Gene expression profiling identifies responsive patients with cancer of unknown primary treated with carboplatin, paclitaxel, and everolimus: NCCTG N0871 (alliance)

Yoon, Han-Seung; Foster, Nathan R.; Meyers, Jeffrey P.; Steen, Preston D.; Visscher, Daniel W.; Pillai, Raji; Prow, Debra M.; Reynolds, Christopher M.; Marchello, Benjamin T.; Mowat, Rex B.; Mattar, Bassam; Erlichman, Charles; Goetz, Matthew P.

doi:10.1093/annonc/mdv543

Cited by 54 publications

(58 citation statements)

References 28 publications

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“…As reviewed by Moran et al, a handful of clinical trials have evaluated the impact of TOO-prediction based site-specific treatment with regards to improved clinical outcome (36). In a small prospective phase II trial, Yoon et al successfully molecularly profiled the TOO of 38 out of 45 confirmed CUP patients with a 2000-gene expression microarray-based assay (41). All of these patients were treated with carboplatin, paclitaxel and everolimus.…”

Section: Chasing the Tissue Of Origin (Too) In Cupmentioning

confidence: 99%

“Metastatic Cancer of Unknown Primary” or “Primary Metastatic Cancer”?

et al. 2020

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Cancer of unknown primary (CUP) is an umbrella term used to classify a heterogeneous group of metastatic cancers based on the absence of an identifiable primary tumor. Clinically, CUPs are characterized by a set of distinct features comprising early metastatic dissemination in an atypical pattern, an aggressive clinical course, poor response to empiric chemotherapy and, consequently, a short life expectancy. Two opposing strategies to change the dismal prognosis for the better are pursued. On the one hand, following the traditional tissue-gnostic approach, more and more sophisticated tissue-of-origin (TOO) classifier assays are employed to push identification of the putative primary to its limits with the clear intent of allowing tumor-site specific treatment. However, robust evidence supporting its routine clinical use is still lacking, notably with two recent randomized clinical trials failing to show a patient benefit of TOO-prediction based site-specific treatment over empiric chemotherapy in CUP. On the other hand, with regards to a tissue-agnostic strategy, precision medicine approaches targeting actionable genomic alterations have already transformed the treatment for many known tumor types. Yet, an unmet need remains for well-designed clinical trials to scrutinize its potential role in CUP beyond anecdotal case reports. In the absence of practice changing results, we believe that the emphasis on finding the presumed unknown primary tumor at all costs, implicit in the term CUP, has biased recent research in the field. Focusing on the distinct clinical features shared by all CUPs, we advocate adopting the term primary metastatic cancer (PMC) to denominate a distinct cancer entity instead. In our view, PMC should be considered the archetype of metastatic disease and as such, despite accounting for a mere 2-3% of malignancies, unraveling the mechanisms at play goes beyond improving the prognosis of patients with PMC and promises to greatly enhance our understanding of the metastatic process and carcinogenesis across all cancer types.

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Section: Chasing the Tissue Of Origin (Too) In Cupmentioning

confidence: 99%

“Metastatic Cancer of Unknown Primary” or “Primary Metastatic Cancer”?

et al. 2020

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“…Bone metastasis from cancer of unknown primary (BMCUP) is defined as a heterogeneous group of biopsy‐proven metastatic bone cancers for which no primary lesion can be detected by thorough diagnostic evaluation, accounting for 10% of all cancer types . BMCUP has very poor prognosis, with roughly 6 to 9 months of survival, not only because of failure to detect or cure primary cancer, but also due to oncological heterogeneity and histological biomarkers, which makes surgical, systemic or target therapies difficult …”

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confidence: 99%

“…Histological markers were detected in known primary tumors treated with sunitinib, including RCC, and studies on mouse models and RCC patients demonstrated antitumor effect of sunitinib against skeletal metastatic RCC through inhibition of osteoclast function, but there were few investigations on survival‐associated histological biomarkers on CUP, probably owing to heterogeneity of the occult primary site . BMCUP requires special attention, not only because of its diminished life quality or survival prognosis, but also several studies demonstrated that bone metastasis was independently associated with poor outcome for patients with CUP in general …”

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confidence: 99%

“…[1][2][3] BMCUP has very poor prognosis, with roughly 6 to 9 months of survival, not only because of failure to detect or cure primary cancer, but also due to oncological heterogeneity and histological biomarkers, which makes surgical, systemic or target therapies difficult. [4][5][6] Sunitinib, an oral tyrosine kinase inhibitor of angiogenesis and tumorigenesis, has been shown effective in treatment of multiple solid tumors, including mainly renal cell carcinoma (RCC), pancreatic neuroendocrine tumors (PNET) and gastrointestinal stromal tumors (GIST). 7,8 In particular, this agent is the treatment of choice for metastatic renal cell carcinoma, but there has been no literature to date to analyze the effectiveness of sunitinib for treatment of CUP, even though considering that this multitarget kinase inhibitor is expected to be effective in multiple solid tumors.…”

mentioning

confidence: 99%

“…[11][12][13] BMCUP requires special attention, not only because of its diminished life quality or survival prognosis, but also several studies demonstrated that bone metastasis was independently associated with poor outcome for patients with CUP in general. 6,7 In this study, an initial attempt was made to investigate the effectiveness of sunitinib in patients with BMCUP, and a further analysis was directed toward both clinical and histological biomarkers to predict sensitivity or resistance to sunitinib therapy in BMCUP.…”

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confidence: 99%

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Tyrosine kinase inhibitor sunitinib therapy is effective in the treatment of bone metastasis from cancer of unknown primary: Identification of clinical and immunohistochemical biomarkers predicting survival

Wang

et al. 2016

Intl Journal of Cancer

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Bone metastasis from cancer of unknown primary (BMCUP) brings poor survival prognosis and its management remains controversial. Sunitinib (SUTENT) proved effective in many sorts of solid tumors but has never been applied for patients with occult primary cancers, and there is no study to identify sensitive or resistant biomarkers for sunitinib therapy in CUP patients. An analysis was carried out to investigate the efficacy of sunitinib by multivariate survival analysis of 286 patients with BMCUP. We further carried out multivariate analysis to identify histological and clinical biomarkers that could predict sensitivity or resistance for sunitinib therapy. Of the 286 patients included from January 2011 to March 2016, sunitinib therapy proved effective to prolong survival in patients with BMCUP. Sensitive and resistant biomarkers were identified in histological specimen of patients receiving sunitinib therapy. Clinical factors were also identified that predict poor survival prognosis for sunitinib therapy. Sunitinib therapy proved effective to prolong survival in patients with BMCUP. Sensitive markers for sunitinib therapy include KDR positivity and early‐developed treatment‐induced hypertension. Resistance factors for sunitinib include VEGF positivity, CAIX positivity and squamous cell carcinoma pathology type. Prolonged symptom time and severe weight loss before therapy seemed to be associated with poor survival prognosis for sunitinib therapy.

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MicroRNA expression profiling with a droplet digital PCR assay enables molecular diagnosis and prognosis of cancers of unknown primary

et al. 2021

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Metastasis is responsible for the majority of cancer-related deaths. Particularly challenging is the management of metastatic cancer of unknown primary site (CUP), whose tissue of origin (TOO) remains undetermined even after extensive investigations and whose therapy is rather unspecific and poorly effective. Molecular approaches to identify the most probable TOO of CUPs can overcome some of these issues. In this study, we applied a pre-determined set of 89 microRNAs (miRNAs) to infer the TOO of 53 metastatic cancers of unknown or uncertain origin. The miRNA expression was assessed with Droplet Digital PCR in 159 samples, including primary tumors from 17 tumor classes (reference set), and metastases of known and unknown origin (test set). We combined two different statistical models for class prediction to obtain the most probable TOOs: the nearest shrunken centroids approach of Prediction Analysis of Microarrays (PAMR) and the Least Absolute Shrinkage and Selection Operator (LASSO) models. The molecular test was successful for all formalin-fixed paraffin-embedded samples and provided a TOO identification within 1 week from the biopsy procedure. The most frequently predicted origins were gastrointestinal, pancreas, breast, lung and bile duct. The assay was applied also to multiple

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Gene expression profiling identifies responsive patients with cancer of unknown primary treated with carboplatin, paclitaxel, and everolimus: NCCTG N0871 (alliance)

Abstract: NCT00936702.

Cited by 54 publications

References 28 publications

“Metastatic Cancer of Unknown Primary” or “Primary Metastatic Cancer”?

“Metastatic Cancer of Unknown Primary” or “Primary Metastatic Cancer”?

Tyrosine kinase inhibitor sunitinib therapy is effective in the treatment of bone metastasis from cancer of unknown primary: Identification of clinical and immunohistochemical biomarkers predicting survival

MicroRNA expression profiling with a droplet digital PCR assay enables molecular diagnosis and prognosis of cancers of unknown primary

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