Beyond traditional therapies: clinical significance of complex molecular profiling in patients with advanced solid tumours-results from a Turkish multi-centre study.

OBJECTIVE: The objective of this multi-centre, real-world study was to examine the potential influence of comprehensive molecular profiling on the development of treatment decisions or adjustments for patients with advanced solid malignancies. We then evaluated the impact of these informed choices on patient treatment outcomes. METHODS: The study encompassed 234 adult patients (mean age: 52.7 ± 14.3 years, 54.7% women) who were diagnosed with solid tumours at 21 different medical centres in Turkey. Remarkably, 67.9% of the patients exhibited metastasis at the time of diagnosis. We utilized an OncoDNA (Gosselies, Belgium) platform (OncoDEEP) integrating next-generation sequencing with additional tests to harvest complex molecular profiling data. The results were analyzed in relation with two specific outcomes: (i) the impact on therapeutic decisions, including formulation or modifications, and (ii) associated treatment response. RESULTS: Out of the 228 patients with final molecular profiling results, 118 (50.4%) had their treatment modified, whilst the remaining 110 (47.0%) did not. The response rates were comparable, with 3.9 versus 3.4% for complete response, 13.6 versus 29.3% for partial response, 66.9 versus 51.7% for progressive disease and 15.5 versus 15.5% for stable disease for treatments informed and not informed by complex molecular profiling, respectively (P = 0.16). CONCLUSION: Our real-world findings highlight the significant impact of complex molecular profiling on the treatment decisions made by oncologists for a substantial portion of patients with advanced solid tumours. Regrettably, no significant advantage was detected in terms of treatment response or disease control rates.

Radioligand Therapy With 177 Lu-PSMA-I&T in Patients With Metastatic Prostate Cancer : Oncological Outcomes and Toxicity Profile.

INTRODUCTION: This study aimed to investigate the oncological outcomes and toxicity profile of 177 Lu-PSMA-I&T radioligand therapy (RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC), as well as our initial experience in metastatic hormone-sensitive prostate cancer (mHSPC). PATIENTS AND METHODS: A total of 38 consecutive patients with metastatic prostate cancer (33 mCRPC and 5 mHSPC) received 177 Lu-PSMA-I&T RLT, with a median of 2 cycles per patient (range, 1-7). Response to RLT was evaluated based on prostate-specific antigen (PSA) changes and imaging response. Clinical progression-free survival and overall survival were used to report oncological outcomes. Toxicity was assessed using the Common Toxicity Criteria for Adverse Events criteria. RESULTS: In mCRPC, 22 (69%), 18 (56%), and 11 (34%) patients achieved any PSA decline, PSA response of ≥30%, and PSA response of ≥50%, respectively. The clinical progression-free survival and overall survival after the first cycle of RLT were 6.3 and 21.4 months, respectively. In mHSPC, 177 Lu-PSMA-I&T RLT resulted in excellent PSA response (93.0%-99.9%) in all cases. Clinical progression and cancer-related mortality occurred in only 1 case. Toxicity profile was favorable in both mHSPC and mCRPC. CONCLUSIONS: 177 Lu-PSMA-I&T RLT demonstrated favorable PSA response (≥30%) in over half of the patients with mCRPC and excellent PSA response in all patients with mHSPC. Toxicity profile was favorable in both mHSPC and mCRPC settings. Further studies are needed to evaluate the role of 177 Lu-PSMA-I&T RLT in the management of metastatic prostate cancer.

Prostate-specific Membrane Antigen Positron Emission Tomography as a Biomarker to Assess Treatment Response in Patients with Advanced Prostate Cancer.

CONTEXT: Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) has superior accuracy for detection of metastatic lesions in patients with prostate cancer (PC). Although PSMA PET has a prominent role in primary and secondary imaging of PC, data on its role in assessing treatment response in advanced PC are limited. OBJECTIVE: To review current data in the literature regarding the impact of antiandrogen therapy on PSMA expression of metastatic sites and the role of serial (baseline and at least 1 follow-up scan) PSMA PET to assess treatment response in patients with metastatic PC. EVIDENCE ACQUISITION: A comprehensive literature search in the PubMed database was performed using the terms "PSMA expression prostate", "PSMA regulation", "PSMA PET response assessment", and "serial PSMA PET". EVIDENCE SYNTHESIS: Serial PSMA PET studies (baseline and at least 1 follow-up scan) provide valuable data regarding PSMA expression changes after systemic treatment in patients with metastatic PC. PSMA PET-detected flare and upregulation of PSMA expression following hormonal intervention seem to be early events resolving after 3 mo of treatment. PSMA PET imaging is essential in selecting patients for 177Lu-PSMA radioligand therapy (RLT). Growing evidence favors its use in assessing treatment responses after RLT. Preliminary evidence indicates the value of PSMA PET for assessment of the treatment response in patients receiving systemic treatment other than RLT for metastatic PC. CONCLUSIONS: PSMA flare following antiandrogen therapy seems to be an early event and thus PET scans should be performed no earlier than 3 mo after the start of treatment. PSMA PET has a promising role in tailoring treatment according to the specific needs of individual patients and assessing responses following systemic treatment in patients with advanced PC. PATIENT SUMMARY: This review describes how a sensitive imaging method can be used to assess the tumor response to treatment for metastatic prostate cancer.

Efficacy of Palbociclib and Endocrine Treatment in Heavily Pretreated Hormone Receptor-positive/HER2-negative Advanced Breast Cancer: Retrospective Multicenter Trial

Background: The synthesis of CDK4/6 inhibitors with endocrine treatment in two series of treatment has been widely accepted as the standard for patients with estrogen receptor-positive metastatic breast cancer. In spite of this, the activity of CDK4/6 inhibitors in patients with metastatic breast cancer who have progressed despite receiving multiple lines of treatment is not well understood. Aims: To report the activity and safety of a CDK4/6 inhibitor (palbociclib) in patients in whom at least three lines of treatment for ER+ metastatic breast cancer had failed. Study Design: Multicenter retrospective observational cohort study. Methods: In this retrospective observational cohort study, we included 43 patients who received palbociclib after at least three lines of systemic treatment for ER+/HER2− metastatic breast cancer. Results: The median progression-free survival in our population was 7 months (25th-75th percentile, 4-10), and the median overall survival was 11 months (25th-75th percentile, 6-19). Although there were some adverse events, palbociclib was generally well tolerated, so dose reduction was needed for only six patients (14%). Conclusion: The efficacy of palbociclib among heavily treated hormone receptor-positive/HER2− patients with advanced breast cancer was acceptable in terms of clinical benefit, and it was generally well tolerated among this population.

Prognostic factors for survival in metastatic renal cell carcinoma patients with brain metastases receiving targeted therapy.

BACKGROUND: The primary objective of our study was to examine the clinical outcomes and prognosis of patients with metastatic renal cell carcinoma (mRCC) with brain metastases (BMs) receiving targeted therapy. PATIENTS AND METHODS: Fifty-eight patients from 16 oncology centers for whom complete clinical data were available were retrospectively reviewed. RESULTS: The median age was 57 years (range 30-80). Most patients underwent a nephrectomy (n = 41; 70.7%), were male (n = 42; 72.4%) and had clear-cell (CC) RCC (n = 51; 87.9%). Patients were treated with first-line suni-tinib (n = 45; 77.6%) or pazopanib (n = 13; 22.4%). The median time from the initial RCC diagnosis to the diagnosis of BMs was 9 months. The median time from the first occurrence of metastasis to the development of BMs was 7 months. The median overall survival (OS) of mRCC patients with BMs was 13 months. Time from the initial diagnosis of systemic metastasis to the development of BMs (<12 months; p = 0.001), histological subtype (non-CC; p<0.05) and number of BMs (>2; p<0.05) were significantly associated with OS in multivariate analysis. There were no cases of toxic death. One mRCC patient with BMs (1.7%) experienced treatment-related cerebral necrosis. All other toxicities included those commonly observed with VEGF-TKI therapy. CONCLUSIONS: The time from the initial diagnosis of systemic metastasis to the development of BMs (<12 months), a non-CC histological subtype, and a greater number of BMs (>2) were independent risk factors for a poor prognosis.

Renal cell cancer: overview of the current therapeutic landscape.

INTRODUCTION: The last decade has witnessed dramatic improvements in the diagnosis, classification and treatment of renal cell cancer (RCC). Besides improvements in surgical techniques in early stages, introduction of novel targeted agents has resulted in improved outcomes in advanced RCC for which no effective treatment existed until recently. AREAS COVERED: This article reviews epidemiology, pathology and pathogenesis, diagnosis, clinical staging, prognostic factors and treatment modalities of early stage and advanced RCC. Expert commentary: Although treatment options are expanding rapidly, practicing physicians face considerable challenges in the decision-making process. Therapeutic agents may have unique side effects and unexpected drug interactions. RCC represents one of the major success stories of clinical oncology in recent years and the progress appears to be far from having reached a plateau. We aim to present a comprehensive in-depth review of RCC in an attempt to provide evidence-based recommendations and future perspectives for practicing oncologists.

Diagnostic value of serum M30 and M65 in patients with nasopharyngeal carcinoma.

M30 and M65 are circulating fragments of cytokeratin 18 released during apoptotic cell death and regarded as markers of cell death in patients with various tumor types. Our aim was to investigate the clinical and prognostic significance of the serum M30 and M65 concentrations in patients with advanced nasopharyngeal carcinoma. Thirty-two patients with nasopharyngeal cancer and 32 control subjects were investigated. Serum samples were obtained on first admission before any treatment was initiated. Serum M30 and M65 concentrations were measured by quantitative enzyme-linked immunosorbent assay. Median serum M30 (181.5 vs. 45.5 U/L, p < 0.001) and M65 (384.2 vs. 179.1 U/L, p < 0.001) concentrations were significantly higher in patients with advanced nasopharyngeal carcinomas than in controls. receiver operating characteristic (ROC) analysis showed that a cutoff for M30 of 225 U/L had a sensitivity of 62.5% and a specificity of 73.9% (area under the curve (AUC) = 0.592, 95% confidence interval (CI) 35.3-83.2, p = 0.44), while a cutoff for M65 of 423.4 U/L had a sensitivity of 75.1% and a specificity of 65.6% (AUC = 0.562, 95 % CI 36.0-76.5, p = 0.60). However, serum M30 and M65 were not important prognostic factors for progression-free survival. There were no statistically significant correlations between serum M30 and M65 concentrations and clinicodemographical variables. Serum M30 and M65 concentrations were found to have a diagnostic value in nasopharyngeal cancer. However, neither M30 nor M65 serum levels played a prognostic role in the outcome in nasopharyngeal cancer patients.

Phase II randomized trial comparing sequential first-line everolimus and second-line sunitinib versus first-line sunitinib and second-line everolimus in patients with metastatic renal cell carcinoma.

PURPOSE: A multicenter, randomized phase II trial, RECORD-3, was conducted to compare first-line everolimus followed by sunitinib at progression with the standard sequence of first-line sunitinib followed by everolimus in patients with metastatic renal cell carcinoma. PATIENTS AND METHODS: RECORD-3 used a crossover treatment design. The primary objective was to assess progression-free survival (PFS) noninferiority of first-line everolimus compared with first-line sunitinib. Secondary end points included combined PFS for each sequence, overall survival (OS), and safety. RESULTS: Of 471 enrolled patients, 238 were randomly assigned to first-line everolimus followed by sunitinib, and 233 were randomly assigned to first-line sunitinib followed by everolimus. The primary end point was not met; the median PFS was 7.9 months for first-line everolimus and 10.7 months for first-line sunitinib (hazard ratio [HR], 1.4; 95% CI, 1.2 to 1.8). Among patients who discontinued first-line, 108 (45%) crossed over from everolimus to second-line sunitinib, and 99 (43%) crossed over from sunitinib to second-line everolimus. The median combined PFS was 21.1 months for sequential everolimus then sunitinib and was 25.8 months for sequential sunitinib then everolimus (HR, 1.3; 95% CI, 0.9 to 1.7). The median OS was 22.4 months for sequential everolimus and then sunitinib and 32.0 months for sequential sunitinib and then everolimus (HR, 1.2; 95% CI, 0.9 to 1.6). Common treatment-emergent adverse events during first-line everolimus or sunitinib were stomatitis (53% and 57%, respectively), fatigue (45% and 51%, respectively), and diarrhea (38% and 57%, respectively). CONCLUSION: Everolimus did not demonstrate noninferiority compared with sunitinib as a first-line therapy. The trial results support the standard treatment paradigm of first-line sunitinib followed by everolimus at progression.

Survival and prognostic factors in adult patients with recurrent or refractory ewing sarcoma family tumours: a 13-years retrospective study in Turkey.

AIM: The aim of the present study was to evaluate the results of treatment and prognostic factors in adult patients with recurrent or refractory Ewing's sarcoma family tumors (ESFT). PATIENTS AND METHODS: We retrospectively evaluated treatment outcomes of 54 consecutive patients with ESFT (aged 15 years or more) with complete medical records, who were treated with multimodal therapies after recurrence at the Istanbul University, Institute of Oncology. RESULTS: The commonly used chemotherapy regimens at relapse were ifosfamide and etoposide (IE), ifosfamide and etoposide plus carboplatin (ICE), and oral etoposide. The median progression-free survival and overall survival for the entire group were 6.3 (95% confidence interval, 3.08-9.60) and 8.6 (95% confidence interval CI, 4.7-12.4) months, respectively. Multivariate analysis using a Cox proportional hazards model showed that non-IE/ICE chemotherapy regimens (p=0.003, hazard ratio=2.38) and the presence extrapulmonary metastases (p=0.045, hazard ratio=2.15) were associated with worse overall survival. CONCLUSION: In primary refractory or relapsed ESFT, the presence of extrapulmonary metastases and treatment with salvage regimens other than ifosfamide and etoposide and/or carboplatin correlate with a poor prognosis.

Port site and peritoneal metastases after robot-assisted radical prostatectomy.

INTRODUCTION: Port site metastasis after minimally invasive urologic surgery is a rare event despite the widespread utility of laparoscopic techniques in the management of urologic malignancies. Herein, we report a case of port site metastasis after robot-assisted radical prostatectomy. PRESENTATION OF CASE: A currently 77-year-old male patient, who was diagnosed with cT2c, Gleason 7 (4+3) prostate adenocarcinoma in our clinic back in 2009, had undergone robot-assisted radical prostatectomy elsewhere. Histopathological examination revealed pT3a, Gleason 9 (4+5) disease. Lymph nodes were negative, however surgical margins were positive on the right side. PSA recurred after 9 months and maximal androgen blockade was initiated. Despite antiandrogenic manipulations, PSA reached 0.83ng/ml, 33 months postoperatively. Concurrently, we noticed a palpable anterior abdominal mass which demonstrated metabolic hyperactivity on PET scanning. Percutaneous biopsy of the lesion confirmed the presence of metastatic adenocarcinoma. PSA did not normalize after the complete excision of the metastatic focus. Repeated PET scan revealed multiple implants on the peritoneal surfaces of various organs. DISCUSSION: Port site and peritoneal metastasis of prostate cancer after robot-assisted radical prostatectomy has not been reported so far. This peculiar dissemination pattern is most probably the result of tumor biology and perioperative factors. CONCLUSION: Although encountered extremely rarely, surgeons should be aware of the possibility of port site and/or peritoneal metastases after minimally invasive radical prostatectomy.

Aflibercept versus placebo in combination with docetaxel and prednisone for treatment of men with metastatic castration-resistant prostate cancer (VENICE): a phase 3, double-blind randomised trial.

BACKGROUND: Docetaxel plus prednisone is standard first-line chemotherapy for men with metastatic castrate-resistant prostate cancer. Aflibercept is a recombinant human fusion protein that binds A and B isoforms of VEGF and placental growth factor, thereby inhibiting angiogenesis. We assessed whether the addition of aflibercept to docetaxel and prednisone would improve overall survival in men with metastatic castrate-resistant prostate cancer compared with the addition of placebo to docetaxel and prednisone. METHODS: VENICE was a phase 3, multicentre, randomised double-blind placebo-controlled parallel group study done in 31 countries (187 sites). Men with metastatic castrate-resistant prostate cancer, adequate organ function, and no prior chemotherapy were treated with docetaxel (75 mg/m(2) intravenously every 3 weeks) and oral prednisone (5 mg twice daily) and randomly allocated (1:1) to receive aflibercept (6 mg/kg) or placebo, intravenously, every 3 weeks. Treatment allocation was done centrally via an interactive voice response system, using a computer-generated sequence with a permuted-block size of four and stratified according Eastern Co-operative Group performance status (0-1 vs 2). Patients, investigators, and other individuals responsible for study conduct and data analysis were masked to treatment assignment. Aflibercept or placebo vials were supplied in identical boxes. The primary endpoint was overall survival using intention-to-treat analysis. This is the primary analysis of the completed trial. The study is registered with ClinicalTrials.gov, number NCT00519285 FINDINGS: Between Aug 17, 2007, and Feb 11, 2010, 1224 men were randomly allocated to treatment: 612 to each group. At final analysis, median follow-up was 35 months (IQR 29-41) and 873 men had died. Median overall survival was 22·1 months (95·6% CI 20·3-24·1) in the aflibercept group and 21·2 months (19·6-23·8) in the placebo group (stratified hazard ratio 0·94, 95·6% CI 0·82-1·08; p=0·38). We recorded a higher incidence of grade 3-4 gastrointestinal disorders (182 [30%] vs 48 [8·0%]), haemorrhagic events (32 [5·2%] vs ten [1·7%]), hypertension (81 [13%] vs 20 [3·3%]), fatigue (97 [16%] vs 46 [7·7%]), infections (123 [20%] vs 60 [10%]) and treatment-related fatal adverse events (21 [3·4%] vs nine [1·5%]) in the aflibercept group than in the placebo group. INTERPRETATION: Aflibercept in combination with docetaxel and prednisone given as first-line chemotherapy for men with metastatic castrate-resistant prostate cancer resulted in no improvement in overall survival and added toxicity compared with placebo. Docetaxel plus prednisone remains the standard treatment for such men who need first-line chemotherapy. FUNDING: Sanofi and Regeneron Pharmaceuticals Inc.

Serum M65 as a biomarker for metastatic renal cell carcinoma.

INTRODUCTION/BACKGROUND: Effective cancer biomarkers for early detection, prognosis, or therapy response prediction are urgently need in metastatic RCC. M30 and M65 are released during apoptotic cell death and precisely reflect epithelial tumor cell death. The aim of this study was to determine the prognostic value of plasma M30 and M65 levels in predicting survival rates for patients with metastatic RCC. PATIENTS AND METHODS: Thirty-nine patients with metastatic RCC and 39 healthy control subjects were included in this study. Serum M30 and M65 levels were measured by ELISA. RESULTS: The median ages of the patients and control subjects were 60 and 58 years, respectively. No difference was detected in the median serum M30 level between the patients and control subjects (53.7 vs. 49.1 U/L; P = .31). The median serum M65 level was significantly higher in patients than in control subjects (334.0 vs. 179.1 U/L; P < .001). Receiver operating characteristic analysis revealed that the best cutoff value for serum M65 level for predicting progression-free survival (PFS) was 313.6 U/L. The median PFS of patients whose M65 levels were ≤ 313.6 U/L was better than that of patients whose M65 levels were > 313.6 U/L (P = .03). CONCLUSION: To the best of our knowledge, this is the first study to evaluate serum M30 and M65 levels in patients with RCC. Serum M65 levels were significantly elevated in patients with metastatic RCC compared with healthy individuals. In addition, the serum M65 level could be predictive of PFS in patients with RCC.

Safety of everolimus by treatment duration in patients with advanced renal cell cancer in an expanded access program.

OBJECTIVE: To retrospectively analyze the effects of treatment duration on outcomes of everolimus treatment of patients in the RAD001 Expanded-Access Clinical Trial in RCC (REACT) program. METHODS: Patients with metastatic renal cell carcinoma refractory to vascular endothelial growth factor receptor-tyrosine kinase inhibitor received everolimus (10 mg once daily), with dosing interruption or modifications allowed for toxicity. All serious and grade 3/4 adverse events and grade 1/2 adverse events leading to a change in drug administration were reported. Tumor response was evaluated using Response Evaluation Criteria In Solid Tumors. RESULTS: The study stratified 1367 evaluable patients into treatment duration groups of <3 months, ≥3 and <6 months, ≥6 months and <1 year, and ≥1 year. Pneumonia, noninfectious pneumonitis, and hyperglycemia occurred more frequently in patients receiving everolimus for ≥1 year but did not result in treatment discontinuations. First occurrence of adverse events presented early in the treatment course for most patients. Treatment duration of ≥6 months was associated with improved disease control rates. CONCLUSION: Everolimus is well tolerated in patients with metastatic renal cell carcinoma for treatment durations≥1 year and not associated with cumulative toxicity.

The clinical effect of a positive surgical margin and adjuvant postoperative radiotherapy in the treatment of resectable desmoid tumors.

Desmoid tumors (DTs) are benign tumors that exhibit fibroblastic proliferation, which arises from fascial or musculoaponeurotic structures. The aim of this study was to investigate the characteristics and outcomes of patients with resectable DTs. A total of 21 patients were included and their clinicopathological characteristics were retrospectively analyzed. The 21 patients (16 females and 5 males) were identified through reviewing the patient charts at our institute. The tumor was located in the lower extremities in 7 cases, in the upper extremities in 4 cases, in the abdominal region in 9 cases and in the neck region in 1 case. Patients who had been initially treated by surgical excision were included in the study. Of these 21 patients, a positive surgical margin (SM) was reported in 11 patients, 7 of whom received postoperative radiotherapy (RT). Ten patients had a negative SM and 6 received RT. A total of 5 patients (46%) in the positive SM group and 4 (40%) in the negative SM group had documented disease relapse (P>0.05). The median relapse-free survival (RFS) was 20.5 months for the patients treated by surgery alone and 50 months for those treated with surgery followed by adjuvant RT (P>0.05). Age, gender, SM and adjuvant RT were not identified as predictors of recurrence. No predictive factors appeared to indicate local DT recurrence following surgery.

Predictive value of marker half-life in relapsed and nonrelapsed nonseminomatous germ cell testicular tumor patients undergoing chemotherapy.

BACKGROUND: The aim of this study was to investigate the influence of a marker half-life (MHL) on relapse in nonseminomatous germ cell testicular tumor patients. METHODS: MHL was retrospectively analyzed in relapsed (n = 37) and nonrelapsed patients (n = 28) undergoing first-line chemotherapy (CT). Before CT and after the second cycle of CT, serum α-fetoprotein (AFP) and ß-human chorionic gonadotropin levels were measured for MHL analysis. The International Germ Cell Cancer Collaborative Group risk classification system was used to assess the correlation between MHL and relapse. MHL was calculated according to a logarithmic formula. RESULTS: Median follow-up was 25 months (range, 6 to 96 mo). A statistically significant difference was not observed between initial AFP (P = 0.266) and ß-human chorionic gonadotropin (P=0.092) in both patient groups. MHL was statistically different between the relapsed and nonrelapsed patients with a good, intermediate, and poor prognosis, except for the half-life of AFP in patients with a poor prognosis. CONCLUSIONS: MHL is an indicator that predicted recurrence. Patients with an MHL longer than expected should be investigated to improve the effectiveness of treatment and should be treated with a recovery regimen.

What is the role of enlarged lymph node resection alone in patients with nonseminomatous germ cell tumor who had stage II or III disease?

BACKGROUND: Retroperitoneal lymph node dissection is an important treatment modality in nonseminomatous germ cell tumors of the testis. However, the role of more limited surgical approaches such as resection of enlarged lymph nodes only is still controversial. PATIENTS AND METHODS: Between January 1991 and December 2010, charts of 94 patients who underwent resection of enlarged retroperitoneal lymph nodes alone were reviewed. Pathologic findings, local recurrence, and adverse effects were noted after this surgical approach. RESULTS: The median age was 25.5 years. Twenty-one (22.6%) patients had lung metastasis, and 5 (5.4%) patients had nonregional lymph node metastasis at the initial visit. Eighty-seven (91.6%) patients received chemotherapy after inguinal orchiectomy, and the other patients had mass resection only for enlarged lymph nodes without prior chemotherapy. In patients who had chemotherapy before surgery, the median retroperitoneal lymph node size before and after chemotherapy cycles was 55 mm and 32.5 mm, respectively. The pathologic assessment of retroperitoneal masses revealed mature teratoma in 51.6% (n = 47) of patients, viable carcinoma in 20.9% (n = 19) of patients, and necrosis or fibrosis in 27.5% (n = 25) of patients. The median follow-up time was 60.2 months (range, 2.7-334.8 months). During follow-up, 5 (5.4%) patients had radiologic relapse at the retroperitoneal area, and 3 patients developed systemic metastases. Six (6.4%) patients died of their disease, 2 (2.1%) patients were alive with disease, 86 (91.5%) patients were healthy at the last follow-up. Ejaculation status was recorded in 56 patients. Antegrade ejaculation had preserved in 53 (94.6%) of these patients. CONCLUSIONS: Resection of enlarged lymph node metastases alone is a reasonable treatment option for patients with nonseminomatous germ cell tumors.

Clinicopathological characteristics and treatment outcomes of adult patients with paratesticular rhabdomyosarcoma (PRMS): A 10-year single-centre experience.

INTRODUCTION: We report our experience with 8 consecutive adults treated for paratesticular rhabdomyosarcoma (RMS) at a single institution between 2000 and 2010. METHODS: After primary surgical excision, 7 patients were classified into group I according to the Intergroup Rhabdomyosarcoma Study Group (IRSG) Postsurgical Grouping Classification, and 1 patient into group IIB. Retroperitoneal node dissection was not a required staging procedure. Adjuvant chemotherapy was administered to 7 of the 8 patients. No additional radiotherapy was administered. RESULTS: The median age at diagnosis was 24 years (range: 18-60). Embryonal histology was the most common (75%) subtype. During follow-up, 3 patients experienced local relapse and 5 distant relapse. The median progression-free and overall survival times were 17.0 ± 9.9 months (range: 5-31) and 27.3 ± 1.3 months (range: 16-58), respectively. CONCLUSION: Paratesticular RMS is an uncommon malignancy in adults. We confirm that patients with localized paratesticular RMS may have different prognoses. Retroperitoneal lymphadenectomy can be avoided as a treatment for paratesticular RMS after radical inguinal orchiectomy.

An international expanded-access programme of everolimus: addressing safety and efficacy in patients with metastatic renal cell carcinoma who progress after initial vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy.

BACKGROUND AND OBJECTIVES: The RECORD-1 trial established the clinical benefit of everolimus in patients with metastatic renal cell carcinoma (mRCC) after failure of initial vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFr-TKI) therapy. The REACT (RAD001 Expanded Access Clinical Trial in RCC) study was initiated to address an unmet medical need by providing everolimus prior to commercial availability, and also to further assess the safety and efficacy of everolimus in patients with VEGFr-TKI-refractory mRCC. PATIENTS AND METHODS: REACT (Clinicaltrials.gov: NCT00655252) was a global, open-label, expanded-access programme in patients with mRCC who were intolerant of, or who had progressed on or after stopping treatment with, any available VEGFr-TKI therapy. Patients received everolimus 10mg once daily, with dose and schedule modifications allowed for toxicity. Patients were closely monitored for the development of serious and grades 3/4 adverse events (AEs). Response was assessed by RECIST every 3months for the first year and every 6months thereafter. RESULTS: A total of 1367 patients were enroled. Safety findings and tumour responses were consistent with those observed in RECORD-1, with no new safety issues identified. The most commonly reported serious AEs were dyspnoea (5.0%), pneumonia (4.7%) and anaemia (4.1%), and the most commonly reported grades 3/4 AEs were anaemia (13.4%), fatigue (6.7%) and dyspnoea (6.5%). Best overall response was stable disease in 51.6% and partial response in 1.7% of patients. Median everolimus treatment duration was 14weeks. CONCLUSION: Everolimus is well tolerated in patients with mRCC and demonstrates a favourable risk-benefit ratio.

Optic disc and choroidal metastasis from sporadic medullary thyroid carcinoma: case report and review of the literature.

BACKGROUND: Choroidal metastasis is a very rare clinical manifestation of thyroid cancer. Herein, we report on a patient with non-familial medullary thyroid carcinoma (MTC), who presented with choroidal metastasis. CASE REPORT: A 63-year-old male patient with MTC presented with sudden loss of vision in his right eye for 1 month. The patient had a history of complete thyroidectomy and chemotherapy for disseminated MTC. Ophthalmological examination showed optic disc and choroidal metastases in the right eye and a small choroidal metastasis in the left eye. The patient was scheduled for external irradiation therapy for the ocular area but died 2 months after choroidal metastasis was diagnosed. CONCLUSIONS: Choroidal metastasis must be considered in MTC patients who develop loss of vision. This is a very rare clinical situation that generally occurs in the late advanced stages of the disease and carries a poor prognosis for these patients.

Response rates and adverse effects of continuous once-daily sunitinib in patients with advanced renal cell carcinoma: a single-center study in Turkey.

OBJECTIVE: Therapy targeted against the vascular endothelial growth factor pathway is a standard of care for patients with metastatic renal cell carcinoma. This study assessed the response rates and toxicity profiles of sunitinib on a continuous once-daily dosing regimen in Turkish patients with metastatic renal cell carcinoma. METHODS: Between April 2006 and August 2010, 74 patients with metastatic renal cell carcinoma who received sunitinib on a continuous, once-daily dosing regimen were included. Sunitinib was administered daily at a dose of either 37.5 mg (94% of the patients) or 25 mg (6% of the patients), without interruption, either as a second-line treatment after interferon-α or as a first-line treatment. Response, toxicity, progression-free survival and overall survival were evaluated. RESULTS: Of the 74 patients, 65 (88%) were diagnosed with clear cell renal cell carcinoma. The median treatment duration was 10 months (range, 2-42 months). The most common treatment-related adverse events were fatigue (75%), stomatitis (51%) and hypertension (50%). The most common Grade 3 or 4 adverse events were anemia (10%) and hand-foot syndrome (7%). Dose reductions were required in 50% of the patients, and early treatment discontinuation was necessary in 16% of the patients. Cardiovascular events were the most common adverse events that resulted in drug discontinuation. The objective response rate and the disease control rate were 30 and 78%, respectively. The median progression-free survival and overall survival were 13 and 25 months, respectively. CONCLUSIONS: Continuous, once-daily administration of sunitinib was generally well tolerated in Turkish patients with advanced renal cell carcinoma in a daily practice setting. This study's response rates were comparable to those in previous randomized trials.