Postchemotherapy Resection Research Articles

A dynamic microRNA profile that tracks a chemotherapy resistance phenotype in osteosarcoma. Implications for novel therapeutics.

Osteosarcoma is a rare primary bone tumor for which no significant therapeutic advancement has been made since the late 1980s despite ongoing efforts. Overall, the five-year survival rate remains about 65%, and is much lower in patients with tumors unresponsive to methotrexate, doxorubicin, and cisplatin therapy. Genetic studies have not revealed actionable drug targets, but our group, and others, have reported that epigenomic biomarkers, including regulatory RNAs, may be useful prognostic tools for osteosarcoma. We tested if microRNA (miRNA) transcriptional patterns mark the transition from a chemotherapy sensitive to resistant tumor phenotype. Small RNA sequencing was performed using 14 patient matched pre-chemotherapy biopsy and post-chemotherapy resection high-grade osteosarcoma frozen tumor samples. Independently, small RNA sequencing was performed using 14 patient matched biopsy and resection samples from untreated tumors. Separately, miRNA specific Illumina DASL arrays were used to assay an independent cohort of 65 pre-chemotherapy biopsy and 26 patient matched post-chemotherapy resection formalin fixed paraffin embedded (FFPE) tumor samples. mRNA specific Illumina DASL arrays were used to profile 37 pre-chemotherapy biopsy and five post-chemotherapy resection FFPE samples, all of which were also used for Illumina DASL miRNA profiling. The National Cancer Institute Therapeutically Applicable Research to Generate Effective Treatments dataset, including PCR based miRNA profiling and RNA-seq data for 86 and 93 pre-chemotherapy tumor samples, respectively, was also used. Paired differential expression testing revealed a profile of 17 miRNAs with significantly different transcriptional levels following chemotherapy. Genes targeted by the miRNAs were differentially expressed following chemotherapy, suggesting the miRNAs may regulate transcriptional networks. Finally, an in vitro pharmacogenomic screen using miRNAs and their target transcripts predicted response to a set of candidate small molecule therapeutics which potentially reverse the chemotherapy resistance phenotype and synergize with chemotherapy in otherwise treatment resistant tumors. Importantly, these novel therapeutic targets are distinct from targets identified by a similar pharmacogenomic analysis of previously published prognostic miRNA profiles from pre chemotherapy biopsy specimens.

Pediatric Primary Yolk Sac Tumour of the Kidney: Recommendations for Pretreatment Diagnosis

Introduction Although nephroblastomas are frequently treated without prior biopsy, there are the occasional other pediatric renal tumors that require different management. In the literature, there are around 30 primary renal germ cell tumors (GCT), including four cases of Yolk sac tumor (YST). We present another primary renal YST.Case report: A five-year-old boy was diagnosed as Wilms tumor on radiology and needle biopsy. He received chemotherapy, with no response. The post-chemotherapy resection specimen revealed a YST.Conclusion: Renal YST may be indistinguishable from Wilms tumor clinically and radiologically. For pre-biopsy chemotherapy management protocols, serum tumor markers such as AFP may be recommended to identify the occasional GCT, including YST. Pre-chemotherapy needle biopsies may lead to misdiagnosis, and may require confirmation by an experienced pathologist or central review.

Preoperative clinical and radiographic predictors of major vascular surgery in patients with testicular cancer undergoing post-chemotherapy residual tumor resection (PC-RPLND).

To evaluate the probability to correctly predict major vascular surgery (MVS) in patients undergoing postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) for testicular cancer. From a database of 504 RPLNDs performed in 434 patients (2008-2018), 78 patients submitted to PC-RPLND for non-seminoma germ-cell cancer after cisplatin-based chemotherapy with available preoperative CT scans were identified. Second PC-PLNDs (Re-Dos), salvage RPLNDs, or RPLNDs for late-relapse were excluded as well as thoraco-abdominal approaches. Preoperative imaging was reviewed by a urologist and a radiologist blinded to operative details. Of 78 patients, 16 (20.5%) underwent MVS (caval and/or aortic replacement or reconstruction). On univariable analyses, transversal diameter, sagittal diameter, tumor volume, aorta- and cava-tumor contact angle, poor IGCCCG score, clinical stage III and preoperative positive markers were predictors of MVS (allp values ≤ 0.01). At multivariable analyses aorta- (cut-off 64°) and cava-tumor contact angle (cut-off 98°) and poor IGCCCG score represented the three most important predictors of MVS (all p values ≤ 0.05). The model constructed has a PPV 100%, NPV 87% and an accuracy of 88%. Presence of aorta-tumor contact angle ≥ 64°, cava-tumor contact angle ≥ 98° and poor IGCCCG score identify correctly 9 out of 10 patients requiring MVS at the time of first PC-RPLND.

EORTC 1707 VESTIGE: Adjuvant immunotherapy in patients with resected gastric cancer following preoperative chemotherapy with high risk for recurrence (ypN+ and/or R1)—An open-label randomized controlled phase II study.

TPS4156 Background: Gastroesophageal adenocarcinoma (GEA) patients with metastatic lymph nodes (ypN+) or a microscopically incomplete surgical resection (R1) following neoadjuvant chemotherapy are at high risk of disease recurrence. Current practice is to continue with the same perioperative chemotherapy used prior to surgery, despite these suboptimal outcomes. Adjuvant immunotherapy with nivolumab has shown efficacy in poor risk GEA patients following chemoradiotherapy and surgery in the CheckMate 577 trial, and nivolumab and ipilimumab have demonstrated activity in advanced GEA. We hypothesise that high risk (ypN+ and/or R1) post resection GEA patients who are treated with nivolumab and ipilimumab will have better disease free survival than patients who continue with standard post-operative chemotherapy. Methods: VESTIGE is an ongoing, international, open label randomized phase II study designed to evaluate the efficacy of adjuvant nivolumab plus ipilimumab versus standard post-operative chemotherapy in high risk (ypN+ and/or R1) post resection GEA patients. Eligible patients (n=240) will be randomised 1:1 to receive post-operative adjuvant chemotherapy (identical regimen as pre-operatively) or nivolumab 3mg/kg IV q2w plus ipilimumab 1mg/kg IV q6w x 1 year. Key inclusion criteria include ypN+ and/or R1 status following neoadjuvant chemotherapy plus surgery and an adequate pre-specified surgical resection. The primary endpoint of the study is disease free survival, with secondary endpoints of overall survival, safety, toxicity and quality of life. Since start of recruitment in August 2019, the trial has recruited 85 of 240 patients at 18 sites in the Czech Republic, France, Germany, Israel, Italy, Norway, Poland, Spain, and United Kingdom. The VESTIGE translational research programme includes collection of pre-treatment biopsies, post-chemotherapy resection specimens and serial liquid biopsy on treatment to explore biomarkers predictive of immune checkpoint blockade efficacy. Clinical trial information: NCT03443856.

Long-term Surveillance of Patients with Complete Response Following Chemotherapy for Metastatic Nonseminomatous Germ Cell Tumor

BackgroundThere is controversy regarding the management of patients with normal markers and residual masses (≤1 cm) after chemotherapy for nonseminomatous germ cell tumors (NSGCTs). ObjectiveTo determine long-term outcomes of a surveillance strategy in such patients. Design, setting, and participantsA retrospective review of our multidisciplinary testicular cancer database was performed. All patients who underwent primary chemotherapy for metastatic NSGCTs were identified between 1981 and 2016. A complete response (CR) was defined as normalization of serum tumor markers and a ≤1 cm residual mass in the largest axial dimension following chemotherapy. All such patients were surveilled. Outcome measurements and statistical analysisOutcome variables of interest were time to death, time to cancer-specific survival, and time to relapse. Overall survival and relapse-free survival were calculated using the Kaplan-Meier method, and the cumulative incidence of cause-specific survival rates was calculated using competing risk analysis. The impact of risk group and chemotherapy regimen on relapse-free survival was assessed using log-rank test. Results and limitationsDuring the study period, 1429 metastatic germ cell tumor patients were treated with primary chemotherapy. CR was achieved in 191 (18.5%) NSGCT patients. The median age at diagnosis was 27.4 yr, with a median follow-up of 81.1 mo. The majority had American Joint Committee on Cancer stage II at diagnosis (I: 23.8%; II: 49.2%; III: 27%) and International Germ Cell Cancer Collaborative Group good-risk disease (good: 78%; intermediate: 17.8%; poor: 4.2%). Of the 191 patients with a CR, 175 (91.6%) never relapsed and remain disease free. Sixteen (8.4%) patients relapsed after a median of 11.3 mo (range 1–332 mo), with over half (nine patients; 4.7%) relapsing in the retroperitoneum only and salvaged successfully with postchemotherapy retroperitoneal lymph node dissection (PC-RPLND) alone. Of these nine patients, only two (1%) had viable disease in the PC-RPLND specimen. The remaining seven patients had relapses outside the retroperitoneum and received salvage chemotherapy ± postchemotherapy resection. Overall, nine (4.7%) patients have died, but only four (2.1%) from testis cancer. ConclusionsOur data, the largest series to date, confirm that surveillance is safe and effective for men who achieve a CR following chemotherapy for metastatic NSGCTs. Patient summarySurveillance is a safe strategy for patients who achieve a complete response following chemotherapy for metastatic testis cancer.

Detection of Circulating Tumor Cells (CTCs) in Patients with Testicular Germ Cell Tumors.

While the majority of patients with advanced testicular germ cell tumors (GCT) achieve complete responses after chemotherapy and if indicated after postchemotherapy resection of residual lesions, about 20% of patients have incomplete responses or show relapses. Moreover, toxicity of chemotherapy is high, and severe adverse chronic effects have been described. Therefore, there is an urgent need for biomarkers that could help to improve tumor staging, and support decision-making, ideally including monitoring of therapy response and prediction of relapse. Besides the well-established serum markers lactate dehydrogenase, α-fetoprotein, and β-subunit of human chorionic gonadotropin, during recent years new noninvasive liquid biopsy markers have been investigated in GCT, including cell-free nucleic acids like microRNAs, and circulating tumor cells (CTCs).Prognostic relevance has been demonstrated for circulating tumor cells (CTCs) in patients with different cancers. However, little is known in GCT patients. Histologically, GCT are a very heterogeneous group of tumors comprising pure seminomas (consisting of cells that remember primordial germ cells) and nonseminomas, which are either undifferentiated (embryonal carcinoma) or differentiated, exhibiting different degrees of embryonic (teratoma) or extraembryonic (yolk sac tumor and choriocarcinoma) differentiation. This heterogeneity hampers capture and detection of CTCs deriving from those tumors using a single method or a single antibody. To date, label-independent capture methods that enrich tumor cells according to the density of GCT cells, which is similar to that of mononuclear cells, have been successfully applied. Since testicular GCT might also express epithelial proteins, methods based on enrichment of CTCs using epithelial markers are promising to detect CTCs in certain subgroups of patients with GCTs as well.Here, we describe and discuss a combination of methods to capture and detect GCT cells with epithelial and germ cell characteristics in blood.

Application of the pathological classification of "CCCG-WT-2016" (2019 revision) for treatment of Wilms tumors

Objective: To describe our experiences in application of the 2019 revision of "CCCG-WT-2016" for the diagnosis of Wilms tumors. Methods: Ninety-one cases of Wilms tumor diagnosed at Shanghai Children's Medical Center from January 2015 to December 2018 were collected. All cases were reviewed by two senior pathologists, including one from China and the other from Singapore, according to the 2019 revision of "CCCG-WT-2016." Results: The specimens were obtained by core biopsy (n=21), primary nephrectomy (n=41), post-chemotherapy nephrectomy/resection (n=18), or biopsy/resection of metastatic/relapse/post-chemotherapy metastatic lesion(s) (n=11). The specimens of core biopsy and primary nephrectomy (n=62) all had favorable histology.Twelve post-chemotherapy nephrectomy cases were subdivided into three risk groups: low risk (n=0), intermediate risk (n=10) and high risk (n=2). Six post-chemotherapy resection cases were subdivided into 3 risk groups:low risk (n=0), intermediate risk (n=5) and high risk (n=1). The remaining 11 cases were comprised of metastatic, relapse, and post-chemotherapy metastatic lesions. The concordance rate of the two senior pathologists was 100%(91/91). Conclusions: The 2019 revision of "CCCG-WT-2016" is clearly written and easy to use. It can serve as the basis of accurate classification for clinical treatment.

Semi-ResMass Study: Residual masses after salvage chemotherapy in men with pure seminoma—A multicenter retrospective analysis.

420 Background: Only scarce data exist on the management of residual masses in men who have received two lines of chemotherapy for advanced seminoma. Due to the lack of data, the role of PET scanning, surgery and other additional treatments is controversial in these men. Methods: Data from men with pure seminoma and residual masses after salvage chemotherapy were retrospectively collected from 10 high-volume centers in 3 European countries. We analyzed the clinical management of residual masses (imaging, surgery, pathological data, and additional treatment modalities) and long-term outcomes. Residual mass was defined as a lesion of ≥1 cm after two lines of platin-based chemotherapy. Results: To date, data from 48 patients (pts) with non-progressing residual masses after second line (salvage) chemotherapy have been collected and are included in this analysis. Median age at diagnosis was 36 years (range 31; 42). A post-chemotherapy PET-FDG was performed in 32 (67%) pts. Surgery was performed in 20/48 (41%) pts irrespectively of FDG uptake (no, n=8; yes, n=5). Complete necrosis was found in 16 (80%), viable seminoma in 3 (15%), and teratoma in 1 pt, respectively. All pts with a negative PET (PET-) who underwent surgery (8/8) had complete necrosis. 5/11 pts with a positive PET (PET+) underwent surgery: 3 had a complete necrosis while 2 had viable seminoma. Among those with a PET+, 3 pts (28%) experienced either viable seminoma in residual masses or a subsequent relapse. The absence of FDG uptake correlated with absence of viable cancer (p=0.04). A second relapse occurred in 5/48 pts (10%). Only 2/20 pts who had residual masses resected post 1st salvage chemotherapy subsequently relapsed (one had viable seminoma in the residuals). At a median follow up of 4 years (IC95% [3.5-5.5]), 41/48 pts (87%) were alive. 7/48 patients died of cancer progression. Conclusions: Most men with residual masses after 1st salvage chemotherapy for advanced seminoma may achieve a cure. Pending validation with more pts in this rare situation, PET-FDG may help guide who should be selected for post-chemotherapy resection. Updated results will be presented at the congress.

EORTC 1707 VESTIGE: Adjuvant immunotherapy in patients with resected gastric cancer following preoperative chemotherapy with high risk for recurrence (ypN+ and/or R1): An open-label randomized controlled phase II study.

TPS467 Background: Gastroesophageal adenocarcinoma patients with metastatic lymph nodes (ypN+) or a microscopically incomplete surgical resection (R1) following neoadjuvant chemotherapy are at high risk of disease recurrence. Current practice is to continue with the same perioperative chemotherapy used prior to surgery, despite these suboptimal outcomes. Immune checkpoint blockade with nivolumab and ipilimumab has demonstrated activity in advanced gastroesophageal adenocarcinoma. We hypothesise that high risk (ypN+ and/or R1) post resection gastroesophageal adenocarcinoma patients who are treated with nivolumab and ipilimumab will have better disease free survival than patients who continue with standard post-operative chemotherapy. Methods: VESTIGE is an ongoing, international, open label randomized phase II study designed to evaluate the efficacy of adjuvant nivolumab plus ipilimumab versus standard post-operative chemotherapy in high risk (ypN+ and/or R1) post resection gastroesophageal adenocarcinoma patients. Eligible patients (n=240) will be randomised 1:1 to receive post-operative adjuvant chemotherapy (identical regimen as pre-operatively) or nivolumab 3mg/kg IV q2w plus ipilimumab 1mg/kg IV q6w x 1 year. Key inclusion criteria include ypN+ and/or R1 status following neoadjuvant chemotherapy plus surgery and an adequate pre-specified surgical resection. The primary endpoint of the study is disease free survival, with secondary endpoints of overall survival, safety, toxicity and quality of life. The trial will recruit 240 patients at 24 number of sites in the Czech Republic, France, Germany, Israel, Italy, Norway, Poland, Portugal, Spain, and United Kingdom. Recruitment commenced July 2019 and is anticipated to take 30 months. The VESTIGE translational research programme includes collection of pre-treatment biopsies, post-chemotherapy resection specimens and serial liquid biopsy on treatment to explore biomarkers predictive of immune checkpoint blockade efficacy. Clinical trial information: NCT03443856.

Cytomorphology of hepatoblastoma with histological correlation and role of SALL4 immunocytochemistry in its diagnosis, subtyping, and prognostication.

Hepatoblastoma (HB) is the most common malignant pediatric liver tumor, and cytology material is often the only tissue available for evaluation before definitive therapy. Subcategorization of HB based on cytomorphological features thus carries an important role in its prognostication. Spalt-like transcription factor 4 (SALL4), a marker of embryonic stem cells that is also found in the fetal liver, is reactivated in certain liver tumors. Limited studies have evaluated its role in HB. This study was aimed at evaluating the cytomorphological features of HB and assessing the utility of SALL4 immunocytochemistry (ICC) in its subtyping and prognostication. Pretherapy fine-needle aspiration smears from patients diagnosed with HB over a period of 9years were retrieved. Aspirates were subclassified on the basis of the cytomorphology and were correlated with the histology wherever it was available. ICC for SALL4 was performed in 33 cases, and nuclear staining was considered positive. A total of 53 HB cases were included with 30 available postchemotherapy resection specimens. All the patients were diagnosed asepithelial HB on cytology, and the cases were subclassified as pure fetal (9 of 53), pure embryonal (2 of 53), or combined epithelial HB (42 of 53). There was good concordance between cytology and histology for subtyping. SALL4 immunostaining displayed strong and diffuse nuclear positivity in the embryonal component whilefocal and weak to negative staining in fetal cells. Fine-needle aspiration cytology serves as a rapid and effective tool for a correct diagnosis of HB before the implementation of chemotherapy, and SALL4 may serve as a useful diagnostic and prognostic marker.

Effect of chemotherapy on cancer stem cells and tumor-associated macrophages in a prospective study of preoperative chemotherapy in soft tissue sarcoma

BackgroundCancer stem cells (CSC) may respond to chemotherapy differently from other tumor cells.MethodsThis study examined the expression of the putative cancer stem cell markers ALDH1, CD44, and CD133; the angiogenesis marker CD31; and the macrophage marker CD68 in soft tissue sarcomas (STS) before and after 4 cycles of chemotherapy with doxorubicin and ifosfamide in 31 patients with high-grade soft tissue sarcoma in a prospective clinical trial.ResultsNone of the markers clearly identified CSCs in STS samples. Macrophages represented a prominent component in viable tumor areas in pre-treatment STS biopsies, ranging from < 5 to > 50%. Furthermore, macrophages expressed CD44 and ALDH1. Macrophage density correlated with baseline maximum standardized uptake value (SUVmax) on fluoro-deoxyglucose positron emission tomography (PET) imaging. Pre-chemotherapy CD68 staining correlated positively with the baseline SUVmax, and negatively with the percent of viable tumor cells in post-chemotherapy resection samples. In particular, cases with more CD68-positive cells at biopsy had fewer viable tumor cells at resection, suggesting a better response to chemotherapy.ConclusionsIn conclusion, ALDH1, CD44, and CD133 are not likely to be useful markers of CSCs in STS. However, our observation of infiltrating macrophages in STS specimens indicates that these immune cells may contribute significantly to STS biology and response to chemotherapy, and could provide a potential target of therapy. Future studies should investigate macrophage contribution to STS pathophysiology by cytokine signaling.

Testicular teratomas: a growing problem?

Testicular teratomas represent a specific entity within the group of germ-cell tumours. They may comprise elements of all three germ layers. In contrast to prepubertal benign teratomas observed in infants and adolescents, postpubertal teratomas originate from the malignant germ-cell precursor. Given the good prognosis and curability of most patients with germ-cell tumour, medical oncologists and urological surgeons must be well acquainted with the principles of teratomas management. Surgery plays the decisive part in teratomas treatment, as these tumours are resistant to radio- and, to some extent, chemotherapy. In this article we concentrate on the management of post-chemotherapy resection of teratomatous masses, with special attention to the phenomenon of 'growing teratoma syndrome' and somatic-type transformation of teratomas. To understand the nature of teratomas better, we begin with a glimpse of their biological, molecular and immunohistochemical features. Managing germ-cell tumours, teratomas in particular, in high-volume reference centres is of utmost importance to maintain and increase the survivorship rate in these patients.

Surgical Management of Patients with Advanced Germ Cell Tumors Following Salvage Chemotherapy: Memorial Sloan Kettering Cancer Center (MSKCC) Experience.

ObjectiveTo characterize clinical and pathologic outcomes of cisplatin-refractory or relapsed germ cell tumor (GCT) patients who underwent retroperitoneal lymph node dissection (RPLND) following salvage chemotherapy with either conventional or high dose regimens. MethodsData were reviewed to identify all patients treated with TIP or TICE salvage chemotherapy between 1994 and 2011(n = 184) at our institution. We report clinicopathologic and outcomes data on 131 patients who were further managed with surgical resection. Using Cox-proportional hazards models, predictors of disease-specific survival (DSS) were analyzed. ResultsMedian follow-up was 7.3 years. Of the 112 patients who underwent postsalvage chemotherapy RPLND, histology was reported as viable GCT in 30 (27%), teratoma only in 26 (23%) and fibrosis in 56 (50%). 5-year DSS for the entire cohort was 74% (95% confidence interval 63%-80%). On multivariable analysis, viable GCT histology at RPLND or extra-RPLND resection predicted for worse DSS (hazard ratio 7.37, P = .003). ConclusionsOur data suggest that approximately half of the patient with cisplatin-refractory or relapsed GCT salvaged with TIP or TICE chemotherapy and evidence of residual disease are at risk of harboring either viable GCT or teratoma. This finding underlines the critical role of surgery in the multimodality approach to the management of this advanced disease entity. If retroperitoneal disease exists prior to salvage chemotherapy, we recommend postchemotherapy resection in all eligible patients.

Mediastinal surgery: modern treatment of primary germ cell tumor of the mediastinum

The mediastinum is the most common location of extragonadal germ cell tumors. Chemotherapy and/or surgery is the mainstay of treatment of these primary mediastinal germ cell tumors. Pure mediastinal seminomas are usually curable with chemotherapy alone, while mature teratomas are treated with surgery alone. The remaining nonseminomatous germ cell tumors are treated with neoadjuvant chemotherapy and post-chemotherapy resection regardless of tumor marker persistence. These typically anterior tumors can be found adjacent to and invading any of the major mediastinal vessels, nerves, lung, and hila. Surgery can be challenging due to tumor size, location, and adherence to important structures. Appropriate pre-surgical planning, positioning, approach, exposure, and intraoperative decision making are all integral to successful resection. We describe the work up and crucial preoperative considerations, various incisions and their applications to tumor size and location, and resectable structures and factors to consider in their removal.

Surgical Treatment for Pulmonary Metastases of Osteosar-Coma

Abstract Introduction. Osteosarcomas represent 40% of bone sarcomas and occur mainly in children and young adults. They are tumors with a high degree of pulmonary metastasis. Pulmonary metastases occur in about 80% of the relapsed patients after primary tumor therapy, whether or not they have received chemotherapy. As therapeutic solutions, both first intention resection of the metastasis and the post-chemotherapy resection or repeated resections in each relapse, represent satisfactory results with prolongation of survival. Material and method. The present study describes a group of 17 patients who were surgically treated for osteosarcoma with different localizations and who presented themselves in the thoracic surgery department during 2011-2016 with suspicion of pulmonary metastases. Three of them were at their second intervention for metastasis resection. Following investigations, 4 of them (23.5%) could not benefit from surgical resection of pulmonary metastases (lesional extension with postoperative vital risk or technical impossibility of metastatic excision). Surgical interventions were curative; lobectomies were performed in 4 cases (30.7%), atypical resections in 8 cases (61.6%) and one pneumonectomy (7.7%). Postoperative progression was favorable in all 13 patients. Discussions and conclusions. Surgical excision of osteosarcoma pulmonary metastases can prolong survival and sometimes even cure disease. In order to benefit from the intervention, the patient should be served by a thoracic surgery clinic in the shortest possible time after the discovery of the pulmonary nodules. Thus, the need for thoracic imaging is required in patients treated for osteosarcoma. Late presentation makes the intervention impossible, particularly because of the lesional extension in the lung parenchyma or the invasion of the adjacent structures, extension given by the number of metastases or their size.

Hepatocellular malignant neoplasm, NOS: a clinicopathological study of 11 cases from a single institution.

The primary aim of this study is to characterize hepatocellular malignant neoplasm, NOS (HEMNOS), a new provisional entity describing a subset of paediatric hepatocellular tumours, which have histological features of neither typical hepatoblastoma (HB) nor hepatocellular carcinoma (HCC). The clinicopathological features of 11 patients with HEMNOS were analysed retrospectively. The median age and serum alpha-fetoprotein level at diagnosis was 7years and 182000ng/ml, respectively. Ten patients presented with pretreatment extent of disease (PRETEXT) stages III/IV multifocal tumours, eight with major vascular involvement, three with lung metastases and three with extrahepatic extension. The original pathology diagnoses were: HB in seven patients, HCC in two and HEMNOS in two. Our pathology review of pre-chemotherapy specimens showed that six tumours had equivocal/overlapping histological features of HB and HCC, four had predominant HB histology along with focal HCC-like histology and one had HB histology. Seven of nine post-chemotherapy resection specimens showed predominant HCC-like histology. Beta-catenin, glypican 3 and spalt-like transcription factor 4 immunostaining showed that all the tumours had a mixed HB/HCC immunophenotype. Telomerase reverse transcriptase immunostaining showed nuclear staining in nine of the 11 tumours. All patients received chemotherapy and achieved gross total primary tumour resection. Nine of the 11 patients were treated with established HB chemotherapy regimens. After a median follow-up of 6.1years (range: 1.2-11.8years), all patients were in remission. HEMNOS is a subtype of HB with focal HCC-like histology, a high-risk clinical profile but favourable outcome following chemotherapy and complete tumour resection.

Management of pure metastatic teratoma in chemotherapy naïve testis cancer patients.

e16043 Background: Management of metastatic testicular cancer often requires post-chemotherapy resection of teratoma. This is well known and described in literature. However, the ability of teratoma to metastasize independently is not as well appreciated, making chemotherapy futile in patients with pure metastatic teratoma. Methods: 15 patients with metastatic teratoma were identified of which 13 had only teratoma in the orchiectomy and 2 had predominantly teratoma. All 15 had normal serum hCG and AFP. Cases were derived from a retrospective review of patients seen from 1989-2016. Results: Mean age of patients was 27 years. 12 patients presented initially with Stage II disease and 2 presented with stage III disease. Median RP mass size was 6 cm with a range of 1.5-24 cm. 2 of 15 patients were treated initially with a single course of chemotherapy with BEP and showed no response. The remaining 13 patients only received resection(s). All 15 patients underwent RPLND with 2 patients requiring additional mediastinal and retrocrural resection and 1 requiring lobectomy. All surgical specimens showed pure teratoma on pathology with no other active germ cells. Patients were followed for a median duration of 5 years and all 15 remain with no evidence of disease at most recent follow up. However, 1 patient needed subsequent surgery for a late relapse of teratoma and 1 patient had a second extra-gonadal primary. Conclusions: Teratoma can metastasize in the absence of other germ cells. Surgical treatment alone for patients with pure metastatic teratoma of any stage can result in cure for the majority of patients and this approach can help avoid unnecessary chemotherapy.

When is surgical resection of metastases in testicular germ cell tumors indicated and is there a scientific basis?

Surgical resection of metastases represents an integral part of curative management in patients with testicular germ cell tumors (GCT). Primary nerve-sparing retroperitoneal lymph node dissection (nsRPLND) for low volume metastases in clinical stagesI-IIB has to be differentiated from the more complex and more extensive postchemotherapeutic procedures. In Europe, primary nerve-sparing retroperitoneal lymph node dissection (nsRPLND) for clinical stageI nonseminomatous GCT (NSGCT) plays asubordinate. In clinical stageIIA/B, nsRPLND is indicated for patients with marker-negative metastases in whom cure rates of about 65% can be achieved with surgery alone. For clinical stageIIA/B seminomas, nsRPLND represents an individual, still experimental procedure with high cure rates. Postchemotherapy residual tumor resection (pRTR) for advanced seminomas is only indicated in the context of aFDG-PET/CT-positive residual mass >3 cm in diameter. For NSGCT, pRTR is indicated in patients with residual masses >1 cm and negative or plateauing tumor markers to resect persisting teratoma or vital cancer. Complete resection of all masses including resection of adjacent vascular, visceral or skeletal metastases is mandatory to achieving the highest cure rate possible. Due to the complexity and the lower rate of significant morbidity and mortality, these procedures should be done at tertiary referral centers.

The role for resection of post-chemotherapy residual liver masses in the management of non-seminomatous germ cell tumor.

e16047Background: To evaluate the oncologic outcomes and histologic concordance of post-chemotherapy residual liver mass resection with post-chemotherapy retroperitoneal lymph node dissection (PC-R...

OC-061 Change in size of hepatic colorectal metastases after completion of chemotherapy is greater than during treatment, but doesn’t influence disease-free survival after resection

Introduction The aim of this study was to assess the change in size of colorectal liver metastases between post-chemotherapy imaging and liver resection and to measure potential associations of this change with disease-free survival. Method Analysis of a prospectively maintained database of patients undergoing liver resection for colorectal liver metastases between 2005 and 2012 was undertaken. Response to chemotherapy was assessed by RECIST criteria. Change in tumour size between completion of chemotherapy and liver resection was measured by comparing the maximum diameter of lesions determined by post-chemotherapy imaging and those determined by examination of the resected specimen. Results In 146 patients the median interval between post-chemotherapy imaging and liver resection was 10.4 weeks (7.1–17.6 weeks). During this period tumour diameter increased in 102 patients (69.9%) and decreased in 37 (25.3%) with a median change of +2.3% per week (–19.4 to +1624%). Tumour behaviour after completion of treatment was not associated with disease-free survival in patients who initially responded to chemotherapy (P = 0.591) or those with stable disease (P = 0.436). Among patients with progressive disease after completion of chemotherapy the median disease-free survival of patients who initially responded (26 months) was longer than in those with stable disease (7 months) (P = 0.002), but there was no association between the rate of increase in size and disease-free survival (P = 0.406). Conclusion Change in tumour size after completion of chemotherapy is variable and can be rapid, especially in patients who initially responded to treatment. It does not however appear to affect outcome and should not be considered an adverse factor when counselling patients. Disclosure of interest None Declared.