Optimization of high-dose methotrexate prophylaxis for central nervous system relapse in diffuse large B-cell lymphoma: a multicenter analysis.

Central nervous system (CNS) relapse of diffuse large B-cell lymphoma (DLBCL) is a rare but devastating event. Intravenous high-dose methotrexate (HD-MTX) is recommended as CNS prophylaxis, but the optimal timing and dose has not been elucidated. Here, we report a multicenter analysis of prophylactic HD-MTX administration for DLBCL. Two hundred eighty-four patients receiving HD-MTX either concurrent with each induction chemotherapy cycle (n = 221) or at the end of induction therapy (EOI, n = 63) were included. Patients with CNS-IPI scoring 4-6, and/or testicular involvement, and/or double/triple hit lymphoma, were stratified into the high-risk group and the others into the moderate-risk group. Concurrent HD-MTX was associated with increased risk of grade 3/4 treatment-related toxicity (OR,1.49; P = 0.006) and subsequent chemotherapy delays (OR, 1.87; P = 0.003) in multivariate analysis. With a median follow-up of 36.0 months, no significant difference in CNS relapse rate was identified between the concurrent and EOI groups (3.2% vs 4.8%, P = 0.34), even in the high-risk group. Analysis on systemic MTX dose suggested that high-dose MTX (≥ 2 g/m2) was associated with better CNS relapse control only in the high-risk group, but not in the moderate-risk group. This study may elucidate the superiority of EOI HD-MTX to some extent. High MTX dose (≥ 2 g/m2) may not be necessary for the moderate-risk patients.

CaboPoint: a phase II study of cabozantinib as second-line treatment in patients with metastatic renal cell carcinoma.

Cabozantinib is an inhibitor of multiple tyrosine kinases, including AXL, MET and VEGF receptors. Here, we describe the rationale and design for the phase II CaboPoint trial (ClinicalTrials.gov identifier: NCT03945773), which will evaluate the efficacy and safety of cabozantinib as a second-line treatment in patients with unresectable, locally advanced or metastatic renal cell carcinoma whose disease has progressed despite checkpoint inhibitor therapy. Patients will be recruited into two cohorts: prior ipilimumab plus nivolumab (cohort A) or prior checkpoint inhibitor-VEGF-targeted therapy (cohort B). All patients will receive once-daily oral cabozantinib 60 mg for up to 18 months. The primary end point is objective response rate. Secondary end points include overall survival, progression-free survival and safety.

Most patients diagnosed with kidney cancer have a type of tumor called renal cell carcinoma (RCC). Most cases of RCC are described as 'clear cell' because the tumor cells appear clear when viewed under a microscope. Cabozantinib is an oral treatment approved for use in some patients with advanced RCC, including those with clear cell disease. Cabozantinib slows RCC progression by targeting pathways that help tumors grow, including inhibition of VEGF. The ongoing CaboPoint study will assess the efficacy and safety of cabozantinib in patients with clear cell RCC that has progressed despite previous anticancer treatment involving an immune checkpoint inhibitor (CPI). CPI therapy helps the body to detect tumors and to launch its own anticancer response. Patients included in CaboPoint must be adults with clear cell RCC that is not suitable for surgery and has either spread within the kidney or to other organs, despite previous CPI-based therapy. In total, 250 patients will be recruited: 125 who received previous combination CPI treatment (ipilimumab plus nivolumab; group A) and 125 who received previous CPI treatment plus anti-VEGF therapy (group B). Patients will start cabozantinib at a dose of 60 mg/day and continue treatment for up to 18 months. The main outcome to be studied will be the number of patients with a reduction in tumor size (objective response rate). The length of time patients live with their disease, the effect of treatment on symptoms and patient safety will also be evaluated. Clinical trial registration: NCT03945773 (ClinicalTrials.gov).

Metal artifact-free MRI-guided re-irradiation for recurrent spinal metastases from thyroid cancer.

BACKGROUND: Soft tissue tumors near metal implants are sometimes difficult to treat with real-time image-guided radiation therapy. Low-field MRI was utilized to clearly delineate the tumor and spinal cord while avoiding metal artifacts, and re-irradiation was performed for recurrent spinal metastases. CASE DESCRIPTION: A 57-year-old woman with a history of thyroid cancer was referred for re-irradiation for recurrent painful bone metastases in the thoracolumbar spine. She had already undergone conventional radiation therapy followed by stereotactic ablative radiotherapy and multiple fusion surgeries. Since the radiation dose to the spinal cord should have been limited, metal artifact-free low-field MRI-guided re-irradiation was performed with no significant adverse events. CONCLUSION: Low-field MRI-guided re-irradiation may be feasible for recurrent spinal metastases, even after metal implants have been placed.

Extended intraoperative peritoneal lavage as prophylactic peritoneal recurrence for locally advanced gastric cancer: a prospective randomized trial.

BACKGROUND: To demonstrate whether extensive intraoperative peritoneal lavage (EIPL) could yield better results in overall survival and less recurrence, regardless of peritoneal cytology, compared to standard peritoneal lavage (SPL). METHODS: A prospective randomised multicenter study including 94 patients (47 per arm) to detect a 20% difference in 3-year overall survival in patients with locally advanced tumours without peritoneal carcinomatosis. Three samples of peritoneal fluid were obtained (at the beginning, the end of procedure and after the assigned peritoneal lavage). Clinicopathological and surgical data were analysed by group. Postoperative complications, location of recurrence and surgical approach were evaluated. Overall survival was calculated by the Kaplan-Meier method and the uni/multivariate analysis for prognostic factors was carried out using Cox regression analysis. RESULTS: A total of 86 patients were analysed (4 excluded per group). No statistical differences were observed in clinicopathological or surgical data between groups, considering both groups well-balanced for analysis. Overall survival at 3 years was 64.3% for SPL vs. 62.3% for EIPL (p 0.421). Only three patients had at least one positive peritoneal cytology (1:2). There were no differences regarding postoperative complications (SPL: 37.2% vs. EIPL: 32.5%, p 0.65) or between location of recurrence and number of recurrences. The number of recurrences did not differ between surgical approaches, but locoregional and peritoneal recurrences were fewer with the laparoscopic approach (p 0.048). CONCLUSIONS: The regular use of extensive peritoneal lavage in patients with locally advanced gastric cancer, regardless of peritoneal cytology, has not been effective as prophylaxis of peritoneal recurrence or better survival.

A case of endocrine mucin-producing sweat gland carcinoma with distant metastasis.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare cutaneous adnexal neoplasm typically arising on the face of older individuals, most commonly around the eyelids. Histopathologic features include a circumscribed proliferation of low-grade epithelioid cells with areas of cystic and cribriform growth, foci of intracytoplasmic and extracellular mucin, and coexpression of endocrine, neuroendocrine, and cytokeratin markers by immunohistochemistry. Given histopathologic and immunohistochemical similarities, EMPSGC is often likened to solid papillary carcinoma of the breast and endocrine ductal carcinoma in situ, and is thought by many to represent a forme fruste of mucinous carcinoma of the skin. To date, the vast majority of reported cases of EMPSGC have been described as having indolent behavior, with no cases of distant metastasis yet reported. Here we report a unique case of EMPSGC that recurred over several years following standard surgical excision and Mohs micrographic surgery, with subsequent metastasis to the parotid gland and axial skeleton.

Endocrine mucin-producing sweat gland carcinoma of the peno-scrotum with systemic metastases: A rare case report.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare adnexal tumor with a predilection for the skin of the eyelid. It has also been reported in other areas of the face. Extra facial location has rarely been reported. They are twice as common in the females as compared to men and frequently affect the elderly between 50 and 80 years of age. It is a low-grade carcinoma with no reported cases of metastases, although a few cases with recurrences have been reported. Since it was first described by Flieder et al. in 1997, fewer than 60 cases have been reported in the literature. We describe one such case of EMPSGC in an adult male occurring at an unusual location, the peno-scrotal junction with systemic metastases to bilateral inguinal and iliac lymph nodes, multiple bones, and pancreas. Unlike previously reported cases, our patient worsened rapidly and succumbed to the disease six months after initiation of chemotherapy and radiotherapy. To the best of our knowledge, this is the first reported case of its kind in modern published literature.

Late onset metastasis from renal cell carcinoma masquerading as a gallbladder polyp.

Renal cell carcinoma (RCC) accounts for approximately 3% of all adult malignancies. A third of people with RCC have metastatic lesions when diagnosed, and another third develop metachronous metastasis during follow-up or after surgical treatment. We report a case of gallbladder metastasis from clear-cell RCC in a 71-year-old woman 13 years after RCC of her right kidney. Preoperative imaging studies showed a suspicious, progressively enlarged gallbladder polyp. The patient underwent open cholecystectomy and lymph node dissection along the hepatoduodenal ligament. The pathology report was compatible with metastatic disease from the kidney that was previously resected. Gallbladder metastasis can occur from RCC several years after initial management. Physicians should be aware of this rare pathology, and intensive follow-up is essential after surgery for RCC.

Cutaneous adnexal carcinosarcoma: Immunohistochemical and molecular evidence of epithelial mesenchymal transition.

Cutaneous carcinosarcomas are rare biphenotypic tumors that simultaneously show epithelial and mesenchymal differentiation. The most common carcinomatous components in skin carcinosarcomas are basal cell carcinoma and squamous cell carcinoma; adnexal carcinomas are rarely encountered. We report a case of an adnexal carcinoma with ductal and squamous differentiation and spindle cell component, which is interpreted as carcinosarcoma. Loss of immunohistochemical expression of E-cadherin and ß-catenin detected in the sarcomatous component suggested epithelial mesenchymal transition (EMT). RNA sequencing analysis identified several gene mutations and alterations such as translocations and upregulations/downregulations, either shared by the two components of the tumor or differentially present in the carcinoma or the sarcoma parts. Thus, mutations in genes, such as TP53, were found in both components of the tumor while mutations in PDGFRA and RB1 (a pathogenic missense mutation) were exclusively present in the sarcomatous areas, further supporting EMT. EMT is a dynamic process by which tumors acquire mesenchymal phenotype while simultaneously losing epithelial properties. Although the pathways involved in EMT have been extensively studied, this phenomenon still needs to be investigated in cutaneous tumors of adnexal origin for a better understanding of their pathogenesis. These molecular changes may represent promising targets for personalized therapies.

MAGEA10 expression is a predictive marker of early hepatic recurrence after curative gastrectomy for gastric and gastroesophageal junction cancer.

BACKGROUND: Resection for hepatic recurrence after gastrectomy in patients with gastric cancer may be curative; however, the prediction of hepatic recurrence remains intractable. Therefore, we aimed to explore predictive markers for hepatic recurrence in gastric and gastroesophageal junction cancer based on genetic information. METHODS: This study recruited 154 patients who underwent curative gastrectomy for pathological stage II or III primary gastric and gastroesophageal junction adenocarcinoma. Genes associated with hepatic recurrence were comprehensively analyzed using whole-exome sequencing and gene expression profiling (GEP), followed by immunohistochemistry analysis for MAGEA10. The cumulative incidences of hepatic recurrence, relapse-free survival, and overall survival were evaluated. RESULTS: A total of 12 patients with early hepatic recurrences were found within 2 years of surgery. Although there were no distinct gene mutations in recurrent patients, upregulation of MAGEA10 was identified in patients with early hepatic recurrence using GEP analysis. Immunostaining for MAGEA10 stained the cell nuclei in 29 (18.8%) of 154 samples. Furthermore, protein expression of MAGEA10 on immunohistochemistry was significantly related to a high MAGEA10 mRNA expression, high cumulative incidences of hepatic recurrence, and poor relapse-free survival. Overall survival did not differ significantly between positive and negative immunohistochemical staining for MAGEA10. The sensitivity and specificity of MAGEA10 staining for early hepatic recurrence were 58.3% and 84.5%, respectively. CONCLUSIONS: MAGEA10 represents a promising predictive marker for early hepatic recurrence after curative gastrectomy for gastric and gastroesophageal junction cancer.

Genome­wide copy number analysis of circulating tumor cells in breast cancer patients with liver metastasis.

The genome­wide copy number analysis of circulating tumor cells (CTCs) provides a promising prognostic biomarker for survival in breast cancer liver metastasis (BCLM) patients. The present study aimed to confirm the prognostic value of the presence of CTCs in BCLM patients. We previously developed an assay for the genome­wide pattern differences in copy number variations (CNVs) as an adjunct test for the routine imaging and histopathologic diagnosis methods to distinguish newly diagnosed liver metastases and recurrent liver metastases. Forty­three breast cancer patients were selected for this study in which 23 newly diagnosed and 20 recurrent liver metastases were diagnosed by histopathology and 18F­FDG PET/CT imaging. CTCs were counted from all patients using the CellSearch system and were confirmed by cytomorphology and three­color immunocytochemistry. Genomic DNA of single CTCs was amplified using multiple annealing and looping based amplification cycles (MALBAC). Then, we compared the CTC numbers of newly diagnosed and recurrent BCLM patients using Illumina platforms. A high CTC frequency (>15 CTCs/7.5 ml blood) was found to be correlated with disease severity and metastatic progression, which suggests the value for CTCs in the diagnosis of BCLM in comparison with pathohistology and PET/CT imaging (P>0.05). Moreover, CTCs isolated from BCLM patients remained an independent prognostic detection factor associated with overall survival (P=0.0041). Comparison between newly diagnosed and recurrent liver metastases revealed different frequencies of CNVs (P>0.05). Notably, the CNV pattern of isolated CTCs of recurrent BCLM patients was similar to recurrent liver metastases (nearly 82% of the gain/loss regions). Functional enrichment analysis identified 25 genes as a CNV signature of BCLM. Among them, were defensin and ß­defensin genes, which are significantly associated with anti­angiogenesis and immunomodulation signaling pathways. High CTC frequencies are effective in the evaluation and differentiation between newly diagnosed liver metastases from recurrent liver metastases. Future clinical studies will be necessary to fully determine the prognostic potential of CTC cluster signatures in patients with BCLM.

Liver resection surgery compared with thermal ablation in high surgical risk patients with colorectal liver metastases: the LAVA international RCT.

BACKGROUND: Although surgical resection has been considered the only curative option for colorectal liver metastases, thermal ablation has recently been suggested as an alternative curative treatment. There have been no adequately powered trials comparing surgery with thermal ablation. OBJECTIVES: Main objective - to compare the clinical effectiveness and cost-effectiveness of thermal ablation versus liver resection surgery in high surgical risk patients who would be eligible for liver resection. Pilot study objectives - to assess the feasibility of recruitment (through qualitative study), to assess the quality of ablations and liver resection surgery to determine acceptable standards for the main trial and to centrally review the reporting of computed tomography scan findings relating to ablation and outcomes and recurrence rate in both arms. DESIGN: A prospective, international (UK and the Netherlands), multicentre, open, pragmatic, parallel-group, randomised controlled non-inferiority trial with a 1-year internal pilot study. SETTING: Tertiary liver, pancreatic and gallbladder (hepatopancreatobiliary) centres in the UK and the Netherlands. PARTICIPANTS: Adults with a specialist multidisciplinary team diagnosis of colorectal liver metastases who are at high surgical risk because of their age, comorbidities or tumour burden and who would be suitable for liver resection or thermal ablation. INTERVENTIONS: Thermal ablation conducted as per local policy (but centres were encouraged to recruit within Cardiovascular and Interventional Radiological Society of Europe guidelines) versus surgical liver resection performed as per centre protocol. MAIN OUTCOME MEASURES: Pilot study - patients' and clinicians' acceptability of the trial to assist in optimisation of recruitment. Primary outcome - disease-free survival at 2 years post randomisation. Secondary outcomes - overall survival, timing and site of recurrence, additional therapy after treatment failure, quality of life, complications, length of hospital stay, costs, trial acceptability, and disease-free survival measured from end of intervention. It was planned that 5-year survival data would be documented through record linkage. Randomisation was performed by minimisation incorporating a random element, and this was a non-blinded study. RESULTS: In the pilot study over 1 year, a total of 366 patients with colorectal liver metastases were screened and 59 were considered eligible. Only nine participants were randomised. The trial was stopped early and none of the planned statistical analyses was performed. The key issues inhibiting recruitment included fewer than anticipated patients eligible for both treatments, misconceptions about the eligibility criteria for the trial, surgeons' preference for one of the treatments ('lack of clinical equipoise' among some of the surgeons in the centre) with unconscious bias towards surgery, patients' preference for one of the treatments, and lack of dedicated research nurses for the trial. CONCLUSIONS: Recruitment feasibility was not demonstrated during the pilot stage of the trial; therefore, the trial closed early. In future, comparisons involving two very different treatments may benefit from an initial feasibility study or a longer period of internal pilot study to resolve these difficulties. Sufficient time should be allowed to set up arrangements through National Institute for Health Research (NIHR) Research Networks. TRIAL REGISTRATION: Current Controlled Trials ISRCTN52040363. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 21. See the NIHR Journals Library website for further project information.

In about 50% of people with bowel cancer, cancer spreads to the liver (colorectal liver metastases) within 5 years of detection and treatment. Liver resection (i.e. surgical removal of a portion of the liver) is the standard treatment in people below 70 years of age who are otherwise well, provided that the liver cancer is confined to a limited part of the liver. Such patients are considered 'low-risk' patients. Older patients and those with major medical problems or extensive cancers are considered 'high-risk' patients, as they are at a higher risk of developing complications following liver resection. Thermal ablation destroys the liver cancers using a needle that heats the cancer deposits until they are destroyed. There is significant uncertainty as to whether or not ablation can offer equivalent survival compared with surgery for 'high-risk' patients. We planned and conducted a randomised controlled trial comparing ablation with surgery to resolve this uncertainty. In this trial, some patients received ablation and others received surgery. The treatment was allocated at random with neither patients nor the study organisers choosing the treatment. The trial had an internal pilot (i.e. a smaller version of the full trial to resolve any 'teething problems' and ensure that a sufficient number of participants can be included in the full trial). Only nine patients were recruited in the 1-year internal pilot, compared with the anticipated recruitment of 45 patients. Therefore, the trial closed early as a result of poor recruitment, and the uncertainty about the best treatment for high-risk patients with colorectal liver metastases continues. The main reasons for the poor recruitment included fewer than anticipated eligible participants, clinicians' unconscious bias towards surgery, and patients' preference for one treatment or the other. In the future, comparisons involving two very different treatments may benefit from a feasibility study or a longer period of pilot study to resolve any difficulties.

The effect of lymph node metastasis on overall survival and disease-free survival in vulvar cancer patients.

OBJECTIVES: To examine the effect of lymphadenectomy on survival in patients with squamous cell vulvar carcinoma. MATERIAL AND METHODS: Patients with squamous cell vulvar cancer who underwent surgery were retrospectively analyzed. All procedures were performed according to current recommendations/standard of treatment. The clinical and pathological features were examined. Sixty-eight patients were studied. The mean age was 64.7 ± 10.9 years. Twenty-three (33.8%) patients had nodal metastasis. Most patients (60.3%) were in stage IB. Adjuvant radiotherapy and chemo-radiotherapy were administered to 33.8% and 25% of the patients, respectively. The median follow-up time was 28.5 (4-183) months. Recurrence occurred in 18 (26.5%) cases. RESULTS: There was no significant difference between node-positive and node-negative patients in terms of age, number of dissected lymph nodes and recurrence. Tumor diameter was significantly higher in the metastatic group. Age and surgical margin positivity were independent prognostic factors for overall survival (OS). Surgical margin positivity and lymph node metastasis had no effect on disease-free survival (DFS). CONCLUSIONS: Our results showed that age and surgical margin positivity were independent prognostic factors for OS. Although surgical margin positivity increased the risk of recurrence in univariate analysis, it was not a significant factor affecting DFS. OS was significantly lower in patients with lymph node metastasis.

Clinicopathological factors of pelvic lymph nodes involvement in advanced serous ovarian cancer.

OBJECTIVES: Retroperitoneal lymph nodes metastases occur frequently in patients with ovarian cancer. Lymphadenectomy increases risk of perioperative complications. In clinical practice to reduce rate of complications aortocaval lymphadenectomy is omitted and solely resection of pelvic lymph nodes is performed. To establish factors affecting metastases to pelvic lymph nodes in advanced ovarian cancer. MATERIAL AND METHODS: A retrospective study among patients with serous advanced ovarian cancer (FIGO IIIB-IVB) was conducted at the 1st Department of Obstetrics and Gynecology, Medical University of Warsaw and Department of Gynecologic Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw. All patients underwent surgical treatment including pelvic lymphadenectomy between 2014 and 2017. Data including age, body mass index (BMI), pretreatment CA125 serum level, tumor volume, grading, one-/both-sided tumor, menopausal status, ascites were analysed as possible factors influencing the pelvic lymph nodes involvement. The statistical analysis was performed with Python software. RESULTS: 87 consecutive patients were eligible for the study. Metastases to pelvic lymph nodes were found in 29 (33.33%) patients. Pretreatment serum CA-125 concentration (652 U/mL vs 360.9 U/mL, p < 0.05) and high grade histology corresponded with pelvic nodal involvement. CONCLUSIONS: The knowledge of factors influencing metastases to pelvic lymph nodes may help clinicians in proper counselling and tailoring of therapy.

Pulmonary recurrence after radical hysterectomy for uterine cervical carcinoma.

Pulmonary spread from carcinoma of the uterine cervix, though uncommon, has been reported in 2.2-9.1% of all cervical cancers. The aim of this study was to evaluate the surgical, clinical, pathological factors and clinical outcomes of cervical cancer patients with pulmonary recurrence (PR).This study included 17 cervical cancer patients with PR after radical hysterectomy. The entire cohort consisted of 413 patients whose surgeries (type III radical hysterectomy + pelvic ± para-aortic lymphadenectomy) had been performed in our Gynaecologic Oncology Clinic between 1993 and 2018. Tumour size, lymph node metastasis and receiving adjuvant therapy were found to be effective for PR on univariate analyses in the main cohort (p = .042, p < .001 and p = .001, respectively). Therefore, performing adjuvant therapy to reduce the PR must be assessed properly with the information of lymph node status and tumour size obtained from the final pathology reports.Impact StatementWhat is already known on this subject? Pulmonary spread from carcinoma of the uterine cervix has been reported in 2.2-9.1% of all cervical cancers. Data related to clinico-pathological features of patients with pulmonary recurrence (PR) is limited. Diagnosis of a PR is considered to worsen the prognosis.What do the results of this study add? Tumour size, lymph node metastasis and receiving adjuvant therapy were found to be effective for PR on univariate analyses.What are the implications of these findings for clinical practice and/or further research? Performing adjuvant therapy to reduce the PR must be assessed properly with the information of lymph node status and tumour size obtained from the final pathology reports in patients with uterine cervical carcinoma.

Spontaneous regression of recurrent hepatocellular carcinoma with multiple lung metastases.

Spontaneous regression (SR) of hepatocellular carcinoma (HCC) is a rare phenomenon but its true incidence is much higher than expected. We report a recurrent HCC who experienced SR both in intrahepatic lesion and lung metastasis. Serum alpha-fetoprotein decreased dramatically from more than 1000 µg/L to normal range. In addition, we reviewed 11 similar case reports published in recent 5 years. We find that the interval from diagnosis to the recognition of SR is very short (4 m, 1-14 m). Therefore, we speculate the mechanism of SR should be a severe systemic reaction, and immune activation is the most likely conjecture.

Long-Term Survival After Multidisciplinary Treatment Including Surgery for Metachronous Metastases of Small Intestinal Gastrointestinal Stromal Tumors after Curative Resection: A Case Report.

BACKGROUND Currently, 3 molecular targeted drugs are available for the treatment of unresectable and recurrent gastrointestinal stromal tumors (GISTs), and result in improved prognoses and rare occurrence of bone metastases. However, there is no established treatment guideline for bone metastases of GIST. CASE REPORT The patient was a 56-year-old male who was diagnosed with leiomyosarcoma in 1997. Partial resection of the small bowel was performed. As part of post-operative follow-up in 2004, a computed tomography scan showed metastatic lesions in the liver and the right femoral neck. Accordingly, partial hepatectomy was performed, followed by artificial femoral head replacement. In 2006, bone metastases were detected in the sternum, cervical and thoracic vertebra, and the right upper arm; therefore, the patient was subjected to radiotherapy. However, further histopathological examination revealed positive findings for CD34+ and KIT cells, prompting a diagnosis of GIST. Imatinib was started. The disease remained stable. However, in 2010, metastasis to the right ilium was detected, after which there was an increase in metastatic lesions in the thoracic vertebra, prompting a diagnosis of progressive disease. Thus, treatment with sunitinib was initiated. In 2012, the patient experienced spinal paralysis due to metastasis in the eighth thoracic vertebra. In 2013, metastases in the right ilium, lungs, and liver were detected. In 2014, the patient died. CONCLUSIONS Multidisciplinary treatment via radiotherapy and surgery for GIST with bone metastases indicates the possibility of extending the overall survival further.

Repeat stereotactic radiosurgery for the management of locally recurrent brain metastases.

PURPOSE: Stereotactic radiosurgery (SRS) is a well-established treatment option for brain metastases (BM). Repeat SRS for progressive BM is an increasingly used paradigm, although little data is available to support this practice. The goal of this study was to assess the safety and efficacy of a second SRS procedure on a previously treated BM. METHODS: We performed a retrospective metastasis-level analysis of patients who underwent two SRS procedures on the same lesion and for whom at least 6 months of radiological follow-up was available. The data collected included patient characteristics, clinical symptoms at time of treatment, SRS parameters, radiological response per RANO-BM criteria, clinical evolution and survival. RESULTS: Seventy-five BM in 56 patients were included in the analysis. Most frequent primary histologies were non-small-cell lung cancer (59%) and breast cancer (19%). At the second SRS, median treatment volume was 1.19 cc (range 0.07-20.6) treated with a median margin dose of 18 Gy (range 12-20) at the 50% isodose line (range 30-80%). Median follow-up was 11 months. Progression per RANO-BM criteria occurred in 31%, yielding actuarial local control at 1, 2, and 5 years of 68%, 54% and 54% respectively. At last follow-up, 10 patients (18%) had improved relative to the initial presentation, while 21 (38%) were stable and 25 (44%) were deteriorated. Radiation-induced edema and radionecrosis occurred in 8.3% and 5% respectively. The median survival from the diagnosis of BM was 30 months. CONCLUSION: Repeat SRS is a safe and effective novel therapeutic approach to consider in carefully selected patients.

Tissue Expression of Melanoma-associated Antigen A6 and Clinical Characteristics of Gastric Cancer.

BACKGROUND: Gastric cancer (GC) exhibits heterogeneous clinical and molecular features, requiring the development of new biomarkers to further understand this disease. Our transcriptomic analysis detected overexpression of melanoma-associated antigen A6 (MAGEA6) in metastatic GC, leading us to determine the clinical significance of MAGEA6 in GC. MATERIALS AND METHODS: Fourteen GC cell lines and 230 pairs of surgically resected gastric tissues were subjected to mRNA expression analysis. Polymerase chain reaction array analysis was performed to identify coordinately expressed cancer-related genes, and immunohistochemistry (IHC) was used to detected MAGEA6 expression in situ. RESULTS: MAGEA6 mRNA levels were positively correlated with the expression of matrix metallopeptidase 9 mRNA. MAGEA6 mRNA levels were higher in GC tissues compared with those in normal adjacent tissues. Patients with high MAGEA6 expression had significantly worse prognosis. MAGEA6 protein levels in primary lesions predicted the likelihood of recurrence. CONCLUSION: Overexpression of MAGEA6 in GC tissues represents a promising biomarker for assessing the malignant phenotype of GC.