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PubMed2005

Long-term remission in a patient with carcinoma of unknown primary site.

BACKGROUND: Cancer of unknown primary site also designated as CUP syndrome usually presents as metastatic disease with a poor prognosis and low remission as well as survival rates. CASE: We report a 46-year-old male with para-aortal and left-sided cervical lymph node metastases. Histological examination of a cervical lymph node revealed papillary carcinoma. Despite thorough investigation, no primary tumor was found. The patient was empirically treated with six courses of the FACP regimen (5-fluorouracil, Adriamycin, cyclophosphamide and cisplatin) combined with radiotherapy (40 Gy) and has remained in complete remission for 124 months. CONCLUSION: This case indicates that treatment of a patient with cancer of unknown primary site may be rewarded by a benign course. However, complete cure remains a very rare event in CUP. Remission can be achieved with a platinum-containing regimen combined with radiotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Cancer of unknown primary site. Deciding how far to carry evaluation.

Management of most patients who present with metastatic cancer from an unknown primary site is challenging. These patients often are debilitated from the onset of their disease, have symptoms that are hard to control, and respond poorly to systemic therapy. The decision regarding the extent of a frequently unrewarding diagnostic evaluation, especially in these days of cost containment, is difficult. Knowing that few will benefit from aggressive therapy, the treating physician should make quality of life the most important goal in caring for these patients.

Adenocarcinoma↗
PubMed2006

Tumor-marker analysis and verification of prognostic models in patients with cancer of unknown primary, receiving platinum-based combination chemotherapy.

OBJECTIVES: To evaluate the usefulness of tumor-marker measurements and to identify prognostic factors in patients with cancer of unknown primary (CUP), receiving platinum-based combination chemotherapy and to verify the adjustment of previously reported prognostic models in this population. METHODS: We conducted univariate and multivariate analyses in consecutive patients with CUP receiving platinum-based combination chemotherapy. Previously reported prognostic models were then validated in this population. RESULTS: A total of 93 patients were analyzed and the response rate to platinum-based chemotherapeutic regimens among the 93 patients was 39.8%. The median time to progression and overall survival period were 4.1 and 12.4 months, respectively. The ST-439 level was significantly higher in patients with histologically confirmed adenocarcinoma than in patients with poorly differentiated adenocarcinoma or poorly differentiated carcinoma. A multivariate analysis indicated that performance status, the number of involved organs, and the serum lactate dehydrogenase level were the prognostic factors of the outcome. Both the previously reported prognostic models for predicting the duration of survival in this population were shown to be valid. CONCLUSION: Tumor-marker measurements are not helpful in the management of patients with CUP. Previously reported prognostic models may be useful for selecting indication for chemotherapy or for stratifying the patients in clinical trial.

Adult↗
PubMed1998

Continuous infusion cisplatin and etoposide chemotherapy for cancer of unknown primary site (CUPS) in Taiwan, a region with a high prevalence of endemic viral infections.

BACKGROUND: To evaluate the efficacy and toxicity of cisplatin/etoposide continuous infusion chemotherapy for cancer of unknown primary site in Taiwan, a region with a high prevalence of endemic viral infections. METHOD: Between April 1994 and February 1996, 20 patients with a diagnosis of CUPS were treated, including 15 males and five females, of average age 63.3 years (range 41-83 years). Continuous intravenous infusion of etoposide 80 mg/m2 and cisplatin 25 mg/m2 was given for 3 days every 3 weeks. Pretreatment tumor marker and viral serology studies were performed for baseline evaluation. Nearly two-thirds of the patients had poorly differentiated carcinoma. The average number of metastatic sites was 2.65 (range 1-4), with liver and lymph node involvement predominating. RESULTS: The overall response rate was 25% (95% CI 17.7-32.3%); 30.7% for poorly differentiated cancers and 25% for well differentiated cancers. Median survival was 4 months (range 1-12 months), 4.8 months for patients attaining partial response. Toxicity was moderate, grade 3 and 4 neutropenia occurred in 55% and grade 3 and 4 thrombocytopenia in 40%; other toxicities were mild. CA125 and CA199 were elevated in more than 50% of patients. Viral serology studies were not significantly different from those of the indigenous population. CONCLUSION: Etoposide and cisplatin combination chemotherapy has modest activity in patients with extensive CUPS and, at the schedule and dosage given, it is associated with moderate toxicity.

Adult↗
PubMed1988

[Metastatic cancer of unknown primary site].

The history, physical examination, radiographic and laboratory studies and histological diagnosis must be completely evaluated to search for the primary tumor. For diagnosis of cervical lymph node metastasis, not only whole body examination but also head and neck examination is important in which quadrascopy (nasopharyngeal, laryngeal and esophageal fiberoscopy and bronchoscopy) must be performed. If the localized lymph node metastasis of unknown primary site (TxNl-3MO); especially neck node, is presented, radiotherapy has an important role in cure. Patients with metastatic cancer of unknown primary site should be considered for early diagnosis and aggressive therapy.

Female↗
PubMed2026

Molecularly Guided Therapy Versus Continued Chemotherapy in Unfavorable Cancer of Unknown Primary: Updated Efficacy and Safety From the Randomized, Phase II CUPISCO Study.

CUPISCO (ClinicalTrials.gov identifier: NCT03498521) demonstrated longer progression-free survival (PFS) with comprehensive genomic profiling (CGP) and subsequent molecularly guided therapies (MGTs), versus standard platinum-based chemotherapy, in patients with previously untreated, unfavorable cancer of unknown primary (CUP) who reached disease control after induction chemotherapy (three cycles). We report efficacy and safety after >1 year of additional follow-up. Eligible patients were randomly assigned (3:1) to MGT (investigator-chosen after discussion in a molecular tumor board) or three further cycles of chemotherapy. The primary end point was PFS. Secondary end points included overall survival (OS) and safety. At data cutoff (December 6, 2024), 436 patients were randomly assigned (326 to MGT; 110 to chemotherapy). Median follow-up was 37.0 months (range, 0.0-67.8). Updated median PFS was 6.1 months (95% CI, 4.7 to 6.5) with MGT and 4.4 months (95% CI, 4.2 to 6.4) with chemotherapy (hazard ratio [HR], 0.75 [95% CI, 0.59 to 0.95]; P = .017); median OS was 15.2 months (95% CI, 13.9 to 18.4) and 12.8 months (95% CI, 9.8 to 15.4), respectively (HR, 0.79 [95% CI, 0.61 to 1.02]; P = .0689). No new safety signals were identified. These updated results aligned with the primary analysis, demonstrating the benefit of CGP with subsequent MGT and highlighting the importance of incorporating CGP at initial diagnosis to guide treatment decisions for patients with unfavorable CUP.

Journal Article↗
PubMed1999

Uses and limitations of FDG positron emission tomography in patients with head and neck cancer.

OBJECTIVE: Numerous authors have reported the potential usefulness of positron emission tomography (PET). These studies have had conflicting results, at least partly owing to limited sample sizes. The objective of this study is to define not only the uses, but also the limitations of PET in patients with head and neck cancer. STUDY DESIGN: Nonrandomized, retrospective analysis of PET at an academic institution. METHODS: The authors performed 146 PET scans on 133 patients with head and neck cancer. Eighteen patients (19 PET scans) with thyroid disorders were excluded. A minimum 1 year of follow-up was available in 84 patients, who were separated into groups based on whether the PET was used to detect unknown primary cancers (n = 20), stage neck nodal and distant metastases (n = 8), monitor response to nonsurgical therapy (n = 22), or detect recurrent or residual cancers (n = 34). The results of PET were compared with results from computed tomography (CT) and magnetic resonance imaging (MRI) performed in the same patients. RESULTS: Of the unknown primary cancers, PET correctly identified 7 of 20 primary sites, giving a sensitivity of 35%. When combined with CT or MRI, the sensitivity increased to 40%. When used for detection of metastatic disease, PET demonstrated five of five nodal metastases (100%) and two of four distant metastases (50%). In evaluating the response to nonsurgical therapy, PET had a sensitivity of 50% and a specificity of 83% for detecting tumor at the primary site and a sensitivity of 86% and a specificity of 73% for detecting nodal disease. When used for evaluation of recurrent/residual disease, PET identified seven of seven cases of local recurrences/residual disease and had a specificity of 85%. PET also detected seven of seven cases of nodal disease and had a specificity of 89%. CONCLUSIONS: For staging purposes, PET is limited by its lack of anatomic detail. However, PET compares favorably with CT and MRI in detecting recurrent/residual cancers. PET imaging complements the more traditional imaging modalities (CT or MRI), especially for an unknown primary cancer.

Carcinoma, Squamous Cell↗
PubMed1995

Microangiopathic hemolytic anemia as an initial presentation of metastatic cancer of unknown primary origin.

Microangiopathic hemolytic anemia (MAHA) is a well-documented but rare complication of disseminated cancer; it usually occurs in the late or terminal stage of cancer. We describe a case of metastatic carcinoma of unknown origin in which MAHA was the initial presentation. A 36-year-old woman came to our hospital with lower back pain and progressive exertional dyspnea for 8 weeks. Hemolytic anemia, thrombocytopenia, and leukoerythroblastosis were found on admission. The peripheral blood smear revealed polychromasia, poikilocytosis, and many schistocytes. Bone marrow biopsy disclosed metastatic carcinoma. After careful workup, we failed to find the primary site of cancer. The anemia and thrombocytopenia responded dramatically to combination chemotherapy with 5-fluorouracil, mitomycin C, and cisplatin. This case indicates that metastatic carcinoma should be included in the differential diagnosis in previously healthy patients with MAHA.

Adenocarcinoma↗
PubMed2005

Cancer of unknown primary (CUP).

Carcinoma of unknown primary (CUP) is one of the 10 most frequent cancers worldwide. It constitutes 3-5% of all human malignancies. Patients with CUP present with metastases without an established primary site. CUP manifests as an heterogenous group of mainly epithelial cancers recognised by distinct clinicopathological entities. The diagnostic work-up includes extensive histopathology investigations and modern imaging technology. Nevertheless, the primary tumour remains undetected most of the time. Certain clinicopathological CUP entities are considered as favourable subsets responding to systemic platinum-based chemotherapy or managed by locoregional treatment. These subsets are: the poorly differentiated carcinomas involving the mediastinal-retroperitoneal nodes, peritoneal papillary serous adenocarcinomatosis in females, poorly differentiated neuroendocrine carcinomas, isolated axillary node adenocarcinomas in females or cervical nodal involvement by a squamous cell carcinoma. Patients who belong to the non-favourable subsets have a worse prognosis.

Female↗
PubMed2005

Laparoscopic radiofrequency thermal ablation for unusual hepatic tumors: operative indications and outcomes.

BACKGROUND: There is increasing experience with laparoscopic radiofrequency ablation for the treatment of patients with hepatic metastasis from colorectal and neuroendocrine cancer and those with hepatocellular cancer. Little is known about the outcomes for patients with other tumor types. METHODS: Between January 1996 and March 2005, 517 patients with 1,500 primary and metastatic liver tumors underwent laparoscopic radiofrequency ablation. Among these, 53 patients (10%) had cancers other than the colorectal, neuroendocrine, or hepatocellular types including sarcoma (n = 18), breast cancer (n = 10), esophagus cancer (n = 4), melanoma (n = 4), lung cancer (n = 3), ovarian cancer (n = 2), pancreas cancer (n = 2), unknown primary cancer (n = 2), cholangiocarcinoma (n = 2), rectal squamous cancer (n = 2), renal cancer (n = 2), papillary thyroid cancer (n = 1), and hemangioendothelioma (n = 1). Unlike the criteria for treatment of the more usual tumor types, these patients had a diagnosis of liver-exclusive disease, as diagnosed by preoperative imaging. They also had failed chemotherapy. RESULTS: The 53 patients underwent ablation of 192 lesions, with 8 patients undergoing repeat treatment. The hospital stay averaged 1 day, and there was no 30-day mortality. Complications included one postoperative hemorrhage, one liver abscess, and one wound infection. Tumors recurred locally for 17% of the lesions over a mean follow-up period of 24 months. The overall median survival was 33 months for the whole series, more than 51 months for breast cancer, and 25 months for sarcoma. CONCLUSION: Laparoscopic radiofrequency ablation can safely and effectively treat hepatic metastasis of these unusual tumor types. The authors believe that this heterogeneous group of patients, selected for their unusual presentation of liver-exclusive disease, may benefit from cytoreduction of their tumor by laparoscopic radiofrequency ablation when other treatment methods have failed.

Catheter Ablation↗
PubMed2001

Localised disease in cancer of unknown primary (CUP): the value of positron emission tomography (PET) for individual therapeutic management.

BACKGROUND: Two to four percent of cancer patients present with CUP syndrome. Median survival for localised disease is 20 and for disseminated disease, seven months. For localised disease, curative treatment is more likely and individual therapeutic strategies become more important. After conservative diagnostic procedures including MRI, the primary is detected in less than 25%. The diagnostic value of PET and its influence on therapeutic strategies was evaluated. PATIENTS AND METHODS: Forty-two patients with localised CUP were investigated from 5 of 98 to 10 of 2000. The presenting site was lymph node metastasis in 34 and visceral metastasis in 8 patients. After a median of 7 (3-11) diagnostic procedures without detection of the primary, but evidence of localised disease, PET was performed with fluorine-18-fluorodeoxyglucose. RESULTS: In 26 of 42 patients (62%), a primary was suggested by PET and confirmed in 18 (43%). In 5 of 18 patients beyond localised disease, additional dissemination, not detected by previous diagnostic measures, was diagnosed by PET. Overall, dissemination was only detected only by PET in 16 of 42 patients (38%). In29 of 42 patients (69%), the PET result influenced selection of the definitive treatment. CONCLUSION: In CUP patients, PET has a certain impact on detection of the primary as well as of the disseminated disease. and may also have a certain impact on therapeutic management.

Adult↗
PubMed1987

Simultaneous radiotherapy and cis-platinum for the treatment of brain metastases. A pilot study.

Thirteen patients with the established diagnosis of brain metastases were treated with weekly intravenous or intra-arterial cis-platinum (40-60 mg/m2) during whole-brain irradiation (5,000 cGy over 5 weeks). Objective tumor response was observed in 12 patients (seven complete responses [CRs] and five partial responses [PRs]), and one patient showed stable disease (NC) following treatment. Chemotherapy- and radiation therapy-related toxicity was mild. There was no enhanced radiation therapy side effects on the normal tissues. Intracarotid cis-platinum with radiotherapy resulted in five CRs, two PRs, and one NC. Intravenous cis-platinum with conventional radiation therapy resulted in two CRs and three PRs. Responses according to tumor type were as follows: lung cancer (three adenocarcinoma, one mixed type, and one small-cell anaplastic carcinoma), two CRs and three PRs; breast cancer, one CR; thyroid cancer, one CR; unknown primary cancer, one CR; and melanoma, one NC. These results represent a relatively high CR rate (53.8%) for an otherwise barely manageable complication of malignant disease. Further controlled studies are recommended.

Adult↗
PubMed1990

[Multi-drug chemotherapy for patients with peritonitis carcinomatosa associated with ascites].

Between 1973 and 1987, 257 patients with ascites were seen in our divisions and 101 deaths due to cancer out of those who received multi-drug anticancer chemotherapy were surveyed: 1) They consisted of 45 ovarian cancers, 15 uterine corpus cancers, 5 uterine cervical cancers and 36 unknown primary cancers, or cancers other than gynecologic malignancies. 2) Survival time from the time of aspiration of ascites tended to be longer in four years from 1977 and 1981 than in four years from 1973. 3) The survival time was different in each patient groups having various combination chemotherapy and the longest was seen in the group of patients who received THP-ADM and CDDP-containing regimen as the next. 4) Patients survived for the longest period when a total amount of ascites less than 100 ml was aspirated and patients whose ascites was drained out more than 50,000 ml were the next longest survivors. 5) Clinical efficacy by multi-drug chemotherapy for malignant ascites was possibly predicted by our drug sensitivity assay by using primary cultured cancer cells.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

Metastatic cancer with unknown primary.

Close cooperation between an experienced pathologist and oncologist is essential in the management of patients with unknown primary carcinoma. A comprehensive pathological examination is crucial and, with undifferentiated tumors, this will include immunohistology and/or electron microscopy. Ample properly processed tissue therefore must be provided. Time-consuming and costly radiographic and imaging studies should be avoided. No matter how extensive the evaluation, in a majority of cases, the primary site will never be found, so a selective search for treatable tumors is most appropriate and cost-effective. With adenocarcinomas, this will include prostate, breast, and ovary; for undifferentiated tumors, small cell bronchogenic carcinoma, lymphomas, and germ cell tumors. Table 4 summarizes recommended studies for diagnosing unknown primary undifferentiated or adenocarcinomas. Women with adenocarcinoma in axillary nodes without a primary site should be treated as having breast cancer. Estrogen and progesterone receptor assays are to be obtained on the axillary biopsy. High and midcervical nodes with metastatic squamous cell carcinoma can be treated effectively and, not infrequently, cured with surgery and radiation therapy, even if the primary site never is detected. If doubt remains, treatment should be selected that offers the best chance of significant palliation or cure--for example, cisplatin-based chemotherapy in possible extragonadal germ cell tumors.

Axilla↗
PubMed1989

[Diagnosis and treatment of unknown primary tumors].

Cancers of unknown origin represent approximately 5% of all cancers and are therefore as frequent as some solid tumors such as gastric or pancreatic cancers. The diagnosis of cancer of unknown origin should be based on a detailed pathological examination including immunohistochemical techniques and electron microscopy; hormonal receptors should also be measured. Besides detailed medical history and physical examination, only a few additional tests should be carried out: routine chemistry including the assay of HCG, alphafoetoprotein and specific antigen of the prostate, chest X-ray, thyroid scan, mammography and abdominal CT scan. Other tests are generally not of sufficient specificity and sensitivity. Unknown primary tumors arising in the cervical area are frequently squamous cell carcinomas corresponding to occult primary tumors of the upper aerodigestive mucosae and are efficiently treated by cervicofacial radiotherapy or lymph node dissection. Women presenting with axillary lymph nodes with no obvious primary tumor should be treated according to the guidelines used for breast cancer. The patients with inguinal lymph nodes of unknown origin are usually treated with radiation therapy. The syndrome of germinal tumors of extragonadic origin corresponds to cases of undifferentiated or poorly differentiated carcinomas in patients under 50 years of age and with one of the following characteristics: involvement of the median organs, lung involvement, lymph node involvement or increase of alphafoetoprotein or HCG. The therapeutic approach recommended for these patients consists of the chemotherapeutic combination used for testicular cancer. For all other patients, the prognosis remains poor. Patients with local symptoms may be treated by radiation therapy; others may receive a combination of fluorouracil, doxorubicin and mitomycin.

Dysgerminoma↗
PubMed1991

Treatment of patients with cancer of unknown primary site.

Advances in the management and treatment of the large, heterogeneous population of patients with carcinoma of unknown primary site have been achieved by recognizing treatable subsets within this group. Each of these subsets has been thoroughly discussed; Table 10-9 summarizes the treatable subsets and the evaluations necessary for their identification. Even within treatable subsets, treatment data remain limited, and optimal therapy is still evolving. Despite these advances, a large group of patients with relatively insensitive tumors remains. Improved therapy for these patients will probably await therapy breakthroughs in the treatment of non-small cell lung cancer, pancreatic cancer, and the various other GI malignancies, since these tumors represent the majority of occult primary sites.

Adenocarcinoma↗