Inoperable stage IV colorectal cancer with intact primary tumor in patients receiving palliative chemotherapy: Does the response to chemotherapy correlate between primary and metastatic sites? An Irish cancer center experience.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 136-136
Author(s):  
Ruba Hamed ◽  
Ronan Andrew McLaughlin ◽  
Hatim Ibrahim ◽  
Greg Korpanty ◽  
Nemer Osman
Keyword(s):  
Stable Disease ◽  
Primary Tumour ◽  
Stage Iv ◽  
Primary Site ◽  
First Line ◽  
Tumour Site ◽  
Response To Chemotherapy ◽  
Stage 4 ◽  
Metastatic Sites ◽  
Line Chemotherapy

136 Background: Colorectal cancer (CRC) is the 3rd most common malignancy in Ireland with over 2700 cases annually. Approximately 20% are diagnosed with stage IV disease. The aim of this study is to evaluate the response to chemotherapy at primary and metastatic sites and review the frequency of intervention required to palliate the intact primary tumour in patients with stage 4 inoperable CRC in an Irish tertiary referral centre. Methods: A retrospective review of medical records was completed, identifying stage 4 CRC patients with primary tumour in situ diagnosed between January 2014 and December 2019, treated with chemotherapy (oxaliplatin or irinotecan based +/- bevacizumab or EGFR monoclonal antibody). Data and survival analysis were obtained using Kaplan-Meier methods. Results: 50 eligible patients were identified; 60% male, 40% female with a median age of 62 years. 2% had a transverse colonic primary, 32% right and 44% left sided and 22% had a rectal primary. 36% presented with liver metastasis only, 4% lung metastasis alone and 20% both. 48% were KRAS, 4% NRAS and 4% BRAF mutation positive while 1 patient was identified as having microsatellite instability. All patient received first-line chemotherapy either oxaliplatin or irinotecan based, 18% with the addition of Bevacizumab and 24% with EGFR monoclonal antibody. Overall response to first-line chemotherapy at the primary site and metastatic sites was assessed radiologically; 42% displaying a partial response, 36% had stable disease while 18% had progression at primary site. At the metastatic sites 50% responded, 10% stable disease and 40% progressed. Complication at primary tumour site included: obstruction 12%, with perforation in 6%, bleeding 10%, pain at tumour site in 6%, and one patient developed an abscess. Overall, after chemotherapy 76% of all patients did not require further intervention to manage primary site. 6% underwent curative surgery with resection of primary and metastatic lesions. Of those who had palliative intervention; 10% underwent palliative colostomy/ileostomy, 12% palliative radiotherapy, and 2% both. Overall survival was 14 months. At time of analysis 14% were alive, 10% receiving treatment and 4% on radiological surveillance. Conclusions: This retrospective study confirms that palliative chemotherapy +/- targeted therapy is effective in controlling the primary tumour in stage 4 inoperable CRC. In addition, it reveals a nearly 80% partial response or stable disease radiologically at the primary site after first-line chemotherapy. Furthermore, progression was significantly lower at primary site compared to distant metastasis (18% vs 40%). Almost 75% did not require palliative intervention for their primary tumour. Overall survival in our centre is higher compared to internationally observed data.

Pan-cancer evaluation of homologous repair deficiency somatic mutations and response to first-line anti-neoplastic therapy.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10535-10535
Author(s):  
Jessica A Lavery ◽  
Samantha Brown ◽  
Gregory J. Riely ◽  
Philippe L. Bedard ◽  
Ben Ho Park ◽  
...  
Keyword(s):  
Somatic Mutations ◽  
De Novo ◽  
Stage Iv ◽  
Progression Free Survival ◽  
First Line ◽  
Major Mechanism ◽  
First Line Therapy ◽  
Oncogenic Mutation ◽  
Line Therapy ◽  
Response To Chemotherapy

10535 Background: Homologous recombination is a major mechanism of defective DNA repair, but it remains uncertain whether homologous repair deficient (HRD) tumors have favorable prognosis or are more/less likely to respond to treatment than tumors lacking such mutations. Objective: To determine whether lung (NSCLC) and colorectal (CRC) HRD+ tumors have better survival or response to chemotherapy than HRD- tumors. Methods: Patients with de novo stage IV NSCLC or CRC who had next generation sequencing (NGS) between 2015-2018 from one of four cancer centers were identified. Records were curated using the PRISSMM framework to ascertain treatment, overall survival (OS) and progression free survival based on imaging (PFS-I) and oncologists’ notes (PFS-M). Each NSCLC or CRC tumor was categorized as HRD+ if NGS revealed an oncogenic/likely oncogenic mutation in: ATM, BAP1, BARD1, BLM, BRCA1, BRCA2, BRIP1, CHEK2, FAM175A, FANCA, FANCC, NBN, PALB2, RAD50, RAD51, RAD51C, RTEL1, or MRE11A based on the OncoKB database. The tumor was categorized as HRD- if no oncogenic mutation in any of these genes was evident and HRD indeterminate (HRD?) if no mutation was identified but the panel did not include all genes. OS, PFS-I and PFS-M from start of first line therapy were reported by HRD status. The percentage with a good response to first line therapy (≥2x the median) and exceptional response (≥3x the median) was estimated for each endpoint. Results: For NSCLC 4% were HRD+, 59% HRD- and 37% HRD?. For CRC there were 5% HRD+, 60% HRD- and 35% HRD?. There were no significant differences for any survival endpoint between patients who were HRD+ vs HRD- in univariable analyses. The proportion of good and exceptional responders to first line systemic chemotherapy also did not vary by HRD status, though patients with HRD+ CRC were potentially more likely to be exceptional responders. Similarly, no differences between HRD+ and HRD- tumors were apparent for the subgroup receiving platinum containing therapy. Conclusions: NSCLC and CRC patients with somatic mutations in HRD oncogenic genes did not differ from patients lacking such a mutation with respect to OS or PFS. CRC patients with HRD+ tumors may be more likely to be exceptional responders, but sample sizes are limited. By May, the analysis will include breast and pancreatic cancer cases.[Table: see text]

Combination of mitotane and locoregional treatments in low-volume metastatic adrenocortical carcinoma

2021 ◽  
Author(s):  
Alice Boileve ◽  
Elise Mathy ◽  
Charles Roux ◽  
Matthieu Faron ◽  
Julien Hadoux ◽  
...  
Keyword(s):  
Adrenocortical Carcinoma ◽  
Stage Iv ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Complete Response ◽  
Tumor Burden ◽  
Interquartile Range ◽  
First Line ◽  
Chemotherapy Administration ◽  
Metastatic Sites

Abstract Purpose European and French guidelines for ENSAT stage IV low tumor burden or indolent adrenocortical carcinoma (ACC) recommend combination of mitotane and locoregional treatments (LRT) in first-line. Nevertheless, the benefit of LRT combination with mitotane has never been evaluated in this selected group of patients. Methods A retrospective chart review was performed from 2003-2018 of patients with stage IV ACC with ≤2 tumoral organs who received mitotane in our center. Primary endpoint was the delay between mitotane initiation and first systemic chemotherapy. Secondary endpoints were progression-free survival (PFS) and overall survival (OS) from mitotane initiation. Adjusted analyses were performed on the main prognostic factors. Results Out of 79 included patients, 48 (61%) patients were female and median age at stage IVA diagnosis was 49.8 years (interquartile-range:38.8-60.0). Metastatic sites were mainly lungs (76%) and liver (48%). Fifty-eight (73%) patients received LRT including adrenal bed radiotherapy (14 patients, 18%), surgery (37 patients, 47%) and/or interventional radiology n(35,44%). Median time between mitotane initiation and first chemotherapy administration was 9 months (Interquartile-range:4-18). Median PFS1 (first tumor-progression) was 6.0 months (CI95%:4.5-8.6). Median OS was 46 months (CI95%:41-68). PFS1, PFS2 and OS were statistically longer in the mitotane plus LRT group compared to the mitotane-only group (Hazard ratio (HR)=0.39 (CI95%:0.22-0.68), HR=0.35 (CI95%:0.20-0.63) and HR=0.27 (CI95%:0.14-0.50) respectively). Ten (13%) patients achieved complete response, all from mitotane plus LRT group. Conclusion Our results endorse European and French guidelines for stage IV ACC with ≤2 tumor-organs and favor the combination of mitotane and LRT as first-line treatment. For the first time, a significant number of complete responses were observed. Prospective studies are expected to confirm these findings.

scholarly journals Survival outcome differences based on treatments used and knowledge of the primary tumour site for patients with cancer of unknown and known primary in Ontario

2018 ◽  
Vol 25 (5) ◽  
Author(s):  
C. S. Kim ◽  
M. B. Hannouf ◽  
S. Sarma ◽  
G. B. Rodrigues ◽  
P. K. Rogan ◽  
...  
Keyword(s):  
Median Survival ◽  
Cox Regression ◽  
Metastatic Cancer ◽  
Primary Tumour ◽  
Primary Site ◽  
Unknown Primary ◽  
Survival Outcomes ◽  
Tumour Site ◽  
Ontario Health Insurance Plan ◽  
Primary Tumour Site

IntroductionPatients with cancer of unknown primary (cup) have pathologically confirmed metastatic tumours with unidentifiable primary tumours. Currently, very little is known about the relationship between the treatment of patients with cup and their survival outcomes. Thus, we compared oncologic treatment and survival outcomes for patients in Ontario with cup against those for a cohort of patients with metastatic cancer of known primary site.Methods Using the Ontario Cancer Registry and the Same-Day Surgery and Discharge Abstract databases maintained by the Canadian Institute for Health Information, we identified all Ontario patients diagnosed with metastatic cancer between 1 January 2000 and 31 December 2005. Ontario Health Insurance Plan treatment records were linked to identify codes for surgery, chemotherapy, or therapeutic radiation related to oncology. Multivariable Cox regression models were constructed, adjusting for histology, age, sex, and comorbidities.Results In 45,347 patients (96.3%), the primary tumour site was identifiable, and in 1743 patients (3.7%), cup was diagnosed. Among the main tumour sites, cup ranked as the 6th largest. The mean Charlson score was significantly higher (p < 0.0001) in patients with cup (1.88) than in those with a known primary (1.42). Overall median survival was 1.9 months for patients with cup compared with 11.9 months for all patients with a known-primary cancer. Receipt of treatment was more likely for patients with a known primary site (n = 35,012, 77.2%) than for those with cup (n = 891, 51.1%). Among patients with a known primary site, median survival was significantly higher for treated than for untreated patients (19.0 months vs. 2.2 months, p < 0.0001). Among patients with cup, median survival was also higher for treated than for untreated patients (3.6 months vs. 1.1 months, p < 0.0001).Conclusions In Ontario, patients with cup experience significantly lower survival than do patients with metastatic cancer of a known primary site. Treatment is associated with significantly increased survival both for patients with cup and for those with metastatic cancer of a known primary site.

Use of combined biomarkers analysis to predict response to chemotherapy in colorectal cancer: A single-institution feasibility study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11074-11074
Author(s):  
J. Rodriguez-Pascual ◽  
E. Garcia ◽  
F. Lopez-Rios ◽  
A. Cubillo ◽  
I. Diaz-Padilla ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Treatment Options ◽  
Molecular Targets ◽  
Individual Case ◽  
Single Institution ◽  
First Line ◽  
Egfr Amplification ◽  
Response To Chemotherapy ◽  
Predict Treatment Response ◽  
Line Chemotherapy

11074 Background: Treatment options for patients (pts) with colorectal cancer (CRC) have increased in the last years. However, there are no validated prospective molecular markers in CRC to select which agents are better to treat any individual case. The aim of this study was to determine the feasibility of developing an implementing a biomarker panel to guide treatment selection in this setting. Methods: Colorectal cancer tumors were prospectively analyzed with a predefined set of 11 molecular targets, including: KRas and PI3K mutations, EGFR amplification (FISH), and ERCC-1, TS, TP expression by IHC. Clinical characteristics and response to chemotherapy were registered. To establish the utility of this panel, we determine as congruent-treatment if the panel predict the best treatment in patients with more of 1 chemotherapy line and no-congruent-treatment if do not. Results: A total of 84 patients were studied. Only 6 % required a repeated biopsy to obtain sufficient tumor for marker analysis. In 81 % of patients was feasible to study almost 8/11 targets. There were 29 pts (39%) with KRas mutant CRC; 3 pts with PI3K mutations (4%, all of them with KRas mutation); and 2 patients with EGFR amplification. ERCC-1 was positive in 5/78 (6.4%) and TS was positive in 47%. None of 54 pts had TP positivity. Clinical floow up was available in 66 pts (44 males, median age 59, 93% ECOG 0–1). Nineteen patients had early CRC; 23 with metastatic CRC treated with a first line chemotherapy and 24 with advanced CRC treated with 2 or more prior regimens. In this last group for whom the response to multiple agents is known, the panel predictive the most effective treatment in 14 of 24 cases. Conclusions: This targeted-therapy-panel is feasible to implement and should be explore to predict treatment response to CRC . No significant financial relationships to disclose.

Clinical characteristics of KRAS mutations in NSCLC and their impact on outcomes to first-line chemotherapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7588-7588
Author(s):  
Mohit Butaney ◽  
Jennifer Porter ◽  
Neal Ian Lindeman ◽  
Pasi A. Janne ◽  
Michael S. Rabin ◽  
...  
Keyword(s):  
Smoking Status ◽  
Egfr Mutations ◽  
Limited Information ◽  
Wild Type ◽  
First Line ◽  
Kras Mutations ◽  
Response To Chemotherapy ◽  
Significant Difference ◽  
The Impact ◽  
Line Chemotherapy

7588 Background: KRAS is one of the most commonly mutated oncogenes in non-small cell lung cancer (NSCLC). While the impact of EGFR mutations and EML4-alk translocations has been well-described, there is limited information about the impact of these somatic mutations on response to chemotherapy. Methods: We retrospectively reviewed the demographics and clinical outcomes of patients with KRAS mutations and compared these to patients who were KRAS wild-type (WT). Eligible pts received 1st-line IV chemo for stage IV NSCLC at DFCI and had known information about both KRAS and EGFR status. Since the biology and impact of EGFR mutations on response to chemo is well-described, we excluded such pts from the analysis. The primary endpoint was progression-free survival (PFS) with first-line chemo; secondary endpoints included radiographic response rate (RR) and overall survival (OS). Results: Between 2/05 and 8/11, there were 63 eligible KRAS pts and 97 eligible WT pts. The groups were similar in age (median 65yrs in both groups), % female (K 62, WT 54) race (K 89% white/6% black, 5% other; WT 86% white,/6% black/8% other), histology (K 90%adeno/8% NSCLC NOS; WT 86% adeno/9%NSCLC NOS), and % of pts receiving 1/2/3 agents in 1st line (K 11/56/33; WT 18/53/30). KRAS pts were less likely to be never or light smokers (4% vs 33% for WT). Nonsmokers were more likely to harbor KRAS transition rather than transversion mutations (3 transition, 1 transversion), while the converse held for smokers (51 transversions, 8 transitions). Median PFS was similar for KRAS vs WT (K .65 vs WT 4.8 months, p=0.81). RR (29% for both groups), disease control rates (K 73% vs WT 78%), and median OS (K 13.5 vs WT 12.1 months, p=.525) were also similar. Outcomes of KRAS pts to 2nd line chemotherapy (PFS 2.2, OS 8.6) are similar to those seen for WT patients in this setting. There was no significant difference in outcomes based on gender, smoking status, drug received (pemetrexed-based vs taxane based), or specific KRAS genotype. Conclusions: Pts with KRAS mutations experience similar outcomes to standard chemotherapy as those who are wild-type for EGFR and KRAS. Going forward, these data can serve as a reference for control arms of KRAS-specific randomized trials.

Preliminary analysis of FOLFIRI regimen with or without bevacizumab as second-line systemic therapy in patients with metastatic gastroenteropancreatic neuroendocrine carcinoma.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 469-469
Author(s):  
Xiaoying Zhao ◽  
Chen Chen Wang ◽  
Wen Zhang ◽  
Xiaodong Zhu ◽  
Weijian Guo ◽  
...  
Keyword(s):  
Partial Response ◽  
Disease Control ◽  
Stable Disease ◽  
Median Number ◽  
Cancer Center ◽  
Second Line ◽  
First Line ◽  
Ki 67 ◽  
Mild Anemia ◽  
Line Chemotherapy

469 Background: Patients with gastroenterpancreatic neuroendocrine carcinomas (NECs) have a very poor prognosis. And the role of the second-line therapy remains unknown. Methods: We retrospectively analyzed 11 patients with gastroenteropancreatic NEC after failure of first-line chemotherapy in the last two years in our cancer center. Data examined included clinical and pathological characteristics at the time of diagnosis, efficacy and safety. Results: Median age was 51 (17-64) years old. Most were male (81.8%). Tumor origin included pancreas (6pts, 54.5%), colon-rectum (3pts, 27.3%), one stomach and one liver. Metastatic disease was evident at diagnosis in all patients (liver metastases: 100%, celiac lymph nodes: 72.7%, bone: 18.2%, pleural effusion and peritoneal metastasis: 18.2%). Median Ki-67 index was 80%. Etoposide-cisplatin combinations as first line chemotherapy were administered in 8 (72.7%) patients and 2 (18.2%) capecitabine based regimen and 1(9.1%) gemcitabine with nab-paclitaxel. All patients received the FOLFIRI regimen with a median number of 8 (3-36) courses. Three patients (27.3%) had partial response, 4 (36.4%) stable disease, and 4 (36.4 %%) tumor progression. But in 6 patients received the FOLFIRI plus bevacizumab, disease control rate was 66.7%, 3 (50.0%) partial response, 1(16.7%) stable disease. The median PFS in all 11 pts was 3.77 (1.77-24.07) months, in 6pts with bevacizumab was 4.77(1.83-24.07) months. The most severe toxicities was grade 3 neutropenia (27.2%), the other adverse effects were mild to moderate, including mild anemia, transient transferase elevation and proteinuria. Conclusions: FOLFIRI regimen is a potentially effective and safe chemotherapy given as second-line in patients with NEC. Additional anti-VEGF therapy with bevacizumab may improve the disease control and PFS time.

Perioperative therapy in patients with metastatic colorectal cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18231-e18231
Author(s):  
Olatunji B. Alese ◽  
Katerina Mary Zakka ◽  
Xingyue Huo ◽  
Renjian Jiang ◽  
Walid Labib Shaib ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Multivariate Analyses ◽  
Stage Iv ◽  
Tumor Location ◽  
Primary Site ◽  
Perioperative Therapy ◽  
Younger Age ◽  
Male Preponderance ◽  
Metastatic Sites

e18231 Background: Knowledge about perioperative systemic therapy in metastatic colorectal cancer (mCRC) is limited. We aim to describe the nationwide pattern of use and survival outcomes of patients with mCRC treated with surgical resection. Methods: Data were obtained from all US hospitals that contributed to the National Cancer Database (NCDB) between 2004 and 2013. Univariate and multivariate analyses was done to identify factors associated with patient outcome. Results: A total of 61,940 patients with stage IV CRC older than 18 years were identified. Mean age was 63.4 years (SD±14), with a male preponderance (54.8%). About 80% were Caucasian and 69.9% had colon cancer. Compared to medical treatment only, resection of both primary and metastatic sites (13.5%; HR 0.40; 0.37-0.44; p < 0.001), or primary site resection alone (49.2%; HR 0.52; 0.48-0.56; p < 0.001) were associated with improved overall survival (OS). Other co-variates associated with improved survival included younger age group, year of diagnosis (2009-2013), colon tumor location, and < 3 metastatic sites (Table). Five-year OS for resection of primary and metastatic site (28.2%) was higher than for primary site resection alone (14.9%) or no surgical treatment (4.7%). Conclusions: Resection of metastatic sites or primary tumor was associated with improved survival in patients with stage IV CRC.[Table: see text]

Association of BAFFR expression in CAFs with overall survival and response to platinum-based chemotherapy in NSCLC.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8537-8537
Author(s):  
Fotinos-Ioannis D. Dimtrakopoulos ◽  
Anastasia E Kottorou ◽  
Anna G Antonacopoulou ◽  
Achilleas Nikolakopoulos ◽  
Nikolaos Panagopoulos ◽  
...  
Keyword(s):  
Alternative Pathway ◽  
Immunohistochemical Analysis ◽  
Disease Stage ◽  
First Line ◽  
Regional Lymph Nodes ◽  
Tissue Samples ◽  
Platinum Based Chemotherapy ◽  
Response To Chemotherapy ◽  
Nsclc Patients ◽  
Line Chemotherapy

8537 Background: Β-cell activating factor receptor (BAFFR) is a surface receptor, which leads to activation of the Nuclear Factor-kappaB (NF-κB) alternative pathway, a pathway with an important role in non-small cell lung cancer (NSCLC). In addition, cancer associated fibroblasts (CAFs) are major players of the tumor microenvironment promoting NSCLC. The aim of this study was to assess the possible associations of BAFFR expression in CAFs with response to first-line chemotherapy doublet and clinical outcome of NSCLC patients. Methods: Immunohistochemical analysis of BAFFR expression on CAFs was performed on tumor and tumor-adjacent formalin fixed and paraffin embedded tissue samples from 124 operated patients with NSCLC. Patients were under follow-up for at least 60 months, while response to chemotherapy was evaluated in patients who relapsed during this period. Results: BAFFR expression, which was noted exclusively in the cytoplasm of CAFs, was associated with OS only in patients with no infiltration of regional lymph nodes. Higher expression levels of BAFFR in CAFs were related to worse 2-, 3- and 5-year survival (P = 0.015, P = 0.027 and P = 0.040, respectively). This finding persisted after multivariate analysis with age, gender, histological subtype, histological differentiation and disease stage as coefficients (P = 0.009; HR, 2.734; 95% CI, 1.283-5.828). In addition, response to first line chemotherapy was associated with BAFFR expression in CAFs (P = 0.025). Patients who progressed had lower BAFFR levels. Furthermore, BAFFR expression in CAFs was associated with patients’ age. In particular, older patients had higher expression of BAFFR compared to patients younger than 55 years (P = 0.010). Additionally, carcinomas with better differentiation had lower expression of BAFFR in CAFs (P = 0.005). Finally, BAFFR expression in CAFs was related to development of metastatic disease (P = 0.033) and particularly in liver (P = 0,017) and in bones (P = 0.003). Conclusions: The present findings suggest that the expression of BAFFR in CAFs may be a useful biomarker with prognostic and predictive value, representing possibly an unknown biological relation, which merits further investigation.

The Combination of Paclitaxel and Carboplatin as First-Line Chemotherapy in Patients With Stage III and Stage IV Ovarian Cancer

1998 ◽  
Vol 21 (5) ◽  
pp. 491-497 ◽  
Author(s):  
Claudio Zamagni ◽  
Andrea Martoni ◽  
Nicoletta Cacciari ◽  
Alfonso Gentile ◽  
Franco Pannuti
Keyword(s):  
Ovarian Cancer ◽  
Stage Iv ◽  
Stage Iii ◽  
First Line ◽  
Line Chemotherapy
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