Whole‐body magnetic resonance imaging in the detection of skeletal metastases in patients with prostate cancer

Whole‐body MRI is an effective method for evaluating the entire skeletal system in patients with metastatic disease. This study aimed to compare whole‐body MRI and radionuclide bone scintigraph in the detection of skeletal metastases in patients with prostate cancer. Patients with prostate cancer at high risk of skeletal metastasis with (i) prostate‐specific antigen of ≥50 ng/mL; (ii) composite Gleason score of ≥8 with prostate‐specific antigen of >20 ng/mL; or (iii) node‐positive disease were enrolled in this prospective study before systemic treatment was initiated. Whole‐body MR images and bone scans of 39 patients were analysed. Seven patients had bone metastases on bone scans, while seven patients had skeletal metastases by whole‐body MRI, with concordant findings only in four patients. Compared with the ‘gold standard’, derived from clinical and radiological follow‐up, the sensitivity for both bone scans and MRI was 70%, and the specificity for both was 100%. Magnetic resonance imaging detected 26 individual lesions compared with 18 lesions on bone scans. Only eight lesions were positive on both. Bone scans detected more rib metastases, while MRI identified more metastatic lesions in the spine. Whole‐body MRI and radionuclide bone scintigraphy have similar specificity and sensitivity and may be used as complementary investigations to detect skeletal metastases from prostate cancer.     

Oncologic outcomes of surgically managed primary pelvic soft tissue sarcoma; tumour biology or surgical constraints of the true pelvis?

BackgroundPelvic soft tissue sarcomas are rare. Potentially curative resection remains challenging due to anatomical constraints of true pelvis and tumour spread through various anatomical hiatus. We sought to review the oncological outcomes of surgically managed cases at our centre and determine whether outcomes differ for patients with localised (limited to pelvis) versus extensive disease (with extra-pelvic extension).MethodsSixty-seven patients who underwent surgical resection with curative intent at the centre for primary, non-metastatic, WHO intermediate to high-grade soft tissue sarcoma of the true pelvis from January 2012 through January 2020 were analysed. Establishment of the extent of disease was made by review of pre-treatment imaging and surgical notes. Oncologic endpoints examined were resection margin, recurrence rate, disease-free and overall survival.ResultsRates of complete oncological resection and disease control were similar for tumours with localised or extensive disease. On logistic regression analysis, tumour grade, and a negative resection margin (R0) correlated with the risk of recurrence (p=<0.05). On further multinomial analysis, R0 resection was associated with improved local control, but not metastatic relapse (p = 0.003).5-year local recurrence-free and distant metastasis-free survival were 61.3% and 67.1%, respectively. Five and 10-year overall survival were 64% and 36%, respectively. Age >50 years and high tumour grade were associated with a worse outcome (p < 0.05).ConclusionsWhen potentially curative surgery is performed for pelvic sarcoma, disease-extent does not influence oncologic outcomes. While a complete oncologic resection determines the risk of local recurrence, tumour grade and metastatic relapse remain primary prognostic determinants for overall survival.     

Future perspectives of uveal melanoma blood based biomarkers

Uveal melanoma (UM) is the most common primary intraocular malignancy affecting adults. Despite successful local treatment of the primary tumour, metastatic disease develops in up to 50% of patients. Metastatic UM carries a particularly poor prognosis, with no effective therapeutic option available to date. Genetic studies of UM have demonstrated that cytogenetic features, including gene expression, somatic copy number alterations and specific gene mutations can allow more accurate assessment of metastatic risk. Pre-emptive therapies to avert metastasis are being tested in clinical trials in patients with high-risk UM. However, current prognostic methods require an intraocular tumour biopsy, which is a highly invasive procedure carrying a risk of vision-threatening complications and is limited by sampling variability. Recently, a new diagnostic concept known as “liquid biopsy” has emerged, heralding a substantial potential for minimally invasive genetic characterisation of tumours. Here, we examine the current evidence supporting the potential of blood circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), microRNA (miRNA) and exosomes as biomarkers for UM. In particular, we discuss the potential of these biomarkers to aid clinical decision making throughout the management of UM patients.Subject terms: Eye cancer, Biomarkers     

Metastasis-directed Therapy in Prostate Cancer: Prognostic Significance of the ESTRO/EORTC Classification in Oligometastatic Bone Disease

AimsOligometastatic disease (OMD) represents a spectrum of clinical scenarios and various classification systems have been proposed. Bone-only OMD can occur in patients with advanced prostate cancer and validated decision-making tools are needed to assist patient selection for metastasis-directed therapy. The aim of the present study was to determine the prognostic utility of a classification system for OMD.Materials and methodsA retrospective review was conducted of all patients with bone-only oligometastatic prostate cancer treated with stereotactic body radiotherapy (SBRT) since November 2011. SBRT was delivered using CyberKnife® and gantry-based linear accelerator platforms. All patients were classified into oligometastatic states based on the European Society for Radiotherapy and Oncology/European Organisation for Research and Treatment of Cancer (ESTRO/EORTC) classification system. Kaplan–Meier and Cox regression analyses were carried out to determine the prognostic utility of this classification system.ResultsIn total, 105 patients with 145 osseous metastases were treated over 119 sessions. The median follow-up after SBRT was 23 months (interquartile range 10–39.8). Twelve patients had died after a median time of 31 months. The 3-year metastatic progression-free survival was 23% (95% confidence interval 13–32) and the 3-year overall survival was 88% (95% confidence interval 80–96). Patients in a metachronous oligometastatic state were 4.50 (95% confidence interval 1.19–17.10, P = 0.03) times more likely to experience metastatic progression compared with those with synchronous oligometastases, and 6.69 (95% confidence interval 1.05–42.50, P = 0.04) times more likely to experience any failure. Hazard ratio magnitudes increased for patients in a repeat oligometastatic state. The multivariate model for both metastatic progression-free survival and failure-free survival found prostate-specific antigen doubling time <4 months (P = 0.002; P = 0.05) to independently predict for progression.ConclusionThe ESTRO/EORTC classification of OMD predicts for progression in patients treated with SBRT for bone-only oligometastatic prostate cancer at our institution. Further validation in prospective series over multiple tumour sites is needed. These characterisation factors should be assessed in patients considered for metastasis-directed therapy together with established prognostic features.     

Skull-base metastases

Summary Metastasis to the skull-base particularly affects patients with carcinoma of the breast and prostate. Clinically, the key feature is progressive ipsilateral involvement of cranial nerves. Five syndromes have been described according to the metastatic site including the orbital, parasellar, middle-fossa, jugular foramen and occipital condyle syndromes. Magnetic resonance imaging (MRI) is nowadays the most useful examination to establish the diagnosis but plain films, CT scans with bone windows and isotope bone scans remain helpful to demonstrate bone erosion. Normal imaging studies do not exclude the diagnosis. The treatment depends on the nature of the underlying tumor. Radiotherapy is generally the standard treatment, while some patients with chemosensitive or hormonosensitive lesions benefit from chemotherapy or hormonotherapy and selected patients from surgical removal. Gamma Knife radiosurgery is sometimes a useful alternative, particularly for previously irradiated skull-base regions, and for small tumors (diameter < 30 mm). The overall prognosis is poor, with an overall median survival of about 2.5 years, probably because skull-base metastases appear late in the course of the disease.     

Prognostic value of the G8 and modified-G8 screening tools for multidimensional health problems in older patients with cancer

BackgroundThe G8 screening tool has been developed to identify older cancer patients requiring a geriatric assessment for tailoring therapy. Little is known about its prognostic value, particularly by tumour site. An optimised version has been recently developed, but no prognostic information is available. We compared the prognostic value of both instruments overall and by tumour site.MethodsData were from a prospective cohort of cancer patients ≥70 years old referred to 1 of 6 French geriatric oncology clinics between 2007 and 2014 (n = 1333). Endpoints were overall 1- and 3-year survival. Cox proportional-hazards models were built to assess the predictive value of abnormal G8 and modified-G8 scores, based on published cut-offs or by classes of increasing risk. Sensitivity analyses involved adjusting for age, gender, treatment, metastasis, and tumour site (digestive, breast, urinary tract, prostate, other solid cancers, and haematological malignancies) and stratifying by tumour site and metastatic status.ResultsAbnormal scores were independently associated with overall 1-year survival: adjusted hazard ratio [aHR] = 4.3[G8]/4.9[modified-G8] and 3-year survival: aHR = 2.9/2.6; all p <0.0001. Associations persisted after stratifying by metastatic status and in most cancer sites (exceptions: colorectal (G8) and upper digestive cancer (both tools) [1-year analysis]; digestive cancers (both tools) [3-year analysis]). For both tools, classes of increasing risk showed a graded relationship with mortality (p < 0.0001).ConclusionsOur results identified both abnormal G8 and modified-G8 scores as strong and consistent predictors of overall survival, regardless of metastatic status or tumour site. These findings strengthen the clinical utility of these instruments in the geriatric oncology setting.     

Lack of correlation between thymidylate synthase levels in primary colorectal tumours and subsequent response to chemotherapy.

The increasing interest in 5-fluorouracil (5-FU) modulation and the development of new antifolates has focused attention in recent studies on the expression of the target enzyme thymidylate synthase (TS) as a determinant of drug sensitivity and resistance. Resistance to TS-directed drugs has been shown to occur in vitro and in vivo with increased expression of the enzyme (determined by enzymatic assays as well as protein and gene expression assays). Several studies have evaluated the role of TS as a prognostic indicator of clinical response to chemotherapy containing TS-directed drugs. We have used a polyclonal antibody to recombinant human TS to establish a silver-enhanced immunogold staining method to localize TS in human tumours. Human tumour cell lines with acquired resistance to TS inhibitors owing to increased levels of TS were used to confirm the specificity of immunostaining. Stained sections were evaluated by image analysis. Immunostaining in tumour sections was greatly reduced (>80%) by preabsorption of the antiserum with recombinant TS. The method was used to determine the extent of TS immunostaining in 134 primary human colorectal tumours. The results were then compared with the clinical outcome and response to chemotherapy for the treatment of subsequent metastatic disease. A wide range (approximately 100-fold) of TS immunostaining was observed in these primary tumour sections. Normal mucosal tissue levels were 5-10 times lower than those observed in the adjacent tumour tissue. The values for TS immunostaining did not correlate with clinical endpoints, such as time from diagnosis to relapse, response to chemotherapy for disseminated disease, nor with Dukes'' staging. This lack of correlation may be because this group of patients was selected on the basis of their need for palliative chemotherapy and did not include patients who were cured of their disease. Also, primary tumour TS expression may not give a good indication of the TS expression in metastatic lesions. The prognostic significance of TS protein expression in primary and metastatic lesions requires further evaluation.     

Disease Burden on PET Predicts Outcomes for Advanced NSCLC Patients Treated with First-Line Immunotherapy

BackgroundFirst-line immunotherapy (IMT), with or without cytotoxic chemotherapy, is now recommended for most patients with advanced non-small cell lung cancer (NSCLC) with no targetable mutations. We reviewed outcomes for NSCLC patients treated with first-line IMT at our institution to test the hypothesis that measures of disease burden on staging FDG-PET/CT have prognostic value.Materials and MethodsPatient, disease, and treatment details were collected. A gradient-based segmentation tool was used to delineate each PET-avid extracranial lesion. Numbers of extrathoracic lesions and metabolic tumor volumes were tabulated. Oligometastatic disease (OMD) was defined as having ≤3 extrathoracic lesions, with any number of thoracic lesions. Progression-free survival (PFS) and overall survival (OS) rates following initiation of IMT were evaluated using the Kaplan-Meier method, and predictors of PFS and OS were assessed using Cox proportional hazards models and logrank tests.ResultsOne hundred twenty-four patients met inclusion criteria, and 1143 lesions were contoured. The presence of OMD was associated with favorable PFS (median 13.1 vs. 6.9 months; P = .016) and favorable OS (median 36.5 vs. 15.4 months; P = .002). In multivariable models, OMD was associated with favorable PFS (HR = 0.64; P = .034) and favorable OS (HR = 0.61; P = .063), and metabolic tumor volumes exceeding the cohort median (88 cc) was associated with inferior OS (HR = 1.85; P = .028).ConclusionFor advanced NSCLC patients receiving first-line IMT, the presence of extrathoracic OMD and low volumetric disease burden on PET are favorable prognostic factors that could be useful stratification factors in clinical trials and may influence clinical decisions about local and systemic therapy.     

The number of high-risk factors is related to outcome in stage II colonic cancer patients

Background

A subgroup of stage II colonic cancer patients are considered to be at high-risk for recurrent/metastatic disease based on 1) tumour obstruction/perforation 2) <10 lymph nodes 3) T4 lesions and 4) lymphangio-invasion. Their prognosis is regarded as comparable to stage III (T1-4N+M0) colonic cancer and it is therefore strongly advised to treat them with adjuvant chemotherapy. The purpose of this study was i) to determine the magnitude of prognostic significance of the conventional high-risk factors and ii) to determine whether the number of high-risk factors influences outcome.

Methods

We retrospectively analyzed 212 stage II colonic cancer patients undergoing surgery between January 2002 and December 2008. No adjuvant chemotherapy was given. Survival analyses were performed.

Results

154/212 (73%) patients were considered to be high-risk patients based on conventional high-risk factors. 58 patients did not meet any high-risk factor, 125 patients met 1 high-risk factor and 29 patients met ≥2 high-risk factors. Median follow up was 40 months.Multivariate analysis identified four independent risk factors for recurrent/metastatic disease: age, obstruction, perforation and lymphangio-invasion.The three-year-DFS-rates for the low-risk group, the high-risk group with 1 high-risk factor and the high-risk group with ≥2 high-risk criteria are 90.4%, 87.6% and 75.9% respectively.Patients meeting ≥2 conventional high-risk criteria had a significantly worse three-year disease free survival (p < 0.002).

Conclusions

Four independent high-risk factors were identified. The number of high-risk factors does influence outcome. More attention should be given to the definition and treatment of high-risk stage II colonic cancer patients.     

Clinical implications of expression of vascular endothelial growth factor in metastatic lesions of ovarian cancers

Vascular endothelial growth factor (VEGF) has been identified as an important factor for tumour angiogenesis, which is essential for the growth, invasion and metastasis of solid tumours. Significantly increased VEGF level from the primary tumour to the metastatic lesion of ovarian cancers was found in 8 of 30 cases. The 24-month survival rate of the patients with significantly increased VEGF level was extremely poor (0/8 = 0%) in comparison with that of patients with no change in the level (15/22 = 68%) from the primary tumour to the metastatic lesion. This indicates that VEGF may contribute to the advancement of metastatic lesions, and that VEGF level in metastatic lesions may be a prognostic indicator.     

Diagnosis and treatment of invasive squamous cell carcinoma of the skin: European consensus-based interdisciplinary guideline

Cutaneous squamous cell carcinoma (cSCC) is one of the most common cancers in Caucasian populations, accounting for 20% of all cutaneous malignancies. A unique collaboration of multi-disciplinary experts from the European Dermatology Forum (EDF), the European Association of Dermato-Oncology (EADO) and the European Organization of Research and Treatment of Cancer (EORTC) was formed to make recommendations on cSCC diagnosis and management, based on a critical review of the literature, existing guidelines and the expert’s experience. The diagnosis of cSCC is primarily based on clinical features. A biopsy or excision and histologic confirmation should be performed in all clinically suspicious lesions in order to facilitate the prognostic classification and correct management of cSCC. The first line treatment of cutaneous SCC is complete surgical excision with histopathological control of excision margins. The EDF–EADO–EORTC consensus group recommends a standardised minimal margin of 5 mm even for low-risk tumours. For tumours, with histological thickness of >6 mm or in tumours with high risk pathological features, e.g. high histological grade, subcutaneous invasion, perineural invasion, recurrent tumours and/or tumours at high risk locations an extended margin of 10 mm is recommended. As lymph node involvement by cSCC increases the risk of recurrence and mortality, a lymph node ultrasound is highly recommended, particularly in tumours with high-risk characteristics. In the case of clinical suspicion or positive findings upon imaging, a histologic confirmation should be sought either by fine needle aspiration or by open lymph node biopsy. In large infiltrating tumours with signs of involvement of underlying structures, additional imaging tests, such as CT or MRI imaging may be required to accurately assess the extent of the tumour and the presence of metastatic spread. Current staging systems for cSCC are not optimal, as they have been developed for head and neck tumours and lack extensive validation or adequate prognostic discrimination in certain stages with heterogeneous outcome measures. Sentinel lymph node biopsy has been used in patients with cSCC, but there is no conclusive evidence of its prognostic or therapeutic value. In the case of lymph node involvement by cSCC, the preferred treatment is a regional lymph node dissection. Radiation therapy represents a fair alternative to surgery in the non-surgical treatment of small cSCCs in low risk areas. It generally should be discussed either as a primary treatment for inoperable cSCC or in the adjuvant setting. Stage IV cSCC can be responsive to various chemotherapeutic agents; however, there is no standard regimen. EGFR inhibitors such as cetuximab or erlotinib, should be discussed as second line treatments after mono- or polychemotherapy failure and disease progression or within the framework of clinical trials. There is no standardised follow-up schedule for patients with cSCC. A close follow-up plan is recommended based on risk assessment of locoregional recurrences, metastatic spread or development of new lesions.     

F-18 fluorodeoxyglucose positron emission tomography in the evaluation of distant metastases from renal cell carcinoma.

PURPOSE: We conducted a study to evaluate the role of F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) in the detection of distant metastases from renal cell carcinoma (RCC).Materials and METHODS: Twenty-four patients with histologically proven clear-cell RCC undergoing surgical evaluation for possible resection of recurrent disease were investigated. All patients had suspected distant metastases based on conventional anatomic imaging techniques (computed tomography and magnetic resonance imaging). A total of 36 distant metastatic sites were identified. Pathology for all sites was obtained by biopsy or after surgical resection. RESULTS: Histologically documented distant metastases from RCC were present in 33 sites (21 patients). Overall sensitivity, specificity, and positive predictive value of FDG-PET for the detection of distant metastases from RCC was 63.6% (21 of 33), 100% (three of three), and 100% (21 of 21), respectively. The mean size of distant metastases in patients with true-positive FDG-PET was 2.2 cm (95% CI, 1.7 to 2.6 cm) compared with 1.0 cm in patients with false-negative FDG-PET (95% CI, 0.7 to 1.4 cm; P =.001). CONCLUSION: FDG-PET is not a sensitive imaging modality for the evaluation of metastatic RCC and may not adequately characterize small metastatic lesions. However, positive FDG-PET is predictive for the presence of RCC in lesions imaged, may complement anatomic radiologic imaging modalities, and may alleviate the need for a biopsy in selected situations. A negative FDG-PET, however does not rule out active malignancy.     

Utility of a serum tumour marker panel in the post-operative follow-up of breast cancer patients with equivocal conventional radiological examinations.

OBJECTIVE: To assess the value of the serum carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA) and breast cancer-associated antigen CA15.3 (CEA-TPA-CA15.3) tumour marker panel in selecting from a group of patients with equivocal bone scintigraphy, chest X-ray or liver echography, those with skeletal, thoracic or liver metastases. Clinical data of 427 breast cancer patients submitted to an intensive follow-up after mastectomy between January 1986 and December 2000 were retrospectively reviewed. METHODS: Among the 427 patients operated on for breast cancer, 221 patients with a total of 332 equivocal instrumental examinations (bone scintigraphy, n = 286; chest X-ray, n = 29; liver echography, n = 17) were reviewed. All 221 patients were followed up clinically, biochemically and instrumentally until there was a clear definition of their condition, metastatic or not, for an average time of 35 months. Positive and negative predictive values of the tumour marker panel in patients with equivocal bone scintigraphy, chest X-ray and liver echography were evaluated; concomitant clinical symptoms were also taken into consideration. RESULTS: Among the 221 patients with equivocal bone scintigraphy, chest X-ray and liver echography, tumour markers showed a positive predictive value of 69, 93 and 83% and a negative predictive value of 98, 86 and 91%, respectively, for the indication of the metastatic or benign origin of the equivocal instrumental imaging. Clinical symptoms were not helpful in predicting metastatic disease (sensitivity, specificity and accuracy of 60, 53 and 54%, respectively). CONCLUSIONS: These data suggest that a short monitoring with the CEA-TPA-CA15.3 tumour marker panel is an important tool to confirm or exclude metastatic disease in those patients who are suspected to have metastases following common instrumental investigations, and it is particularly important to avoid false positive diagnoses.     

Current applications and future direction of MR mammography

Compared with triple assessment for symptomatic and occult breast disease, magnetic resonance mammography (MRM) offers higher sensitivity for the detection of multifocal cancer, which is important in selecting patients appropriately for breast-conserving surgery. It is an ideal tool for the screening of patients with a high risk of breast cancer or where there is axillary disease or nipple discharge and conventional imaging has not revealed the primary focus. Techniques are now available to biopsy lesions only apparent on MRM. MRM can differentiate scar tissue from tumour; therefore, it is useful in patients in which there is possible recurrent disease. Clinical and X-ray mammographic assessment of response to neoadjuvant chemotherapy may be unreliable because of replacement of the tumour with scar tissue. MRM can identify responders and nonresponders with more accuracy. It is the modality of choice for the assessment of breast implants for rupture with accuracy higher than X-ray mammography and ultrasound. Advances in both spatial and temporal resolutions, the imaging sequences employed, pharmacokinetic modelling of contrast uptake, the use of dedicated and now phased-array breast coils, and gadolinium-based contrast agents have all played their part in the advancement of this imaging technique. Despite the limitations of patient compliance, scan-time and cost, this review describes how MRM has become a valuable tool in breast disease, especially in cases of diagnostic uncertainty. However, MRM must make the transition from research institutions into routine clinical practice.     

Evaluation of contrast Sonazoid-enhanced ultrasonography for the detection of hepatic metastases in breast cancer

Background

The present study was aimed to evaluate the usefulness of contrast Sonazoid-enhanced ultrasonography (US) for the detection of hepatic metastases in breast cancer patients and compare the clinical efficacy and sensitivity of this technique with conventional contrast unenhanced B-mode US in follow-up examinations of breast cancer patients with liver metastasis.

Methods

We assessed a total of 84 hepatic tumors from 24 patients diagnosed with or suspected of having metastatic cancer. These hepatic nodules were diagnosed through imaging, including dynamic magnetic resonance imaging (MRI), contrast-enhanced computed tomography (CECT) scan, B-mode US or contrast Sonazoid-enhanced US (SEUS). Differences in the sensitivity between US and SEUS were compared using MR imaging, CECT, and follow-up imaging.

Results

A total of 79 nodules were diagnosed as metastatic tumors. The remaining nodules were diagnosed as benign tumors (hepatic hemangioma: n = 3; local fatty change: n = 2). SEUS precisely detected the presence or absence of hepatic tumors in the 24 patients examined, showing a sensitivity of 98.8 % (83 of 84 lesions) for total imaged solid liver lesions, with an accuracy of 98.7 % (78 of 79 lesions) for total metastatic breast cancer lesions. In contrast, conventional B-mode US imaging revealed hepatic tumor lesions at a sensitivity of 66.7 % (56 of 84 lesions) and an accuracy of 64.6 % (51 of 79 lesions), respectively. Furthermore, the false positive and false negative rates were, respectively, 6.33 and 29.1 % for B-mode US and 0 and 1.3 % for SEUS. Moreover, twenty-seven metastatic tumors and five benign lesions (3 hemangiomas and 2 focal fatty changes/sparings) were imaged using SEUS but not conventional B-mode US. Significant differences in diagnostic accuracy rates between contrast Sonazoid-enhanced US and conventional B-mode US were observed (Wilcoxon signed rank test: p = 0.0009). No severe adverse events occurred during SEUS after the administration of Sonazoid, except for a grade 1 skin reaction and nausea in one patient.

Conclusion

These results suggested that Sonazoid could be safely administrated to breast cancer patients with liver metastatic disease. Thus, contrast Sonazoid-enhanced US is a feasible and more effective method than B-mode US for the detection of hepatic metastasis, particularly for small metastatic breast cancer lesions less than 14 mm in diameter, showing significant high sensitivity and accuracy.

     

When Should we Irradiate the Primary in Metastatic Lung Cancer?

Metastatic lung cancer encompasses a heterogenous group of patients in terms of burdens of disease, ranging from patients with extensive metastases to those with a limited number of metastatic lesions (oligometastatic disease). Histopathological heterogeneity also exists within two broad categories, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), portraying different patterns and evolution of disease. Local consolidative therapy to the primary tumour and metastatic sites, including surgery and/or radical dose radiotherapy, is increasingly being used to improve survival outcomes, particularly in the context of oligometastatic disease, with or without the use of molecular targeted therapy and immunotherapy. Recently, randomised studies in oligometastatic NSCLC have shown that local consolidative therapy may confer a survival advantage. This review explores whether treating just the primary tumour with radiotherapy may similarly produce improved clinical outcomes. Such a treatment strategy may carry less potential toxicity than treating multiple sites upfront. The biological rationale behind the potential benefits of treating just the primary in metastatic malignancy is discussed. The clinical evidence of such an approach across tumour sites, such as breast and prostate cancer, is also explored. Then the review focuses on treating the primary in NSCLC and SCLC with radiotherapy, by first exploring patterns of failure in metastatic NSCLC and second exploring evidence on survival outcomes from studies in metastatic NSCLC and SCLC. It is challenging to draw conclusions on the clinical benefit of treating the primary cancer in isolation from the evidence available. This highlights the need to collect data within the ongoing clinical trials on the clinical outcome and toxicity of radiotherapy delivery to primary thoracic disease specifically. This challenge also identifies the need to design future clinical trials to produce randomised evidence for such an approach.     

Annexin‐A2 as predictor biomarker of recurrent disease in endometrial cancer

Endometrial carcinomas, the most common malignant tumour of the female genital tract, are usually diagnosed at an early stage with uterine‐confined disease and an overall favourable prognosis. However, up to 20% of endometrial carcinomas will end up in recurrent disease, associated with a drop in survival and representing the major clinical challenge. Management of this group of risk patients relies on robust biomarkers that may predict which endometrial carcinomas will relapse. For this, we performed a proteomic analysis comparing primary lesions with recurrences and identified ANXA2 as a potential biomarker associated with recurrent disease that we further validated in an independent series of samples by immunohistochemistry. We demonstrated in vitro a role for ANXA2 in the promotion of metastasis rather than interfering with sensitivity to radio/chemotherapy. In addition, ANXA2 silencing resulted in a reduced metastatic pattern in a mice model of endometrial cancer dissemination, with a limited presence of circulating tumor cells. Finally, a retrospective study in a cohort of 93 patients showed that ANXA2 effectively predicted those endometrioid endometrial carcinomas that finally recurred. Importantly, ANXA2 demonstrated a predictive value also among low risk Stage I endometrioid endometrial carcinomas, highlighting the clinical utility of ANXA2 biomarker as predictor of recurrent disease in endometrial cancer. Retrospective and prospective studies are ongoing to validate ANXA2 as a potential tool for optimal stratification of patients susceptible to receive radical surgery and radio/chemotherapy.     

Capromab Pendetide imaging of prostate cancer

Capromab Pendetide imaging illustrates the successful translation of monoclonal antibody technology from the laboratory to the clinic. It provides a means of identifying otherwise occult soft tissue metastases in patients with adenocarcinoma of the prostate. When utilized with other clinical, pathological and laboratory findings, Capromab Pendetide imaging enables more accurate disease staging and monitoring than is afforded by other imaging modalities such as CT and MRI. In the primary disease setting Capromab Pendetide imaging should be reserved for use in patients with negative bone scans who are at high risk for metastatic disease based on such factors as advanced clinical stage, high Gleason score and significantly elevated serum PSA or alkaline phosphatase. Due to low sensitivity for small-volume disease, a negative Mab scan may not eliminate the need for a staging lymph node dissection but should encourage further consideration of local treatment options. Capromab Pendetide should be used with caution in patients at low risk for metastatic disease. Positive scan findings in low risk patients should be confirmed before altering the treatment plan since some false positive scans should be anticipated in a population with low disease prevalence. Capromab Pendetide imaging has not been shown to be reliable in determining the local extent of the primary tumor but new techniques involving co-registration of SPECT and CT images show promise in this regard. In the patient with recurrent disease following primary therapy, the predictive value of Capromab Pendetide imaging of the prostate or prostate fossa is limited, particularly following RT. Its more important role in this setting is to identify lymph node metastases in the high risk patient with a negative bone scan who might otherwise be a candidate for local salvage therapy. A large prospective study is needed for confirmation, but preliminary data suggest that Capromab Pendetide imaging is helpful in identifying those patients with PSA elevation after radical prostatectomy who are most likely to benefit from salvage RT. As with any imaging technique, Capromab Pendetide has strengths and weaknesses that must be understood to maximize patient benefit by utilizing the scan in clinical settings where it is most likely to be useful and least likely to be misleading. Capromab Pendetide is a technically demanding procedure best performed and interpreted at sites with experience and expertise.     

Molecular markers of adrenocortical tumors

Adrenocortical tumors are common and incidentally discovered in up to 14% of axial imaging studies performed for other indications. Most of these tumors are nonfunctioning but may require removal because of the risk of adrenocortical carcinoma. Unfortunately, most clinical and imaging features are still not accurate enough to allow definitive diagnosis and an increasing number of patients undergo adrenalectomy to exclude a cancer diagnosis. Adrenocortical carcinoma is an aggressive malignancy with no effective therapy for patients with locally advanced and metastatic disease. Studies using new genomic approaches including mRNA, miRNA, methylation, and CGH profiling have identified dysregulated genes and pathways that may have clinical implications in improved molecular diagnosis and prognostication of adrenocortical cancer (ACC). In this review, we highlight recent advances in the molecular diagnosis of adrenocortical tumors. Published 2012. J. Surg. Oncol. 2012; 106:549-556. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.