High SPIN4 Expression Is Linked to Advanced Nodal Status and Inferior Prognosis in Nasopharyngeal Carcinoma Patients

Nasopharyngeal carcinoma (NPC), characterized by the infiltration of lymphocytes, is a malignancy derived from the epithelium of the nasopharynx. Despite its sensitivity to radiation and chemotherapy, NPC has a high propensity for recurrence and metastasis. Although lymph node levels have been indicated as an independent prognostic factor for NPC, there has been no precise prognostic biomarker to predict clinical outcomes for NPC before advanced disease. In the present study, we surveyed differentially expressed genes in NPC via the next-generation sequencing (NGS)-based Oncomine database and identified the spindlin family member 4 (SPIN4) gene as the most relevant to advanced nodal status. We collected 124 tumor samples from NPC patients receiving biopsy, and the expression level of SPIN4 was evaluated by immunohistochemistry. The results showed that tumors with high SPIN4 expression were significantly correlated with advanced nodal status (p < 0.001) and advanced AJCC stages (p < 0.001). High SPIN4 expression in tumor samples was an unfavorable prognostic factor for all three endpoints at the univariate level: disease-specific survival (DSS), distal metastasis-free survival (DMeFS), and local recurrence-free survival (LRFS) (all p < 0.05). High SPIN4 expression remained independently prognostic of worse DMeFS (p = 0.049) at the multivariate level. Using bioinformatics analysis, we further found that high SPIN4 level may link tight junctions to cancer cell survival. Collectively, these results imply that high SPIN4 expression is linked to an aggressive clinical course, including advanced nodal status and poor survival in NPC patients, emphasizing the promising prognostic utility of SPIN4 expression.

High SPINK4 Expression Predicts Poor Outcomes among Rectal Cancer Patients Receiving CCRT

Background: Patients with rectal cancer can prospectively be favored for neoadjuvant concurrent chemoradiotherapy (CCRT) to downstage before a radical proctectomy, but the risk stratification and clinical outcomes remain disappointing. Methods: From a published rectal cancer transcriptome dataset (GSE35452), we highlighted extracellular matrix (ECM)-linked genes and identified the serine protease inhibitor Kazal-type 4 (SPINK4) gene as the most relevant among the top 10 differentially expressed genes associated with CCRT resistance. We accumulated the cases of 172 rectal cancer patients who received neoadjuvant CCRT followed by surgery and collected tumor specimens for the evaluation of the expression of SPINK4 using immunohistochemistry. Results: The results revealed that high SPINK4 immunoexpression was significantly related to advanced pre-CCRT and post-CCRT tumor status (both p < 0.001), post-CCRT lymph node metastasis (p = 0.001), more vascular and perineurial invasion (p = 0.015 and p = 0.023), and a lower degree of tumor regression (p = 0.001). In univariate analyses, high SPINK4 immunoexpression was remarkably correlated with worse disease-specific survival (DSS) (p < 0.0001), local recurrence-free survival (LRFS) (p = 0.0017), and metastasis-free survival (MeFS) (p < 0.0001). Furthermore, in multivariate analyses, high SPINK4 immunoexpression remained independently prognostic of inferior DSS and MeFS (p = 0.004 and p = 0.002). Conclusion: These results imply that high SPINK4 expression is associated with advanced clinicopathological features and a poor therapeutic response among rectal cancer patients undergoing CCRT, thus validating the prospective prognostic value of SPINK4 for those patients.

New clinical and biological insights from the international TARGIT-A randomised trial of targeted intraoperative radiotherapy during lumpectomy for breast cancer

Background The TARGIT-A trial reported risk-adapted targeted intraoperative radiotherapy (TARGIT-IORT) during lumpectomy for breast cancer to be as effective as whole-breast external beam radiotherapy (EBRT). Here, we present further detailed analyses. Methods In total, 2298 women (≥45 years, invasive ductal carcinoma ≤3.5 cm, cN0–N1) were randomised. We investigated the impact of tumour size, grade, ER, PgR, HER2 and lymph node status on local recurrence-free survival, and of local recurrence on distant relapse and mortality. We analysed the predictive factors for recommending supplemental EBRT after TARGIT-IORT as part of the risk-adapted approach, using regression modelling. Non-breast cancer mortality was compared between TARGIT-IORT plus EBRT vs. EBRT. Results Local recurrence-free survival was no different between TARGIT-IORT and EBRT, in every tumour subgroup. Unlike in the EBRT arm, local recurrence in the TARGIT-IORT arm was not a predictor of a higher risk of distant relapse or death. Our new predictive tool for recommending supplemental EBRT after TARGIT-IORT is at https://targit.org.uk/addrt. Non-breast cancer mortality was significantly lower in the TARGIT-IORT arm, even when patients received supplemental EBRT, HR 0.38 (95% CI 0.17–0.88) P = 0.0091. Conclusion TARGIT-IORT is as effective as EBRT in all subgroups. Local recurrence after TARGIT-IORT, unlike after EBRT, has a good prognosis. TARGIT-IORT might have a beneficial abscopal effect. Trial registration ISRCTN34086741 (21/7/2004), NCT00983684 (24/9/2009).

Loosening Neuro-Optic Structures Dosimetric Constraints Provides High 5-Year Local Recurrence-Free Survival With Acceptable Toxicity in T4 Nasopharyngeal Carcinoma Patients Treated With Intensity-Modulated Radiotherapy

ObjectiveWhether the original dosimetric constraints of neuro-optic structures (NOS) are appropriate for patients with nasopharyngeal carcinoma (NPC) undergoing intensity-modulated radiotherapy (IMRT) remains controversial. The present study compared the survival rates and radiation-induced optic neuropathy (RION) occurrence between T4 NPC patients whose NOS were irradiated with a near maximum dose received by 2% of the volume (D2%) &gt;55 Gy and ≤55 Gy. Moreover, the NOS dosimetric parameters and their correlation with RION occurrence were also evaluated.MethodsIn this retrospective study, 256 T4 NPC patients treated with IMRT between May 2009 and December 2013 were included. Patient characteristics, survival rates, dosimetric parameters, and RION incidence were compared between the D2% ≤55 Gy and D2% &gt;55 Gy groups.ResultsThe median follow-up durations were 87 and 83 months for patients in the D2% &gt;55 Gy and D2% ≤55 Gy groups, respectively. The 5-year local recurrence-free survival rates were 92.0 and 84.0% in the D2% &gt;55 Gy and D2% ≤55 Gy groups (P = 0.043), respectively. There was no significant difference in the 5-year overall survival (OS) between both groups (D2% &gt;55 Gy, 81.6%; D2% ≤55 Gy, 79.4%; P = 0.586). No patients developed severe RION (Grades 3–5), and there was no significant difference (P = 0.958) in the incidence of RION between the two groups. The maximum dose of NOS significantly affected the RION incidence, with a cutoff point of 70.77 Gy.ConclusionAppropriately loosening NOS dosimetric constraints in order to ensure a more sufficient dose to the target volume can provide a better 5-year local recurrence-free survival and acceptable neuro-optic toxicity in T4 NPC patients undergoing IMRT.

Prognostic value of Ki-67 in nasopharyngeal carcinoma: a meta-analysis

The prognostic value of Ki-67 in nasopharyngeal carcinoma (NPC) was controversial according to previous studies. We aimed to clarify the association between K-67 expression and survival in NPC through meta-analysis. We conducted a meta-analysis to explore the potential prognostic effect of Ki-67 on overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and local recurrence-free survival (LRFS) in NPC. A total of 13 studies comprising 1314 NPC patients were included. High Ki-67 expression was associated with poor OS (hazard ratio [HR]=2.70, 95% confidence interval [CI]=1.97–3.71, p&lt;0.001), DFS (HR=1.93, 95% CI=1.49–2.50, p&lt;0.001), and LRFS (HR=1.86, 95% CI=1.11–3.12, p=0.019). However, there was no significant association between Ki-67 and DMFS (HR=1.37, 95% CI=0.78–2.38, p=0.270). Furthermore, the prognostic role of Ki-67 was maintained throughout different sample sizes, analyses of HR, and study designs for OS and DFS in various subgroups. Elevated Ki-67 expression is a reliable prognostic factor for poorer survival outcomes in NPC.

Efficacy of hyperthermic isolated limb perfusion in the treatment of locally recurrent high-grade soft tissue sarcoma of the extremities

Background This novel study compared the use of tumor necrosis factor (TNF)-alpha and melphalan-based isolated limb perfusion (TM-ILP) to the standard treatment of locally recurrent soft tissue extremity sarcoma. The aim was to assess whether TM-ILP positively influences the recurrence-free survival of locally recurrent high-grade soft tissue sarcoma (STS) of the extremities. Methods We retrospectively analyzed our clinical database for patients with STS. Variables were analyzed using chi-square test or Mann-Whitney rank-sum test. Furthermore, Kaplan-Meier survival plots were calculated and a proportional hazard regression model was developed. Results Out of 448 patients with extraabdominal STS treated between August 2012 and December 2015, 52 cases involving 47 patients had locally recurrent STS. Twenty-eight of these patients were treated with TM-ILP prior to surgical resection (TM-ILP-group), and 24 were treated with standard therapy (without TM-ILP). The 3-year recurrence-free survival for the TM-ILP-group was estimated at 75% (95% confidence interval (CI), 71.5–78.5). Local recurrence-free survival in the standard group was significantly lower (LRFS: 43.4%, 95% CI 38.7–48.1, p = 0.026). Multivariable analysis revealed resection with negative margins, lower number of previous recurrences, and TM-ILP as positive predictors for recurrence-free survival. Conclusions TM-ILP and consecutive resection of residual tumor with negative resection margins significantly improves local recurrence-free survival for patients with a first local recurrence of high-grade STS in the extremities.

MBCL-10. LOCAL RECURRENCE AND SURVIVAL OUTCOMES OF MEDULLOBLASTOMA (MB) IN ADOLESCENT AND YOUNG ADULT PATIENTS (AYA)

OBJECTIVE The aim of this study is to evaluate the local recurrence-free survival (LRFS) and overall survival (OS) of MB in AYA patients at our institute. METHOD Patients 15–39 years old with MB who was sent for post-operative radiation therapy (RT) in 2007 - 2017 at our institute were included. Kaplan-Meier statistics were used to estimate the LRFS and OS. RESULTS Seven patients were included. The median age at RT was 18.3 years (16.7–28.6 years). Male was more common than female, 5 males vs. 2 females. NTR or GTR was achieved in 71.4% (5 in 7 patients). Only one patient had metastatic disease (M1) and received combined chemotherapy-RT. The rest 6 patients were received RT alone, all were M0. The median craniospinal irradiation (CSI) dose and total RT dose were 36Gy (23.4-46Gy) and 54Gy (54-56Gy), respectively. Five patients had available follow-up MRI brain. Local recurrence (LR) was found in one patient at 4.3 years after finished RT. Her initial treatment was subtotal resection (STR) followed by RT alone; CSI 36 Gy and posterior fossa boost to 55.8Gy. The 2-years and 5-years LRFS were 100% and 66.7%, respectively. Both 2-years and 5-years OS were 100%. The median follow-up time was 7.6 years (0.4–11.5 years). CONCLUSION Our study shows high 2-years LRFS and OS of post-operative RT alone in AYA MB. Combined chemotherapy-RT should be considered in STR or M1. More number of patients and molecular histopathology subtype reports are still needed to confirm this report.

Mucinous and Non-Mucinous Rectal Adenocarcinoma—Differences in Treatment Response to Preoperative Radiotherapy

There is a need to personalize the treatment for rectal cancer patients. The aim of this study was to analyze therapy response and prognosis after preoperative radiotherapy in rectal cancer patients with mucinous adenocarcinoma compared to those with non-mucinous adenocarcinoma. The study included retrospectively collected data from 433 patients, diagnosed with rectal cancer in the South East health care region in Sweden between 2004 and 2012. Patients with non-mucinous adenocarcinoma that received short-course radiotherapy before surgery had better overall survival, cancer specific survival, and disease-free survival, as well as distant- and local-recurrence-free survival (p = 0.003, p = 0.001, p = 0.002, p = 0.002, and p = 0.033, respectively) compared to the patients that received long-course radiotherapy with concomitant capecitabine. The results were still significant after adjusting for sex, age, stage, differentiation, and chemotherapy in the neoadjuvant and/or adjuvant setting, except for local-recurrence-free survival that was trending towards significance (p = 0.070). In patients with mucinous adenocarcinoma, no difference in survival was seen when comparing patients that had short-course radiotherapy and patients that had long-course radiotherapy. However, none of 18 patients with mucinous adenocarcinoma treated with long-course radiotherapy had local tumor progression, compared to 7% of 67 patients with non-mucinous adenocarcinoma. The results indicate that mucinous adenocarcinoma and non-mucinous adenocarcinoma may respond differently to radiotherapy.