different clinical and molecular features. Several retrospective analyses showed that the survival benefit of anti-EGFR-based tx is limited to RAS/BRAF wt L-sided mCRC pts, which a larger effect in the first-line setting. Few data are available concerning the anti-EGFR efficacy according to primary tumor site in third line. Methods: Pts affected by RAS/BRAF wt mCRC treated with third-line anti-EGFR-based tx or R/T were retrospectively collected. The objective of the analysis was to compare tx activity and efficacy according to tumor site. Primary endpoint was PFS; secondary endpoints were OS and RR. PFS and OS analyses were performed using Kaplan-Meier method, and survival curves were compared using the log-rank test. RR was evaluated according to RECIST criteria and it was compared in the two groups using Fisher’s exact test. Statistical significance was set at p = 0.05 for a bilateral test. Univariate and multivariate analyses for PFS and OS were performed. Results: A total of 76 RAS/BRAF wt mCRC pts, treated with third-line anti-EGFR-based tx or R/T, were enrolled. Of those, 19 (25%) pts had R-sided tumor (9 pts received anti-EGFR tx and 10 pts received R/T) and 57 (75%) pts had L-sided tumor (30 pts received anti-EGFR tx and 27 pts received R/T). As shown in the table, a significant PFS and OS benefit in favor of anti-EGFR tx vs R/T was observed in L-sided pts, while no difference both in PFS and OS was observed in R-sided pts. RR was significantly higher in L-sided pts treated with anti-EGFR vs R/T, no difference was shown in R-sided pts. At the multivariate analysis, tx regimen was indipendently associated with PFS in L-sided pts, but not in R-sided pts. Conclusions: Our study confirmed the results deriving from the retrospective analysis of the phase III study 20020408. Our results demonstrated a different benefit from third-line anti-EGFR tx according to primary tumor site, confirming the role of L-sided tumor in predicting benefit from third-line anti-EGFR vs R/T, while no difference was observed in R-sided tumors. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.4082
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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  • 9
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    Italian real world artificial intelligence (AI) based analysis of early-onset colorectal cancer: The ERCOLE study.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. e15539-e15539
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. e15539-e15539
    Abstract: e15539 Background: Early-onset colorectal cancer (EOCRC), defined as CRC diagnosed among individuals younger than 50 yrs, is becoming a public health issue, with rising incidence reported worldwide. In the US, EOCRC is the leading cause of cancer-related death among males aged 20-49 yrs and is second among female aged 40-49 yrs. Italy lacks a national cancer registry and available data regard mostly northern regions. Fondazione Policlinico Gemelli (FPG) Hospital is a national referral center for CRC (especially for middle and southern regions), ranking first for surgical procedures. Therefore, mining incidence rate at FPG Hospital contributes to provide a full picture of EOCRC incidence trend in Italy. Methods: The objective of this study was to assess the trends of EOCRC incidence at FPG along 15 yrs. Real world data collected from everyday clinical practice in the FPG Hospital Data Warehouse were extracted within the Gemelli GENERATOR framework. Study population was identified from records of pts from 2005 to 2019 matching two main inclusion criteria: pts hospitalized with a diagnosis of CRC (ICD-9 codes at discharge included in 153.* and 154. *, captured form structured data source); or pts with at least one pathology report of CRC (selected using clinically-validated text mining techniques from unstructured data source). Variables of interest, including demographics and surgical procedures, were extracted using SAS (SAS(R) Institute suite for ETL). Study population was stratified according to age (≤50yrs; 〉 50yrs), gender and tumor site. Primary endpoint was the annual percent change (APC). APC was estimated using the joint regression method with a maximum of 2 joint points allowed. Statistical analyses were conducted using R (v4.2.1). Results: 18606 consecutive single pts were included, of those 10.9% were EOCRC. From 2005 to 2019 a statistically significant APC increase for EOCRC was observed overall (9.2, CI 6.5-11.9, p 〈 .001) and regardless of gender (male: 8.0, CI 4.7-11.3, p 〈 .001; female: 10.1, CI 7.5-12.8, p 〈 .001). Splitting the timeframe, a major trend was observed between 2010 and 2013 (APC: 30.5, 34.4 and 27.5, respectively overall, in male and in female pts). Primary tumor location was available for 10690 (of those 9.3% were EOCRC). Analyzing primary tumor location, a trend toward increased and decreased APC for EOCRC was observed for R-sided (3.6, p .105) and L-sided (-2.0, p .312) tumors, respectively, while a statistically significant increase was observed for rectum (4.5, p .02), specifically between 2012 and 2019 (13.1, p .02). Conclusions: This AI-based real world analysis confirms a rising incidence for EOCRC in Italy. Data has solid external consistency. Further analyses on familial history, life styles and MMR status are planned. The appropriate threshold age to start the screening needs to be addressed.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.e15539
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 10
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    Clinical, pathological and prognostic features of rare BRAF mutations (MTs) in metastatic colorectal cancer (mCRC): A bi-institutional retrospective analysis (REBUS study).
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. 3554-3554
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 3554-3554
    Abstract: 3554 Background: Recently, 3 classes of BRAF MTs have been described. BRAF V600 MTs, which identify mCRC with poor prognosis and not benefitting from anti-EGFR drugs, belong to class 1. Class 2 and 3 include BRAF non-V600 MTs, which occur in about 1-2% mCRC and are associated to favourable prognosis and specific clinicopathologic features. Class 2 and 3 differ in kinase activity and sensitivity to anti-EGFR: class 2 are activated and RAS-independent MTs; class 3 are kinase-dead and sensitive to inhibition of This study aims to retrospectively evaluate features and prognostic role of rare BRAF non-V600 compared to BRAF V600E MTs in mCRC pts treated at 2 Italian Institutions. Methods: mCRC pts harboring BRAF MTs, assessed by means of NGS, pyrosequencing or RT-PCR, treated between Jan-13 and Dec-18 at 2 Italian Institutions, were retrospectively analyzed. Clinico-pathological and treatment characteristics and survival data were collected. Results: 55 pts bearing BRAF MTs were identified. Of those, 46 (84%) harbored a V600E and 9 (16%) a non-V600 MT. Within the non-V600 group, 3 MTs (K601E, G469A, G469R) belonged to class 2, while 5 MTs (G466E, G466A, 2 D594G, D594N), belonged to class 3. One pt harboured a T599I MT, whose kinase activity is unknown. Compared to BRAF V600E mCRC, BRAF non-V600 mCRC were more frequently left-sided ( p .017) and displayed a lower grade ( p .045). In addition, non-V600 mCRC pts had a lower tumor burden (involving one metastatic site) ( p .026) and underwent more frequently to resection of metastases with radical intent (77.7 vs 18%; p .000175). mOS was significantly longer in the non-V600 compared to the V600E group (61.3 vs 20.4 m; HR 0.41, 95%CI 0.18-0.93; p .05). No difference in activity and efficacy of anti-EGFR agents was observed between class 2 and 3. Conclusions: Despite the small size of our retrospective analysis, the results were consistent with previous evidences. BRAF non-V600 MTs identified a subgroup of mCRC, differing both in terms of clinicopathologic characteristics and prognosis from BRAF V600 mCRC. Interestingly, the better prognostic features allowed more frequently radical resection of metastases, positively impacting on survival.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.3554
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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