Outcomes of intracranial non-germinomatous germ cell tumors: a retrospective Asian multinational study on treatment strategies and prognostic factors.

PURPOSE: Non-germinomatous germ cell tumors (NGGCTs) are rare pediatric conditions. This multicenter study using Asian multinational patient data investigated treatment outcomes and prognostic factors for NGGCTs. METHODS: Medical records of 251 patients with NGGCTs treated from 1995 to 2015 were retrospectively analyzed from participating centers in Asian countries (Korea, Taiwan, Singapore, and Japan). RESULTS: The median follow up was 8.5 years (95% CI 7.8-9.9). In the total cohort, 5-year event-free survival (EFS) and overall survival (OS) rates were 78.2% and 85.4%, respectively. In 17.9% of the patients, diagnosis was determined by tumor markers alone (alpha-fetoprotein ≥ 10 ng/mL (Korea) or > 25 ng/mL (Taiwan and Singapore), and/or ß-human chorionic gonadotropin (ß-hCG) ≥ 50 mIU/mL). Patients with immature teratomas and mature teratomas comprised 12.0% and 8.4%, respectively. The 5-year EFS rate was higher in patients with histologically confirmed germinoma with elevated ß-hCG (n = 28) than those in patients with malignant NGGCTs (n = 127). Among malignant NGGCTs, patients with choriocarcinoma showed the highest 5-year OS of 87.6%, while yolk sac tumors showed the lowest OS (68.8%). For malignant NGGCT subgroups, an increase in serum ß-hCG levels by 100 mIU/mL was identified as a significant prognostic factor associated with the EFS and OS. CONCLUSION: Our result shows excellent survival outcomes of overall CNS NGGCT. However, treatment outcome varied widely across the histopathologic subgroup of NGGCT. Hence, this study suggests the necessity for accurate diagnosis by surgical biopsy and further optimization of diagnosis and treatment according to the histopathology of NGGCTs. Future clinical trials should be designed for individualized treatments for different NGGCTs subsets.

Prognostic value of the 21-gene recurrence score for regional recurrence in patients with estrogen receptor-positive breast cancer.

PURPOSE: To evaluate the prognostic value of the 21-gene recurrence score (RS) for regional recurrence (RR) in patients with estrogen receptor-positive breast cancer. METHODS: We reviewed the medical records of 446 patients who underwent 21-gene RS assay after breast-conserving surgery or mastectomy. The high-RS group was defined as patients who were (1) older than 50 years with an RS of 26 or higher, or (2) 50 years or younger with an RS of 16 or higher. RESULTS: The 5-year rates of local recurrence (LR), RR, and distant metastasis (DM) were 2.2%, 2.7%, and 4.7%, respectively. The 5-year overall survival (OS) rate was 99.1%. Of the patients, 269 (60.3%) had low-RS, while 177 (39.7%) had high-RS. The 5-year OS rate of the high-RS group was significantly lower than that of the low-RS. The 5-year rates of RR and DM in the high-RS group were significantly higher than those in the low-RS group, while the LR rates did not differ significantly. In multivariable analysis, the high-RS group had a significant relationship with increased RR rate (p = 0.037). Patients who had both high-RS and clinical high-risk features had a significantly higher 5-year RR rate (7.9%) compared with other groups. CONCLUSIONS: High-RS was an independent risk factor for RR. The significantly higher RR rate of patients with both high-RS and clinical high-risk features compared with other groups suggests that this patient group can be a potential candidate for regional nodal irradiation.

Evaluation of the Prognostic Stage in the 8th Edition of the American Joint Committee on Cancer in Patients with Breast Cancer and Internal Mammary Lymph Node Metastasis.

BACKGROUND/AIM: This study evaluated the prognostic value of the 8th edition of American Joint Committee on Cancer (AJCC) cancer staging system for patients with internal mammary lymph node (IMN) metastases. MATERIALS AND METHODS: Of the patients with breast cancer who were treated between 2009 and 2013, 66 were diagnosed as cN3b. We restaged the patients and analyzed the prognostic value of the prognostically staged groups. RESULTS: With a median follow-up of 53.9 months, the 5-year overall survival rates of patients with IIIA, IIIB, and IIIC stages were 100%, 95%, and 50% (p=0.001), while the progression-free survival rates were 100%, 83%, and 50% (p=0.005). CONCLUSION: Despite the small number of patients, the prognostic stage provided accurate information for IMN metastasized breast cancer, which will lead to more accurate prognosis predictions and optimal treatment selection.

Postoperative Radiotherapy for Pancreatic Cancer with Microscopically-positive Resection Margin.

AIM: To analyze the outcomes in pancreatic cancer (PC) cases with a microscopically-positive resection margin (R1 resection) treated with postoperative radiotherapy (PORT). PATIENTS AND METHODS: We retrospectively analyzed the outcomes in 62 patients who received PORT for PC with R1 resection between 2001 and 2012. All patients received three-dimensional conformal radiotherapy. Concurrent chemotherapy was administered to 58 patients. RESULTS: The median follow-up was 20.1 months. The median survival was 22.0 months and the 3-year overall survival rate was 25%. The 3-year disease-free survival and local recurrence-free survival rates were 12% and 54%, respectively. Local recurrence occurred in 23 patients (44%), distant failure in 45 (87%), and both in 16 (31%). By multivariate analysis, the postoperative cancer antigen 19-9 (CA19-9) level and adjuvant chemotherapy were independent prognostic factors for survival. CONCLUSION: PORT is associated with a relatively favorable survival outcome in PC with R1 resection. Chemotherapy and postoperative CA19-9 level were significant prognostic factors for survival.

Treatment outcome of radiation therapy for intracranial germinoma: adaptive radiation field in relation to response to chemotherapy.

AIM: To determine the optimal radiotherapy (RT) target volume in correlation with tumor response to chemotherapy in patients with intracranial germinoma. PATIENTS AND METHODS: Seventy-two patients received chemotherapy followed by RT. The RT field was tailored to chemotherapy response. RESULTS: Five-year recurrence-free survival (RFS) was 87% and overall survival was 97%. RT field was significantly associated with RFS, with 5-year RFS rates of 95%, 91%, and 62% in those who received craniospinal irradiation, whole-brain/whole-ventricle RT, and focal RT, respectively (p=0.01). In the complete-response group after chemotherapy, 5-year RFS rates were 100% after whole-brain RT/whole-ventricle RT and 70% after focal RT (p=0.04). In the partial-response group, 5-year RFS rates after craniospinal irradiation, whole-brain RT, and focal RT were 100%, 85%, and 33%, respectively (p<0.01). CONCLUSION: Regardless of response, those treated with focal RT had an excessively high relapse rate. Whole-brain/whole-ventricle RT could be applied to patients who show a complete response to chemotherapy, but the optimal strategy for patients with partial response needs further investigation.

Adjuvant radiotherapy for stage III/IV urothelial carcinoma of the upper tract.

AIM: In order to define the role of adjuvant radiotherapy (RT), the clinical outcomes of patients with stage III/IV urothelial carcinoma of the upper urinary tract (UTUC) were reviewed. PATIENTS AND METHODS: Clinical data from a total of 127 patients who underwent radical nephroureterectomy with bladder cuff were analyzed. While 36 patients underwent adjuvant RT following surgery, 91 were treated with surgery-alone. Differences in risk-adjusted treatment outcomes between the two groups were assessed using a multivariable Cox proportional-hazards model and inverse probability of treatment weighting with propensity score for balancing covariates including use of chemotherapy between the two groups was estimated. RESULTS: With a median follow-up of 38.3 months, 3-year actuarial locoregional recurrence-free survival rates were 89% vs. 61% in the RT vs. non-RT groups, respectively (p=0.01). Three-year bladder recurrence-free survival rates were 73% and 52% in favor of the RT group (p=0.02). After adjustment for differences in covariates, the risks of locoregional, bladder, and disease recurrence were found significantly lower in the RT group. CONCLUSION: Adjuvant RT may be beneficial in terms of locoregional and bladder control in patients with stage III/IV UTUC. Further prospective studied are needed to verify these findings.

Can concurrent chemoradiotherapy replace surgery and postoperative radiation for locally advanced stage III/IV tonsillar squamous cell carcinoma?

AIM: To compare surgery and postoperative radiotherapy (PORT) with the non-surgical combination of chemotherapy and radiation therapy (CCRT) for locally advanced squamous cell carcinoma (SCC) of the tonsil by measuring treatment outcomes and treatment-related complications. PATIENTS AND METHODS: The records of 114 patients with non-metastatic stage III/IV tonsillar SCC treated between July, 1998 and December, 2010 were reviewed retrospectively. Among the 114 patients, 65 received PORT and 49 received CCRT. In the PORT group, treatment included wide surgical resection of the tumor with neck dissection and administration of PORT to the primary tumor bed with a median dose of 60 Gy. In the CCRT group, a median dose of 70 Gy was delivered to the gross tumor, and 46 patients received concurrent chemotherapy with i.v. cisplatin. The median follow-up time was 58 months in the PORT group and 44 months in the CCRT group. RESULTS: There was no significant difference between PORT and CCRT in terms of 5-year locoregional recurrence-free survival (88.4% vs. 91.4%, p=0.68), distant metastasis-free survival (88.9% vs. 92.3%, p=0.60), disease-free survival (79.5% vs. 84.2%, p=0.63) or overall survival (78.9% vs. 88.9%, p=0.45). More CCRT patients than PORT patients experienced grade 3 (or higher) hematological toxicities and grade 2 pharyngitis during treatment. Chronic toxicity, manifested as swallowing difficulty, dry mouth and trismus, was similar between the two treatment groups. CONCLUSION: CCRT provides similar levels of local and distant control in patients with locally advanced tonsillar SCC as PORT, yet fails to show any superiority in preserving functions such as swallowing, saliva production, and mastication.