P16.02 Impact of Number and Location of Metastatic Sites on Survival in Stage IV ICI-Treated NSCLC

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.

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Surgery provides survival benefit over systemic therapy alone for stage IV triple negative breast cancer: A propensity matched analysis of the National Cancer Database.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e13054 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e13054-e13054

Author(s):

Lifen Cao ◽

Jonathan T. Bliggenstorfer ◽

Kavin Sugumar ◽

Christopher W. Towe ◽

Pamela Li ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Systemic Therapy ◽

Survival Benefit ◽

Triple Negative ◽

Stage Iv ◽

National Cancer Database ◽

Propensity Matching ◽

N Stage ◽

Metastatic Sites

e13054 Background: Conflicting data exist regarding benefit of surgery of the primary site for stage IV breast cancer, in which systemic therapy is standard of care and patient characteristics may bias treatment decisions. Metastatic triple negative breast cancer (TNBC) is an aggressive subtype with limited therapy options and poor prognosis. Our aim was to assess whether surgery for the primary tumor in stage IV TNBC provides a survival advantage over systemic therapy alone. Methods: The National Cancer Database was queried for patients with de-novo stage IV TNBC who received systemic therapy alone or systemic therapy and surgery of the primary breast site 2004-2016. Patients receiving surgery for metastatic tumor sites or with incomplete follow up data were excluded. 1:1 propensity matching was performed for demographics, comorbidities, clinical T and N stage, and metastatic sites to minimize confounding factors. Survival outcomes were analyzed using a stratified log-rank test and Cox proportional hazard regression analysis. Results: Of 2989 patients, 782 (26.21%) underwent surgery plus systemic therapy and 2207 (73.84%) were treated with systemic therapy alone. The majority of all patients were aged 51-70 with low co-morbidity, and treated in metropolitan areas. Patients treated at academic facilities (OR = 0.67, p = 0.025), with multiple metastatic sites (OR = 0.59, p < 0.001), or advanced clinical N stage (OR = 0.55, p < 0.001) were less likely to undergo surgery. Of those who completed surgery, 58% had unilateral mastectomy, and 63% had axillary lymph node dissection. Propensity matching identified 507 ‘paired’ patients with similar characteristics in the surgery and systemic therapy alone groups. After multivariable adjustment, surgery was associated with superior overall survival compared with systemic therapy alone (HR 0.73, P < 0.001). Older age (HR = 1.47, p < 0.001), greater comorbidity (HR = 1.28, p < 0.001) and multiple metastatic sites (HR = 1.53, p < 0.001) significantly decreased overall survival in the matched cohort. Median survival was shortest in the systemic therapy alone group (12.8 months, 95% CI 11.3-14.5) and longest in those undergoing systemic therapy plus simple mastectomy (18 months, 95% CI 14.3-21.2), though approximately 4 months of median survival was added for all patients undergoing any surgery vs. systemic therapy alone (p = 0.0001). Conclusions: In stage IV TNBC, surgical resection of the primary tumor site in addition to systemic therapy may provide a survival benefit in selected patients. Though in this retrospective study the sequence of treatment was unknown, surgery could be considered for low disease burden as in other malignancies with oligometastatic disease. Additional research is needed to determine if these findings persist in prospective studies and for other hormone-receptor subtypes.

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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.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.136 ◽

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.

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The Clinicopathological features and survival outcomes of patients with different metastatic sites in stage IV breast cancer

BMC Cancer ◽

10.1186/s12885-019-6311-z ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 17

Author(s):

Ru Wang ◽

Yayun Zhu ◽

Xiaoxu Liu ◽

Xiaoqin Liao ◽

Jianjun He ◽

...

Keyword(s):

Breast Cancer ◽

Brain Metastasis ◽

Cancer Patients ◽

Stage Iv ◽

Clinicopathological Features ◽

Breast Cancer Patients ◽

Kaplan Meier ◽

Stage Iv Breast Cancer ◽

Multivariable Analyses ◽

Metastatic Sites

Abstract Background The features and survival of stage IV breast cancer patients with different metastatic sites are poorly understood. This study aims to examine the clinicopathological features and survival of stage IV breast cancer patients according to different metastatic sites. Methods Using the Surveillance, Epidemiology, and End Results database, we restricted our study population to stage IV breast cancer patients diagnosed between 2010 to 2015. The clinicopathological features were examined by chi-square tests. Breast cancer-specific survival (BCSS) and overall survival (OS) were compared among patients with different metastatic sites by the Kaplan-Meier method with log-rank test. Univariable and multivariable analyses were also performed using the Cox proportional hazard model to identify statistically significant prognostic factors. Results A total of 18,322 patients were identified for survival analysis. Bone-only metastasis accounted for 39.80% of patients, followed by multiple metastasis (33.07%), lung metastasis (10.94%), liver metastasis (7.34%), other metastasis (7.34%), and brain metastasis (1.51%). The Kaplan-Meier plots showed that patients with bone metastasis had the best survival, while patients with brain metastasis had the worst survival in both BCSS and OS (p < 0.001, for both). Multivariable analyses showed that age, race, marital status, grade, tumor subtype, tumor size, surgery of primary cancer, and a history of radiotherapy or chemotherapy were independent prognostic factors. Conclusion Stage IV breast cancer patients have different clinicopathological characteristics and survival outcomes according to different metastatic sites. Patients with bone metastasis have the best prognosis, and brain metastasis is the most aggressive subgroup.

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Prognostic value of distant metastatic sites in stage IV endometrial cancer: A SEER database study of 2948 women

International Journal of Gynecology & Obstetrics ◽

10.1002/ijgo.13084 ◽

2020 ◽

Vol 149 (1) ◽

pp. 16-23 ◽

Cited By ~ 2

Author(s):

Yan Liu ◽

Shuqi Chi ◽

Xing Zhou ◽

Rong Zhao ◽

Chengyu Xiao ◽

...

Keyword(s):

Endometrial Cancer ◽

Prognostic Value ◽

Stage Iv ◽

Seer Database ◽

Database Study ◽

Metastatic Sites

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Cisplatin(P)-including triplets versus P-free doublets in the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC): SICOG 0101 randomized trial

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.7103 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 7103-7103 ◽

Cited By ~ 2

Author(s):

P. Comella ◽

S. Palmeri ◽

G. De Cataldis ◽

G. Filippelli ◽

R. Cioffi ◽

...

Keyword(s):

Advanced Nsclc ◽

Locally Advanced ◽

Stage Iv ◽

Standard Of Care ◽

Rank Test ◽

Stage Iiia ◽

Log Rank Test ◽

Grade 3 ◽

Metastatic Sites ◽

Nsclc Patients

7103 Background: We previously reported that triplets with P-gemcitabine (G) plus vinorelbine (V) (PGV) or paclitaxel (T) (PGT) prolonged the survival (S) of advanced NSCLC patients (pts) in comparison with P-based doublets (PG or PV). Aims of the present study were: (1) to compare (log-rank test) the S of P-based triplets vs P-free doublets, and (2) to compare (Fisher test) safety and response rate (RR) of T- and V-regimens. Methods: A 2x2 factorial design was adopted. Pts aged ≤ 70 years, with PS (ECOG) < 2, inoperable stage IIIA, IIIB, or IV NSCLC were randomly treated with: GV = G 1,000 mg/m2 + V 25 mg/m2 on day (D) 1 and 8; GT = G 1,000 mg/m2 + T 125 mg/m2 on D 1 and 8; PGV = P 50 mg/m2 on D 1 and 8 + GV; PGT = P 50 mg/m2 on D 1 and 8 + GT. In all arms, cycles were repeated Q 3 weeks. Only responder pts after 3 cycles received further chemotherapy (CT). Thoracic RT was delivered after CT to pts with intra-thoracic disease. 330 events were required to have a 90% power to demonstrate (two-sided P < 0.05) a 30% reduction of hazard of death. Results: From April 2001 to December 2005, 431 pts were recruited in the 4 arms. Characteristics in % were well balanced in P-based triplets and P-free doublets: males, 84/91; PS 0, 25/23; squamous cell carcinoma, 38/42; weight loss, 22/29; stage IV, 66/65; CNS metastases, 5/8; ≥ 2 metastatic sites, 29/30. So far, 411 pts were assessed for response: RR of triplets vs doublets was 88/204 (43%) vs 68/207 (33%) (P = 0.020), and of T-based vs V-based regimens was 40% vs 36% (P = 0.218). To date, 313 deaths were registered: median and 1-year S were 10.6 mo. and 41% for pts treated with triplets, and 10.4 mo. and 39% for pts treated with doublets (P = 0.786). Over initial 3 courses, occurrence of grade ≥ 3 toxicity (T vs V, % pts) was: neutropenia, 18% vs 30% (P < 0.004); febrile neutropenia, 4% vs 7%; platelets, 7% vs 12% (P = 0.056); anemia, 5% vs 7%; vomiting, 1% vs 2%; diarrhea, 6% vs 3%; stomatitis, 3% vs 0.5%. Grade ≥ 2 neurotoxicity occurred in 1% of both groups. Conclusions: Activity was significantly higher with P-based triplets, but they did not affect the OS. T-based regimens were equally active and less toxic than V-based regimens. Therefore, the GT regimen may represent a new standard of care for advanced NSCLC pts. No significant financial relationships to disclose.

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Phase II single institution study of sequential biochemotherapy (BCT) for patients (pts) with stage IV melanoma (M)

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.8580 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 8580-8580

Author(s):

P. R. Bojanapally ◽

D. T. Alexandrescu ◽

V. Rusciano ◽

P. H. Wiernik ◽

J. P. Dutcher

Keyword(s):

Median Survival ◽

Phase Ii ◽

Performance Status ◽

Single Agent ◽

Stage Iv ◽

Experimental Therapy ◽

Ecog Performance Status ◽

Maximum Benefit ◽

Prospective Phase ◽

Metastatic Sites

8580 Background: The utility of BCT for M remains controversial. A prospective phase II study was conducted to assess the clinical benefit of BCT in patients with stage IV M. Methods: Between March 2005 and March 2006 11 pts (6 Male and 5 Female with a median age of 54 (range 36 - 82)) with metastatic M were treated with paclitaxel 225 mg/m2 via continuous 24 hour IV infusion every 3 wks for 4 cycles or maximum benefit followed by HD IL2, 1.33 mg/m2 every 8 hours for 5 days of wk1 and wk3 based on pts tolerance to a maximum of 12 doses per wk. 2 Male pts received IL2 followed by paclitaxel. Pts had a ECOG performance status of 0 - 2, with a median time of 60 months since diagnosis of disease (range 7 to 240 months). 11 pts (92%) had multiple metastatic sites (50% had lung mets, 58% had liver mets) and 4 pts (33%) had prior chemotherapy or immunotherapy. Results: Of the 13 assessable pts one achieved a PR after paclitaxel and CR after IL2 continuing at 20+ months. One had SD for 1 year after receiving HD IL2 and SD for 6 months while on paclitaxel independently, One had PR for 6 months on paclitaxel and one had MR with paclitaxel for 3 months. 9 pts (69%) had PD on paclitaxel and again on IL2, with a median survival from treatment of 7 months, 2 of these got no IL2 due to rapid PD. An overall response rate of 30% (1 CR on paclitaxel + IL2 , 1 PR on paclitaxel, 2 SD (including MR) on paclitaxel) was seen with a median survival from treatment of 15 months. Conclusions: In this study there may be prolonged survival among responders, which may be due to synergy of sequential BCT, or may reflect single agent activity of each drug. BCT should still be considered as an experimental therapy and further evaluated. No significant financial relationships to disclose.

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Comprehensive genomic profiling of neuroendocrine carcinoma of the prostate.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.187 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 187-187

Author(s):

Sumanta K. Pal ◽

Matthew I. Milowsky ◽

Julia Andrea Elvin ◽

Siraj Mahamed Ali ◽

Jean H. Hoffman-Censits ◽

...

Keyword(s):

Neuroendocrine Carcinoma ◽

Stage Iv ◽

Mtor Inhibitors ◽

Mtor Pathway ◽

Tumor Type ◽

Genomic Profiling ◽

Genomic Alterations ◽

Carcinoma Of The Prostate ◽

Comprehensive Genomic Profiling ◽

Metastatic Sites

187 Background: Neuroendocrine carcinoma of the prostate (NCAP) is an aggressive high grade malignancy that often presents as metastatic disease. Current treatments of this tumor have only modest benefit leading investigators to query whether comprehensive genomic profiling (CGP) would have potential to discover novel targets of therapy. Methods: DNA was extracted from 40 microns of FFPE sections from 37 consecutive cases of relapsed/metastatic NCAP. CGP was performed on hybridization-captured, adaptor ligation based libraries to a mean coverage depth of 583X for up to 315 cancer-related genes plus 37 introns from 14 genes frequently rearranged in cancer. Genomic alterations (GA) included base substitutions (SUB), INDELs, copy number alterations (CNA) and fusions/rearrangements. Clinically relevant GA (CRGA) were defined as GA linked to drugs on the market or under evaluation in mechanism driven clinical trials. Results: The median age of the men in this study was 65.1 years (range 43 to 83 years). All (100%) cases were positive for neuroendocrine markers on immunohistochemical staining and were Stage IV at the time of CGP. Samples used for sequencing were obtained from the primary tumor in 9 (24%) of NCAP and from metastatic sites in 28 (76%) of NCAP (12 liver, 6 LN, 2 each from bladder, pelvis and soft tissue, and 1 each from rectum, bone, urethra and ureter. There were 213 total GA (5.8 GA/sample) and 47 CRGA (1.3 CRGA/sample). The most frequent GA were non-CRGA mutations in TP53 (68%) and RB1 (51%). TMPRSS:ERG fusions were identified in 32% of cases whereas AR was altered in 8% (1 mutation and 2 amplifications). The most frequent CRGA involved PTEN (32%), BRCA2 (14%), FGFR1 (5%), PIK3CA (5%) and AKT2 (3%). No alterations in BRAF were identified. Clinical responses to MTOR inhibitors in patients with MTOR pathway alterations will be presented. Conclusions: NCAP has distinctive genomic alterations from classic acinar CAP including reduced frequencies of alterations in TMPRSS:ERG and AR and frequent RB1 mutations. Multiple alterations in the MTOR pathway identified in this infrequent tumor type suggest that these patients may be candidates for MTOR inhibitors and other targeted therapies.

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Perioperative therapy in patients with metastatic colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e18231 ◽

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]

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Machine learning based predictive model of early mortality in stage III and IV prostate cancer

10.1101/2020.04.15.20065938 ◽

2020 ◽

Author(s):

Robert Chen

Keyword(s):

Prostate Cancer ◽

Machine Learning ◽

Cancer Survival ◽

Stage Iv ◽

Clinical Decision ◽

Early Mortality ◽

Stage Iii ◽

Clinical Endpoints ◽

Metabolomic Data ◽

Metastatic Sites

AbstractProstate cancer remains the third highest cause of cancer-related deaths. Metastatic prostate cancer could yield poor prognosis, however there is limited work on predictive models for clinical decision support in stage III and IV prostate cancer.We developed a machine learning model for predicting early mortality in prostate cancer (survival less than 21 months after initial diagnosis). A cohort of 10,303 patients was extracted from the Surveillance, Epidemiology and End Results (SEER) program. Features were constructed in several domains including demographics, histology of primary tumor, and metastatic sites. Feature selection was performed followed by regularized logistic regression. The model was evaluated using 5-fold cross validation and achieved 75.2% accuracy with AUC 0.649. Of the 19 most predictive features, all of them were validated to be clinically meaningful for prediction of early mortality.Our study serves as a framework for prediction of early mortality in patients with stage II and stage IV prostate cancer, and can be generalized to predictive modeling problems for other relevant clinical endpoints. Future work should involve integration of other data sources such as electronic health record and genomic or metabolomic data.

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