Adjuvant Radiotherapy for Upper Tract Urothelial Carcinoma: Systematic Review and Meta-Analysis.

PURPOSE: Upper tract urothelial carcinoma (UTUC) is a rare form of malignancy comprising only 5% of urothelial cancers. The mainstay of treatment is radical nephroureterectomy (RNU) with bladder cuff excision. Neoadjuvant or adjuvant chemotherapy is often used in locally advanced disease. The role of adjuvant radiotherapy (RT), however, remains controversial. To further explore the potential role of adjuvant RT, we performed a systematic review and meta-analysis of the literature from 1990 to present. METHODS AND MATERIALS: We identified 810 candidate articles from database searches, of which 67 studies underwent full-text review, with final inclusion of 20 eligible studies. Among the included studies, there were no randomized controlled trials and a single prospective trial, with the remainder being retrospective series. We performed quantitative synthesis of the results by calculating the pooled odds ratios (OR) for the primary outcome of locoregional recurrence (LRR) and secondary outcomes of overall survival (OS), cancer-specific survival (CSS) and distant recurrence (DR). RESULTS: Adjuvant RT, which was mostly prescribed for locally advanced or margin-positive disease following RNU, significantly reduced locoregional recurrence risk OR 0.43 (95% CI: 0.23-0.70), and the effect remained significant even following subgroup analysis to account for adjuvant systemic therapy. The effect of adjuvant RT on 3-year OS, 5-year CSS and DR was non-significant. However, 5-year OS was unfavourable in the adjuvant RT arm, but study heterogeneity was high, and analysis of small-study effects and subgroups suggested bias in reporting of outcomes. CONCLUSIONS: Adjuvant RT in the setting of locally advanced UTUC improves locoregional control following definitive surgery, but does not appear to improve OS. Higher-quality studies, ideally randomized controlled trials, are needed to further quantify its benefit in this setting, and to explore multi-modal treatments that include systemic agents given concomitantly or sequentially with RT, which may offer an OS benefit in addition to the locoregional control benefit of RT.

Stereotactic Ablative Radiotherapy for the Management of Spinal Metastases: A Review.

Importance: Rising cancer incidence combined with improvements in systemic and local therapies extending life expectancy are translating into more patients with spinal metastases. This makes the multidisciplinary management of spinal metastases and development of new therapies increasingly important. Spinal metastases may cause significant pain and reduced quality of life and lead to permanent neurological disability if compression of the spinal cord and/or nerve root occurs. Until recently, treatments for spinal metastases were not optimal and provided temporary local control and pain relief. Spinal stereotactic ablative radiotherapy (SABR) is an effective approach associated with an improved therapeutic ratio, with evolving clinical application. Objective: To review the literature of spinal SABR for spinal metastases, discuss a multidisciplinary approach to appropriate patient selection and technical considerations, and summarize current efforts to combine spinal SABR with systemic therapies. Evidence Review: The MEDLINE database was searched to identify articles reporting on spinal SABR to September 30, 2018. Articles including clinical trials, prospective and retrospective studies, systematic reviews, and consensus recommendations were selected for relevance to multidisciplinary management of spinal metastases. Results: Fifty-nine unique publications with 5655 patients who underwent SABR for spinal metastases were included. Four comprehensive frameworks for patient selection were discussed. Spinal SABR was associated with 1-year local control rates of approximately 80% to 90% in the de novo setting, greater than 80% in the postoperative setting, and greater than 65% in the reirradiation setting. The most commonly discussed adverse effect was development of a vertebral compression fracture with variable rates, most commonly reported as approximately 10% to 15%. High-level data on the combination of SABR with modern therapies are still lacking. At present, 19 clinical trials are ongoing, mainly focusing on combined modality therapies, radiotherapy prescription dose, and oligometastic disease. Conclusions and Relevance: These findings suggest that spinal SABR may be an effective treatment option for well-selected patients with spinal metastases, achieving high rates of local tumor control with moderate rates of adverse effects. Optimal management should include review by a multidisciplinary care team.

Clinical stage I synchronous bilateral testicular germ cell tumor with different histopathology: a case report.

Bilateral testicular germ cell tumors (BTGCT) occur in 1 to 4% of patients with testicular cancer and of these, 10-15% are synchronous. Overall, BTGCT represents less than 0.5% of all new cases of testicular cancer. There are few reports in the literature of synchronous BTGCT with different histology. We present the case of a 30-year-old man who presented to our genitourinary tumor unit with a bilateral increase of testicular volume. After initial assessment, a testicular ultrasound showed the presence of solid tumors in both testes. Staging studies were negative for metastatic disease. The patient was referred to the fertility clinic for sperm banking and later underwent a bilateral radical orchiectomy. The histopathology evaluation revealed a 5.5 cm right-sided mixed germ cell tumor and a 1.5 cm left-sided testicular seminoma. Because patient's poor compliance for surveillance was identified as a risk factor for relapse and poor outcome, adjuvant chemotherapy was favored. The patient underwent one cycle of bleomycin, etoposide and cisplatin (BEP). After four years of follow up, the patient shows no evidence of relapse, either clinically or radiologically. In men unlikely to carry out successful surveillance; active treatment is the preferred option for preventing disease recurrence, even in patients with no risk factors. The physician must consider all available therapeutic measures in this scenario to achieve the best possible therapeutic result.

Design and Implementing Pharmacogenomics Study in Cancer.

The advances in technology has shifted healthcare from a "one size fits all" model to focus on personalized therapy. Understanding the relationship of genome variations and its effect on drug response has led to individualized drug selection, maximizing drug efficacy and improving toxicity profile. The developments in pharmacogenomics has led to the discovery of predictive and prognostic biomarkers, and has transformed cancer research leading to the creation of pharmacogenomics databases. While challenges associated with the implementation of pharmacogenomics based medicine exist, integrating data amongst collaborative networks will be crucial for researchers to identify all the functional elements of the human genome sequence. Future advances in the area of pharmacogenomics research will eventually lead to the identification of the right therapeutic drug for the right patient.

Honorary and ghost authorship in reports of randomised clinical trials in oncology.

BACKGROUND: The International Committee of Medical Journal Editors (ICMJE) has developed guidelines for responsible and accountable authorship. Few studies have assessed the frequency and nature of ghost and honorary authorship in publications of oncology trials. MATERIALS AND METHODS: Reports of randomised clinical trials evaluating systemic cancer therapy published from July 2010 to December 2012 in six high-impact journals were identified systematically. Ghost authorship was determined to be present in any scenario where investigators or statisticians listed in the protocol were not included as authors and not acknowledged in the report of the trial. The list of contributions for authors of published articles was recorded, and we defined an article as having an honorary author if any author did not meet all three criteria established by ICMJE in 1985. RESULTS: Two hundred publications were identified. For 61 articles, protocols with listed investigators were available, and 40 (66%) of these articles met our definition of ghost authorship. Medical writers were involved in 89 articles (45%), and assistance was acknowledged only in sponsored trials. Contributions of each author were provided in 195 articles, and 63 (33%) articles met our definition for honorary authorship. Funding source was not a predictor for either honorary or ghost authorship. Journal impact factor was positively associated with honorary authorship (odds ratio = 1.03; 95% confidence interval = 1.004-1.065; P = 0.03), but not with ghost authorship. CONCLUSION: Ghost and honorary authorship are prevalent in articles describing trials for systemic therapy of cancer. Guidelines should be enforced to improve transparency and accountability.

Chromophobe renal cell carcinoma: a review of an uncommon entity.

Renal cell carcinoma is the most common neoplasm of the kidney. It is a heterogeneous disease, comprised of different histological variants with a distinct clinical course, genetics and response to treatment. The various subtypes identified include clear cell, papillary and chromophobe, among others. Chromophobe renal cell carcinoma is a rare variant and accounts for 5% of all cases. These tumors are macroscopically larger when compared with other forms and are commonly diagnosed at an early stage. Despite significant advances in renal cell carcinoma therapeutics in the past decade, no standard treatment has been identified for advanced chromophobe renal cell carcinoma. Nevertheless, new molecular insights have recently become available. A familial form of renal cell carcinoma, the Birt-Hogg-Dubé syndrome, has been described and the knowledge obtained has opened research opportunities in the therapeutic arena of chromophobe renal cell carcinoma. The following manuscript will endeavor to provide an overview of this uncommon entity including pathology, epidemiology, genetics, clinical aspects, and current and future treatment options.