Local Relapse-free Survival Research Articles

Sacral chordoma: a clinical review of 101 cases with 30-year experience in a single institution

BACKGROUNDLocal recurrence rates are high in sacral chordoma patients. Adjuvant radiotherapy may play a role in increasing local control. Patients with locally recurrent tumors continue to comprise a significant proportion of the sacral chordoma population and appear to have worse prognosis than those with primary tumors. High-quality studies comparing presentation and treatments for primary and first local recurrent sacral chordoma tumors are sparse. PURPOSETo determine: whether there is a difference in how primary and tumors at first recurrence present; the overall survival, local relapse-free survival, and distant relapse-free survival rates and prognostic factors for patients presenting with a primary tumor; overall survival, local relapse-free survival, and distant relapse-free survival rates and prognostic factors for patients presenting with a first local relapse; if there any differences in overall survival, local relapse-free survival, and distant relapse-free survival rates between patients presenting with a primary tumor and those with a first local relapse. STUDY DESIGNRetrospective case series. PATIENT SAMPLEOne hundred one sacral chordoma cases. OUTCOME MEASUREOverall survival, local relapse-free survival, and distant relapse-free survival rates. METHODSBetween 1978 and 2013, 131 patients with sacral chordoma were seen. Of them, 17 patients (13%) presented with a history of more than one local recurrence. One patient (1%) presented with multiple distant metastases. Ten patients (8%) had less than 36 months of follow-up and had no event (eg, death, local recurrence, or distant metastasis). A total of 102 patients met our inclusion criteria: patients with primary or first recurrent tumors, without metastatic disease, who underwent surgery and with at least 36 months of follow-up. One patient (1%) died intraoperatively; therefore, 101 patients were included in the present analysis. Cox proportional hazards regression analysis was performed for primary and local recurrent tumor separately and to compare primary and local recurrent tumors. RESULTSWe analyzed 73 primary and 28 first time recurrent sacral chordomas. Tumor size at presentation was different for primary and recurrent tumors (primary median size: 158 cm3, interquartile range [IQR]: 46–634; recurrent median size: 39 cm3, IQR: 14–175; p=.001). Overall survival at 5 and 10years for the primary tumors was 79% and 59%, respectively. Local relapse-free survival at 5years was 86%. For primary tumors, not receiving radiation was an independent predictor for worse local relapse-free survival (hazard ratio [HR]: 0.20; 95% confidence interval [CI]: 0.0043–0.90; p=.004) and increased tumor size was an independent predictor for both worse overall survival (HR: 1.68; 95% CI: 1.38–2.42; p=.004) and worse distant relapse-free survival (HR: 2.25; 95% CI: 1.47–3.44; p<.001). For recurrent tumors, the 5- and 10-year overall survival was 65% and 40%, respectively. Local relapse-free survival at 5years was 79% for recurrent tumors. On bivariate analysis, increased tumor size was a significant predictor for worse survival (LR median: 338 mL; IQR: 218–503 mL; no LR median: 26 mL; IQR: 9–71 mL). A trend was seen toward better distant relapse survival for tumors presenting as a primary tumor (HR: 0.51; 95% CI: 0.25–1.06; p=.072). CONCLUSIONUsing a combination of surgical resection and adjuvant radiotherapy allowed us to obtain a good overall survival, local relapse-free survival, and distant relapse-free survival in patients presenting with either a primary tumor or with a first time local recurrent tumor.

Reirradiation for isolated local recurrence of prostate cancer: Mono-institutional series of 64 patients treated with salvage stereotactic body radiotherapy (SBRT).

To evaluate high-precision external beam reirradiation (re-EBRT) for local relapse of prostate cancer (PCa) after radiotherapy. This retrospective study included patients with biochemical failure and evidence of isolated local recurrence of PCa after radical/salvage EBRT or brachytherapy that received salvage stereotactic body radiation therapy (SBRT, re-EBRT). Biopsy was not mandatory if all diagnostic elements were univocal (prostate specific antigen evolution, choline-positron emission tomography or magnetic resonance imaging). Salvage SBRT (re-EBRT) was delivered with image-guided radiation therapy (RapidArc®, VERO® and CyberKnife®). Data of 64 patients were included, median age at salvage SBRT was 73.2 years, median pre-salvage SBRT prostate specific antigen was 3.89 ng ml-1 . Median total dose was 30 Gy in five fractions, biologically effective dose (BED) of 150 Gy. One acute G3 genitourinary event and one late G3 genitourinary event were observed. No G ≥ 3 bowel toxicity was registered. At the median follow-up of 26.1 months, tumor progression was observed in 41 patients (64%). 18 patients (28%) experienced local relapse. 2-year local control, biochemical and clinical relapse free survival rates were 75, 40 and 53%, respectively. With BED ≥130 Gy 1-year biochemical and clinical progression-free survival rate were 85 and 90%, respectively. Salvage SBRT (re-EBRT) for isolated local PCa recurrence is a safe, feasible and noninvasive salvage treatment. Further investigation is warranted to define the optimal patient selection, dose and volume parameters. Salvage SBRT reirradiation for the locally recurrent PCa offer a satisfactory tumor control and excellent toxicity profile, if BED ≥130 Gy is administered.

A comparison of neoadjuvant chemotherapy with gemcitabine versus docetaxel plus cisplatin in locoregionally advanced nasopharyngeal carcinoma: a propensity score matching analysis.

PurposeTo compare the efficacy and safety of neoadjuvant chemotherapy (NACT) with gemcitabine (GEM) vs docetaxel plus cisplatin (CDDP) in locoregionally advanced nasopharyngeal carcinoma (NPC).MethodsA total of 222 patients with locoregionally advanced NPC between February 2012 and May 2014 in our hospital who received NACT with GEM or docetaxel plus CDDP combined with concurrent chemoradiotherapy (CCRT) were retrospectively analyzed. Fifty-two patients treated with GEM plus CDDP (GP) combined with CCRT were matched with 52 patients who received docetaxel plus CDDP (TP) combined with CCRT.ResultsWith a median follow-up time of 60 months (range, 14–72 months), the 5-year overall survival, progression-free survival (PFS), local relapse-free survival and distant metastasis-free survival (DMFS) rates were 78.8%, 66.0%, 81.0% and 75.9%, respectively, in the GP group and 79.4%, 60.5%, 79.6% and 73.6%, respectively, in the TP group. No statistically significant survival differences were found between the two groups. In multivariate analysis, T3–4 and N2–3 were prognostic factors for poor 5-year PFS and DMFS (all P-values <0.05). Patients in the TP group experienced less grade 3–4 thrombocytopenia but more grade 3–4 leucopenia and neutropenia than those in the GP group (all P-values <0.05). There were no significant differences between the two groups in other toxicities (all P-values >0.05).ConclusionNACT with GP or TP regimen achieved comparable clinical outcome with acceptable toxicities. Both regimens might be a treatment option for patients with locoregionally advanced NPC.

Prognostic value of gross tumor regression and plasma Epstein Barr Virus DNA levels at the end of intensity-modulated radiation therapy in patients with nasopharyngeal carcinoma

PurposeTo assess gross tumor regression and plasma Epstein–Barr virus (EBV)-DNA levels at the end of intensity-modulated radiation therapy (IMRT) and its prognostic impact on patients with nasopharyngeal carcinoma (NPC). Participants and MethodsIn total, 397 patients with non-metastatic, histologically confirmed NPC were retrospectively examined. All patients underwent magnetic resonance imaging of the nasopharynx and neck, and plasma EBV DNA assays before treatment and at the end of IMRT. ResultsThe estimated 5-year loco-regional, local and regional relapse-free survival rates for patients with complete response (CR) and non-CR of the total tumor, primary tumor and metastatic lymph nodes at the end of IMRT were 94.9% vs. 85.8%, 96.6% vs. 87.3%, and 98.7% vs. 89.8%, respectively (P < 0.05). The estimated 5-year loco-regional relapse-free survival (LRRFS) rates for patients with persistent tumor with and without boost irradiation were 95.3% vs. 83%, respectively (P = 0.034). The estimated 5-year overall survival (OS), failure-free survival (FFS) and distant metastasis-free survival (DMFS) rates for patients with negative and positive plasma EBV DNA at the end of IMRT were 83.1% vs. 50.3%, 81.5% vs. 49.3%, and 87.6% vs. 61.5%, respectively (P < 0.001). Multivariate analyses indicated that regression of the total tumor and boost irradiation was an independent predictor of LRRFS, and plasma EBV DNA levels were independent predictors of OS, FFS and DMFS. ConclusionsGross tumor regression and plasma EBV DNA levels at the end of IMRT served as predictors of poor prognosis for patients with NPC. The patients with persistent tumor and/or positive plasma EBV DNA might require timely strengthening treatment.

Randomized phase III study to evaluate the value of omission of prophylactic neck dissection for stage I/II tongue cancer: Japan Clinical Oncology Group study (JCOG1601, RESPOND)

For stage I/II tongue cancer patients, it is controversial whether prophylactic neck dissection should be performed with partial glossectomy. Based on the evidence of the primary tumor's depth of invasion as a predictive factor of occult lymph node metastases and a prognostic factor of disease-free survival, randomized phase III trial was initiated in November 2017 to evaluate the omission value for prophylactic neck dissection for stage I/II tongue cancer with 3-10 mm of depth of invasion. In 5 years, 440 patients will be accrued from 28 institutions. The primary end point of the study is the overall survival, whereas the secondary end points are relapse-free survival, local relapse-free survival, proportion of unresectable relapse and of cervical lymph node relapse, post-operative function (paralysis of the accessory and facial nerves and subjective symptoms) and adverse events. This trial has been registered with the UMIN Clinical Trials Registry (registration number: UMIN000030098; http://www.umin.ac.jp/ctr/index.htm).

Serum MicroRNAs in Predicting the Efficacy of Chemoradiotherapy for Locally Advanced Esophageal Squamous Carcinoma

Chemoradiotherapy is the main treatment for locally advanced esophageal squamous cell cancer, yet the molecular mechanisms underlying its response and outcomes remain elusive. MicroRNAs (miRNAs) are closely related with tumor genesis, diagnosis and prognosis. Serum miRNAs, steadily expressed and easily to test, are expected to be ideal markers in predicting chemoradiotherapeutic efficacy. Our study is to explore whether serum miRNAs can predict the clinical outcomes for locally advanced esophageal squamous cell carcinoma patients. Patients with primary pathologically diagnosed esophageal squamous cell carcinoma, with disease of stage T3-4/N1, M0-M1a, who received chemoradiotherapy were enrolled. Before starting the treatment, patients received a baseline blood draw for miRNA expression profiling. Tumor assessment and follow up were performed every 3 months. According to overall survival time and local regional relapse free survival time, patients were divided into good and poor outcome groups. We selected 15 patients in each group （Group A with good prognosis, Group B with poor prognosis) and their characteristics were without significant differences from chi-square test. We surveyed the expression of 769 miRNAs of these 30 patients, using ABI TaqMan miRNA chip method. MiRNAs with RQ value≤0.5 or ≥2 and P value ≤0.05 were defined to be associated with therapeutic efficacy. From August 2007 to December 2010, 30 patients were selected for miRNA profiling. The gender(P=0.543), age (P=0.477), location(P=0.519) , and stage(P=0.879) were comparable between the 15 patients from Group A and the 15 patients from Group B. The median survival time of the two group were with significant differences(P<0.001). High level of miR-624, miR-338 and miR-196 were observed in Group A compared with Group B. The RQ values were 3.6269、4.3804 and 3.6661, respectively and P values were 0.0499,0.0191, and 0.0129，respectively. Moreover, log-rank test indicated that patients with high levels of miR-328 (P=0.019) and miR-374a(P=0.044) had more favorable overall survival compared with patients with low levels. Another result from log-rank test is that patients with high levels of miR-323a(P=0.004) and low levels of miR-222(P=0.024) had poor locoregional relapse free survival. We developed a prognostic serum miR-328, miR-374a, miR-323a, miR-222, miR-624, miR-338 and miR-196 signature in an independent dataset of patients with locally advanced esophageal squamous cell carcinoma who received chemoradiotherapy. These preliminary results indicated that miRNAs might serve as promising molecular prognostic markers and new therapeutic targets for esophageal carcinoma.

Long-Term Therapeutic Outcome and Prognostic Factors for Patients with Nasopharyngeal Carcinoma Receiving Intensity-Modulated Radiation Therapy: An Analysis of 608 Patients from Low-Endemic Regions of China

This study aimed at evaluating the long-term outcome and prognostic factors of patients with nasopharyngeal carcinoma (NPC) from low-endemic regions of China who received definitive intensity-modulated radiotherapy (IMRT). Clinical data from 608 patients with newly-diagnosed non-metastatic NPC who have received initial treatment at our cancer center from January, 2008 to December, 2013 were retrospectively reviewed. All patients received definitive IMRT, and 87.7% received platinum-based chemotherapy. Survival data were analyzed by Kaplan-Meier method, and Log-rank test and Cox regression analyses were performed to determine the prognostic factors. The median follow-up duration was 51 months (follow-up rate, 98.5%; range, 10-106 months) for the entire cohort. The 5-year overall survival (OS) rate was 79.6%. The 5-year local relapse-free survival rate (LRFS), region relapse-free survival rate (RRFS), distant metastasis-free survival rate (DMFS) and progression-free survival rate (PFS) were 92.4%, 93.4%, 79.2% and 74.2%, respectively. A total of 153 patients have experienced treatment failure, with distant metastasis as the primary cause in 77.1% (118/153). Patients with T4 or N3 diseases had much poorer prognosis than other subcategories. The 5-year OS rates for patients with T1-T4 diseases were 87.9%, 82.1%, 83.3% and 69.2%, respectively. The 5-year OS rates for patients with N1-N3 were Stage T4 and N3 were closely associated with distant metastasis, with metastatic rate of 29.2% and 45.5%, respectively. Multivariate analysis revealed that prognosis was primarily influenced by T stage, N stage and clinical stage, with N stage and T stage acting as the independent prognostic factor for OS, PFS, RRFS and DMFS, and clinical stage for OS, PFS, LRFS and DMFS. IMRT provides patients with non-metastatic NPC with satisfactory long-term survival. T stage, N stage and clinical stage are important prognostic factors for NPC patients. Patients with T4 or N3 diseases have significantly increased distant metastatic rates and poor survival.

Long-term Follow-up Results of CT-guided Daily Adaptive Radiation Therapy for Localized Prostate Cancer.

To examine whether CT-guided daily adaptive radiation therapy (ART) can be safely administered against localized prostate cancer. Twenty-six patients with localized prostate adenocarcinoma were irradiated through opposed AP/PA fields up to 46 Gy, then CT-guided daily ART was performed through opposed lateral fields until 76 Gy at 2 Gy/fraction. Biochemical relapse-free survival was 89% at 3 years and 85% at 5 years and 76% at 7 years after ART, respectively. The 3-, 5- and 7-year local relapse-free survival rates were 100%, 100% and 95%, respectively. The 5-year incidence rates of grade 1 and 2 late gastrointestinal adverse events were 15.4% (n=4) and 3.8% (n=1), respectively, and those of grade 1 and 2 late genitourinary adverse events were 3.8% (n=1) and 0% (n=0), respectively. CT-guided daily ART was well tolerated and suggested a good long-term tumor control with minimal adverse events.

Single fraction of accelerated partial breast irradiation in the elderly: early clinical outcome

BackgroundTo analyze the clinical outcome of elderly women with early breast cancer who underwent accelerated partial breast irradiation (APBI) based on a post-operative single fraction of multicatheter interstitial high dose–rate brachytherapy (MIB).MethodsA single institution retrospective cohort study was performed focusing on elderly patients (≥ 65 years old) presenting a low-risk breast carcinoma treated by lumpectomy plus axillary evaluation followed by MIB. A single fraction of 16 Gy was prescribed on the 100% isodose. Clinical outcome at 3 years was reported based on local relapse free survival (3-y LRFS), specific survival (SS) and overall survival (OS). Acute (< 180 days after APBI) and late toxicity were evaluated. Cosmetic results were clinically evaluated by the physician.ResultsBetween January 2012 and August 2015, 48 women (51 lesions) were treated. Median age was 77.7 years (range: 65–92) with a median tumor size of 12 mm (range: 3–32). Five patients (pts) presented an axillary lymph node involvement (4 Nmic, 1 N1). Invasive ductal carcinoma was the most frequent histology type (86.3%). With a median follow–up of 40 months (range: 36–42), no local relapse occurred while 1 pt. developed axillary relapse (2.1%). The 3-y LRFS, SS and OS rates were 100%, 100% and 93.1% respectively. Forty-five acute events were remained. The most frequent acute toxicity was grade (G) 1 hyperpigmentation (26.7%), 3 pts. (6.3%) presented G3 acute toxicity (2 breast hematomas, 1 breast abscess). No ≥ G3 late toxicity was observed while 15 late toxicities occurred (G1: 13 events - 86.7%) mainly breast fibrosis). The rate of excellent cosmetic outcome was 76.4%.ConclusionWe reported promising and encouraging clinical outcome of a post-operative single fraction of MIB ABPI in the elderly. This approach leads to consider a sfAPBI as an attractive alternative to intra-operative radiation therapy while all the patients will be good candidates for APBI in regards to the post-operative pathological report. More mature results (number of patients and follow-up) are needed.

A matched cohort study of radio-chemotherapy versus radiotherapy alone in soft tissue sarcoma patients.

Adjuvant radiotherapy is the standard postoperative treatment after conservative surgery in high risk soft tissue sarcoma. The role of adjuvant chemotherapy is still debated. Therefore, a matched cohort analysis was performed in high risk soft tissue patients to analyse differences in terms of clinical outcome and toxicity between patients treated with concomitant radio-chemotherapy (RTCT) and radiotherapy (RT) alone. For each patient in RT group was selected a patient in the RTCT group matching for age, T stage and grading. Acute and late toxicity were recorded, overall survival, recurrence free survival and distant metastases free survival were analysed and compared between the two groups. Ninety patients were selected, half of patients underwent radio-chemotherapy and half received radiotherapy alone. During the treatment Grade 3 dermatitis was recorded in 15 (16.7%) patients, 6 (6.7%) patients associated chemotherapy and during follow up 12 (13.3%) patients developed grade 2 late fibrosis, 3 (3.3%) joint stiffness and 1 (1.1%) patient experienced a bone fracture. There were no differences in the rate of acute and late toxicity between RTCT and RT alone group. Nineteen (21.1%) patients developed local recurrence, overall 5-year local relapse free survival was 83%. There were no differences between the two groups. 29 patients developed distant metastases, 14 (15.6%) patients in the RTCT group and 15 (16.7%) patients in the RT group. The 5-year distant metastases free survival was 67%. Age >65 years was the only independent factor affecting distant recurrence (HR=5.7, 95% CI 2.7-11.9; p=0.001). At the time of analysis 15 (16.7%) patients were dead, 6 (6.7%) patients in the RTCT group and 9 (10%) patients in the RT group. 5-years overall survival was: 88%. At multivariate analysis age >65 years was an independent prognostic factor of overall survival (HR=3.7, 95% CI 1.2-12.1, p = 0.037). Prospective randomized studies with large size population and with subgroup analysis for histological subtypes are necessary to clarify the role of adjuvant chemotherapy in soft tissue sarcoma patients. Tailored treatment has to be considered in elderly soft tissue patients to guarantee a better outcome in this high risk and fragile population.

MRI of Extramural Venous Invasion in Locally Advanced Rectal Cancer: Relationship to Tumor Recurrence and Overall Survival.

Purpose To study the relationship between MRI-defined extramural venous invasion (EMVI) prior to treatment and prognosis in patients with locally advanced rectal cancer treated with neoadjuvant chemotherapy-radiation therapy followed by surgery. Materials and Methods This retrospective study included 517 patients with locally advanced rectal cancer evaluated from August 2008 to December 2014. Baseline and posttherapy MRI and follow-up data were retrieved for all patients. After training by using 328 cases with pathologic evaluation of EMVI after therapy, radiologists evaluated baseline MRI for EMVI status in addition to tumor size and characteristics, nodal status, and invasion of the mesorectal fascia. Reader reproducibility was determined by using κ coefficient. Kaplan-Meier curves and adjusted Cox models were used to determine the relationship of baseline MRI parameters to overall survival, metastasis-free survival, and local relapse-free survival. Results Among 517 patients, 335 (64.8%) were men; the mean age was 55.6 years ± 11.5 (standard deviation). At baseline, radiologists identified 259 of 517 (50%) patients with EMVI by using MRI. In adjusted analysis, EMVI and mesorectal fascial invasion at baseline MRI were predictors of metastasis-free survival (hazard ratio, 0.3 and 0.6; P ˂ .01 and P ˂ .02, respectively) and overall survival (hazard ratio, 0.5 and 0.5; P = .01 and P = .02, respectively). EMVI was the only factor associated with local relapse-free survival (hazard ratio, 0.3; P ˂ .01). The κ coefficient for determination of EMVI was 0.80. Conclusion Extramural venous invasion (EMVI) can be reliably evaluated with MRI. The presence of EMVI was associated with greater risk of local and distant tumor recurrence and overall death in patients with locally advanced rectal cancer treated with neoadjuvant chemotherapy-radiation therapy. © RSNA, 2018 Online supplemental material is available for this article.

Validation and suggestion of eighth T classifications of the UICC/AJCC staging system for nasopharyngeal carcinoma patients: a retrospective analysis.

With the aim to validate the applicability of the eighth T classifications of AJCC/UICC staging system for nasopharyngeal carcinoma patients. We compare the seventh and eighth T classifications of the UICC/AJCC staging system in 382 newly diagnosed nasopharyngeal carcinoma patients without cervical lymph node metastasis who were staged with magnetic resonance imaging and treated by intensity-modulated radiotherapy. Univariate analysis was performed using the log-rank test and multivariate analyses with the Cox proportional hazards model were used to evaluate the prognostic values between adjacent stage categories. The Akaike information criterion and Harrell's concordance index were applied to compare the two systems. The median follow-up time was 61.1 months. For local relapse-free survival and distant metastasis failure-free survival, the eighth editions had superior prognostic value to the seventh edition. The Akaike information criterion value was smaller and Harrell's concordance index value was larger for the eighth edition compared with the seventh edition staging system. Our research also found that the difference in overall survival, local relapse-free survival and distant metastasis failure-free survival rates between T1 and T2 patients was not significant according to the eighth edition of the UICC/AJCC staging system, indicating that the discrimination among T1-2 patients was diminished. Intensity-modulated radiotherapy with elective neck irradiation provides excellent local-regional control for nasopharyngeal carcinoma patients and the eighth T classification seems to be superior to the seventh T classification. Since local control has improved in the modern era, the study considered that the staging system could be further improved and simplified by downstaging the current T2 classification patients to T1 with modern treatment. Researchers are attempting to incorporate individualized prognostic factors, such as Epstein-Barr virus DNA, into nomogram.

Concurrent Daily Cisplatin and High-Dose Radiation Therapy in Patients With Stage III Non-Small Cell Lung Cancer

The purpose of this study was to determine survival, local and distant control, toxicity, and prognostic factors in patients with stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiation therapy (CCRT). Consecutive patients with stage IIIA and IIIB NSCLC (N=154) staged with 18F-fluorodeoxyglucose positron emission tomography/computed tomography were retrospectively selected (2005-2015). CCRT consisted of daily low-dose cisplatin (6mg/m2) combined with 24 fractions of 2.75Gy to a total dose of 66Gy. During a median follow-up period of 22months (range, 1-92months) the median overall survival was 36months. The 1-, 2-, 3-, and 5-year survival rates were 79% (95% confidence interval [CI], 73%-86%), 61% (95% CI, 54%-70%), 52% (95% CI, 43%-60%), and 40% (95% CI, 31%-51%), respectively. The local relapse-free survival at 5years was 55% (95% CI, 44%-69%). Metastasis-free survival at 5years was 53% (95% CI, 44%-65%). The incidence of severe gastrointestinal disorders (grade 3-5) was 11%, among which grade 3 radiation esophagitis was 8.4%. The incidence of severe respiratory, thoracic, and mediastinal disorders (grade 3-5) was 8.4%, among which grade 3 radiation pneumonitis was 1.3%. Predictors of overall survival were lymph node gross tumor volume (GTV) (hazard ratio [HR], 1.007; 95% CI, 1.000-1.012) and sex (HR, 0.500; 95% CI, 0.320-0.870) in favor of women. Although lymph node GTV was a predictor of treatment toxicity (HR, 1.010; 95% CI, 1.000-1.013), tumor GTV was the predictor for distant metastasis during follow-up (HR, 1.002; 95% CI, 1.001-1.003). CCRT with daily low-dose cisplatin for locally advanced stage III NSCLC resulted in promising overall survival (3-year survival rate of 52% and 5-year survival rate of 40%) with low toxicity. Lymph node GTV, tumor GTV, andsex were predictors of overall survival, treatment toxicity, and distant metastasis.

Breast-conserving therapy for primary Ductal Carcinoma in Situ in The Netherlands: A multi-center study and population-based analysis

ObjectiveThe aim of this study was to analyse the efficacy of breast-conserving therapy (BCT) for women with primary DCIS in a population-based setting. MethodsData were used from five Radiotherapy centres in The Netherlands from 2000 to 2010, all treated with BCT. Of all the cases, 59.2% received a boost of radiotherapy after their whole breast irradiation (WBI), irrespective of margin status. ResultsA total of 1248 cases with primary DCIS were analysed. The 10-years LRFS was 92.9%. Age ≤50 years and a positive margin were significantly related to local relapse free survival (LRFS). Having a boost had no impact on LRFS, showing a nearly equal recurrence pattern in patients with and without a boost. Separate analyses were done on patients who had received and not received a boost of radiotherapy after WBI. We noted 9.1% contra-lateral breast tumours. The 10-years disease specific survival (DSS) rate was 99.0%. ConclusionsDCIS of the breast and treated with BCT results in excellent LRFS and DSS. Primary surgical lumpectomy with negative margins followed by WBI seems to be the treatment of choice in DCIS treated with BCS with respect to IBTR.

The detrimental effects of radiotherapy interruption on local control after concurrent chemoradiotherapy for advanced T-stage nasopharyngeal carcinoma: an observational, prospective analysis

BackgroundPrevious studies have reported radiotherapy interruption (RTI) is associated with poor local control in two-dimensional radiotherapy (2DRT) era. However, it remains unclear whether RTI still affects local control for advanced T stage (T3–4) in the intensity-modulated radiation therapy (IMRT) era. We aim to evaluate whether RTI affects local control for T3–4 NPC treated with definitive IMRT.MethodsIn this observational prospective study, 447 T3–4 NPC patients treated with IMRT plus concurrent chemotherapy were included. All patients completed the planned radiotherapy course, and RTI was defined as the actual time taken to finish the prescribed course of radiotherapy minus the planned radiotherapy time. Receiver operating characteristic (ROC) curve was used for determined the cutoff point of RTI. The effects of RTI on local control were analyzed in multivariate analysis.ResultsAt 5 years, the local relapse-free survival (LRFS) and overall survival (OS) rates were 93.7 and 85.7%, respectively. The cutoff RTI for LRFS was 5.5 days by ROC curve. Compared to patients with RTI > 5 days, patients with RTI ≤ 5 days had a significantly lower rate of LRFS (97% vs. 83%; P < 0.001). In multivariate analysis, RTI was a risk factor independently associated with LRFS (HR = 9.64, 95% CI, 4.10–22.65), but not for OS (HR = 1.09, 95% CI, 0.84–1.64).ConclusionsThe current analysis demonstrates a significant correlation between prolonged RTI and local control in NPC, even when concurrent chemotherapy is used. We consider that attention to RTI seems to be warranted for patients with advanced T-stage NPC in the era of IMRT.

Technical feasibility of endoscopic submucosal dissection for local failure after chemoradiotherapy or radiotherapy for esophageal squamous cell carcinoma

Salvage endoscopic submucosal dissection (ESD) after chemoradiotherapy can be technically difficult as a result of radiation-induced fibrosis. We aimed to evaluate the technical feasibility of ESD for local failure after chemoradiotherapy for esophageal squamous cell carcinoma (ESCC) and for other primary lesions within the irradiation field. Consecutive patients treated with ESD for superficial ESCC between December 2009 and May 2017 were investigated retrospectively and stratified into group A (33 patients, 35 lesions; local failure at the primary site after chemoradiotherapy), group B (25 patients, 34 lesions; second primary lesions within the irradiation field), and group C (550 patients, 596 lesions; radiotherapy-naïve superficial ESCC). We evaluated procedural success rate, en bloc resection rate, 1-year local relapse-free survival (LRFS) rate, procedure time, and incidence of major adverse events. The rates of procedural success and en bloc resection, respectively, were significantly lower in group A (89%, 86%) than in groups B (100%, 100%) and C (100%, 98%). The 1-year LRFS rates were 86%, 100%, and 99% in groups A, B, and C, respectively, and significantly lower in group A than in group C. Serious adverse events including perforation were not observed in groups A and B; perforation occurred only in group C (2.8%). ESD is technically feasible in patients with local failure, especially as initial salvage treatment and as treatment for second primary lesions within the irradiation field.

HERG1 channel expression associates with molecular subtypes and prognosis in breast cancer

BackgroundBreast cancer (BC) is the most frequent malignancy among females worldwide. Despite several efforts and improvements in early diagnosis and treatment, there are still tumors characterized by an aggressive behavior due to unfavorable biology, thus quite difficult to treat. In this view, searching for novel potential biomarkers is mandatory. Among them, in the recent years data have been gathered addressing ion channel as important players in oncology.MethodsA retrospective pilot study was performed on 40 BC samples by means of immunohistochemistry in order to evaluate hERG1 potassium channels expression in BC.ResultsWe provide evidence that hERG1 is expressed in all the BC samples analyzed. hERG1 expression was significantly associated with molecular subtype with the highest expression in Luminal A and the lowest in basal-like tumors (p = 0.001), tumor grading (the highest hERG1 expression in well-moderate differentiated tumors, p = 0.020), estrogen receptors (high hERG1 expression in ER-positive samples, p = 0.008) and Ki67 proliferative index (high hERG1 scoring in samples with low proliferative index, p = 0.038). Also, a p value close to significance was noticed for the association between hERG1 and HER2 expression (p = 0.079). At the survival analysis, patients with high hERG1 expression turned out to have a longer progression-free survival, although statistical significance was not reached (p = 0.195). The same trend was observed analyzing local relapse free-survival (LRFS) and metastases-free survival (MFS): patients with higher hERG1 scoring had longer LRFS and MFS (p = 0.124 and p = 0.071, respectively).ConclusionsThe results of this pilot study provide the first evidence that the hERG1 protein is expressed in primary BC, and its expression associates with molecular subtype. hERG1 apparently behaves as a protective factor, since it contributes to identify a subset of patients with better outcome. Overall, these data suggest that hERG1 might be an additional tool for the management of BC, nevertheless further investigations are warranted to better clarify hERG1 role and clinical usefulness in BC.

30 Gy single dose stereotactic body radiation therapy (SBRT): Report on outcome in a large series of patients with lung oligometastatic disease

ObjectivesTo evaluate the local control (LC) and long term adverse effects in a series of patients with lung metastases who received 30 Gy in single dose with stereotactic technique. Materials and MethodsBetween December 2008 and April 2016, a total of 166 lung metastases in 129 patients affected by oligometastatic disease were treated at our Institution with stereotactic body radiotherapy (SBRT). Mainly, the primary tumors were non small-cell lung cancer and colorectal cancer (45.2% and 28.8%, respectively). Prognostic factors were also assessed. ResultsThe median follow-up was 38 months. Local progression occurred in 24 (14.4%) lesions in 21 patients. Intra-thoracic progression (new lung lesions or thoracic lymph node metastases) occurred in 59 (45.7%) patients. Forty-five (34.8%) patients had distant progression after a median time of 14 months. The 3- and 5-years local relapse-free survival (LPFS) were 80.1% and 79.2% (median not reached), respectively. One-hundred forty-eight patients were evaluated for late toxicity (follow-up >6 months): 51 (34.4%) patients had grade ≤2 fibrosis, 11 (7.4%) patients experienced grade 3 fibrosis. Two (1.3%) cases of rib fracture occurred. One case of toxic death (grade 5) has been reported. Median OS was 39 months. At the univariate analysis, lesion diameter ≤18 mm correlated significantly with a longer LPFS (p = 0.001). At the multivariate analysis, lesion diameter <18 mm was predictive for longer LPFS (p = 0.006). Also, oligometastases from primary colorectal cancer was a significant predictive factor for worse LPFS (p = 0.041) and progression-free survival (p = 0.04). ConclusionsTo our knowledge, the current study represents the largest series on the use of SBRT 30 Gy single dose for lung metastases. Our results confirm the effectiveness and safety of this schedule administered in selected oligometastatic patients. Further prospective series could better validate these results.

Localized Myxofibrosarcomas: Roles of Surgical Margins and Adjuvant Radiation Therapy

The objective of this study was to describe the outcome and prognostic factors for adults treated for localized myxofibrosarcoma. We conducted a retrospective multicenter study of 425 nonmetastatic patients who underwent surgery between January 1996 and December 2015 in FrenchNational Group and were enrolled in the Conticabase. Pathologic diagnosis was systematically reviewed by expert pathologists. The endpoints were relapse-free and metastasis-free survival. Log-rank tests and Cox models have been used to identified prognostic factors. Median age was 66years; 53% were males; 85% of cases occurred in limbs or superficial trunk; median size was 60mm; 47% and 39% were grades 2 and 3, respectively; 66% had R0 resection and 34% R1 resection. Adjuvant radiation therapy was given to 65% of patients, neoadjuvant radiation therapy to 3%, neoadjuvant chemotherapy to 7%, and adjuvant chemotherapy to 13%. The median follow-up was 51months. The 5-year local relapse-free survival was 67%; independent prognostic factors for local relapse were R1 resection (hazard ratio [HR]=1.26; P=.001) and adjuvant radiation therapy (HR=0.35; P=.0001) (ie, R1 resection and no adjuvant radiation therapy increase the hazard ratio). In stratified analysis, adjuvant radiation therapy was beneficial after R0 resection (P=.0020) and after R1 resection (P=.0001). The 5-year overall survival was 80%. The 5-year metastasis-free survival was 83%. Independent prognostic factorsfor metastatic relapse were grade 3 disease (HR=1.975; P=.0001) and tumor size (HR=1.006; P=.001). This large series of myxofibrosarcoma confirms the high rate of local relapse. Combination of R0 resection and adjuvant radiation therapy provided the best local control. In parallel with an increasing rate of R0 resection and adjuvant radiation therapy, we observed a constant improvement in both metastatic and local relapse-free survival during the study.

Intensity-modulated radiotherapy combined with endostar has similar efficacy but weaker acute adverse reactions than IMRT combined with chemotherapy in the treatment of locally advanced nasopharyngeal carcinoma.

The present study is to compare the efficacy and adverse effects of intensity-modulated radiotherapy (IMRT) combined with endostar and IMRT combined with concurrent chemotherapy on locally advanced nasopharyngeal carcinoma (NPC).A total of 23 patients with stage III-IVa NPC were included in the present study, and randomly divided into experimental group (10 cases treated with IMRT + endostar) and control group (13 cases treated with IMRT + chemotherapy of cis-dichlorodiamineplatinum). Endostar was intravenously administered from the first day of IMRT. The patients received a total of 2 cycles (14 days each) separating by a 7-day interval.IMRT combined with endostar did not have significantly different recent efficacy compared with IMRT combined with chemotherapy. IMRT combined with endostar and IMRT combined with chemotherapy had 2-year overall survival (OS) rates of 100.0% and 69.6%, respectively, without significant difference between each other (χ2 = 1.446, P = .299). The 2-year local relapse-free survival (LRFS) of the 2 groups were 100.0% and 81.3%, respectively, without significant difference between each other (χ2 = 1.000, P = .317). The 2-year distant metastasis-free survival (DMFS) of the 2 groups were 100.0% and 73.5% (χ2 = 1.591, P = .207), respectively. The 2-year progression-free survival (PFS) of the 2 groups were 100.0% and 67.3% (χ2 = 2.164, P = .141), respectively. However, the cumulative survival curves of OS, LRFS, DMFS, and PFS were separated between the 2 groups. The result that IMRT combined with endostar did not have significantly different long-term efficacy than IMRT combined with chemotherapy probably due to limited case number and short follow-up time. IMRT combined with endostar resulted in significantly lower grades of leucopenia, nausea/vomiting, weight loss, and oral mucositis compared with IMRT combined with chemotherapy. The grades of late adverse reactions of IMRT combined with endostar were not different from those of IMRT combined with chemotherapy.The present study demonstrates that, compared with IMRT combined with chemotherapy, IMRT combined with endostar has similar efficacy in the treatment of locally advanced NPC, but significantly weaker acute adverse reactions, which improve the life quality of NPC patients.