Single Metastatic Site Research Articles

Carcinoma colon masquerading as bleeding per vagina.

Isolated vaginal metastasis from colorectal cancer is a rare entity with very few reports in the literature. Here we report a patient who presented with bleeding per vagina from a vaginal mucosal lesion. Biopsy of the vaginal lesion indicated a metastatic adenocarcinoma from a colorectal primary. Further workup of the patient with colonoscopy and Positron emission tomography (PET CT) indicated a primary in the sigmoid colon. As the patient had a single site of metastasis, she was planned for definitive management. The colonic primary, as well as the vaginal deposit were managed surgically. Further, the patient received adjuvant chemotherapy as well as adjuvant external beam radiation to the site of the vaginal lesion. Vaginal metastases from colorectal primary are usually part of systemic dissemination with multiple metastatic sites and hence has poor prognosis. When the patient presents with an isolated metastasis in the vagina., the survival appears reasonable as per the few reports available in the literature. Due to the rarity of the presentation, there are no standard treatment guidelines available. Surgical management, radiation and adjuvant chemotherapy have been used in varying combinations in the reports available in the literature. To conclude, vaginal metastasis should be included in the differential diagnosis of patients presenting with vaginal bleeding, especially with a history of colorectal carcinoma. Available limited evidence suggests that isolated vaginal metastasis from colorectal cancer that is amenable to local surgical resection has a reasonable outcome. Hence, isolated vaginal metastasis should be treated with curative intent in a multidisciplinary context like other sites of oligometastatic disease.

The effect of adrenalectomy on overall survival in metastatic adrenocortical carcinoma.

Although complete surgical resection provides the only means of cure in adrenocortical carcinoma (ACC), the magnitude of the survival benefit of adrenalectomy in metastatic ACC (mACC) is unknown. To assess the effect of adrenalectomy on survival outcomes in patients with mACC in a real-world setting. Patients with mACC were identified within the Surveillance, Epidemiology, and End Results database (SEER 2004-2020) and we tested for differences according to adrenalectomy status. Patients aged ≥18 years with metastatic ACC at initial presentation who were treated between 2004-2020. Primary tumor resection status (Adrenalectomy vs no-adrenalectomy). Kaplan-Meier plots, multivariable Cox regression models and landmark analyses were used. Sensitivity analyses focused on use of systemic therapy, contemporary (2012-2020) vs. historical (2004-2011), single vs. multiple metastatic sites and assessable specific solitary metastatic sites (lung only and liver only). Of 543 patients with mACC, 194 (36%) underwent adrenalectomy. In multivariable analyses, adrenalectomy was associated with lower overall mortality without (hazard ratio [HR]: 0.39; p<0.001), as well as with three months' landmark analyses (HR: 0.57, p=0.002). The same association effect with three months' landmark analyses was recorded in patients exposed to systemic therapy (HR: 0.49, p<0.001), contemporary patients (HR: 0.57, p=0.004), historical patients (HR: 0.42 , p<0.001), and in those with lung only solitary metastasis (HR: 0.50, p=0.02). In contrast, no significant association was recorded in patients naïve to systemic therapy (HR: 0.68, p=0.3), those with multiple metastatic sites (HR: 0.55, p=0.07) and those with liver only solitary metastasis (HR: 0.98, p=0.9). The current results indicate a potential protective effect of adrenalectomy in mACC, particularly in patients exposed to systemic therapy and those with lung-only metastases.

Evolving patterns of metastatic spread, treatment, and outcome for patients with oligometastatic colorectal cancer

IntroductionThe assessment and management of oligometastatic colorectal cancer has evolved over the last two decades. We aimed to examine trends in the presentation, management and outcomes of patients presenting with liver-only disease, given recent changed standards for baseline imaging, and evolving definitions of resectability. Patients with lung-only disease can provide a contemporaneous control group. MethodsProspectively maintained data from the multi-site Treatment of Recurrent and Advanced Colorectal Cancer Registry were reviewed over three consecutive periods; 2009–2013, 2014–2018, and 2019–2023. Survival outcomes were determined by Kaplan-Meier method. ResultsOf 4613 patients with metastatic colorectal cancer, median age was 66 years (interquartile range 56–76), and 2356 (51 %) patients had a single metastatic site. Compared to the earlier periods, patients diagnosed in 2019–2023, were younger, had better ECOG scores and were more likely to have three or more metastatic sites. The proportion of patients with liver-only metastases decreased over the three consecutive periods, from 32.0 % (n = 462), to 27.0 % (n = 498) to 25.9 % (n = 33), p < 0.001, however the proportion of liver-only metastases patients undergoing resection increased from 41.5 to 59.3 %, p < 0.001. The incidence and resection rate of lung-only metastases was unchanged over time. ConclusionThe increasing number of metastatic sites and reduced number of patients with liver-only metastases is potentially explained by the increased use of FDG-PET imaging at baseline. The increased proportion of patients with liver-only disease undergoing resection may be explained by advancement in surgical techniques, improvements in systemic therapies and the evolving definition of resectable disease. SynopsisThe pattern and treatment of metastatic colorectal cancer has evolved over the last two decades. This study examines the trends in presentation management and outcomes of patients with metastatic colorectal cancer using a multi-site database.

Clinical characteristics, survival analysis and influencing factors of distant metastasis in patients with acromelanomas: A retrospective study.

The prognosis of acromelanomas (AM) is worse. The objective of this study was to investigate the clinical features of distant metastasis of AM and the factors affecting the survival and prognosis of patients. In this study, a retrospective study was conducted to select 154 AM patients admitted to Nanjing Pukou People's Hospital from January 2018 to April 2021 for clinical research. The clinical characteristics of distant metastasis were statistically analyzed, and the survival curve was drawn with 5-year follow-up outcomes. The median survival time of the patients was calculated, and the clinicopathological features and peripheral blood laboratory indexes of the surviving and dead patients were analyzed. Logistic regression model was used to analyze the risk factors affecting the prognosis of AM patients. In this study, 154 patients with AM were treated, including 88 males and 76 females, aged from 27 to 79 years old, with an average age of (59.3 ± 11.7) years old. Among them, 90 cases had distant metastasis. The main metastatic sites were lung (47.78%) and lymph nodes (42.22%). Among them, single site metastasis accounted for 41.11% and multiple site metastasis 58.89%. 89 cases survived and 65 cases died. The survival time was 22 months to 60 months, and the median survival time was 48.0 months. The Breslow thickness, stage at diagnosis, distant metastasis, site of metastasis and ulceration were compared between the survival group and the death group (P < .05). serum lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR) and lymphocyte monocyte ratio (LMR) were compared between the survival group and the death group (P < .05). The results of Logistic regression model showed that LDH ≥ 281 U/L, NLR ≥ 2.96, LMR ≤ 3.57, newly diagnosed stage > stage II, distant metastasis, multiple site metastasis and tumor ulcer were independent risk factors for poor prognosis of AM patients (P < .05). Patients with AM had a higher proportion of distant metastasis, mainly lung and lymph node metastasis. Increased LDH, increased NLR, decreased LMR, higher initial stage, distant metastasis, multiple site metastasis, and combined tumor ulcer were closely related to the poor prognosis of patients after surgery.

Correlation between metastatic site and immunotherapy efficacy in patients with advanced dMMR/MSI colorectal cancer: Real-World Italian multicentric retrospective study (Colon-MSI).

e15544 Background: Immune checkpoint inhibitors (ICIs) are the gold standard therapy in metastatic colorectal cancer (mCRC) patients (pts) with microsatellite instability (MSI). The Colon-MSI study aimed to describe a cohort of MSI mCRC pts treated with ICIs before Italian pembrolizumab approval and to evaluate the efficacy, safety, and possible predictive factors of response in a real-world setting. Methods: We retrospectively collected data of pts with MSI mCRC treated with ICIs before June 30, 2023, in 16 Italian Cancer Centers. The OS was calculated from the diagnosis of metastatic disease, and the PFS from the beginning of ICIs. We explored the correlation between clinicopathological factors, survival outcomes, and treatment response. Results: Between January 2021 and June 2023, we reported 83 consecutive pts with data available. Among all, the median age was 61 years (23-86), 42 (51%) were female, and 45 (54%) had a ECOG PS 0; 35 (42%) pts were at stage IV at diagnosis, and 61 (74%) had right colon tumor site. The most common metastatic sites were liver (35%), lymph nodes (43%), peritoneum (31%), and lung (15%); 48 (58%) pts had a single metastatic site. 33 (39%) pts had a mucinous adenocarcinoma, 32 (39%) BRAF mutated, 32 (39%) RAS mutated, and 26% presented a Lynch syndrome. The majority of pts (69%) were pre-treated, and 26 pts (31%) received ICIs in first line. Nivolumab alone or plus Ipilimumab, and Pembrolizumab, were administered in 23 (28%), 3 (4%), and 57 (68%) pts, respectively. The median follow-up was 23 (1-65) months (m) and the median duration of treatment was 23 m (0-65) with 27 pts still ongoing. Treatment-related severe toxicities (G3 or G4) were observed only in 5.6% of pts. The median OS and PFS were not reached; the mean OS was 45.6 m (IC 95% 39.6-51.6) and the mean PFS was 38.8 m (IC 95% 32.5-45.1). Complete response (CR) was observed in 20 pts (24%), partial response (PR) in 28 (34%), stable disease (SD) in 19 (23%) and progression disease (PD) in 16 (19%). Overall response (ORR) was observed in 48 pts (57.8%; 95 %IC 0.31- 0.53), and disease control rate in 67 pts (80.7%; 95% IC 0.11– 0.29). Lung metastatic site was associated with poorer outcome in terms of OS (p = 0.001, HR 3.88 IC 95% 1.7-8.9), PFS (p = 0.045 HR = 2.31 IC95% 1-5.2), and ORR (p = 0.015 OR = 6.19 IC95% 1.4-26.9). Significantly worse PFS was also observed in pts with liver metastasis (p = 0.009 HR = 2.5 IC 95% 1.3-4.9). Conclusions: Our data confirm that ICIs are effective and well-tolerated treatment in MSI mCRC pts, with long-term clinical outcomes reported. These results suggest an unfavorable correlation between lung and liver metastasis and the ICI response. Further biomolecular analysis will be provided in the future.

Single organ metastatic sites in non-small cell lung cancer: Patient characteristics, treatment patterns and outcomes from a large retrospective Canadian cohort

BackgroundThere is a paucity of information about the characteristics, treatment patterns, and outcomes of non-small cell lung cancer (NSCLC) patients with single organ metastasis (SOM). MethodsThis retrospective cohort study includes all patients with a diagnosis of stage IV NSCLC diagnosed from 2014 to 2016 and treated at Princess Margaret Cancer Centre. We compared baseline characteristics and patterns of metastatic sites between patients with SOM versus multiple (M)OM. Additionally, we identified treatment modalities and outcomes for patients with SOM. Cox multivariable models (MVA) were utilized to evaluate differences in overall survival (OS) between the SOM and MOM cohorts. ResultsOf 893 pts analyzed, 457 (51 %) had SOM, while 436 (49 %) had MOM at initial diagnosis. Demographics were comparable between the two groups. Brain was the most common site of metastasis for SOM patients. When compared to the MOM group, the SOM group had lower percentages of liver and adrenal metastases. Amongst SOM patients, 54 % received single modality treatment, and 20 % did not receive any treatment for their SOM. In MVA, patients with liver (HR 2.4), bone (HR 1.8), and pleural (HR 1.7) metastasis as their SOM site had the worst outcomes, with median OS of 6.8 months, 12.1 months, and 13.0 months respectively. Patients with SOM had a significantly improved median OS compared to those with MOM (15.9 months vs. 10.6 months; HR 0.56, 95 % CI 0.47–0.66, p < 0.001). ConclusionIn NSCLC patients who presented with SOM, survival correlated with the initial organ involved and was better overall compared to patients with MOM. SOM NSCLC may benefit from specific management strategies and SOM patients could be considered as a specific subgroup for survival analyses in observational and non-randomized interventional studies. In clinical trials, SOM can be considered as a stratification factor in the future.

Metastatic pattern and prognosis in patients with lung adenosquamous carcinoma: A surveillance, epidemiology, and end results-based population study

BackgroundLung adenosquamous carcinoma (ASC) is a rare tumor with high invasive and metastatic potential. Few studies have explored metastatic patterns in patients with advanced-stage ASC. MethodsPatients diagnosed with ASC in the Surveillance, Epidemiology, and End Results database from 2010 to 2015 were selected. Descriptive statistics were obtained to characterize the metastatic sites of the study participants. The Kaplan–Meier method was applied to compare survival curves among patients with different metastatic patterns. Cox regression analysis was performed to evaluate risk factors for metastasis. ResultsA total of 858 eligible patients with ASC were enrolled; the mean age was 71.5 years (standard deviation ± 7.8 years). There was a slightly higher proportion of male patients (54.0 %). A total of 63.2 % of patients harbored single-site metastasis (median OS: 5 months), 23.6 % of patients had two-site metastasis (median OS: 4 months), and approximately 10 % of patients harbored three or more sites metastasis (median OS: 3 months). Bone (56.9 %) was the most frequent site of metastasis (median OS: 4 months), followed by lung metastasis (37.6 %, median OS: 5 months), liver metastasis (22.1 %, median OS: 5 months), and brain metastasis (21.4 %, median OS: 4 months). Chemotherapy decreased the risk of death by 70 % (HR = 0.296, 95 % CI 0.241–0.363), 70 % (HR = 0.302, 95 % CI 0.224–0.406), 78 % (HR = 0.218, 95 % CI 0.151–0.314), and 70 % (HR = 0.302, 95 % CI 0.231–0.396) in patients harboring bone, liver, brain and lung metastases, respectively. The brain increased the risk of death by 50 % (HR = 1.501, 95 % CI 1.209–1.865), 64 % (HR = 1.644, 95 % CI 1.126–2.402), and 128 % (HR = 2.284, 95 % CI 1.653–3.157) in patients harboring bone, liver and lung metastases, respectively. ConclusionPatients with advanced-stage ASC have unfavorable outcomes. Early detection and aggressive treatment can improve patients outcomes.

Patterns of initial distant metastases in 151 patients undergoing surveillance for treated Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is associated with high rates of recurrence and distant metastatic progression. Current guidelines for surveillance imaging are not evidence based. Better characterization of the pattern of distant metastatic spread will better inform surveillance and facilitate earlier detection of metastases. This retrospective study aimed to assess potential relationships between primary tumour site and site of initial distant metastasis, time to distant metastasis, overall survival (OS) and MCC-specific death (MSD). Patients with local or regional (Stage I-III) disease who were treated with curative intent and progressed to Stage IV were included in this study (n = 151). Fisher's exact test was used to assess differences in patterns of initial distant metastases based on primary tumour site. Time to initial distant metastasis was calculated from date of MCC diagnosis. OS and MSD were calculated from date of initial distant metastasis to date of death from any or MCC-related causes, respectively. Of 151 patients included in analysis, 89 (58.9%) had a single initial distant metastatic site, and 62 (41.1%) had multiple sites. Patients with upper limb primary tumours were significantly less likely to develop distant lymph node or liver metastases (p = 0.02 and 0.04, respectively). Median time to distant metastasis was 11 months (IQR 6.7-17.9 months). Median OS was 15.3 months, and was shorter for patients with liver (7.0 months, p = 0.0004) or bone metastases (8.9 months, p < 0.0001). Using skin/soft tissue metastasis as a reference group, patients with multiple metastatic sites had significantly higher hazards of MSD (HR = 3.46 univariate, 3.77 multivariate analysis). Time to distant metastasis, OS and MSD did not differ by viral status. Sites of initial distant metastasis are related to primary tumour sites and survival outcomes. Because patients often have multiple initial metastases, full-body cross-sectional rather than region-specific imaging may facilitate earlier detection of metastatic disease.

Risk-adapted locoregional radiotherapy strategies based on a prognostic nomogram for de novo metastatic nasopharyngeal carcinoma patients treated with chemoimmunotherapy

To develop a prognostic nomogram for individualized strategies on locoregional radiation therapy (LRRT) in patients with de novo metastatic nasopharyngeal carcinoma (dmNPC) treated with chemoimmunotherapy. Ninety patients with dmNPC treated with chemoimmunotherapy and diagnosed between 2019 and 2022 were included in our study. Cox regression analysis was performed to identify independent prognostic factors for overall survival (OS) and progression-free survival (PFS) to establish a nomogram. With a median follow-up of 17.5 months, the median PFS and OS were 24.9 months and 29.4 months, respectively. Sixty-nine patients and twenty-one patients were included in the LRRT group and without LRRT group, respectively. Multivariate analysis revealed that younger age, lower EBV DNA copy number before treatment, a single metastatic site, more cycles of chemotherapy and immunotherapy were significantly associated with better OS. A prognostic nomogram was constructed incorporating the above 5 independent factors, with a C-index of 0.894. Patients were divided into low- and high-risk cohorts based on nomogram scores. A significant improvement in OS was revealed in the LRRT group compared with the without-LRRT group for patients in the high-risk cohort (HR = 2.46, 95% CI 1.01–6.00, P = 0.049), while the OS was comparable between the two groups in the low-risk cohort. Our study indicates that LRRT may be associated with better prognosis in high-risk patients with dmNPC in the era of immunotherapy.

Impact of Metastatic Site in Favorable-Risk Renal Cell Carcinoma Receiving Sunitinib or Pazopanib

BackgroundAlthough in metastatic renal cell carcinoma (mRCC) patients with intermediate and poor risk the benefit of combination strategies versus tyrosine kinase inhibitor (TKI) has been ascertained, in those with favorable risk data are ambiguous. Herein, we investigated the impact of number and type of metastatic site in patients with favorable risk to contribute to the best therapeutic choice. Material and MethodsMulticenter data regarding patients with favorable risk mRCC carcinoma receiving first-line TKIs, sunitinib or pazopanib, were retrospectively collected. We divided our population into 2 groups based on the number of metastatic sites and analyzed its impact on tumor response and efficacy outcome. The Kaplan-Meier method was used to estimate efficacy outcomes and the log-rank test to examine differences between subgroups. ResultsA total of 107 patients with a median age of 69 years were included in the final analysis. Patients with 1 metastatic site, compared with patients with > 1 site, had a significantly longer overall survival (OS) (not reached vs. 66 months) and a trend, although not statistically significant, of better progression-free survival (PFS) (31 vs. 17 months). In patients with 1 metastatic site, liver involvement was correlated with worse PFS and OS at the univariate analysis (P = .01) and was confirmed as independent poor prognostic factor for PFS at multivariate analysis. ConclusionIn conclusion, we reported a longer OS in favorable risk mRCC patients receiving TKI with only 1 metastatic site. Nevertheless, in patients with a single metastatic site, hepatic involvement correlated with worse PFS compared to other metastatic sites.

Construction and validation of a novel prognostic nomogram for predicting overall survival in lung adenocarcinoma patients with different patterns of metastasis

ObjectiveMetastasis of lung cancer is an important factor affecting survival. The present study proposed to establish and verify a nomogram for predicting overall survival (OS) in lung adenocarcinoma (LUAD) patients with different patterns of metastasis.MethodsA total of 9727 patients diagnosed with metastatic LUAD patients from 2010 to 2015 were enrolled based on surveillance, epidemiology and end results (SEER) Database and then randomly divided into training and validation cohorts, and 136 patients in our Cancer Center were enrolled as the external validation cohort. Univariate and multivariate analyses were performed to evaluate the prognostic impact on OS. A prognostic nomogram was constructed and evaluated by C-index, calibration curve, decision curve analysis (DCA), and risk stratification system.ResultsUltimately, 6809 and 2918 patients diagnosed with metastatic LUAD in the training and validation cohorts were enrolled in the study, respectively. A male sex, a later T and N stage, a larger tumor size, treatment including no surgery, no chemotherapy and no radiotherapy, metastasis sites were found to be independent risk factors in LUAD patients for worse OS, and then incorporated into the nomogram. The frequency of bone metastasis was the highest, and in single site metastasis, the prognosis of liver metastasis was the worst. Two-site metastasis is more common than three-site and four-site metastasis, and co-metastasis eventually leads to a worse survival outcome. The C-index value of nomogram for predicting OS were 0.798, 0.703 and 0.698 in the internal training, validation and external validation cohorts, separately. The calibration curves for the 6-months, 1-year and 2-year showed significant agreement between nomogram models and actual observations. The DCA curves indicated nomogram was more beneficial than the AJCC TNM stage. Patients were further divided into low-risk and high-risk groups according to nomogram predicted scores and developed a survival risk classification system.ConclusionsOur prognostic nomogram is expected to be an accurate and individualized clinical predictive tool for predicting OS in LUAD patients with different patterns of metastasis.

The Impact of Metastasis Histopathology on Oncologic Outcomes for Patients with Surgically Resected Metastatic Renal Cell Carcinoma.

Multiple prognostic models exist to assess survival among patients with metastatic clear cell renal cell carcinoma (m-ccRCC). However, the relative contribution of histopathologic features of the metastasis has not been extensively studied. Herein, we compared models using clinical, primary tumor, and metastatic features to predict cancer-specific survival (CSS) for patients with surgically resected m-ccRCC. We studied 266 patients who had undergone nephrectomy between 1970 and 2019 and who had a single site of metastasis completely resected. Two versions of the m-ccRCC score published by Leibovich et al were calculated: using grade and necrosis from the primary tumor and using grade and necrosis from the metastasis. Predictive abilities of these 2 versions and a third model that included metastatic features only were compared using c-indexes from Cox proportional hazards models. A total of 197 patients died from RCC at a median of 2.3 years (IQR 1.1-4.5); median follow-up among survivors was 13.2 years (IQR 10.0-14.5). The Leibovich score using grade and necrosis from the metastasis (c=0.679) had similar predictive ability compared to the original Leibovich score using grade and necrosis from the primary tumor (c=0.675). A third model (c=0.707) demonstrated that metastasectomy within 2 years after nephrectomy, presence of bone metastasis, high grade, and sarcomatoid differentiation in the metastasis were significantly associated with CSS. Scoring algorithms calculated using histopathologic features of the metastasis can be used to predict CSS for patients with surgically resected m-ccRCC. These findings are of particular importance for instances when primary tumor histopathology is not readily available.

Site of metastasis (SoM) and its impact on clinical outcomes in 8 cancer cohorts.

6590 Background: The prognosis of metastatic cancer is in general poor. This can be affected by several factors including age, histology, treatment choices &amp; SoM etc. Methods: This retrospective study leverages ConcertAI’s deeply curated Patient360 datasets for 8 solid cancers to assess the impact of SoM on the outcomes of patients. For the purpose of this analysis, we focused on the most common SoM (bone, brain, lung &amp; liver). Patients had either a Single SoM (SSM) or Multiple SoM (MSM) and we focused this analysis on patients with SSM. The overall survival (OS) &amp; progression free survival (PFS) from the date of metastasis as well as the time to metastasis (TTM) from initial diagnosis were determined for each cohort. We also computed a consolidated OS &amp; PFS for all patients with MSM. Results: 140K patients were included in this study of which 60K patients had a SoM. The distribution of SoM is dependent on the primary cancer type. For example, in breast &amp; prostate cancer, bone metastasis accounts for 50-80 % of the metastatic cohort whereas it is only 8-21% in lung &amp; melanoma. As expected, the overall values of OS/PFS were primarily governed by the primary cancer type (Table), but this analysis provides further interesting insights: 1. Within a cohort, there were significant differences in the prognosis of patients based on the SoM . Brain &amp; liver had a poorer prognosis compared to the other SoM across most cohorts. 2. The relative prognosis for some SoM were dependant on the primary cancer type. For example, there was a very significant difference between the OS/PFS values in the breast cancer cohort when comparing brain vs bone as SoM. However, in the lung cancer cohort, this difference was less pronounced, and the trend was flipped. 3. For some cohorts the SSM for certain sites had a worse prognosis than the MSM. In breast cancer the OS of the brain &amp; liver SoM was worse than the MSM. 4. The TTM is also dependent on the primary cancer and there is a correlation between the average TTM and the OS of the cohort. Conclusions: The patterns of cancer metastasis and the absolute and relative prognosis for a particular SoM is dependent on the primary cancer type. Such insights from a large real-world data study can impact clinical decisions regarding the aggressiveness of treatment based on the primary cancer type as well as the metastatic site. [Table: see text]

Management of Early-onset Metastatic Colorectal Cancer (ERMIONE): A single institution analysis.

3593 Background: Despite rising incidence and mortality reported worldwide for CRC diagnosed in pts aged &lt; 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 &lt; .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.

Efficacy of immunotherapy in MSI metastatic colorectal cancer patients: A Real-World Italian multicentric retrospective study (Colon-MSI Study).

e15595 Background: The treatment with Immune checkpoint inhibitors (ICIs) is the gold standard therapy in metastatic colorectal cancer (mCRC) patients (pts) with microsatellite instability (MSI). The aim of the study was to describe a cohort of MSI mCRC pts treated with ICIs, before pembrolizumab approval, to evaluate efficacy and toxicity in a real-world setting and to identify possible predictive factors of response. Methods: We retrospectively collected data of pts with MSI mCRC treated with ICIs (anti-PD1 or anti-CTLA-4 antibodies, or in combination) before June 30, 2021, in 14 Italian Cancer Centers. The OS was calculated from the diagnosis of metastatic disease, and the PFS from the beginning of ICIs. Survival analyses were stratified between treatment naïve and pre-treated pts. We explored the correlation between clinicopathological factors and refractory pts who underwent progression disease (PD) within 3 months from the start of ICI. Results: In this preliminary analysis, we reported 60 consecutive pts with data available. Among all, 30 (50%) were male, 37 (62%) with ECOG PS 0-1; 21 (35%) were at stage IV, and 37 (62%) had right colon tumor site. The most common metastatic sites were lymph nodes, liver, and peritoneum, and 34 (57%) pts had a single metastatic site. 23 (38%) pts had a mucinous adenocarcinoma, and 20 (33%) were BRAF mutated. Nivolumab, Pembrolizumab, and Ipilimumab plus Nivolumab were administered in 24 (40%), 34 (57%), and 2 (3%) pts, respectively, and as first-line therapy in 13 (22%) pts. The median duration of treatment was 22 months (0-43), with 21 pts still ongoing. 13 (22%) pts were refractory to ICIs, and only 4 (7%) pts discontinued treatment for G3-G4 adverse events. The OS, PFS and DCR were different between treatment naïve and pre-treated pts with a positive trend (not statistically significant) toward untreated pts (Table 1). Male gender (p = 0.03), stage IV (p = 0.04), and ≥ 2 metastatic sites (p = 0.01) were significantly associated with refractory ICIs pts, but none of these factors was correlated with poor outcomes in multivariate analysis. Conclusions: Our preliminary data confirm that immunotherapy is an effective and well-tolerated treatment in MSI mCRC pts, with long-term clinical outcomes reported. These results suggest better outcomes when ICIs are administered in the first-line setting. Further analysis will be provided after the completion of the accrual. [Table: see text]

Dynamics of disease progression during treatment with Osimertinib in patients with EGFR T790M-positive non-small cell lung cancer.

Patterns of treatment failure and subsequent treatment in non-small cell lung cancer (NSCLC) patients treated with osimertinib are scarcely known. We analyzed the disease progression during osimertinib treatment to identify potential treatment strategies. We identified advanced NSCLC patients who commenced osimertinib treatment after progression on previous epidermal growth factor receptor (EGFR)-tyrosine-kinase inhibitor (TKI) from June 2014 to November 2018 from electronic records. Patients' tumor characteristics, efficacy outcomes, affected organs from radiology studies, and treatment modalities before and after osimertinib were analyzed. Eighty-four patients were included. At osimertinib initiation, bone (50.0%) and brain (41.9%) were the commonest single metastatic sites, whereas thoracic involvement (73.3%) was more frequent than bone (27.4%) or brain (20.2%) metastasis during disease progression on osimertinib. Oligo-progressive disease (PD) and central nervous system (CNS)-sanctuary PD were observed in 15 (17.9%) and 3 (3.6%) patients, respectively. Most patients without brain metastasis (BM) at osimertinib initiation remained BM-free (46/49, 93.9%), and 60% of patients (21/35) with pre-existing BM showed intracranial disease control despite extracranial PD. The resistance mechanisms to osimertinib were explored in 23 patients (27.4%), and T790M-loss was observed in 14 patients (60.9%) who had worse survival outcomes than those without T790M-loss (progression-free survival, 5.4 vs. 16.5 months, p = 0.02; overall survival, not reached, p = 0.03). PD during osimertinib treatment occurred preferentially in the thorax and pre-existing sites. Extracranial PD prevailed over intracranial PD regardless of baseline BM and prior brain radiation. These results support osimertinib's intracranial efficacy and may guide treatment strategies for EGFR-mutated NSCLC with BM.

Metastasis pattern and prognosis in children with neuroblastoma

BackgroundWe aimed to investigate the different metastases and prognoses of neuroblastoma (NB) and determine the risk factors of metastasis.MethodData of 1224 patients with NB were obtained from the Surveillance, Epidemiology and End Results database (2010–2018). Pearson’s chi-square test, Kaplan–Meier analysis, multivariable logistic regression and Cox regression analysis were used to determine the factors associated with prognosis.ResultsThe overall incidence of NB was an age-adjusted rate of 8.2 patients per 1,000,000 children. In total, 1224 patients were included in our study, with 599 patients (48.9%) exhibiting distant metastases. Compared to patients with non-metastatic NB, a greater proportion of patients with metastatic NB were under 1 year, male, had an adrenal primary site, unilateral tumour, a tumour size > 10 cm, neuroblastoma-not otherwise specified (NB-NOS), second malignant neoplasms and were more likely to choose radiotherapy and chemotherapy. Multivariate Cox regression showed that metastasis was an independent risk factor for overall survival (OS) and cancer-specific survival (CSS). The survival rate of non-metastatic patients with NB was better than those with metastasis (OS: hazard ratio (HR): 0.248, P < 0.001; CSS: HR: 0.267, P < 0.001). The bone and liver were the two most common isolated metastatic sites in NB. However, no statistical difference was observed in OS and CSS between the only bone metastasis group, only liver metastasis group and bone metastasis combined with liver metastasis group (all P > 0.05). Additionally, age at diagnosis > 1 year (odds ratio (OR): 3.295, P < 0 .001), grades III–IV (OR: 26.228, P < 0 .001) and 5–10 cm tumours (OR: 1.781, P < 0 .001) increased the risk of bone metastasis of NB. Moreover, no surgical treatment (OR: 2.441, P < 0 .001) increased the risk of liver metastasis of NB.ConclusionMetastatic NB has unique clinicopathological features, with the bone and liver as the most common single metastatic sites of NB. Therefore, more aggressive treatment is recommended for high-risk children with NB displaying distant metastases.

Rhabdomyosarcoma with isolated lung metastases: A report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group.

To determine outcomes of children with rhabdomyosarcoma (RMS) with isolated lung metastases. Data were analyzed for 428 patients with metastatic RMS treated on COG protocols. Categorical variables were compared using Chi-square or Fisher's exact tests. Event-free survival (EFS) and overall survival (OS) were estimated using Kaplan-Meier method and compared using the log-rank test. Compared with patients with other metastatic sites (n=373), patients with lung-only metastases (n=55) were more likely to be <10 years of age, have embryonal histology (embryonal rhabdomyosarcoma), have N0 disease, and less likely to have primary extremity tumors. Lung-only patients had significantly better survival outcomes than patients with all other sites of metastatic disease (p<.0001) with 5-year EFS of 48.1 versus 18.8% and 5-year OS of 64.1 versus 26.9%. Patients with lung-only metastases, and those with a single extrapulmonary site of metastasis, had better survival compared with patients with two or more sites of metastatic disease (p<.0001). In patients with ERMS and lung-only metastases, there was no significant difference in survival between patients ≥10 years and 1-9 years (5-year EFS: 58.3 vs. 68.2%, 5-year OS: 66.7 vs. 67.7%). With aggressive treatment, patients with ERMS and lung-only metastatic disease have superior EFS and OS compared with patients with other sites of metastatic disease, even when older than 10 years of age. Consideration should be given to including patients ≥10 years with ERMS and lung-only metastases in the same group as those <10 years in future risk stratification algorithms.

Abstract P4-02-05: Predictors of long-term durable response in de novo HER2 positive metastatic breast cancer and the real world treatment experience at two institutions

Abstract Purpose Modern HER2-directed therapies enable some patients with de novo HER2+ metastatic breast cancer (MBC) to achieve long-term, durable responses (DR), which can be defined as no progression of disease since initial diagnosis. Clinical and pathologic factors that predict DR continue to be elucidated. Expert opinion dictates indefinite HER2-directed therapies for patients who achieve DRs, but real-world examples of this practice are lacking in the literature. Methods This is a retrospective study of all patients with de novo HER2+ MBC at two major academic institutions who received at least one dose of trastuzumab between 2012-2019. DR is defined as absence of progression/death at any point after diagnosis. Controls are patients with evidence of progression/death. Age, ER/PR status, sites of metastasis, surgical resection of primary tumor and initial treatment were analyzed as predictors of DR using an unpaired T test, with p&amp;lt; 0.05 chosen as threshold for significance. For patients with DR, time to complete (CR) and partial response (PR) according to RECIST 1.1 were recorded, as was the duration and treatment patterns surrounding trastuzumab and pertuzumab. Patients were defined as having cardiotoxicity if they experienced a decline in cardiac ejection fraction at any point while on trastuzumab therapy leading to treatment delays or discontinuation. Results 96 patients with de novo HER2+ MBC, 28 with DR and 68 with progression, were identified. The average follow up of patients with DR was 90 months (range 27-224), compared to 58 months (range 1-208) in controls. The entire cohort of 96 patients had a median PFS of 23.5 months and a median OS of 88 months. Among the 28 patients with DR, 2 achieved stable disease, 10 patients had documented PR at 4 months on average (range 2-6 months), and 26 patients had CR at 7.7 months on average (range 2-19 months). Among patients with DR, nine patients have been receiving trastuzumab for over ten years with no evidence of disease and one patient opted to discontinue trastuzumab. 75% of patients with DR had a single metastatic site, compared with 47% of patients with progression (OR 3.7, p=0.01). 64% of patients with DR received a regimen containing trastuzumab, pertuzumab, and a taxane, while 28% of patients who progressed did (OR 4.5, p&amp;lt; 0.001). 57% of patients with DR underwent surgical removal of breast primary, compared with 24% of patients who progressed (OR 4.3, p=0.002.) Age, and ER/PR status did not predict DR. (Table 1) Six patients (6.3%) developed reduced ejection fraction requiring treatment interruption or cessation, five in the group who progressed, one in the DR group. Conclusion Nearly a third of patients with de novo HER2+ MBC achieved DR. Factors that correlate with DR include single metastatic site, initial trastuzumab, pertuzumab and taxane therapy, and surgical resection of primary tumor. This suggests that in selected patients, a more aggressive up front approach including surgical resection, and agents such as carboplatin, and trastuzumab deruxtecan deserves further study. Among patients with DR, indefinite trastuzumab administration is the norm with minimal cardiotoxicity but the impact of this on quality of life and financial toxicity are not well described. Table 1: Clinical characteristics of de novo HER2 positive metastatic breast cancer that predict durable response Citation Format: Claire E. Smith, Paul K. Marcom, Mitri Zahi, Naomi Ko. Predictors of long-term durable response in de novo HER2 positive metastatic breast cancer and the real world treatment experience at two institutions [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-02-05.

Prognostic Impact of Metastatic Site in Patients Receiving First-Line Sorafenib Therapy for Advanced Hepatocellular Carcinoma.

Extrahepatic spread is a well-known negative prognostic factor in patients with advanced hepatocellular carcinoma (HCC). The prognostic role of different metastatic sites and their response rate to systemic treatment is still being debated. We considered 237 metastatic HCC patients treated with sorafenib as first-line therapy in five different Italian centers from 2010 to 2020. The most common metastatic sites were lymph nodes, lungs, bone and adrenal glands. In survival analysis, the presence of dissemination to lymph nodes (OS 7.1 vs. 10.2 months; p = 0.007) and lungs (OS 5.9 vs. 10.2 months; p < 0.001) were significantly related to worse survival rates compared with all other sites. In the subgroup analysis of patients with only a single metastatic site, this prognostic effect remained statistically significant. Palliative radiation therapy on bone metastases significantly prolonged survival in this cohort of patients (OS 19.4 vs. 6.5 months; p < 0.001). Furthermore, patients with lymph node and lung metastases had worse disease control rates (39.4% and 30.5%, respectively) and shorter radiological progression-free survival (3.4 and 3.1 months, respectively). In conclusion, some sites of an extrahepatic spread of HCC have a prognostic impact on survival in patients treated with sorafenib; in particular, lymph nodes and lung metastases have worse prognosis and treatment response rate.