Cancer of unknown primary—Epidemiological trends and relevance of comprehensive genomic profiling

Binder, Carmen; Matthes, Katarina L.; Korol, Dimitri; Rohrmann, Sabine; Moch, Holger

doi:10.1002/cam4.1689

Cited by 46 publications

(46 citation statements)

References 61 publications

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“…The majority of CUPs are adenocarcinoma, although squamous, as in our patient, high-grade neuroendocrine and poorly differentiated carcinomas all exist as histopathologic CUP subtypes [2][3][4]. Although advances in standard of care and targeted therapy have led to survival improvements in many areas of oncology, CUP outcomes remain poor with median survivals of 8-12 months [5]. Furthermore, although the incidence of CUP cases has decreased, the overall survival of CUP patients has not improved in over 30 years [5].…”

Section: Discussionmentioning

confidence: 71%

“…Although advances in standard of care and targeted therapy have led to survival improvements in many areas of oncology, CUP outcomes remain poor with median survivals of 8-12 months [5]. Furthermore, although the incidence of CUP cases has decreased, the overall survival of CUP patients has not improved in over 30 years [5].…”

Section: Discussionmentioning

confidence: 99%

“…Sequencing is commonly performed on samples from the tumor biopsy, although liquid biopsy of circulating tumor cells (CTC) or tumor-free DNA exists. The reported ability to predict an origin varies wildly from as low as 33% to nearly 100% [5,[7][8][9][10]. A single genetic signature or panel of mutations has not been identified.…”

Section: Discussionmentioning

confidence: 99%

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Molecular Profiles of Brain and Pulmonary Metastatic Disease in Cancer of Unknown Primary

et al. 2020

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Cancers of unknown primary (CUP) are histologically confirmed malignancies but for which further investigation cannot identify a primary site. Improvements in histopathologic modalities for diagnosis have lessened the frequency of CUPs to 3%-5% of all malignancies compared with historical estimates of 5%-10%. Despite this, there is an ongoing debate as to whether CUPs are malignancies where the primary is not found or if they are otherwise a fully separate entity. Improvements in molecular analysis holds promise for improved identification and treatment of CUPs with mixed preliminary results. Here we present a woman with CUP and metastases in her brain and lung. We performed genomic profiling to compare the molecular makeup of each site in order to establish treatment targets. The Oncologist 2020;25:555-559 KEY POINTS • Cancer of unknown primary remains a diagnostic and therapeutic challenge. • Molecular analysis may provide improvements in diagnosis and novel treatment options. • Different sites of metastatic disease have subtle variations in molecular profile. • Sequencing of different sites may offer therapeutic options that are either already approved or available in clinical trial.

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

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Molecular Profiles of Brain and Pulmonary Metastatic Disease in Cancer of Unknown Primary

et al. 2020

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“…Carcinomas of unknown primary (CUPs) are a heterogeneous group of metastatic tumors for which a standardized diagnostic work-up fails to identify the site of origin at the time of diagnosis (1). CUPs account for 3-5% of all malignancies (2,3) and disappointingly the overall survival in CUP population has not improved over the last decades, despite advancements in the knowledge of biology of solid tumors (4). This is partly due to a lack of therapeutic options, with chemotherapy regimens using either platinum or taxanes or both not having proved to prolong survival in patient with CUP (5).…”

Section: Introductionmentioning

confidence: 99%

The Quest for Improving Treatment of Cancer of Unknown Primary (CUP) Through Molecularly-Driven Treatments: A Systematic Review

et al. 2020

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Background: Carcinomas of unknown primary (CUP) account for 3-5% of all malignancy and, despite a reduction in incidence, the overall survival has not improved over the last decade. Chemotherapy regimens have not provided encouraging results. New diagnostic technologies, such as next generation sequencing (NGS), could represent a chance to identify potentially targetable genomic alterations in order to personalize treatment of CUP and provide insights into tumor biology. Methods: A systematic review of studies of patients with CUP, whose tumor specimen was evaluated through a NGS panel, has been performed on June 10th, 2019 according to PRISMA criteria from PubMed, ASCO meeting library and Clinicaltrial.gov. We have identified potentially targetable alterations for which approved/off-label/in clinical trials drugs are available. Moreover, we have included case reports about CUP patients treated with targeted therapies driven by NGS results in order to explore the clinical role of NGS in this setting. Results: We have evaluated 15 publications of which eleven studies (9 full-text articles and 2 abstracts) have analyzed the genomic profiling of CUPs through NGS technology, with different platforms and with different patients cohorts, ranging from 16 to 1,806 patients. Among all these studies, 85% of patients demonstrated at least one molecular alteration, the most frequent involving TP53 (41.88%), KRAS (18.81%), CDKN2A (8.8%), and PIK3CA (9.3%). A mean of 47.3% of patients harbored a potentially targetable alteration for which approved/off-label/in clinical trials drugs were available. Furthermore, we have identified 4 case reports in order to evaluate the clinical relevance of a specific targeted therapy identified through NGS. Conclusions: NGS may represent a tool to improve diagnosis and treatment of CUP by identifying therapeutically actionable alterations and providing insights into tumor biology.

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“…Patients with cancer of an unknown primary (CUP) comprise approximately 5–15% of total cerebral metastases cases [ 8 , 22 , 24 , 26 , 33 ]. Patients presenting with intracranial metastases from a CUP may not be considered for the same surgical treatment options as those afforded to patients with a known primary cancer (CKP) as knowledge of the primary disease’s prognosis typically facilitates treatment decisions [ 2 ]. The approach of reserving surgery until a primary is diagnosed may negate the potential benefits of early surgical management, as is more readily offered to those patients with CKP metastases.…”

Section: Introductionmentioning

confidence: 99%

Survival outcomes following craniotomy for intracranial metastases from an unknown primary

et al. 2020

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Introduction Management of patients with intracranial metastases from an unknown primary tumor (CUP) varies compared to those with metastases of known primary tumor origin (CKP). The National Institute for Health and Care Excellence (NICE) recognizes the current lack of research to support the management of CUP patients with brain metastases. The primary aim was to compare survival outcomes of CKP and CUP patients undergoing early resection of intracranial metastases to understand the efficacy of surgery for patients with CUP. Methods A retrospective study was performed, wherein patients were identified using a pathology database. Data was collected from patient notes and trust information services. Surgically managed patients during a 10-year period aged over 18 years, with a histological diagnosis of intracranial metastasis, were included. Results 298 patients were identified, including 243 (82.0%) CKP patients and 55 (18.0%) CUP patients. Median survival for CKP patients was 9 months (95%CI 7.475-10.525); and 6 months for CUP patients (95%CI 4.263-7.737, p = 0.113). Cox regression analyses suggest absence of other metastases (p = 0.016), age (p = 0.005), and performance status (p = 0.001) were positive prognostic factors for improved survival in cases of CUP. The eventual determination of the primary malignancy did not affect overall survival for CUP patients. Conclusions There was no significant difference in overall survival between the two groups. Surgical management of patients with CUP brain metastases is an appropriate treatment option. Current diagnostic pathways specifying a thorough search for the primary tumor pre-operatively may not improve patient outcomes.

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Cancer of unknown primary—Epidemiological trends and relevance of comprehensive genomic profiling

Cited by 46 publications

References 61 publications

Molecular Profiles of Brain and Pulmonary Metastatic Disease in Cancer of Unknown Primary

Molecular Profiles of Brain and Pulmonary Metastatic Disease in Cancer of Unknown Primary

The Quest for Improving Treatment of Cancer of Unknown Primary (CUP) Through Molecularly-Driven Treatments: A Systematic Review

Survival outcomes following craniotomy for intracranial metastases from an unknown primary

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