First Site Of Metastatic Disease Research Articles

Sarcoma brain metastases: Tertiary cancer center experience.

Brain metastasis (BM) from bone and soft tissue sarcomas (STS) is very rare and mostly predicts dismal prognosis. Owing to its' rarity, data on optimal therapy including surgical management, chemotherapy, and radiotherapy is scarce. We sought to assess the prevalence, disease characteristics, and outcomes of BM in bone and STS patients treated at a single institution. A retrospective chart review was performed for consecutive bone and STS patients treated at King Hussein Cancer Center from 2007 to 2020. Patients with BM were identified. Survival was estimated by the Kaplan-Meier method. Factors of possible effect on OS was examined in univariate analysis. Survival comparisons were carried out by the log-rank test. A total of 1,548 bone and STS patients were treated at our center during the eligibility period. We identified 18 patients (1.1%) who had BM at initial presentation (n = 16, 1.0%) or during follow up (n = 2; 0.1%). Fourteen patients (77.8%) were male. The median age was 29.5 years (range: 0.1-60 years). The primary tumor was most commonly located in the extremities (61%). Ten different histopathological subtypes were encountered; Ewing sarcoma (ES) was the most common (n = 4; 28%). Twelve patients (67%) had lung metastasis as the first site of metastatic disease. BM was detected at a median time of 12 months following sarcoma diagnosis (range: 1-71 months). A total of 10 patients (56%) had solitary metastasis and 4 patients (22.2%) had hemorrhagic metastasis. The most common location of brain metastatic lesions was the occipital lobe (n = 4; 22.2%). Thirteen patients received treatment for metastatic brain sarcoma. The most common treatment modality was radiotherapy, received by a total of 10 patients (55.5%), followed by surgical intervention performed in a total of 5 patients (27.7%), The other treatment modalities included combined chemo-radiotherapy (n = 2), targeted therapy plus chemotherapy, and targeted therapy plus radiotherapy (n = 1, each). At a median follow up of 10 months following detection of BM, the median OS was 4.0 months; (95% CI: 2.54-5.46). We did not identify any factor that influenced OS in univariate analysis. Sarcoma BM is exceedingly rare and herald's dismal prognosis. ES was a major histological subtype accounting for BM metastasis in our series.

Abstract PS14-22: Clinical characteristics, prognostic factors and treatment comes of patients with bone-only metastatic breast cancer

Abstract Introduction: Despite efforts in advancing early detection programs, 5-20% of breast cancer patients present with distant metastases at diagnosis. Bone is the most frequent site of breast cancer metastasis, noted in 60-80% of metastatic breast cancer (MBC) patients, and is the first site of metastatic disease in 25-40% of patients. The outcome of patients with bone-only MBC (BOM) is usually better than those with visceral metastasis. However, differences between those who present with De-novo BOM and those who progress to bone-only disease following a diagnosis of early stage breast cancer is not clear. Such differences in clinical course might have an implication on aggressiveness of treatment.The aim of the study is to present the clinical and pathological features along with treatment outcomes of breast cancer patients with BOM in relation to timing and type of bone metastasis. Known prognostics factors that affects treatment outcome will be presented.Patients and Methods: Patients with De-novo and those who progressed after an initial diagnosis of early-stage breast cancer with bone-only metastasis diagnosed, treated and followed up at our institution between 2006 and 2018 were included. Data related to characteristic such as, grade, hormonal status, HER-2 status were collected from our electrical medical records, pathology and radiology reports. De-novo BOM was defined as bone metastasis diagnosed at presentation or within the first 4 months of follow up. Results: A total of 242 patients fulfilled our inclusion criteria and were included in the analysis. The median age (range) at diagnosis was 52 (27-80) years. Majority of the patients (77.3%) had De-novo BOM and multiple sites of bone involvement was identified in 82.6%. High- grade (G-III), HER2-positive and hormone receptor (HR)-negative disease were identified in 27.2%, 18.2% and 8.7%, respectively. Majority of the patients were treated with endocrine therapy while 31(12.9%) patients received chemotherapy at presentation.With a median follow up of 37.7 months, 185 (76.4%) of patients progressed, the median time to progression was 17.1 months (range 3-280m). The median overall survival (OS) for patients with de novo BOM disease was significantly shorter than those who developed subsequent bone metastasis; 40.8 months (95% CI, 51.1-184.1) compared to 80.9 months (95% CI, 36.4-47.9), p < 0.001. Tumor grade, HR status and type of bone lesions (lytic or sclerotic) have significant impact on 5-year OS as detailed in Table-1 Conclusions: Bone-only metastasis breast cancer is distinct clinical entity with a favorable prognosis and a prolonged overall survival. Several risk features for poor OS were identified and might be useful tool to design future clinical trials to trigger upscaling endocrine therapy to include newly introduced resistance modulating agents. Characteristics5-year Progression-Free Survival5-year Overall SurvivalPercentageP-valuePercentageP-valueAge (year)<5022.70.5544.90.21≥5022.739.2Tumor gradeI27.30.00564.90.01II23.343.6III9.626.6HER2Negative23.10.0343.60.79Positive15.632.9Estrogen receptors (ER)Negative16.30.1513.70.005Positive23.144.5Progesterone receptors (PR)Negative17.70.0920.60.004Positive23.345.5Number of bone lesionsMultiple20.60.0839.10.08Single34.554.8Type of bone metastasisLytic28.20.9346.00.01Sclerotic21.554.9Mixed14.643.0Time of bone metastasisDe novo13.4<0.00135.5<0.001Late49.060.5 Citation Format: Lina Marei, Dina Braik, Ayat Taqash, Hikamt Abdel-Razeq. Clinical characteristics, prognostic factors and treatment comes of patients with bone-only metastatic breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-22.

Addition of Primary Metastatic Site on Bone, Brain, and Liver to IMDC Criteria in Patients With Metastatic Renal Cell Carcinoma: A Validation Study.

The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria have been largely adopted in clinical practice. In a recent retrospective study, we assessed that the addition of the first site of metastatic disease to brain, bone, and liver improves prognostic stratification of patients with metastatic renal cell carcinoma (mRCC). Here, we performed an external validation in patients with mRCC. Our aim was to evaluate if the addition of a new independent variable could improve IMDC prognosis prediction and reduce heterogeneity within risk categories. We selected all 1073 patients treated at a single institution for mRCC and included in the Institute Gustave Roussy Renal Cell Carcinoma database. All patients included received at least 1 line of targeted therapy or immune checkpoint inhibitors. Univariate and multivariate analyses (Cox regression model) were performed. Bootstrap validation of the final model was also carried out for internal validation. The IMDC modified classification was defined by the addition of the seventh variable, and we defined the modified IMDC good-risk criteria as 0 risks, intermediate-risk as 1 to 2 risks, and poor-risk as 3 or more risks. The presence of brain, bone, and/or liver as the first site of metastatic disease plus the other variables included in the IMDC score were statistically significant variables associated with overall survival (OS) after univariate and multivariate analysis and bootstrap validation. Finally, 122 (15%) patients had a modification of their initial risk category. The median OS in the poor-, intermediate-, and favorable-risk groups was 10, 26, and 52 months, respectively (P< .001). The bias-corrected concordance index in patients receiving immune checkpoint inhibitors (n= 241) was 0.71. The addition of brain, bone, and/or liver metastases as an additional variable to the other IMDC variables improves the prognostic predictive power of the model.

CApecitabine plus Radium-223 (Xofigo\u2122) in breast cancer patients with BONe metastases (CARBON): study protocol for a phase IB/IIA randomised controlled trial

BackgroundA substantial proportion of breast cancer patients develop metastatic disease, with over 450,000 deaths globally per year. Bone is the most common first site of metastatic disease accounting for 40% of all first recurrence and 70% of patients with advanced disease develop skeletal involvement.Treatment of bone metastases currently focusses on symptom relief and prevention and treatment of skeletal complications. However, there remains a need for further treatment options for patients with bone metastases. Combining systemic therapy with a bone-targeted agent, such as radium-223, may provide an effective treatment with minimal additional side effects.Methods/designCARBON is a UK-based, open-label, multi-centre study which comprises an initial safety phase to establish the feasibility and safety of combining radium-223 given on a 6-weekly schedule in combination with orally administered capecitabine followed by a randomised extension phase to further characterise the safety profile and provide preliminary estimation of efficacy.DiscussionThe CARBON study is important as the results will be the first to assess radium-223 with chemotherapy in advanced breast cancer. If the results find acceptable rates of toxicity with a decrease in bone turnover markers, further work will be necessary in a phase II/III setting to assess the efficacy and clinical benefit.Trial registrationISRCTN, ISRCTN92755158, Registered on 17 February 2016.

Development of central nervous system metastases as a first site of metastatic disease in breast cancer patients treated in the neoadjuvant trials GeparQuinto and GeparSixto

BackgroundThe incidence of central nervous system (CNS) metastases in breast cancer patients is rising and has become a major clinical challenge. Only few data are published concerning risk factors for the development of CNS metastases as a first site of metastatic disease in breast cancer patients. Moreover, the incidence of CNS metastases after modern neoadjuvant treatment is not clear.MethodsWe analyzed clinical factors associated with the occurrence of CNS metastases as the first site of metastatic disease in breast cancer patients after neoadjuvant treatment in the trials GeparQuinto and GeparSixto (n = 3160) where patients received targeted treatment in addition to taxane and anthracycline-based chemotherapy.ResultsAfter a median follow-up of 61 months, 108 (3%) of a total of 3160 patients developed CNS metastases as the first site of recurrence and 411 (13%) patients had metastatic disease outside the CNS. Thirty-six patients (1%) developed both CNS metastases and other distant metastases as the first site of metastatic disease. Regarding subtypes of the primary tumor, 1% of luminal A-like (11/954), 2% of luminal B-like (7/381), 4% of HER2-positive (34/809), and 6% of triple-negative patients (56/1008) developed CNS metastases as the first site of metastatic disease.In multivariate analysis, risk factors for the development of CNS metastases were larger tumor size (cT3–4; HR 1.63, 95% CI 1.08–2.46, p = 0.021), node-positive disease (HR 2.57, 95% CI 1.64–4.04, p < 0.001), no pCR after neoadjuvant chemotherapy (HR 2.29, 95% CI 1.32–3.97, p = 0.003), and HER2-positive (HR 3.80, 95% CI 1.89–7.64, p < 0.001) or triple-negative subtype (HR 6.38, 95% CI 3.28–12.44, p < 0.001).ConclusionsEspecially patients with HER2-positive and triple-negative tumors are at risk of developing CNS metastases despite effective systemic treatment. A better understanding of the underlying mechanisms is required in order to develop potential preventive strategies.

Incidence, patterns and prognosis of first distant recurrence after surgically treated early stage endometrial cancer: Results from the multicentre FRANCOGYN study group

Patterns of distant metastatic failure of endometrial cancer (EC) by specific anatomic site are not well described in the literature. In this manuscript, we evaluated the metastatic patterns of EC cancer and analysed the potential distribution of metastatic disease in this malignancy. MethodsA total of 1444 women with EC were identified. Of which we extracted women with locoregional and distant recurrence or with distant recurrence alone. Women were scored based on first site of metastasis: multiple versus one site: bone, brain, lung, liver or sus diaphragmatic lymph nodes. Results110 women developed distant metastatic disease with (n = 37(33.6%)) or without (n = 73(66.4%)) locoregional recurrence, including 39 women with exclusive first site of metastatic disease and 34 women with multiple sites of metastatic disease. When considering all women, the most common exclusive first site of metastasis was lung (42.8%). The median time to develop distant metastases was shorter after the completion of treatment for exclusive brain metastatic disease compared with other sites of metastatic− disease (7 months vs, 9 for lung, 10 for liver, 19 for bone and 27 months for sus-diaphragmatic LN; P = 0.004). The rate of 3-year overall survival was higher in the sus-diaphragmatic LN metastase group (83.3% vs 50.6% for lung, 37.3% for bone, 16.7% for brain and 0% for liver; P = 0.0059). ConclusionThe present study has demonstrated the site-specific patterns of metastases. These data support current clinical practice of screening for site-specific metastatic disease after initial treatment of early stage EC based on concerning women-specific signs or symptoms.

Abstract P1-07-11: Risk factors for the development of brain metastases (BM) in 506 patients with HER2-positive breast cancer (HER2+ BC): A single institutional retrospective analysis

Abstract Introduction: BC is the most common malignancy in women. HER2+ BC is the 2nd leading cause of BM after lung cancer. The prognosis of BC patients with BM is poor. Determining risk factors for the development of BM is warranted in order to establish more accurate screening for patients at risk. Material and Methods: This is a retrospective analysis of patients with HER2+ BC treated at Institut Jules Bordet, Belgium, between 2000 and 2014. Patients' charts were reviewed for disease characteristics, treatment regimens for primary and metastatic disease as well as clinical outcomes. Statistical analyses were conducted with SAS 9.4 using Cox regression analyses, log-rank test and Kaplan-Meier method. Results: A total of 506 patients with HER2+ BC were included in the analysis. Median age was 52.7 years (range, 21.5-89.2 years). In total, 138 (27.3%) were diagnosed with metastatic BC and 74 (14.6%) had BM. Among the 138 metastatic patients, 12 (8.7%) had BM as a first site of metastatic disease and 3 (2.2%) developed BM as only site of distant relapse. Median overall survival (OS) for patients with BM was 1.74 years (range, one month-3.2 years). In multivariate analysis, risk factors for the development of BM at time-point of initial BC diagnosis were de-novo metastatic disease (hazard ratio [HR] 4.46; p&amp;lt;0.0001), postmenopausal status (HR 16.65; p&amp;lt;0.0001), and adjuvant breast radiotherapy (HR 1.79; p=0.0198). Identified risk-factors for BM at the time-point of metastatic disease were postmenopausal status (HR 1.90; p=0.0464), the presence of lung metastases (HR 2.61; p=0.0004), an interval of more than one year between initial BC diagnosis and development of metastatic disease (HR 1.91; p=0.0179) and age of &amp;lt;40 years (HR 1.78; p=0.0353). In this cohort, biological factors such as hormone receptor status, degree of HER2 amplification and tumor grade had no impact on the development of BM both in univariate and multivariate analysis. Furthermore, the type of systemic treatment in the adjuvant or metastatic setting (chemotherapy, anti-HER2 treatment) did not modulate the risk for BM. The combination of local treatment (surgery, stereotactic radiosurgery [SRS] or whole brain radiotherapy [WBRT]) and anti-HER2 directed therapy as first-line therapy for BM was associated with an improvement in overall survival (OS) that was more pronounced for tyrosine kinase inhibitors (HR 0.13; 95% confidence interval [CI] 0.05-0.33); p&amp;lt;0.0001) than for trastuzumab and/or pertuzumab (HR 0.53; 95% CI 0.24-1.15; p=0.1085). Conclusion: The development of BM is a common complication in patients experiencing metastatic HER2+ BC. Until now, no imaging screening for BM is recommended in this patient population. Compared to WBRT, surgery and SRS are associated with an improvement in OS and/or less cognitive impairment. However, these treatment approaches are limited to patients with less extensive BM disease. In this context, randomized trials examining the role of MRI screening for BM in metastatic HER2+ BC with high risk features are warranted. Citation Format: Maurer C, Tulpin L, Dumitrescu C, de Azambuja E, Moreau M, Paesmans M, Nogaret J-M, Piccart M, Awada A. Risk factors for the development of brain metastases (BM) in 506 patients with HER2-positive breast cancer (HER2+ BC): A single institutional retrospective analysis [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-07-11.

Prognosis of leptomeningeal metastases from melanoma: A case series of 28 patients.

e13550 Background: Leptomeningeal metastasis (LM) are reported in 5-25% of patients with melanoma. However, only very few large contemporary cohorts of melanoma patients with LM have been published. Methods: We report on a case series of 28 consecutive patients with LM from melanoma (BRAF mutated in 14 cases, of 19 tested) diagnosed between April 2007 and April 2016, and treated for LM using a combination of systemic treatment, intra-cerebrospinal fluid (CSF) therapy and radiotherapy according to prior treatments and the presentation of LM. Results: The median age at LM diagnosis was 49.5 years (range 27-73). Median ECOG-performance status was 2 (0-4). Concomitant brain metastases were present in all but 4 patients at LM diagnosis. LM was the first site of metastatic disease for only 2 patients. Median time from melanoma diagnosis to LM diagnosis was 0.33 years in patients with metastatic disease at melanoma diagnosis (4 patients) and 4.5 years in patients without metastatic disease at melanoma diagnosis (24 patients). First line treatment for LM was a combination of intra-CSF (liposomal cytarabine) and systemic treatments in 25 cases, and systemic treatment alone in 3 cases. Systemic treatments include chemotherapy (n = 18), targeted therapy (BRAF inhibitor n = 9; MEK inhibitor, n = 3) and immunotherapy (n = 4). No radiotherapy was performed. Ten patients received more than one line of treatment for LM. Median progression-free survival with first line treatment was 1.75 months. Responses or stabilization (for at least 2 months) were observed in only 7 patients. Median overall survival (OS) for the whole cohort was 3.08 months. Conclusions: The prognosis of patients with LM from melanoma remains poor. The role of new agents such as targeted therapies and immunotherapy for the treatment of LM is still not well defined. Adequate use of intrathecal chemotherapy, targeted therapy and immunotherapy could improve the survival of these patients.

Radiofrequency ablation in the treatment of liver metastases from colorectal cancer

Colorectal cancer (CRC) is the most common malignant tumour and the third leading cause of cancer deaths in USA. For advanced CRC, the liver is the first site of metastatic disease; approximately 50 % of patients with CRC will develop liver metastases either synchronously or metachronously within 2 years after primary diagnosis. Hepatic resection (HR) is the only curative option, but only 15-20% of patients with liver metastases from CRC (CRLMs) are suitable for surgical standard treatment. In patients with unresectable CRLMs downsizing chemotherapy can improve resectability (16%). Modern systemic chemotherapy represents the only significant treatment for unresectable CRLMs. However several loco-regional treatments have been developed: hepatic arterial infusion (HAI), cryosurgical ablation (CSA), radiofrequency ablation (RFA), microwave ablation and selective internal radion treatment (SIRT). During the past decade RFA has superseded other ablative therapies, due to its low morbidity, mortality, safety and patient acceptability. The objective of this study was to systematically review the role of radiofrequency ablation (RFA) in the treatment of CRLMs. We performed electronic searches in the following databases:CENTRAL, MEDLINE and EMBASE. Current trials were identified through the Internet using the Clinical-Trials.gov site (to January 2, 2012) and ASCO Proceedings. The reference lists of identified trials were reviewed for additional studies. Randomized clinical trials (RCTs), quasi-randomised or controlled clinical trials (CCTs) comparing RFA to any other therapy for CRLMs were included. Observational study designs including comparative cohort studies comparing RFA to another intervention, single arm cohort studies or case control studies have been included if they have: prospectively collected data, ten or more patients; and have a mean or median follow-up time of 24 months. Patients with CRLMs who have no contraindications for RFA. Patients with unresectable extra-hepatic disease were also included.Trials have been considered regardless of language of origin. A total of 1144 records were identified through the above electronic searching. We included 18 studies: 10 observational studies, 7 Clinical Controlled Trials (CCTs) and an additional 1 Randomized Clinical Trial (RCT) (abstract) identified by hand searching in the 2010 ASCO Annual Meeting. The most appropriate way of summarizing time-to-event data is to use methods of survival analysis and express the intervention effect as a hazard ratio. In the included studies these outcome are mostly reported as dichotomous data so we should have asked authors research data for each participant and perform Individual Patient Data (IPD) meta-analysis. Given the study design and low quality of included studies we decided to give up and not to summarize these data. Seventeen studies were not randomised and this increases the potential for selection bias. In addition, there was imbalance in the baseline characteristics of the participants included in all studies. All studies were classified as having a elevate risk of bias. The assessment of methodological quality of all non-randomized studies included in meta-analysis performed by the STROBE checklist has allowed us to identify several methodological limits in most of the analysed studies. At present, the information from the single RCT included (Ruers 2010) comes from an abstract of 2010 ASCO Annual Meeting where the allocation concealment was not reported; however in original protocol allocation concealment was adequately reported (EORTC 40004 protocol). The heterogeneity regarding interventions, comparisons and outcomes rendered the data not suitable. This systematic review gathers information from several controlled clinical trials and observational studies which are vulnerable to different types of bias. The imbalance between characteristics of patients in the allocated groups appears to be the main concern. Only one randomised clinical trial (published as an abstract), comparing 60 patients receiving RFA plus CT versus 59 patients receiving CT alone, was identified. This study showed that PFS was significantly higher in the group that received RFA. However, it was not able to provide information on overall survival. In conclusion, evidence from the included studies are insufficient to recommend RFA for a radical oncological treatment of CRLMs.

Abstract 477: Evaluation of tumor uptake and retention in a mouse model of breast cancer brain metastases by I-124 positron emission tomography (PET) imaging

Abstract The central nervous system (CNS) is emerging as the first site of metastatic disease in women with breast cancer. Women with hormone unresponsive tumors and/or HER-2 overexpressing tumors are disproportionately affected. Breast cancer brain metastasis represents a unique therapeutic challenge because of the limited access to the CNS of many anticancer drugs. Radioiodide (131I) therapy may provide a therapeutic alternative since over 70% of invasive breast cancers, and some brain metastases express the sodium-iodide symporter (NIS). The rationale for this approach is based on the success of 131I radioablative therapy for thyroid cancers. Objectives: To evaluate CNS permeability, kinetics of radioiodine uptake and retention in our NIS expressing breast cancer brain metastasis (BCBM) mouse model. Methods: A brain-seeking clone of the hormone independent ((ER-/PR-/HER2-) human breast cancer cell line MDA-MB-231 (231BR) was transduced with a lentiviral vector carrying a bicistronic cassette with NIS and the firefly luciferase (Fluc) genes separated by an internal ribosomal entry site (IRES). Single cell clones were selected and characterized for iodide uptake and bioluminescence. 1 Million NIS-Fluc-MDAMB231 cells were implanted subcutaneously in the mammary fat pad (mfp) of nude mice (NCr nude) and tumor growth was monitored by serial in vivo bioluminescent imaging and external tumor volume measurements. NIS-Fluc mfp tumor xenografts were then explanted, 1×1 mm pieces excised and inserted stereotactically into the basal ganglia of the mouse. Bioluminescence imaging was used to follow intracranial tumor growth over time. Kinetics of 123I uptake and biodistribution in mfp xenografts mice was evaluated by ex vivo radioactive count and biodistribution of 124I was evaluated in vivo by positron emission tomography (PET) imaging on BCBM mice. Results: Brain tumors 124I uptake was evident on the PET 1 hour post injection of the tracer, with values ranging from 1.60 to 3.25 % injected dose/gram of tissue (%ID/g) whereas thyroid uptake was between 6.99 and 11.19 %ID/g. At 20 hours post injection, the brain tumors showed a sustained 124I retention while uptake in most other organs (except thyroid and stomach) was close to background levels; brain tumor to normal brain tissue mean uptake ratio was ranging from to 217.12 to 541.50 (versus 2.02 to 2.68 at 1 hour post injection). The kinetics of 124I uptake was in agreement with the data obtained from the ex vivo counts in mfp xenografts. Conclusions: We have characterized the kinetics of iodide uptake and retention in a model of breast cancer brain metastases. We showed that NIS expressing BCBM are able to concentrate and retain 124I for prolonged period of time. These results together with dosimetric calculations will allow us to adjust the dosage and timing for 131I therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 477.

Liver as the First and Only Metastatic Site for Prostate Cancer: A Rare Presentation

Purpose: Prostate cancer most frequently metastasizes to the bone (83-98%) and the viscera (45%). Ascitis and Liver metastasis of prostate cancer without bony involvement is very rare. We report one such case. Case: A 67 year old Caucasian male with history of Stage II (T1c NO MO) prostate adenocarcinoma with Gleason score 8 S/P brachytherapy and radiation therapy 6 months previously, presented with 2 day history of right sided abdominal pain associated with nausea and vomiting. Urine output had also progressively decreased and he was found to be in acute renal failure. On examination, he had a distended abdomen and examination consistent with ascites. There was no palpable lymphadenopathy. Abdominal CT showed massive ascites, bilateral renal cysts and non obstructing renal calculi. His Liver Function tests showed Alkaline phosphatase 407 U/L, AST 865 U/L and ALT 107 U/L. Ascitic fluid cytology revealed adenocarcinoma with special immunostains consistent with his history of prostate cancer. His PSA increased from 2.6 (6 months previous) to 180 ng/ml. MRI of the abdomen showed hepatomegaly with multiple masses throughout all lobes of liver, highly suspicious for multi focal HCC. His AFP was normal. Liver biopsy revealed the diagnosis of metastatic prostate adenocarcinoma. Bone scan was negative for any metastatic disease. He was started on Lupron® injections and daily Casodex®. Discussion: Bone is the most frequent site of metastasis in prostate cancer. Bubendorf, et al. reported 25% liver metastasis in an autopsy series of 1,589 patients with hormone refractory prostate cancer. However, in most of these pts the primary tumor was larger than 8 cm and there was involvement of other organs. Pouessel, et al. reported 28 patients with prostate cancer. Six patients had liver as the first site of metastatic disease and for only one of them, liver was found to be the only metastatic site. The median time for initial diagnosis was 38 months. Conclusion: We believe the case described here is one of the very rare instances in which liver is the first and only metastatic site for prostate cancer.

Outcome after Resection of Hepatic and Pulmonary Metastases of Colorectal Cancer

IntroductionMultimodal therapies (especially surgery of metastases and “aggressive” chemotherapy) in patients with metastases of colorectal cancers (CRC) are increasingly performed and may provide long-term survival in selected patients with more than one location of metastases. In the current literature, there are only few studies with relatively low patient numbers reporting on the outcome after resection of both hepatic and pulmonary metastases of CRC. We therefore evaluated survival of patients who underwent sequential resection of hepatic and pulmonary metastases under potentially curative intention. Material and MethodsFrom 1987 until 2006, 44 patients (32% female; median age, 58 years) with hepatic and pulmonary CRC metastases underwent resections at both metastatic sites. The primary CRCs were in 50% rectal and in 50% colonic carcinomas (61% node positive, all with free resection margins). Metastases occurred synchronously (regarding primary CRC) in 32% of the patients. In 86%, liver resection was performed prior to pulmonary resection. The first resection of metastases was performed a median of 16 months after resection of the primary CRC; the median interval between the first and the second resection of metastases was 7 months. Forty-seven percent of the patients also underwent at least a third metastasectomy. During resection of the first and second site of metastases, free margins were achieved in 98% and 95%, respectively. Survival analysis was performed using Kaplan–Meier and Cox regression methods. ResultsThe 5-year survival rates (SV) were 64% after initial surgery of CRC, 42% after the first resection of metastases, and 27% after the last metastasectomy. Patients with synchronous metastases had a 5-year SV after first metastasectomy of 43% and in patients with metachronous metastases of 41% (n.s.). The location of the primary tumor (20% 5-year SV in rectal vs. 57% in colonic cancer; p < 0.02) and the lung as primary site of metastatic disease (5-year SV 0% vs. 60% in patients with primarily hepatic metastases only; p < 0.001) significantly influenced survival in univariate analysis. Patients with rectal cancer had a significantly higher frequency of the lung as first metastatic site (46%) compared to patients with colonic cancer (14%; p < 0.03). Multivariate survival analysis revealed the lung as first metastatic site and as the sole significant independent factor for the outcome (p < 0.001; relative risk vs. liver first metastases 4.7). ConclusionIn selected patients with metastasized CRC resection of both hepatic and pulmonary metastases may improve survival rates or even provide long-term survival. Patients with lung as the first site of metastatic disease (either lung only or in combination with hepatic metastases) have a significantly worse outcome than patients with metastases primarily confined to the liver.

The gallbladder as the first site of metastatic disease in a patient with melanoma

Hematol Oncol Stem Cell Ther 1(3) July 2008 hemoncstem.edmgr.com 197 The first case of primary melanoma of the galla bladder was published in 1907, based on aua topsy findings of 40ayearaold female.1 There have only been 20 further cases of primary melanoma of the gallbladder published since that time. Secondary melanoma, by comparison, is much commoner, accounta ing for oneahalf of the metastatic tumors observed in this organ.2 We present this case to highlight the occura rence of melanoma metastatic to the gallbladder and to promote earlier investigations and/or interventions in patients with biliary symptoms who have a history of melanoma.

Clinical Course of Breast Cancer Patients With Metastases Limited to the Liver Treated With Chemotherapy

The purpose of this retrospective analysis was to describe the clinical course of patients with breast cancer with liver metastases alone who were treated on doxorubicin/cyclophosphamide or taxane-containing chemotherapy protocols at the M. D. Anderson Cancer Center. A total of 2,193 patients with metastatic breast cancer were treated on prospective clinical protocols at the University of Texas M. D. Anderson Cancer between 1973 and 2003. Among those, 132 were identified as having the liver as the first site of metastatic disease. The following information was obtained from the medical records: gender, age, race, performance status, menopausal status, hormonal receptor status, laboratory data, primary treatment, prior systemic treatment, disease-free interval, extent of metastatic disease, response to chemotherapy, site of progression, time to tumor progression, overall survival, and cause of death. Of the patients 62% received anthracycline-based regimens and 38% received anthracycline- and taxane-based regimens on various clinical protocols as the initial therapy for metastatic disease. The median follow-up of the patients was 52 months. The overall objective response rate was 66.4%; 16.4% of the patients achieved complete responses. The median time to progression was 14 months. Progression-free survival rates were 56% and 30% at 12 and 24 months, respectively. The median overall survival was 25 months. Sixteen patients (12.1%) survived longer than 60 months. There was a statistically inverse relation between a high lactate dehydrogenase level and achieving a complete response (P < 0.05). Age > or =50 years, extent of liver metastases, performance status, and lactate dehydrogenase and albumin levels are significantly related to progression-free survival (P < 0.05). Year of liver metastases diagnosis, extent of liver metastases, performance status, and albumin level are significantly related to overall survival (P < 0.05). This retrospective analysis demonstrated that patients with liver metastases only had high objective response rates and encouraging results for median survival obtained with currently available cytotoxic agents.

Liver metastases in prostate carcinoma: clinical characteristics and outcome

To assess the clinical characteristics and outcome of patients with liver metastases in prostate carcinoma. From January 1995 to December 2005, 345 patients with metastatic prostate cancer were prospectively recorded in the database of the Montpellier Cancer Centre, France. The clinical characteristics and outcome of 28 patients who developed liver metastases during the course of the disease were analysed. Six patients had liver metastases as the first site of metastatic disease, and for one of them, liver was the only metastatic site. All but one patient had hormone-refractory disease. Serum measurement of neuroendocrine markers showed increased levels of chromogranin A and neurone-specific enolase in 84% and 44% of patients, respectively. Six patients had a pathological analysis; there were two different histological patterns in liver biopsies, i.e. four were adenocarcinomas with a moderate (one patient) or poor (three) differentiation and two were neuroendocrine carcinomas. Three patients had no treatment because of a poor performance status. One patient had hormone therapy for synchronous liver metastases at diagnosis as the first-line treatment; other patients were treated with chemotherapy. The median (range) overall survival was 6 (1-27) months; the median survival of patients for whom liver was part of the initial metastatic pattern was 14 months. Liver metastases are not very rare but appear to be a rather late event in the course of the disease. They are frequently associated with neuroendocrine characteristics.

Superficial parotidectomy in the treatment of cutaneous melanoma of the head and neck.

The preauricular lymph nodes are frequently the first site of metastatic disease from primary malignant melanoma of the upper two-thirds of the face or the anterior scalp. For these patients, or those with adjacent metastatic nodal disease, the prognosis is poor. The median survival of 13 such patients presented was 2 years, with two long-term survivors at 4 and 6 years. Palliative surgery can, however, prevent uncontrolled locoregional disease. Patients with palpable preauricular and cervical node disease should be treated by facial nerve-preserving parotidectomy and radical neck dissection. When no cervical nodes are palpable in patients with preauricular node metastasis, peroperative jugulodigastric node biopsy and frozen-section histopathological examination are useful to select patients for radical neck dissection.

Bisphosphonates in Metastatic Breast Cancer

Bone is the most common site of metastatic involvement in breast cancer. About 20–30% of patients with breast cancer have osseous metastases as the first site of metastatic disease and about 60–70% of patients will develop metastases to the bone during the course of their disease. Although bone metastases have usually only limited impact on overall survival, they cause significant morbidity due to pain, pathological fractures, hypercalcemic episodes or spinal cord compression. Bisphosphonates are a class of agents that can effectively reduce the number of serum calcium levels and activity of osteoclasts and therefore reduce bone complications in breast cancer. Bisphosphonates are the current standard of care in patients with tumour-induced hypercalcemia (TIH) since they achieve rapid normalisation in the majority of patients. Zoledronic acid, a third generation bisphosphonate, has recently been shown to be significantly more effective than the previous standard, pamidronate, in the treatment of TIH. In patients with bone metastases, large randomised clinical trials have shown the efficacy of bisphosphonates in addition to hormone therapy or chemotherapy in reducing and delaying skeletal complications and associated pain and in improving quality of life. A clear positive impact on overall survival, however, has not been observed. The optimal duration of treatment is currently unclear. Therefore, treatment with bisphosphonate should be continued until evidence of substantial decline in patient's general performance status. Until recently, best results were obtained with intermittent intravenous therapy with aminobisphosphonates resulting in a risk reduction of developing skeletal complications of at least 13%. There is evidence for a dose effect with pamidronate resulting in higher efficacy at doses of 90 mg compared to 45 or 60 mg. New data indicate a potential benefit of zoledronic acid over pamidronate in patients with osteolytic metastases. Oral bisphosphonates can also effectively reduce the risk of skeletal events. Treatment with oral aminobisphosphonate pamidronate was limited by gastrointestinal toxicity, however, oral ibandronate has recently been shown to be tolerable and highly effective. These data might increase the role of oral bisphosphonates in the treatment of metastatic breast cancer. In patients without evidence of bone involvement, three randomised trials have failed to show a clear benefit for bisphosphonates. Thus, bisphosphonate treatment cannot be recommended in this setting outside clinical trials. In conclusion bisphosphonates (intravenous or oral) are an effective treatment in patients with advanced breast cancer and clinically evidence bone metastases. They can reduce skeletal events and improve quality of life and are therefore recommended in all patients with bone metastases.

Recent advances in the care of the patient with malignant melanoma.

The authors review the recent advances in the surgical care, staging, and adjuvant treatment of the patient with melanoma. Melanoma care has not changed significantly in the last 20 years, and the controversy of elective lymph node dissections in this disease continues to be discussed. Two advances in the care of the patient with melanoma have occurred in the last 3 years to make this an exciting time for clinicians and to offer more hope for the patients with this disease. The concept of the sentinel lymph node (SLN), defined by Morton as the first node in the lymphatic basin that drains the primary melanoma, has been documented to contain the first site of metastatic disease. This technology can be used to stage nodally the melanoma patient, identifying the subgroup of patients (stage III) who have a 5-year survival rate less than 50%. Members of this group are candidates for effective adjuvant therapies. A review of the surgical techniques of melanoma care, including recently reported new studies of elective node dissection (ELND) and SLN biopsy in patients with melanoma was performed. In addition, the Eastern Cooperative Oncology Group (ECOG) 1684 trial, which was the basis for the Food and Drug Administration approval of adjuvant interferon-alpha-2b (IFN-alpha-2b) is discussed. The Intergroup Melanoma Trial has reported a survival benefit for performing ELND in patients with melanoma and tumor thickness between 1 and 2 mm or in patients that are younger than 60 years of age. With six reports in the literature that show there is an order to melanoma nodal metastases and that the SLN histology is reflective of the histology of the remainder of the nodal basin, the more conservative SLN biopsy can be performed to adequately stage nodally the patient with melanoma. Patients with nodal metastases who are rendered free of disease with surgical resection have the most to benefit from adjuvant IF-alpha-2b. If one considers only the lymph node-positive group of patients, the survival benefit associate with adjuvant IFN is significant (p = 0.008). New standards of care for the melanoma patient have been established. Patients at high risk for recurrence have been shown to experience a survival benefit with adjuvant IFN-alpha-2b. With these data, the argument can be made that all patients with melanoma greater than 1 mm should have a nodal staging procedure. Selective lymphadenectomy with SLN biopsy is the least morbid procedure that can be used to obtain this information. If surgeons do not have the nuclear medicine or pathology support to perform lymphatic mapping, then the guidelines of the Intergroup Melanoma Study should be used to apply ELND in a selective fashion. In this way, patients are identified with micrometastatic disease early in their clinical course and can be offered the survival benefit of adjuvant therapy.

1024 Axillary surgery can be avoided in selected breast cancer patients: Analysis of 401 patients

Until now axillary, dissection has been considered an integral part of breast cancer treatment and is routinely carried out even after the introduction of breast conserving surgery into clinical practice. However we believe that axillary surgery can be avoided in selected breast cancer patients. In this perspective we have analyzed 401 breast cancer patients who underwent breast surgery without axillary dissection from January 1986 to June 1994. In these patients axillary dissection was spared in consideration of some reasons, principally age, small breast cancer and previous contralateral tumor. 323 (81%) patients were in post-menopausal whereas 78 (19%) in pre-menopausal status and the mean age was 62.9 years (range 30–83). No patients had clinically involved nodes in homolateral axilla, and 312 patients (78%) had no palpable node. 216 out of 401 patients (53.6%) had a pathological tumor diameter ≤1 cm, 133 (33.6%) were between 1 and 2 cm, whereas 38 (9.5%) had a tumor size > 2 cm. The remaining 4 patients had no evaluable diameter due to previous incisional biopsy. The histological diagnosis was ductal infiltrating carcinoma in 188 cases (46.9%), associated to DCIS in 73 cases (18.2%) or to lobular infiltrating carcinoma (LIC) in 17 cases (4.2%). LIC was present only as histotype in 59 cases (14.7%). Breast conservative surgery was performed in 383 patients (95.6%) and only 18 patients (4.4%) underwent total mastectomy in consideration of the presence of extensive intraductal component. 257 patients (64.1%) received radiotherapy to the operated breast. In elderly patients an adjuvant hormonotherapy was preferred considering the hormonal receptorial status. An accurate follow-up > 24 months was obtained in 209 patients (mean 46.5 months, range 24–93); 25 patients died, 12 for uncorrelated or unknown causes. 20 patients had distant metastases only and 2 patients had axillary and distant metastases syncronally. 27 patients had clinically axillary metastases as only and first site of metastatic disease: 21 patients underwent full axillary dissection showing pathological metastases in 17 cases. The mean number of metastatic nodes was 6 (1–32) and the mean diameter of the primary tumour in these metastatic cases was 16.8 mm. Only one case had a tumour diameter

Pulmonary Metastatic Disease in Ameloblastoma

Ameloblastoma is a rare disease of odontogenic origin with indeterminate metastatic potential. The first site of metastatic disease is usually the lung. We report aggressive surgical treatment of a patient with bilateral disease with five subsequent recurrences. A review of the literature suggests that in the absence of effective chemotherapy or radiation, surgery should be considered the treatment of choice for metastatic ameloblastoma confined to the lung.