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In the near future, immunotherapy with checkpoint inhibitors will not only reach the relevant ENT clinics, but also the oncologically integrated ENT practice, since more and more patients under long-term therapy (currently up to 2 years) also have to be seen during clinical follow-up in the specialist practice. In this respect, we also consider as necessary that the basics of immuno-oncology in head and neck tumors are already taught as part of the ENT specialist training. In this review article, the background and the definitions of the therapy sections (first, second line treatment, marker, etc.) should be discussed in detail and the basic tools for understanding this new therapy option should be provided. Since 2017, we have been experiencing a high level of approval dynamics for checkpoint inhibitors in Germany, which is to be assessed as an expression of a new effective principle of action and, after surgery, radiation and chemotherapy, is establishing a fourth strong pillar in the multimodal spectrum against head and neck tumors. Right from the start, the checkpoint inhibitors in the first phase 1b, 2 and 2b studies achieved overall response rates of 16-22 % with overall survival rates of 6-8 months in seriously ill patients with HNSCC who already had a first- and/or even second-line therapy. Nivolumab and Pembrolizumab are currently approved in Germany for the first and second line therapy of relapsed/metastatic squamous cell carcinoma of the head and neck region (HNSCC), Cemiplimab for recurrent/metastatic cutaneous squamous cell carcinoma and Avelumab for metastatic recurrent Merkel-cell carcinoma. The synopsis article about immune checkpoint inhibitors is intended to convey the basic understanding of the principle of action, the indication, toxicity management and the further development within trials in head and neck oncology.

Despite advances in the treatment of gynaecological malignancies, both recurrent endometrial and cervical cancers when not amenable to localised therapy (surgery or radiotherapy), remain incurable with limited prognosis and effective treatment options. Chemotherapy remains the standard of care for women with metastatic endometrial or cervical cancers. The addition of bevacizumab to first-line chemotherapy for metastatic cervical cancer patients represents a significant step forward in improving survival. More recently, immunotherapeutic strategies targeting the PD-1/-L1 pathway have shown clinical activity in both endometrial and cervical cancers. The increased understanding of the molecular biology of these cancers is shaping target-specific treatments. Here we summarise current treatment options and results from clinical trials of immunotherapy and other targeted therapies that have already changed, or have the potential to change, clinical practice in metastatic/recurrent endometrial and cervical cancer.

Renal cell carcinoma with sarcomatoid dedifferentiation is an entity of RCC that has undergone an anaplastic transformation with both a carcinomatous and a sarcomatous component. The standard treatment in metastatic patients is immunotherapy. The aim of this article is to describe our case of metastatic recurrent RCC with sarcomatoid dedifferentiation in a 59 year old male patient treated with nephrectomy and multiple metastasectomies followed by Cabozantinib. Consecutive PET-CT scans showed no evidence of recurrence, three years after the last metastasectomy, and the patient is having currently a normal life. Sarcomatoid dedifferentiation remains a poor prognosis factor in RCC. Surgery for metastases followed by Cabozantinib may be a therapeutic option in metastatic young patients. However, a prospective randomized trial would be the best option to validate this approach.

Purpose Temsirolimus is effective in the treatment for metastatic non-clear cell renal cell carcinoma (nccRCC) with poor prognosis. We aim to investigate the efficacy and tolerability of temsirolimus in treatment of naïve Asian patients with metastatic/recurrent nccRCC. Materials and Methods From January 2008 to July 2017, data of treatment-naïve, metastatic/recurrent nccRCC patients, who were treated with temsirolimus according to the standard protocol, were collected. The primary end-point was progression-free survival (PFS). Secondary end points were overall survival (OS), objective response rate (ORR), and tolerability of temsirolimus. Results Forty-four metastatic/recurrent nccRCC patients, 10 from prospective and 34 from retrospective groups, were enrolled; 24 patients (54%) were papillary type, and other histology subtypes included 11 chromophobes (25%), two collecting ducts (5%), one Xp11.2 translocation (2%), and six others (14%). The median PFS and OS were 7.6 months and 17.6 months, res-pectively. ORR was 11% and disease control rate was 83%. Patients with prior nephrectomy had longer PFS (hazard ratio [HR], 0.16; 95% confidence interval [CI], 0.06 to 0.42; p < 0.001) and OS (HR, 0.15; 95% CI, 0.05 to 0.45; p < 0.001). Compared to favorable/intermediate prognosis group, poor prognosis group had shorter median PFS (4.7 months vs. 7.6 months [HR, 2.91; 95% CI, 1.39 to 6.12; p=0.005]) and median OS (9.2 months vs. 17.6 months [HR, 2.84; 95% CI, 1.23 to 6.56; p=0.015]). Conclusion Temsirolimus not only benefits poor-risk nccRCC patients, but it is also effective in favorable or intermediate-risk group in Asians. Temsirolimus was well-tolerated with manageable adverse events.

Background The use of immunomodulating therapy to treat various cancers has been on the rise and these immune checkpoint inhibitors are known to cause ocular side effects. In this article a case of acute exudative polymorphous vitelliform maculopathy (AEPVM) is reported which developed during a first line treatment with pembrolizumab. Case presentation A 54-year-old woman was referred because of blurry vision in both eyes with a yellow spot in the central visual field of the left eye. These symptoms started after four treatments with pembrolizumab (a monoclonal antibody against the programmed cell death receptor-1) for a metastatic recurrent vaginal mucosal melanoma. Her best corrected visual acuity was 10/10 in both eyes with a correction of + 2.00 bilaterally. There were no inflammatory findings in the anterior segment or the vitreous. Fundoscopy revealed an attenuation of the foveal reflex with subtle yellow-white subretinal macular deposits (vitelliform lesions) in both eyes. Fluorescein angiography did not show staining or leakage in the mid-phase, neither a late staining. Spectral-domain optical coherence tomography of the macula illustrated bilateral neurosensory retinal detachment with a thick, highly reflective band at the outer photoreceptor segment. En face structural OCT at the level of the photoreceptors showed focal areas of increased signal corresponding to hyperreflective vitelliform material. The treatment with pembrolizumab was ceased immediately. During the following visits we slowly saw an improvement of the neurosensory retinal detachment. After almost four months a total resolution of the subretinal fluid was visualized in both eyes without the use of additional treatment, though the vitelliform deposits persisted. Conclusions The development of AEPVM in melanoma patients could be triggered by treatment with Pembrolizumab. Pembrolizumab has the potential to disturb indirectly the retinal pigment epithelium homeostasis with accumulation of lipofuscin deposits and subretinal fluid, both signs of AEPVM.

Background The role of surgery in patients with metastatic, recurrent or unresectable locally advanced gastrointestinal stromal tumors (GIST) who respond to imatinib mesylate (IM) treatment is still not formally defined. Therefore, we systemically searched and analyzed the available literature to evaluate the oncologic benefits of surgery in this specific population. Methods A systematic literature search of the PubMed, Embase, and Cochrane Library databases was performed to identify relevant articles on July 16, 2020. Pooled data analysis was also performed using Review Manager. Results Totally 10 studies including 1188 patients (410 patients in the surgery group and 778 patients in the no surgery group) were included in the final analysis. No significant differences in baseline clinical characteristics were found except that patients in the surgery group were significantly younger (WMD, -5.02, 95% CI, -8.38 to -1.67, P = 0.003). In the overall population, pooled data showed a significant improvement in overall survival (OS) (HR, 0.62; 95% CI, 0.53 to 0.73; P P P P = 0.009). Conclusions Surgery prolongs the OS and PFS of patients with metastatic, recurrent, or unresectable locally advanced GIST who respond to IM treatment. Future prospective, multicenter RCTs are warranted.

Simple Summary The aim of this review is to assess the available literature of the pharmacological treatment of patients with metastatic, recurrent or persistent cervical cancer not amenable by surgery or radiotherapy. The results and toxicities of cisplatin-based doublets are exhaustively described. The combinations of cisplatin plus paclitaxel with or without bevacizumab is the most active regimen in these clinical setting. Immune-check-point inhibitors and molecularly-targeted agents are promising fields of research. Abstract Cervical cancer patients with distant or loco-regional recurrences not amenable by surgery or radiotherapy have limited treatment options, and their 5-year overall survival (OS) rates range from 5% to 16%. The purpose of this paper is to assess the results obtained with chemotherapy and biological agents in this clinical setting. Several phase II trials of different cisplatin (CDDP)-based doublets and a phase III randomized trial showing a trend in response rate, progression-free survival, and OS in favor of CDDP + paclitaxel (PTX) compared with other CDDP-based doublets have been reviewed. The factors predictive of response to chemotherapy as well as the benefits and risks of the addition of bevacizumab to CDDP + PTX have been analyzed. The FDA has recently approved pembrolizumab for patients with recurrent or metastatic cervical cancer in progression on or after chemotherapy whose tumors were PD-L1 positive. Interesting perspectives of clinical research are represented by the use of immune checkpoint inhibitors alone or in addition to chemotherapy, whereas PARP inhibitors and PI3K inhibitors are still at the basic research phase, but promising.

Despite advances in the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer, the disease is rarely curable. In this review, we focus on the use of cyclin-dependent kinase (CDK) 4/6 inhibitors, examining clinical experience and the mechanisms underlying the development of resistance, and evaluating treatment options after failure to respond to CDK4/6 inhibitors. Current basic research supports the use of mammalian target of rapamycin inhibitors after CDK4/6 inhibitor failure; however, more data are needed, particularly regarding treatment sequencing. Real-world data studies may help to fill the current knowledge gap, particularly where large-scale randomized controlled studies are not feasible.

Effective induction of antitumor T cells is a pivotal goal of cancer immunotherapy. To this end, lentiviral vectors (LV) are uniquely poised to directly prime CD8 T-cell responses via transduction of dendritic cells in vivo and have shown promise as active cancer therapeutics in preclinical tumor models. However, until now, significant barriers related to production and regulation have prevented their widespread use in the clinic. We developed LV305, a dendritic cell-targeting, integration-deficient, replication incompetent LV from the ZVex platform, encoding the full-length cancer-testis antigen NY-ESO-1. LV305 is currently being evaluated in phase 1 and 2 trials in metastatic recurrent cancer patients with NY-ESO-1 positive solid tumors as a single agent and in combination with anti-PD-L1. Here we report on the first patient treated with LV305, a young woman with metastatic, recurrent, therapy-refractive NY-ESO-1 synovial sarcoma. The patient developed a robust NY-ESO-1-specific CD4 and CD8 T-cell response after 3 intradermal injections with LV305, and subsequently over 85% disease regression that is continuing for >2.5 years posttherapy. No adverse events >grade 2 occurred. This case demonstrates that LV305 can be safely administered and has the potential to induce a significant clinical benefit and immunologic response in a patient with advanced stage cancer.

This abstract was not presented at the symposium.

Background: We have previously reported the prognostic role of humoral antigen spreading response against prostate-related antigen (PRA) for metastatic recurrent breast cancer (mrBC) patients who received personalized peptide vaccine (PPV) therapy (Toh U, SABCS 2015). The prognostic effect was additionally evaluated by the clinical relevant factors including intrinsic subtype, the regimens of combined chemo-hormonal therapies in present study. Methods:We analyzed serum IgG responses to all of the peptide candidates included PRAs (PSA, PAP and PMSA) after PPV therapy by the Luminex systemusing peripheral blood samples from 77 vaccinated mrBC patients. The clinical factors and relevant events were statistically evaluated. Results: After 6 and 12cycles of PPV therapy, the serum IgG of anti-PSA, anti-PAP, and/or anti-PMSA increased significantly in 31 patients (PRA response group), and the median progression free survival (PFS) and median overall survival (OS) were 8.1 and 14.3 months, but were 5.1 and 10.8 months, respectively, in the remaining 46 patients with no anti-PRA IgG response (PRA non-response Group). The anti-PRA IgG level was marginally correlated withPFS (p=0.059) and OS (p=0.082) between these two groups, which was a significant prognostic factor for PFS (Log-rank: 0.009) in estrogen-positive cancer patients (ER+). The statistical analyses showed that the clinical outcome was in favor of > 60 year-old patients, those with longer PPV therapies (>3 months), and those who received combined standard hormonal therapies or bisphosphonate/anti-RANKL therapy. Conclusions: This study indicated a clinical significance between the pre-and post- PPV therapy measurement of serum anti-PRA IgG in patients with mrBC, which may be a useful prognostic marker for monitoring peptide vaccine treatment outcomes, particularly for patients > 60 years with ER+ breast cancer. These results also suggest that the immunotherapeutic peptide vaccine could be efficiently combined with hormonal therapy, anti-HER2 therapy, and bisphosphonate/anti-RANKL therapy in mrBC patients. Citation Format: Toh U, Saku S, Iwakuma N, Takao Y, Okabe M, Akashi M, Yamada A, Shichijo S, Itoh K, Akagi Y. Prognostic factors for therapeutic personalized peptide vaccines in patients with metastatic recurrent breast cancer [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 P3-05-09.

Introduction/Background In the phase III GOG240 trial, combining bevacizumab with paclitaxel and cisplatin/topotecan for advanced cervical cancer significantly improved overall and progression-free survival. The single-arm phase II CECILIA study (NCT02467907) evaluated bevacizumab with a more widely used chemotherapy backbone. Methodology The primary objective was to determine the safety of bevacizumab/carboplatin/paclitaxel for advanced cervical cancer, defined by the frequency and severity of gastrointestinal (GI) perforation/fistula, GI-vaginal fistula and genitourinary (GU) fistula. Eligible patients had metastatic/recurrent/persistent cervical cancer not amenable to curative surgery and/or radiotherapy. Patients with ongoing bladder/rectal involvement, prior cobalt radiotherapy, history of fistula/GI perforation, or bowel resection ≤6 weeks or chemoradiation ≤3 months before starting bevacizumab were excluded. Patients received bevacizumab 15 mg/kg, paclitaxel 175 mg/m2 and carboplatin AUC5 q3w until disease progression, unacceptable toxicity or consent withdrawal. If any drug was stopped for toxicity, the remaining drug(s) could be continued alone. Results Between July 2015 and December 2016, 150 patients began treatment. Baseline characteristics at study entry were: 20%/53%/27% with persistent/recurrent/de novo metastatic disease; 71%/58%/59% with prior radiotherapy/chemoradiation/platinum. Median treatment duration was 6.7 (range Conclusion Bevacizumab can be combined with carboplatin/paclitaxel chemotherapy in the cervical cancer population treated in CECILIA. The fistula/GI perforation incidence is in line with GOG240. Efficacy results are encouraging. Disclosure Nicoletta Colombo:advisor/consultant for Roche, PharmaMar, AstraZeneca, Tesaro, Clovis, Pfizer, MSD, BIOCAD, Takeda, Lilly; travel/accommodation expenses from Roche, PharmaMar, Tesaro. Lydia Dreosti: honoraria for advisory/consultancy roles from Eli Lilly, MSD; travel/accommodation expenses from Janssen, Merck. Mary McCormack: honoraria from AstraZeneca, Roche. Angelica Nogueira-Rodrigues: honoraria for advisory boards/consultancy from Roche, AstraZeneca, MSD; research funding to institution from Roche, MSD. Giovanni Scambia, Andrzej Roszak: no conflict of interest. Margarita Donica: employee of F Hoffmann-La Roche; shares in Novartis. Bulent Ulker: contracted to work on behalf of F Hoffmann-La Roche. Antonio Gonzalez-Martin: advisory boards for Roche, AstraZeneca, Tesaro, Clovis, Pfizer, ImmunoGen, PharmaMar, MSD, Genmad; speaker bureau for Roche, PharmaMar, Tesaro, AstraZeneca; research funding to institution from Roche, Tesaro. Andres Redondo: honoraria from AstraZeneca, Roche Farma, Tesaro, Clovis, Pharmamar, Lilly, Eisai; advisory boards for AstraZeneca, Roche Farma, Tesaro, Clovis, Pharmamar, Lilly; travel/accommodation from AstraZeneca, Tesaro, PharmaMar, Roche Farma; research funding to institution from Eisai, PharmaMar, Roche Farma.

Background/aim Malignant melanoma is a rare disease in the pediatric population and there are no recommendations regarding its management in children, while the current standard of care in metastatic or unresectable melanoma in adult patients includes immunotherapy (anti-CTLA-4 and anti-PD-1 antibodies). Advances in the management of adults with melanoma offer the prospect of promising therapeutic options for children. Case report We describe a case of a 7-year-old patient with recurrent metastatic melanoma, for whom pembrolizumab was used as an adjuvant therapy on compassionate use basis. Conclusion Due to adverse events, the treatment was discontinued after 5 months of pembrolizumab, but with 12-months of follow-up, patient remains in complete remission.

Objective: The effectiveness of paclitaxel-cisplatin-ifosfamide triplet regimen (TIP) was reported to be superior to that of paclitaxel-cisplatin doublet. However, the efficacy of paclitaxel-cisplatin-bevacizumab triplet (TPA) and TIP has not been compared. Here, we compared the efficacy and safety of TIP and TPA in patients with metastatic, recurrent, or persistent cervical cancer. Methods: We retrospectively reviewed the medical records of patients with recurrent, persistent, or metastatic cervical cancer who were at the Samsung Medical Center, Seoul, Korea between January 2005 and September 2018. Of the 161 patients included in the study, 92 had received TIP and 71 had received TPA. For the study, we compared the response rates, progression-free survival (PFS), overall survival (OS), and safety in the 2 treatment groups. Results: The response rates of patients who received TIP and TPA were comparable (64.1% vs 73.2%, P = 0.239). Histology (squamous vs nonsquamous) was the only prognostic factor that affected the response to therapy (odds ratio, 0.259; 95% confidence interval [CI], 0.119-0.562; P = 0.001). The PFS after TIP and TPA treatment was similar: 12.0 months (95%CI, 10.26-13.74) vs 11.5 months (95%CI, 10.18-12.83), respectively. In a Cox proportional hazard model, objective response to therapies was the only independent prognostic factor for both PFS and OS. However, different types of therapy (TIP vs TPA) did not affect the oncological outcomes for either PFS or OS. Although hematologic toxicity was significantly higher in the TIP-treated group than in the TPA-treated group, both regimens were safe and well-tolerated. Conclusions: The effectiveness and safety of TIP was comparable to TPA in terms of response rates, survival, and adverse effects. TIP could be an effective alternative in the treatment of cervical cancer when TPA is contraindicated or unaffordable.

e18510 Background: SNS-301 is a first-in-class immune activating agent targeting human aspartyl (asparaginyl) β-hydroxylase (ASPH). ASPH is overexpressed in +20 tumor types. SNS-301 is an inactivated λ-bacteriophage, engineered to express a highly immunogenic fragment of ASPH fused to the phage gpD coat protein, previously shown to safely and effectively generate CD4, CD8 and B cell responses in a Phase I study (NCT04034225). Anti-PD-1 antibodies such as pembrolizumab and nivolumab can induce durable clinical responses in 13-16% SCCHN patients. While ASPH is frequently expressed in SCCHN, effective de novo responses to this tumor-specific antigen may be limited due to immune tolerance. Our hypothesis is that SNS-301 will break tolerance and trigger a significant anti-ASPH T-cell immune response, which in combination with anti-PD-1 blockade, will result in improved anti-tumor responses in this difficult-to-treat patient population. Methods: This is a Phase I/II study of SNS-301 delivered intradermally in combination with pembrolizumab. The population consists of 30 patients with ASPH+ locally advanced unresectable or metastatic/recurrent SCCHN who are actively receiving pembrolizumab or nivolumab for ≥12 weeks and have a best response of stable disease (SD) or first evidence of progressive disease (PD). A safety run-in will be performed for safety and any dose limiting toxicities (DLT) using a modified rolling six design prior to proceeding to full enrollment. Patients will provide a pre-SNS-301 tumor sample, an on-treatment tumor biopsy and an optional biopsy at PD to characterize the tumor microenvironment and correlate with clinical outcomes. SNS-301 in combination with pembrolizumab is given until confirmed PD or unacceptable toxicity. Study Objectives: Safety, tolerability and anti-tumor activity such as objective response rate, duration of response, progression-free and overall survival, immune responses, tumor/immune biomarkers and their associated treatment outcome. Results: Three patients have been enrolled. There have been no DLTs. Emerging safety data includes G1 adverse events with one G1 injection site pain. Patient status includes 1 PD and 2 patients with SD of at least six weeks duration. Immunological analyses will be presented. Conclusions: Early safety/efficacy warrant further evaluation of this combination therapy. Trial will be proceeding to full enrollment after the safety run-in is completed. Clinical trial information: NCT04034225.

The advent of imatinib mesylate (IM) has dramatically revolutionized the prognosis of advanced and metastatic/recurrent gastrointestinal stromal tumors (GISTs). The objective of this retrospective study is to investigate the safety and efficacy of combination of surgery following IM treatment in the management of advanced and metastatic/recurrent GISTs. We further explore the long-term clinical outcomes in these who underwent therapy of preoperative IM.Eligible patients with GISTs before the onset of the IM therapy and were periodically followed up in the outpatient clinic were included in this study. Detailed clinical and pathologic characteristics were obtained from the medical records of our institution. Univariate and multivariate regression analyses were performed to use for the evaluation of potential prognostic factors.A total of 51 patients were included in the study, of these patients, 36 patients underwent surgery and median duration of preoperative IM is 8.2months (range 3.5-85 months). Significant median tumor shrinkage rate was 29.27% (95% confidence interval 21.00%-34.00%) observed in these patients who responded to IM, and partial response and stable disease were achieved in 24 patients (47.06%) and 23 patients (45.10%), respectively, in light of the RECIST guideline (version 1.1). After the median follow-up of 43.70 months (range 14.2-131.1 months), 1- and 3-year overall survival (OS) were estimated to be 96.1% and 94.0%, respectively, and there was a significant improvement in OS for patients who received surgical intervention versus those who did not.Our study consolidates that patients were received preoperative IM therapy could shrink the size of tumors and facilitate organ-function preservation. The long-term analysis on this study supports that surgical intervention following IM therapy benefits for patients with primary advanced and recurrent or metastatic GISTs on long-term prognosis.

ObjectiveWe conducted a population-based analysis of patient outcomes following treatment with bevacizumab and platinum–based chemotherapy for metastatic, recurrent, or persistent cervical carcinoma.MethodsEligible cases were identified using the BC Cancer provincial pharmacy database. Cases with small cell component or inadequate clinical follow-up were excluded. Overall response to therapy, progression-free survival (PFS), overall survival (OS), and toxicities were documented.ResultsTwenty-seven eligible cases were included with a median follow-up of 12.1 months. The median age at recurrence/metastatic diagnosis was 49 years (range, 27–83 years). Twenty-three of 27 women received carboplatin, paclitaxel, and bevacizumab as first-line treatment, and 4 of 27 as second-line treatment. The median number of cycles of bevacizumab delivered was 5.5 (range, 1–21). The overall response rate was 44% (12/27), with 11% (3/27) complete response and 33% (9/27) partial response. Median PFS and OS for the entire cohort were 5.3 and 12.1 months, respectively. In first-line therapy, the median PFS and OS were 6.3 and 17.5 months, respectively. Common toxicities included anemia (grade 1/2) 73% (19/27), and the following grade 2 or greater: neutropenia 38% (n = 10) with 1 occurrence of febrile neutropenia, hypertension 30% (n = 8), and thrombosis 22% (n = 6). The fistula rate was 3.7% (n = 1).ConclusionsIn this population-based analysis, the combination of bevacizumab and platinum–based chemotherapy as first-line therapy for metastatic, recurrent, or persistent cervical carcinoma was safely delivered and had outcomes comparable to results from the GOG 240 phase III trial.

Carcinoma breast presenting with paraneoplastic cerebellar degeneration is a rare scenario. We report a case of a 52-year-old woman, which is a follow-up case of completely treated carcinoma breast presenting with paraneoplastic cerebellar degeneration which, on investigation, revealed metastatic disease with recurrence at previous scar site and metastasis to contralateral axilla. The patient was given pulse methyl prednisolone therapy and underwent wide local excision of nodule and right axillary lymph node dissection with 14 cycles of trastuzumab and paclitaxel as adjuvant therapy. However, there was no detectable change in neurological symptoms at 6-month follow-up postoperatively. This case report highlights the need for clinicians to be aware of all possible presentations of carcinoma breast and its recurrence, including rare manifestations as in this case.

The incidence of well‑differentiated thyroid cancer (WDTC) is rapidly increasing. Poor survival follows distant metastasis (DM) and recurrence. In the present study, we aimed to analyze the expression alterations in different stages of WDTC and the regulatory mechanism of DM and the recurrence of DM. A male patient diagnosed with follicular thyroid cancer and distant metastasis in the eleventh thoracic vertebrae received total thyroidectomy and the removal of a metastatic lesion. A local relapse was found in the vertebrae after four‑time iodine‑131 treatment. We performed mRNA and microRNA microarray on the paracancerous, cancerous, metastatic and metastatic recurrent tissue. In combination with the data of The Cancer Genome Atlas (TCGA), we used bioinformatics approaches to analyze the common alterations and microRNA‑mRNA interactions among the processes of tumorigenesis and metastasis. Metastatic lesions and recurrent lesions were used to investigate the molecular mechanism of tumor evolution and recurrence in this case. A total of four mRNAs and two microRNAs were newly found to be related to patient survival in WDTC. The microRNA‑mRNA interactions were predicted for the overlapped mRNAs and microRNAs. Lineage deregulation of genes, such as C‑X‑C motif chemokine receptor 4 (CXCR4) and thyroglobulin (TG) were found from the tumorigenic stage to the metastatic stage. The ribosome pathway was highly enriched in the bone metastasis compared with the cancerous tissue. The downstreaming effects of p53 were impaired in the recurrent lesion due to deregulation of several functional genes. The integrated analysis with TCGA data indicated several prognostic markers and regulatory networks for potential treatment. Our results also provided possible molecular mechanisms in which the ribosome and p53 pathways may respectively contribute to bone metastasis and local recurrence of metastasis.

The treatment of metastatic and recurrent uterine leoimyosarcoma (uLMS) has evolved rapidly in the past several years. Leoimyosarcoma is extremely aggressive and responds poorly to traditional chemotherapeutics. Recent regulatory approval of novel treatment options has significantly expanded the therapeutic armamentarium, and the addition of these therapies has challenged clinicians to select and optimally sequence these new compounds. Additionally, the potential role of immunotherapy is being assessed in current uLMS clinical trials. Given the increasing number of agents available both in the U.S. and globally, a treatment template that addresses optimal sequencing based upon expert consensus would be useful. Current guidelines, although listing various options, lack granularity by line of therapy. Most patients with leiomyosarcoma, even in early stage, are treated with surgery followed by adjuvant chemotherapy despite uLMS being relatively chemoresistant. Adjuvant chemotherapy often includes the combination of gemcitabine and docetaxel with or without doxorubicin in first-line systemic therapy, but these cytotoxic agents only provide patients with advanced disease a 5-year survival Implications for Practice Recent regulatory approval of novel treatment options has significantly expanded the therapeutic armamentarium, and the addition of these therapies has challenged clinicians to select and optimally sequence these compounds. This review will focus on examination of current guidelines and consensus building for optimal sequencing of systemic therapies for advanced or recurrent uterine leoimyosarcoma.

Background: To investigate the prevalence of indications for radiotherapy (RT) in patients with metastatic/recurrent/inoperable cancer. We also sought to analyze such patients’ clinical and radiological characteristics for indications of radiotherapy in those patients who had either surveillance or an initial assessment done by computed tomography (CT). Methods: Two diagnostic radiologists and a radiation oncologist evaluated a total of 13,225 consecutive patients from January 2012 to December 2012 at a single Japanese institution. Patients with metastatic/recurrent/ inoperable cancer were selected for further study. After two diagnostic radiologists identified patients with a detectable cancerous lesion, a radiation oncologist subsequently investigated whether there was any indication for RT. The oncologist also evaluated the relationship between patients’ clinical/radiological factors, and patients with or without indications for RT. Results: Two diagnostic radiologists selected 329 patients showing a detectable gross cancerous lesion. In this patient group, a radiation oncologist identified 196 patients with metastatic/recurrent/inoperable cancer, of which 96 patients (49%) showed an indication for RT. According to both univariate and multivariate analyses, ≤4 lesions were significantly associated with patients who showed an indication for RT (P = 0.0002 and P 0.001, respectively). Conclusions: In screening CT images, approximately half of all patients with metastatic/recurrent/inoperable cancer showed an indication for RT. Moreover, ≤4 lesions and/or the existence of a symptomatic, localized lesion were highly suggestive of an indication for RT. These findings would be of considerable interest to radiation oncologists planning appropriate treatments for cancer patients.

Malignant phyllodes tumor of the breast is extremely rare but what is rarer is its occurrence in adolescent girls younger than 18 years. It has a propensity for rapid growth and metastases. We present an uncommon presentation of recurrent and metastatic malignant phyllodes tumor in a 17-year-old female.

Esophageal cancer recurrence rates after esophagectomy are high, and locally recurrent or distant metastatic disease has poor prognosis. Management is limited to palliative chemotherapy and symptomatic interventions. We report our experience of four patients who have undergone successful liver resection for metastases from esophageal cancer. All underwent esophagectomy and were referred to our unit with metastatic recurrent liver disease, two with solitary metastases and two with multi-focal disease. The patients underwent multidisciplinary assessment and proceeded to a course of neoadjuvant chemotherapy followed by open or laparoscopic liver resection. Three patients were male, and the mean age was 57.5 (range 44-71) years. Response to chemotherapy ranged from partial to complete response. Following liver resection, two patients developed recurrent disease at 5 and 15 months, and both had disease-specific mortality at 10 and 21 months, respectively. The other two patients remain disease free at 22 and 92 months. Recurrent metastatic esophageal cancer continues to have a poor prognosis, and the majority of patients with liver involvement will not be candidates for hepatic resection. However, this series suggests that in selected patients, liver resection of metastases from esophageal cancer combined with neoadjuvant and adjuvant chemotherapy is feasible, but further research is required to determine whether this can offer a survival advantage.

Recurrences of tumours of the upper aerodigestive tract are frequent despite the improvement of the primary treatment and they limit the rate of survival long-term. They occur in patients with multiple co-morbidities, often associated with sequelae or side effects of earlier treatments. The salvage treatment will add a cumulative toxicity and therapeutic options are limited. The choice will go from curator to palliative treatment. The report benefit-risk must be assessed in each case depending on the terrain and prognostic factors that have been identified, such as performance status, the time between initial disease and the recurrence, the site and the stratification of the recurrence. In operable non-metastatic recurrence surgery remains the treatment of choice. Multimodal treatment involving surgery, radiation therapy and chemotherapy in this context is being evaluated. Non-operable tumors have long been considered only in a palliative context. The evaluation of detailed irradiation as bifractionnated radiotherapy combined with chemotherapy helped establish protocols allowing long-term survivals and consider these treatments as potentially curators. However, the toxicity of these treatments is important. That is why the technical innovations of the radiation and the development of new chemotherapeutic agents today offer opportunities remaining to assess. The use of irradiation targeted by intensity-modulated radiation therapy (IMRT), and stereotactic radiotherapy by decreasing the irradiated volume should decrease the toxicity. Generally better tolerated than conventional chemotherapy agents, targeted therapies also took their places associated with radiotherapy in the treatment of these patients already treated. Cetuximab was the first agent obtaining an indication. Other agents are being evaluated in metastatic recurrent tumors, including exploring the possibilities of radiopotentialisation nanoparticles and the inhibitors of apoptosis proteins.

Introduction. Papillary thyroid carcinoma (PTC) is the most common malignant thyroid tumor. A great majority of the cases live a disease-free life with quite favorable prognosis. There are lots of variants of PTC and a few of them exhibit aggressive behaviour. Typical example is the tall cell variant (TCV). Patients experience a greater incidence of recurrence, nodal and extranodal metastases, tumor associated mortality than other variants of PTC. Studies related to TCV almost always compared it with its patient population of PTC according to risk factors and clinicopathologic features. The aim of this study is to evaluate the risk factors in metastatic/recurrent TCV. Materials and Methods. This is a retrospective cohort study of 1813 patients with differentiated thyroid carcinoma treated with radioiodine between 1992 and 2011. 56 of these patients are TCV. 34 of them developed metastasis/recurrence and 22 lived a disease-free life during the 23-year follow-up. We evaluated the risk factors in these metastatic and nonmetastatic subgroups. Results. We found tumor size, preablation thyroglobulin level, vascular invasion, preablation central and lateral cervical lymph node metastasis, preablation lung metastasis and stage independent risk factors. However age, preablation thyroglobulin level and stage appeared together as striking factors impacting metastasis in multivariate analysis. Conclusion. Higher ablation doses up to 250-300 mCi should be administered to TCV patients having advanced stage (III,IV), pretty high preablation thyroglobulin level (over 400 ng/ml) and older age (over 52 years) especially with large tumor size (over 3.5 cm) and initial cervical lymph node metastasis.

Cisplatin and nedaplatin show significant antitumor activity and have been widely used for esophageal squamous cell carcinoma (ESCC). However, it is still unclear whether the efficacy and safety of nedaplatin-based regimens are comparable to those of cisplatin-based regimens in patients with metastatic/recurrent or advanced ESCC. Therefore, we conducted a systematic review and meta-analysis to compare the efficacy and safety of these two regimens for the treatment of metastatic/recurrent and advanced ESCC. We systematically searched Pubmed, Web of Science, and the Cochrane Database, as well as abstracts presented at conferences (all up to January 2015), for randomized-controlled and nonrandomized clinical trials that compared cisplatin-based and nedaplatin-based regimens in patients with metastatic/recurrent or advanced ESCC. Data were extracted from the original studies by two independent reviewers. This meta-analysis was performed using Review Manager (RevMan) Version 5.3 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014) software. Ten eligible trials, including 598 patients diagnosed with metastatic/recurrent or advanced ESCC, were included in our analysis. Our results demonstrated that the nedaplatin-based regimens were comparable to the cisplatin-based regimens in terms of overall survival (OS) (hazard ratio, HR: 1.22, 95% confidence interval, CI: 0.86–1.74, p = 0.26) and overall response rate (ORR) (risk ratio, RR: 0.92, 95% CI: 0.77–1.10, p = 0.37) and generated fewer grade 3 and 4 side effects including nausea (RR: 3.41, 95% CI: 1.67–6.96, p

Purpose The clinical characteristics and outcomes of patients with metastatic recurrent cervical cancer remain poorly understood. The goals of the present study were to investigate the survival outcomes according to the recurrence site in a large cohort of cervical cancer patients. Methods and Materials Of 1322 patients with primary cervical cancer from 2000 to 2013, 205 with recurrence after primary or adjuvant postoperative radiation were enrolled retrospectively. Aggressive salvage therapy (AST), which was defined as salvage therapy that aimed not only to relieve symptoms but also to ablate recurrent tumors by the single or combined application of surgical resection of local recurrence, metastasectomy, or metastasis-directed irradiation, followed by chemotherapy, was performed according to our institutional guidelines. The patterns of recurrence, application rate and mode of AST, and survival outcomes were evaluated retrospectively under approval from the institutional review board. Results Regarding the pattern of recurrence, distant-only (DO) recurrence was most common (59.5%), followed by combined (21.5%), central (cervix or vaginal stump; 10.7%), and pelvic (pelvic lymph nodes or pelvic side wall; 8.3%) recurrence. Two subgroups (distant lymph nodes and lung parenchyma) of the DO group demonstrated remarkably good prognosis and were categorized as type A DO; the other subgroups were labeled type B DO. Patients with type A DO recurrence constituted 36% of all recurrences and 83.8% of them received AST. The 5-year overall survival rates were significantly greater in the type A DO group than in the other groups (44.8% in the type A DO group, 12.6% in the pelvic group, and 6.8% in the type B DO group). Conclusions We identified a patient subgroup with favorable outcomes after salvage therapy, type A DO, defined as recurrence in the distant lymph nodes only or in the lung parenchyma only. A future prospective trial is needed to investigate whether AST improves survival in this group.

The hematological malignancy is a well-known complication following breast carcinoma (BC), but the type of malignancy that occurs and treatment regimens followed are still under evaluation. The literature mostly describes therapy-related acute myeloid leukemia and myelodysplastic syndrome associated with BC. Chronic lymphocytic leukemia (CLL) is extremely rare following BC and is mostly described in patients treated with radiotherapy. Herein, we present a rare case of CLL detected at the time of recurrence in a 61-year-old female patient with a previous history of BC solely treated with surgery. She presented simultaneously with metastatic recurrent carcinoma and CLL.

t A c e ( i Background Invasive cervical cancer was once one of the most common malignancies to affect women in the United States. Although it remains a worldwide epidemic with greater than 500,000 new cases diagnosed annually, resulting in 250,000 deaths each year, the incidence of the disease in developed countries has decreased over the preceding 60 years. In 2009, it was estimated that there were 11,270 new cases of nvasive cervical cancer and approximately 4070 deaths. The vast majority of these deaths occur among patients with untreated locally advanced and metastatic disease as well as those whose disease recurs after definitive therapy for locally advanced lesions. The reasons for the decreased incidence of invasive cervical cancer in developed nations can be attributed primarily to screening programs using cervical cytology (ie, Papanicolaou testing). Because screening is available mainly to women who have health care coverage or who are able to pay out of pocket, advanced cases of disease now occur predominantly among poor women in developed countries and throughout impoverished regions of the world. Women diagnosed with invasive disease through screening programs are most likely to be found to have early-stage, and hence, curable lesions. Although algorithms exist that incorporate high-risk human papillomavirus DNA co-testing into screening programs that use cervical cytology, the degree of impact of dual modality of screening on ortality rates from cervical cancer is unclear at the present time. imilarly, vaccines that have been licensed by the United States Food

Background Therapy for gastrointestinal stromal tumors (GIST) has changed significantly with the use of imatinib mesylate (IM). Despite the success of this drug in metastatic GIST, disease progression remains a perplexing clinical issue suggesting the need for multimodality management. There have been no prospective studies either evaluating the neoadjuvant use of IM in primary GIST or as a preoperative cytoreduction agent for metastatic GIST. Methods RTOG 0132/ACRIN 6665 was a prospective phase II study evaluating safety and efficacy of neoadjuvant IM (600 mg/day) for patients with primary GIST or the preop use of IM in patients with operable metastatic GIST. The trial continued postop IM for 2 years. Results Sixty-three patients were entered (52 analyzable), 30 patients with primary GIST (Group A) and 22 with recurrent metastatic GIST (Group B). Response (RECIST) in Group A was (7% partial, 83% stable, 10% unknown), in Group B (4.5% partial, 91% stable, 4.5% progression). Two-year progression free survival (Group A 83%, Group B 77%). Estimated overall survival (Group A 93%, Group B 91%). Complications of surgery and IM toxicity were minimal. Conclusion This trial represents the first prospective report of preop IM in GIST. This approach is feasible, requires multidisciplinary consultations, and is not associated with notable postop complications. J. Surg. Oncol. 2009;99:42–47. © 2008 Wiley-Liss, Inc.

BackgroundTo determine the efficacy and safety profile of the combination of cisplatin and 5-fluorouracil modulatedboth by methotrexate and leucovorin in metastatic/recurrent squamous cell carcinoma of the head and neck.MethodsTwenty-eight patients were treated with cisplatin 40 mg/m2/day continuous infusion for 24 hours on day 1;high-dose 5-fluorouracil 2,000 mg/m2/day and leucovorin 100 mg/m2/day continuous infusion for 48 hours on days 1and 2; methotrexate 40 mg/m2/day as a bolus infusion 4 hours before 5-fluorouracil and leucovorin on day 1. The treat-ment was repeated every 2 weeks in a cycle.ResultsThe overall response rate was 25%, and 14% of the patients achieved stable disease status. Subgroup analy-sis demonstrated significantly improved overall survival in the disease-control group (12.0 months vs. 5.3 months,p < 0.001). Only 3 (10.7%) patients developed grade 3–4 neutropenia, and none developed grade 3–4 non-hematologictoxicity.ConclusionThis multiagent-containing regimen has an excellent safety profile and improved survival in disease-controlgroup of patients with metastatic/recurrent squamous cell carcinoma of the head and neck.

Purpose To update the 2004 American Society of Clinical Oncology (ASCO) guideline on initial hormonal management of androgen-sensitive, metastatic, recurrent, or progressive prostate cancer (PCa). Methods The writing committee based its recommendations on an updated systematic literature review. Recommendations were approved by the Expert Panel, the ASCO Health Services Committee, and the ASCO Board of Directors. Results Seven randomized controlled trials (four new), one systematic review, one meta-analysis (new), one Markov model, and one delta-method 95% CI procedure for active controlled trials (new) informed the guideline update. Recommendations Bilateral orchiectomy or luteinizing hormone–releasing hormone agonists are recommended initial androgen-deprivation treatments (ADTs). Nonsteroidal antiandrogen monotherapy merits discussion as an alternative; steroidal antiandrogen monotherapy should not be offered. Combined androgen blockade should be considered. In metastatic or progressive PCa, immediate versus symptom-onset institution of ADT results in a moderate decrease (17%) in relative risk (RR) for PCa-specific mortality, a moderate increase (15%) in RR for non–PCa-specific mortality, and no overall survival advantage. Therefore, the Panel cannot make a strong recommendation for early ADT initiation. Prostate-specific antigen (PSA) kinetics and other metrics allow identification of populations at high risk for PCa-specific and overall mortality. Further studies must be completed to assess whether patients with adverse prognostic factors gain a survival advantage from immediate ADT. For patients electing to wait until symptoms for ADT, regular monitoring visits are indicated. For patients with recurrence, clinical trials should be considered if available. Currently, data are insufficient to support use of intermittent androgen blockade outside clinical trials.

Nitisinone blocks the tyrosine pathway and may be effective in treating neuroblastoma. A 33-month-old male with heavily treated metastatic, recurrent, N-MYC amplified neuroblastoma received nitsinone (0.8 mg/kg/day escalated to 5.0 mg/kg/day). Dramatic tumor regression and resolution of pain without toxicity were observed. At 10 weeks, the tumor progressed. Nitisinone, low dose cyclophosphamide and doxorubicin subsequently produced a very good partial response. At 18 months the disease progressed. The child succumbed 21 months after starting nitisinone. Nitisinone produced an increase in tyrosine and catecholamine metabolite (HVA, VMA, and metanephrines) levels. Nitisinone may be a promising agent in metastatic neuroblastoma.

To define the efficacy of thalidomide on the overall survival of patients with metastatic recurrent gynecologic sarcomas.All patients with sarcoma or carcinosarcoma of gynecologic origin and documented recurrence or persistence of disease after appropriate surgery, radiation therapy and/or chemotherapy were recruited to the study. All patients were ambulatory and had measurable disease that could be documented on CT scan. Patients were started on 200 mg/day of thalidomide orally every night and escalated by 100-200 mg every 7 to 14 days. The length of the treatment was separated into 2 cycles with the first 84 days defined as the first cycle and the next 56 days as the second cycle. Common Toxicity Criteria were used to record toxicities. Because thalidomide was postulated to induce cytostasis, the end-points were progression-free and overall survival in this mixed group of patients.Seventeen patients were enrolled. The drug was not well tolerated because of constipation, fatigue, worsening performance status, drowsiness and sleepiness. The total dosage of medication given to each patient ranged from 3200 mg to 40,500 mg. The maximum dosage reached in each patient ranged from 300 mg to 750 mg, with the total time of treatment ranging from 13 to 99 days. All patients had progression of disease with a median progression-free survival time of 1.84 months (CI 1.54-2.79 months) and a median overall survival of 6.64 months.Thalidomide has no activity in patients with advanced or recurrent gynecologic sarcomas and was not well-tolerated. The overall survival was7 months. The progression-free survival was3 months, and, since the therapy was not tolerated well, we unanimously decided to close the study at this point. Despite the poor result, we still believe in the strategy of anti-angiogenesis and will continue to pursue other potential treatment options using the same concept.

This study examined pre- and post-loss levels of posttraumatic stress symptoms (intrusion and avoidance) in partners of metastatic/recurrent breast cancer patients, and the relationship of these symptoms to past, current, and anticipatory stressors. The results indicate that 34% (17/50) of the partners experienced clinically significant symptom levels prior to the patients' deaths. Prior to loss, partners' symptoms were positively associated with their current level of perceived stress and anticipated impact of the loss; whereas following loss, partners' symptoms were predicted by higher pre-loss levels of symptoms, past family deaths, and anticipated impact of the loss. Limitations and treatment implications of the present research and directions for future research are discussed. Copyright © 2004 John Wiley & Sons, Ltd.

Purpose To develop a clinical practice guideline for the management of men with metastatic, recurrent, or progressive carcinoma of the prostate. The focus of this document is on the use, combinations, and timing of various forms of androgen deprivation therapy (ADT) for the palliation of men with androgen-sensitive disease. Methods An expert panel and writing committee were formed. The questions to be addressed by the guideline were determined, and a systematic review of the literature was performed, which included a search of online databases, bibliographic review, and consultation with content experts. A priori criteria were used to select studies for analysis and study authors were contacted when necessary. Results There were 10 randomized controlled trials, six systematic reviews, and one Markov model available to inform the guidelines. Conclusion A full discussion between practitioner and patient should occur to determine which therapy is best for the patient. Bilateral orchiectomy or luteinizing hormone releasing hormone agonists are the recommended initial treatments. Nonsteroidal antiandrogen therapy may be discussed as an alternative, but steroidal antiandrogens should not be offered as monotherapy. Patients willing to accept the increased toxicity of combined androgen blockage for a small benefit in survival should be offered nonsteroidal antiandrogen in addition to castrate therapy. Until data from studies using modern medical diagnostic/biochemical tests and standardized follow-up schedules become available, no specific recommendations can be issued regarding the question of early versus deferred ADT. A discussion about the pros and cons of early versus deferred ADT should occur.

We present a case of cisplatin-induced syndrome of inappropriate antidiuretic hormone (SIADH) in a patient with metastatic recurrent urothelial carcinoma. Cisplatin-induced SIADH is an uncommon but potentially life-threatening toxicity. Pharmacogenetic characteristics may result in different toxicity profiles in different populations. With such widespread use of cisplatin in a diverse range of cancers, prompt recognition is crucial to detect and prevent severe neurological sequelae.

167 Background: The aim of this study is to identify the prognostic role of serum value of IgG antibody against prostate related-antigen (PRA), including prostate-specific antigen (PSA), prostate specific membrane antigen (PSMA), and prostate acid phosphatase (PAP) in mrBC patients. Methods: Peripheral blood samples of 77 patients with mrBC were analyzed for serum anti-PRA IgG levels before and after 6th and 12th PPV therapy prospectively. Most of the peptides used for PPV are derived from cancer associated antigens expressing in various types of advanced cancers, but the peptides derived from PRAs were not used in this study. Results: After PPV therapy, total serum levels of anti-PRA IgG were significantly increased in 31 mrBC patients (Group 1) compared with remaining 46 rmBC patients (Group 2). Either serum anti-PSA, anti-PAP, and/or anti-PMSA IgGs showed a significant increase in patients of Group 1 after 6th (p=0.045) and 12th PPV treatment (p < 0.001), irrespective of their intrinsic subtypes. The median PFS and median OS of Group 1 patients were 8.1 and 14.3 months, while those of Group 2 patients were 5.1 and 10.8 months, respectively. Anti-PRA IgG levels were significantly associated with PFS (p=0.0073; HR: 0.37) and OS (p=0.025; HR: 0.43) between these two groups, whereas no significant relation was found with age, clinical response rate, and recurrent metastatic status. Conclusions: The Group 1 patients with elevated anti-PRA IgG may have better prognosis compared to Group 2 patients who showed no IgG elevation after PPV treatment for rmBC. These results indicated a clinical significance between pre-and post- treatment measurement of serum anti-PRA IgGs in mrBC patients receiving PPV therapy, and may be a useful prognostic marker for monitoring the outcome to PPV treatment of breast cancer.

countries, in which carcinoma of the uterine cervix still is the most common cause of death related to gynecologic cancer. Most deaths relate to recurrent disease after initial treatment of earlier-stage disease with either surgery or concurrent chemoradiation. Although highly selected patients can be treated successfully with surgery and/or radiation in the recurrent-disease setting, the mainstay of therapy for the vast majority of patients with recurrent carcinoma of the cervix will be systemic therapy in the form of chemotherapy. This debate, whether or not patients with recurrent cervical cancer should be treated with cisplatin/paclitaxel, focuses on what constitutes the optimal systemic therapy for these patients with recurrent disease. In the great spirit of the debate, this side could take the position that not all patients with recurrent disease should be treated with chemotherapy and that selected patients may be candidates for surgery with potentially curative results. Instead, this article will point to solid reasons for not treating most patients with paclitaxel/cisplatin.

OBJECTIVES: Despite its rising popularity, reports on the use of preoperative imatinib mesylate (IM) in patients with advanced gastrointestinal stromal tumor (GIST) are limited. This study aims to explore the clinical efficacy of preoperative IM in patients with primarily unresectable or metastatic/recurrent GIST. METHODS: Between September 2009 and February 2014, patients with primarily unresectable or metastatic/recurrent GIST treated by a single medical team were recruited and considered for preoperative IM therapy. Re-examination was conducted regularly and abdominal enhanced CT data, blood biochemistry and responses to IM were recorded. RESULTS: A total of 18 patients were enrolled, including 13 with a primary tumor (7 stomach, 3 small bowel, 2 rectal and 1 pelvic tumor) and 5 with recurrent or metastatic GIST (2 with liver metastasis, 2 with anastomotic recurrence and 1 with pelvic GIST). The median follow-up time was 9.5 months (range of 3-63). The median tumor sizes before and after initiation of IM treatment were 9.1 cm and 6.0 cm (p = 0.003) based on the CT findings, respectively. All patients showed a decrease in tumor burden and the median tumor size reduction was 35%. Sixteen of the 18 patients showed a partial response to IM and two possessed stable disease. Nine of the 18 patients (50%) underwent surgical resection of primary or metastatic/recurrent tumors, with a median of 7 months of IM therapy. One case each of multivisceral resection and tumor recurrence were noted. CONCLUSIONS: IM as a preoperative therapy is feasible and safe for unresectable or metastatic/recurrent GIST that can effectively decrease tumor size, facilitating resection.

Background Detection of neuroendocrine tumor (NET) disease progression is a key issue in determining management. Currently, assessment is by imaging (MRI/CT and Octreoscan®) and plasma Chromogranin A (CgA) measurement. Case presentation We report use of a NET-specific multigene PCR-derived blood transcript signature (NET Index) to assess disease and correlated CgA and gene transcripts with MRI, CT, Octreoscan®, 11C-5HTP-PET/CT and 68Ga-DOTA-PET/CT in a patient with NET. Conclusions Our results identify limitations in evaluating disease status by CgA and identify that a PCR-based test is more sensitive. Alteration in NET blood gene transcript levels prior to image-based tumor confirmation suggests this parameter may also have utility as an index of therapeutic efficacy.