Clinical Oncology

RFA experiences, indications and clinical outcomes Abstract Backgound Early-stage breast cancer is increasingly detected by screening mammography, and we aim to establish radiofrequency ablation therapy (RFA) as a minimally invasive, cost-efficient, and cosmetically acceptable local treatment. Although there were many studies on resection after RFA, none of them provided sufficient evidence to support RFA as a standard therapy for breast cancer. Results In our Phase I study, localized tumors with a maximum diameter of 2 cm, preoperatively diagnosed by imaging and histopathology, were treated with RFA. A 90% complete ablation rate was confirmed histopathologically. Our phase II multicenter study of RFA without resection for early breast cancer will evaluate the long-term safety and efficacy of RFA as well as its cosmetic results, which are a perceived advantage of this technique. We started a phase III multicenter study to demonstrate the non-inferiority of RFA compared with standard treatment (breast-conserving surgery) in terms of ipsilateral breast tumor recurrence (IBTR) rate, which is the best index of local control. Conclucion To standardize RFA for breast cancer, the results of our multicenter study, Radiofrequency Ablation Therapy for Early Breast Cancer as Local Therapy (the RAFAELO study) that began in 2013, are eagerly awaited.

Control of intracranial disease is associated with improved survival in patients with brain metastasis from hepatocellular carcinoma Abstract Background Brain metastasis is a rare event in patients with hepatocellular carcinoma (HCC). This retrospective study aimed to identify the prognostic factors and determine the outcomes of patients with brain metastases from HCC. Methods About 86 patients with brain metastases (0.6%) from HCC were identified from two institutions; of them, 32 underwent tumor-removing surgery or stereotactic radiosurgery (SRS) with or without adjuvant whole brain radiotherapy (WBRT) (group 1), 30 had WBRT alone (group 2), and 24 received conservative treatment (group 3). Estimates for overall survival (OS) after brain metastases were determined, and clinical prognostic factors were identified. Results The median OS after development of brain metastases was 50 days. About 75 (87.2%) patients had lung metastases at the time of brain metastasis diagnosis. Group 1 showed better OS, followed by group 2 and group 3, sequentially (p < 0.001). Univariate analyses showed that treatment with curative intent (surgery or SRS), Child–Pugh class A, alpha-fetoprotein level < 400 ng/ml, and recursive partitioning analysis classification I or II were associated with improved survival (p < 0.001, 0.002, 0.029, and 0.012, respectively). Multivariate analysis showed that treatment with curative intent and Child–Pugh class A was associated with improved OS (p < 0.001 and 0.009, respectively). Conclusion Although the overall prognosis of patients with brain metastases from HCC is extremely poor, patients actively treated with surgery or radiosurgery have prolonged survival, suggesting that interventions to control intracranial disease are important in these patients.

Adjuvant therapy in renal cell carcinoma: the perspective of urologists Abstract Background Until recently, there was no approved adjuvant therapy (AT) for renal cell carcinoma (RCC) unless sunitinib was approved in the US. We evaluated clinical opinion and estimated use regarding different treatment options and patient selection of AT in RCC patients based on current scientific data and individual experience in Germany. Methods We conducted an anonymous survey during a national urology conference in 01/2017. Answers of 157 urologists treating RCC patients could be included. Questions were related to practice setting, treatment of RCC, follow-up strategy, physicians’ personal opinion and individually different important parameters regarding S-TRAC and ASSURE-trial. Results 82% were office based. 67% were located in larger cities. 83% reported that nephron-sparing surgery (NSS) was performed in tumors with diameter < 4 cm. Follow-up was done mainly in concordance with guideline recommendations. 68% treated an average of 2.9 patients/year with systemic therapy. Therapy was predominantly advocated using sunitinib (94%). Urologists were informed about S-TRAC and ASSURE-trial. For 47%, reported hazard ratio is the most important parameter to understand trial results followed by overall survival (OS) in 46%, disease-free survival in 38%, and results of other trials in 34%. The most convincing parameter to decide on AT is OS (69%). 62% placed their confidence in ASSURE over STRAC-trial. 44% would use AT for 12 months. Nodal involvement was the most common denominator for use of AT. 82% favor sunitinib as AT. Conclusions A minority of urologists would use AT and are more confident in ASSURE-trial. Reluctance of prescribing AT mainly is based on lack of OS data and conflicting trial results.

Optimal treatment strategy for rectal cancer based on the risk factors for recurrence patterns Abstract Background For rectal cancer, multimodality therapeutic approach is necessary to prevent local recurrence and distant metastasis. However, the efficacy of additional treatments, such as neoadjuvant chemoradiotherapy (nCRT), neoadjuvant chemotherapy (NAC), and lateral pelvic lymph node dissection (LPLND), has not been scrutinized. Methods Recurrence patterns were categorized into local recurrence and distant metastasis. Local recurrence was classified into two types: (1) pelvic cavity recurrence and (2) LPLN recurrence. First, we analyzed the risk factors for each recurrence pattern. Second, based on the status of clinically suspected involvement of circumferential resection margin (cCRM), the efficacy of additional treatments was investigated. Results A total of 240 patients was enrolled. nCRT was performed for 25 (10%), NAC was for 46 (19%), and LPLND was for 35 patients (15%). As the recurrence patterns, pelvic cavity recurrence occurred in 15 (6%), LPLN recurrence in 8 (3%), and distant metastasis in 42 patients (18%). Five-year overall survival and relapse-free survival were 87% and 70%, respectively. Multivariate analysis indicated that pelvic cavity recurrence was associated with cCRM status and tumor histology, that LPLN recurrence was with serum carcinoembryonic antigen level and LPLN swelling, and that distant metastasis was with clinical N category. In the cCRM-positive subgroup (n = 66), cumulative rate of pelvic cavity recurrence was lower in the nCRT group than in the NAC or non-NAC/nCRT group (P = 0.02 and 0.09, respectively). Conclusion cCRM status was associated with pelvic cavity recurrence, and LPLN swelling was with LPLN recurrence. nCRT could reduce pelvic cavity recurrence in cCRM-positive subgroup.

Cryosurgery for primary breast cancers, its biological impact, and clinical outcomes Abstract Recently, a number of new minimally invasive image-guided percutaneous ablation treatments, including cryoablation, radiofrequency ablation, microwave ablation, high-intensity focused ultrasound, laser ablation, and irreversible electroporation have been developed. Several studies have shown the feasibility and safety of these cryoablation therapies for the treatment of benign breast tumors and small invasive breast cancer. Although the complete response rate of cryoablation for breast cancer is reported to be relatively good, most studies enrolled a small number of patients, and so reliable conclusions could not be drawn. In this review, we introduce the mechanisms of action of cryoablation, and summarize the current literature on the efficacy and safety of cryoablation for breast cancer. Cryoablation also induces an immunomodulatory effect, which is an interesting topic of research in the era of immune checkpoint inhibitors. Cryoablation for primary tumor may enhance the treatment effect of immune checkpoint inhibitors in patients with breast cancer. Further investigations of this new therapeutic strategy are needed.

CT and clinical characteristics that predict risk of EGFR mutation in non-small cell lung cancer: a systematic review and meta-analysis Abstract Introduction To systematically analyze CT and clinical characteristics to find out the risk factors of epidermal growth factor receptor (EGFR) mutation in non-small cell lung cancer (NSCLC). Then the significant characteristics were used to set up a mathematic model to predict EGFR mutation in NSCLC. Materials and methods PubMed, Web of Knowledge and EMBASE up to August 17, 2018 were systematically searched for relevant studies that investigated the evidence of association between CT and clinical characteristics and EGFR mutation in NSCLC. After study selection, data extraction, and quality assessment, the pooled odds ratios (ORs) were calculated. Then from May 2017 to August 2018, all NSCLC received EGFR mutation examination and CT examination in our hospital were chosen to test the prediction model by receiver operating characteristic (ROC) curves. Results Seventeen original studies met the inclusion criteria. The results showed that the ORs of ground-glass opacity (GGO), air bronchogram, pleural retraction, vascular convergence, smoking history, female gender were, respectively, 1.93 (P = 0.003), 2.09 (P = 0.03), 1.59 (P < 0.01), 1.61 (P = 0.001), 0.28 (P < 0.01), 0.35 (P < 0.01). The result of speculation, cavitation/bubble-like lucency, lesion shape, margin, pathological stage were, respectively, 1.19 (P = 0.32), 0.99 (P = 0.97), 0.82 (P = 0.42), 1.02 (P = 0.90), 0.77 (P = 0.30). 121 NSCLC received EGFR mutation test were included to test the prediction model. The mathematical model based on the results of meta-analysis was: 0.74 × air bronchogram + 0.46 × pleural retraction + 0.48 × vascular convergence − 1.27 × non-smoking history − 1.05 × female. The area under the ROC curve was 0.68. Conclusion Based on the current evidence, GGO presence, air bronchogram, pleural retraction, vascular convergence were significant risk factors of EGFR mutation in NSCLC. And the prediction model can help to predict EGFR mutation status.

Lymph node ratio has impact on relapse and outcome in patients with stage III melanoma Abstract Background Even though both the involvement of regional lymph nodes and the number of metastatic lymph nodes are regarded as major determinants of survival in cutaneous melanoma, the extent of node dissection has been analyzed as an independent prognostic indicator in only a few studies. This study aims to determine how the lymph node ratio (NR) (ratio of positive nodes to total nodes removed) might predict the disease relapse and survival in node-positive melanoma. Materials and methods A total of 317 patients with stage III primary melanoma were included in the study and reviewed retrospectively. All patients had nodal staging (N) by radical lymph node dissection. Patients were divided into three groups based on NR1 ≤ 10%, NR2 10–25%, and NR3 > 25%. Results The median age was 50 years (range 16–86) and men were predominant (59.3%). The majority of the patients had thicker Breslow depth (> 2 mm) (83.3%), higher mitotic rate (> 2/mm2) (64.1%) and ulcerated lesions (69.4%). The median number of positive nodes was 1 (range 1–32). The largest group was N1 (52.4%), which was followed by N2 (29.6%) and N3 (18%). The ratios of patients were 37.5%, 35.3%, and 27.1% in NR1, NR2, and NR3, respectively. The median number of excised lymph nodes was 13 (range 1–73). For all patients the estimated 5-and 10-year relapse-free survival (RFS) rates were 41% and 39%, respectively; and the estimated 5-and 10-year overall survival (OS) rates were 51% and 42%, respectively. Nodular histopathology, ulcerated lesions, higher mitotic rates, and higher node substages were the independent variables that were inversely correlated with survival for all patients; and NR was one of the significant prognostic factors and strongest predictors of relapse and survival (p = 0.03 and p = 0.01, respectively). Conclusion Our results suggest that, apart from the conventional nodal status, NR is an independent prognostic factor-regarding both RFS and OS in stage III cutaneous melanoma.

Radiotherapy alone as a possible de-intensified treatment for human papillomavirus-related locally advanced oropharyngeal squamous cell carcinoma Abstract Background Human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) is defined by p16 positivity and/or HPV DNA positivity. Because survival of patients with HPV-related OPSCC after chemoradiotherapy is favorable, a de-intensified treatment is expected to lead to less morbidity while maintaining low mortality. The association of tumor p16 and HPV DNA status with survival after radiotherapy alone remains unknown. Methods We retrospectively examined survival of 107 patients with locally advanced OPSCC after radiotherapy alone (n = 43) or chemoradiotherapy (n = 64) with respect to tumor p16 and HPV DNA status, using Cox’s proportional hazard model. Results Survival after radiotherapy alone was significantly worse in p16-positive/HPV DNA-negative locally advanced OPSCC than in p16-positive/HPV DNA-positive locally advanced OPSCC. In bivariable analyses that included T category, N category, TNM stage, and smoking history, the survival disadvantage of p16-positive/HPV DNA-negative locally advanced OPSCC remained significant. There was no significant difference in survival after chemoradiotherapy between p16-positive/HPV DNA-positive locally advanced OPSCC and p16-positive/HPV DNA-negative locally advanced OPSCC. Survival in p16-positive/HPV DNA-positive locally advanced OPSCC after radiotherapy alone was similar to that after chemoradiotherapy, which stayed unchanged in bivariable analyses after adjustment of every other covariable. Survival of p16-negative/HPV DNA-negative locally advanced OPSCC was poor irrespective of treatment modality. Conclusions Survival in p16-positive locally advanced OPSCC differs depending on HPV DNA status. Radiotherapy alone can serve as a de-intensified treatment for p16-positive/HPV DNA-positive locally advanced OPSCC, but not for p16-positive/HPV DNA-negative locally advanced OPSCC.

Resection of pancreatic metastatic renal cell carcinoma: experience and long-term survival outcome from a large center in China Abstract Purpose This study aimed to determine the outcome of pancreatic metastatic renal cell carcinoma (PmRCC) after treatment and share the relevent results. Methods In total, 13 patients with PmRCC were diagnosed and treated in our institution from December 2013 to October 2017. We retrospectively reviewed the records and analyzed the patient demographics, perioperative outcomes, and overall survival. Simultaneously, our experience including treatment and misdiagnosis was shared. Results The median time between nephrectomy and reoperation for pancreatic recurrence was 11 years (range 1–20 years). Four patients had multiple tumors and nine patients had solitary tumor. Five patients accepted distal pancreatectomy, and five patients underwent pancreaticoduodenectomy. One patient underwent total pancreatectomy, one patient underwent duodenum-preserving pancreatic head resection plus distal pancreatectomy, and one patient underwent exploratory laparotomy and gastrointestinal bypass due to widespread metastasis with clear obstructive symptoms. The misdiagnosis rate of preoperative diagnosis at our center was 69.2% (9/13). The median follow-up duration was 26 months (range 7–53 months, until June 2018). By the end of follow-up, 12 patients were alive and one patient died of gastrointestinal bleeding within 1 month after surgery. Conclusions PmRCCs are uncommon, but pancreatic metastasectomy has a relatively good prognosis and may, therefore, be a good therapeutic choice for patients with PmRCCs. Because PmRCC occurs long after the primary tumor resection, long-term follow-up is necessary. Besides, detailed medical history and specific manifestation in imaging features could contribute to avoiding misdiagnosis.

Saddle pulmonary embolism and in-hospital mortality in patients with cancer Abstract Purpose Saddle pulmonary embolism (PE) has been associated with an increased risk of 1 year mortality when compared to non-saddle PE among patients with cancer. We sought to evaluate the association between saddle PE and in-hospital outcomes among patients with comorbid cancer. Methods The 2013 and 2014 United States National Inpatient Sample was used to identify adult patients hospitalized for acute PE. Only patients with an International Classification Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code indicating comorbid cancer were included. Identified admissions were stratified into the following 2 cohorts: saddle (defined as ICD-9-CM code = 415.13) and non-saddle PE. Multivariable logistic regression was performed to determine the association between saddle PE and the odds of in-hospital mortality after adjustment for age ≥ 80 years and sex. Results A total of 10,660 admissions for acute PE in patients with comorbid cancer were identified. Of which, 4.5% (n = 475) had a saddle PE. Median age was 67 years (interquartile range = 58–76) and 48.9% were male. In-hospital mortality occurred in 6.1% of patients. Upon multivariable adjustment, the odds of in-hospital mortality were higher in saddle versus non-saddle PE (odds ratio = 1.51; 95% confidence interval 1.08–2.10). Conclusion In this retrospective study of admissions for acute PE in patients with comorbid cancer, saddle PE was associated with a higher odds of in-hospital mortality.