abstract: Cancer of unknown primary (CUP): does cause of death and family history implicate hidden phenotypically changed primaries?

Blogger's Note: paid subscription required to view full paper, the 'burning' question in the abstract is what other 7 cancers ??
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Cancer of unknown primary (CUP): does cause of death and family history implicate hidden phenotypically changed primaries?

Abstract

Background: Cancer of unknown primary (CUP) is diagnosed at the metastatic stage. We aimed to identify hidden primary cancers in CUP patients by comparison with cancers in family members. We take use of the fact that the cause of death in CUP patients is often coded as the cancer in the organ of fatal metastasis. 

Patients and methods: Forty-one thousand five hundred and twenty-three CUP patients were identified in the Swedish Family-Cancer Database, and relative risks (RRs) were calculated for cancer in offspring when family members were diagnosed with CUP and died of the cancer diagnosed in offspring. 

Results: The RR for lung cancer in offspring was 1.85 when a family member was diagnosed with CUP and died of lung cancer. Significant familial associations were found for seven other cancers. Many familial associations were also significant when offspring CUP patients died of the cancer diagnosed in family members. 

Conclusions: The cause of death after CUP diagnosis frequently matched the cancer found in a family member, suggesting that the CUP had originated in that tissue. The metastasis had probably undergone a phenotypic change, complicating pathological tissue assignment. These novel data suggest that some CUP cases are phenotypically modified primary cancers rather than cancers of unknown primaries.

abstract: Role of Definitive Radiation Therapy in Carcinoma of Unknown Primary in the Abdomen and Pelvis

Role of Definitive Radiation Therapy in Carcinoma of Unknown Primary in the Abdomen and Pelvis

 Objectives

Carcinoma of unknown primary (CUP) in the abdomen and pelvis is a heterogeneous group of cancers with no standard treatment. Considered by many to be incurable, these patients are often treated with chemotherapy alone. In this study, we determined the effectiveness of radiation therapy in combination with chemotherapy in patients with CUP in the abdomen and pelvis.

Patients and Methods

Medical records were reviewed for 37 patients with CUP treated with radiation therapy for disease located in the soft tissues and/or nodal basins of the abdomen and pelvis at the University of Texas M.D. Anderson Cancer between 2002 and 2009. All patients underwent chemotherapy, either before or concurrent with radiation therapy. Patients were selected for radiation therapy on the basis of histologic type, disease extent, and prior therapy response. Twenty patients underwent definitive radiation therapy (defined as radiation therapy targeting all known disease sites with at least 45 Gy) and 17 patients underwent palliative radiation therapy. Only 6 patients had surgical resection of their disease. Patient and treatment characteristics were extracted and the endpoints of local disease control, progression-free survival (PFS), overall survival (OS), and treatment-related toxicity incidence were analyzed.

Results

The 2-year PFS and OS rates for the entire cohort were 32% and 57%, respectively. However, in patients treated with definitive radiation therapy, the rates were 48% and 76%, and 7 patients lived more than 3 years after treatment with no evidence of disease progression. Nevertheless, radiation-associated toxicity was significant in this cohort, as 40% experienced Grade 2 or higher late toxicities.

Conclusions

The use of definitive radiation therapy should be considered in selected patients with CUP in the soft tissues or nodal basins of the abdomen and pelvis.

Carcinoma of unknown primary, Chemoradiation, Conformal radiation therapy, Intensity-modulated radiation therapy, Lymph node metastasis

open access: PLoS ONE: Immunohistochemical Profile for Unknown Primary Adenocarcinoma (CUP) (lung, digestive, gynecologic, prostate, liver, kidney, breast, urothelial, unclassified)

Background

Development of tailored treatment based on immunohistochemical profiles (IPs) of tumors for cancers of unknown primary is needed.

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The primary tumor sites based on the immunohistochemical profiles (IPs) for the 71 unknown primary patients were the lung for 17 patients, digestive organs for 13, gynecological organs for 9, prostate for 7, liver/kidney for 6, breast for 4, urothelial for 2, and were not unclassified for 13 patients (Table 2).Figures 2 and 3 show typical IHC results for the breast and lung profiles.

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Methodology/Principal Findings

"We developed an algorithm based on primary known adenocarcinoma for testing sensitivity and specificity. Formalin-fixed paraffin-embedded tissue samples from 71 patients of unfavorable subsets of unknown primary adenocarcinoma were obtained. We examined 15 molecular markers using the algorithm incorporating these IPs and classified the tumours into 9 subsets based on the primary tumour site. The sensitivity and specificity of this algorithm were 80.3% and 97.6%, respectively."

"Apparent primary sites were lung in 17 patients, digestive organs in 13, gynecological organs in 9, prostate in 7, liver or kidney in 6, breast in 4, urothelial organ in 2, biliary tract and pancreatic profile in none, and unclassified in 13."

Response evaluation (treatment plan) and survival analysis:

"...... Response rates by profile are listed in Table 2. A higher response rate was observed for the gynecological profile (67%) than for the other profiles...."

Discussion:

"...Further, we consider gynecologic profile may not be necessary to be classified into ovary, endometrial, and cervical adenocarcinoma in the situation of adenocarcinoma of unknown primary because chemotherapies for these cancer become similar in advanced disease [32], [33]..."

The algorithm we generated for orienting primary has value:

"Immunohistochemistory is generally done in routine work for the diagnosis of adenocarcinoma of unknown primary in many cancer centers. Therefore, there is no additional skill or tool in the procedure of diagnosis [10], [25]."

"This study has some limitations. First, the prognostic value of each IP was potentially underpowered, as the number of patients in each subgroup was somewhat small, not allowing the response rate, PFS, and OS to be compared to historical control data. Second, the results need to be validated in a prospective manner by applying standard treatments for identified primary profiles, to go beyond simply identifying prognostic factors for unknown primary adenocarcinoma....

"In this study, we revealed the prognostic value of a panel composed of immunohistochemistry profiles for patients with adenocarcinoma of unknown primary who received platinum doublet chemotherapy. Orienting primary sites either IHC or cDNA microarray in patients with CUPs is not good enough, we need to examine survival benefit when applying organ-oriented standard chemotherapies for patients with CUPs.
Our results may encourage a prospective randomized trial to compare standard platinum doublet chemotherapy with treatment determined by the IP. This approach may assist in developing new treatment strategy compared to a single arm platinum combination trial"