Local Relapse-free Survival Research Articles

Comparison of the seventh and eighth editions of the UICC/AJCC staging system for nasopharyngeal carcinoma: analysis of 1317 patients treated with intensity-modulated radiotherapy at two centers

BackgroundIn the intensity-modulated radiotherapy (IMRT) era, great improvement has been made in survival of nasopharyngeal carcinoma (NPC). The 7th edition of the International Union against Cancer/American Joint Committee on Cancer (UICC/AJCC) staging system seems “outdated ” as it mainly based on the study in 2D/3D era, and thus the 8th edition has made some amendments according to recent studies. We aimed to compare and evaluate these two editions of staging system for NPC in patients treated with intensity-modulated radiotherapy.MethodsA total of 1317 patients with biopsy-proven, non-metastatic NPC treated with IMRT between 2009 and 2014 at two institutions were retrospectively assessed. All patients were assessed by magnetic resonance imaging and restaged according to the 7th and 8th editions. Prognostic factors for local relapse-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) were assessed and compared using the Kaplan-Meier method and log-rank test. The Cox proportional hazards model was also used to calculate the hazard ratio (HR).ResultsIn both 7th and 8th edition, insignificant difference could be observed between T2 and T3 disease, T2 and T4 disease (all P > 0.05) for LRFS, while the difference of LRFS between T3 and T4 disease was significant in the previous edition (P = 0.001) but insignificant (P = 0.279) after revision. For OS, highly similar survival curve could be seen between T2 and T3 disease in both edition (all P > 0.1). DMFS and OS were not significantly different between N3a and N1-3b categories of the 7th edition (all P > 0.05). In contrast, obvious segregation was observed between N3 and the other N categories after the revision and combination in the 8th edition (all P < 0.05). DFS and OS were not significantly different between stage IVA and IVB of the 7th edition (P = 0.057 and P = 0.365, respectively); therefore, combining these stages in the 8th edition was reasonable.ConclusionThe overall stages and N categories of the 8th edition of the UICC/AJCC staging system provide better segregation of survival outcomes than the 7th edition. The 8th edition is also more clinically applicable as it has reduced ambiguity and revised out-of-date definitions. However, the T categories need further optimizing as the 8th edition failed to solve the problem of similar survival between adjacent T-classification, which has been exited since 7th edition.

Oncological outcomes of robotic-assisted laparoscopic versus open lateral lymph node dissection for locally advanced low rectal cancer.

The long-term outcomes of robotic-assisted laparoscopic lateral lymph node dissection (RALLD) have not been fully investigated. This study aimed to assess the oncological and long-term outcomes of RALLD for rectal cancer through comparison with those of open lateral lymph node dissection (OLLD) in a retrospective study. Between September 2002 and October 2014, the medical data of 426 patients who underwent total mesorectal excision with lateral lymph node dissection for primary rectal cancer were collected. Of these, 115 patients were excluded after data collection (stage IV, n = 61; total pelvic exenteration, n = 31; multiple cancer, n = 20; conventional laparoscopic surgery, n = 3). Before matching, 311 patients with clinical stage II/III were analyzed. Using exact matching, patients were stratified into RALLD (n = 78) and OLLD (n = 78) groups. Pathological findings and long-term outcomes were compared between the groups. The pathological stage and number of harvested lymph nodes showed no significant differences between the groups. The rate of positive resection margin in the RALLD group tended to be lower compared with that of the OLLD group (p = 0.059). The median follow-up duration was 54.0months in 156 patients. The 5-year overall survival rate was 95.4 and 87.8% in the RALLD and OLLD groups, respectively (p = 0.106). The 5-year relapse-free survival rate was 79.1 and 69.9% in the RALLD and OLLD groups, respectively (p = 0.157). The 5-year local relapse-free survival rate was 98.6 and 90.9% in the RALLD and OLLD groups, respectively (p = 0.029). The short- and long-term outcomes indicated that RALLD may be a useful modality for locally advanced low rectal cancer.

Patterns of local failures and suggestions for reduction of clinical target volume for nasopharyngeal carcinoma patients without cervical lymph node metastasis.

BackgroundTo demonstrate the robustness of clinical target volume delineation for nasopharyngeal carcinoma (NPC) patients, this study makes a detailed analysis of the initial irradiated dose of the recurrent site and local failure patterns after intensity-modulated radiation therapy (IMRT). Based on this analysis, further improvement of delineation recommendations may be made in order to improve the quality-of-life in NPC, without decreasing the local control and survival rate.MethodsIn total, 382 newly diagnosed non-metastatic NPC patients were retrospectively enrolled, receiving elective neck irradiation to levels II, III, and VA. For patients with local failure, the location and extent of local failures were transferred to the pretreatment planning computed tomography (CT) for dosimetric analysis. The dose of radiation received by GTVr (gross tumor volume of recurrence) was calculated and analyzed with dose-volume histogram (DVH). Failures were classified as: “in field” if 95% of GTVr was within the 95% isodose, “marginal” if 20%–95% of GTVr was within the 95% isodose, or “outside” if less than 20% of GTVr was inside the 95% isodose.ResultsWith a median follow-up time of 61.3 months, 12 patients developed local recurrence (10 cases available). The 5-year overall survival, local relapse–free survival, regional relapse–free survival, distant metastasis failure–free survival, and disease–free survival were 87.8%, 95.2%, 99.1%, 93.3%, and 82.5%, respectively. Dose conformity with IMRT was excellent, and the recurrence was mainly within 3 years after the first treatment. The dosimetric analysis showed that seven failures were classified as “in-field”, two failures as “marginal”, and only one failure as “out-field”. Most local relapse sites located just the same site of primary tumor and most anatomic sites were at low risk of concurrent bilateral tumor invasion.ConclusionsIMRT with elective neck irradiation provides excellent local control for NPC patients without cervical lymph node metastasis. In-field failures are the main patterns for local recurrence, and the radioresistant subvolumes within the gross tumor volume are needed to be identified. This study proposed suggestions for reduction of target volume during IMRT treatment for NPC patients.

Proteins of the retinoblastoma pathway, FEN1 and MGMT are novel potential prognostic biomarkers in pancreatic adenocarcinoma

BackgroundWe studied the expression of some major proteins involved in cell-cycle regulation and DNA repair, the roles of which are not well known in pancreatic ductal adenocarcinoma (PDAC), but which have a significant impact on carcinogenesis of many other cancers. MethodsWe immunohistochemically assessed expression levels of the cell-cycle regulators Rb1, p16 and cyclin-dependent kinase 4 (CDK4), and the DNA repair enzymes O6-methylguanine-DNA-alkyltransferase (MGMT) and flap endonuclease-1 (FEN1) separately in malignant tissue and benign tissue from resection margins in 102 cases of PDAC. Nearly all (95.1%) patients had undergone pancreaticoduodenectomy. ResultsThe studied proteins showed wide but somewhat variable expression in both benign and malignant pancreatic tissues. Strong CDK4 expression in islets of Langerhans predicted poor relapse-free survival (RFS) (HR 2.874; 95% CI 1.261–6.550; p = .012) and within T3–4 tumors CDK4 expression in adenocarcinoma cells also predicted poor disease-free survival (DFS) (RR 2.148; 95% CI 1.081–4.272; p = .029). Strong MGMT expression was associated in N1 patients with weak local relapse-free survival (RFS), DFS and overall survival; all significantly in Cox regression analysis. FEN1 was also an independent predictor of decreased DFS (in the whole study population) and worse RFS (in the patients with T3–4 tumors). ConclusionsMajor cell-cycle regulator also have predictive significance, but further studies are required to evaluate this.

Treatment of hepatic metastases with computed tomography-guided interstitial brachytherapy.

The aim of the present study was to evaluate the efficacy, safety and tolerability of local treatment of liver metastases of various types of cancer using brachytherapy with computed tomography (CT) imaging. Retrospective analysis of 61 patients with unresectable hepatic metastases treated with CT-guided interstitial high dose rate (HDR) brachytherapy of the liver between April 2014 and December 2016 was performed. Patients were treated with a single fractional dose of 15-25 Gy. Statistical analysis was performed on local relapse free survival (LRFS), progression free survival (PFS) and overall survival (OS) rates across the group. In the 6 and 12-month follow-up periods, the 6- and 12-month LRFS rates were 88.7 and 70.7%, PFS rates were 78.1 and 53.8% and the OS rates were 96.7 and 79.6%, respectively. In the Cox regression analysis, the 100% isodose was a statistically significant predictor of LRFS (P=0.01) and PFS (P=0.02), but it was not significant in OS (P=0.07). The 90% isodose was a statistically significant predictor of LRFS (P=0,03) but not significant in PFS (P=0.17) or OS (P=0.25). In all patients, no serious complications were observed. Overall, 30% of patients experienced pain at the injection site, and 50% exhibited nausea or vomiting. In 2 patients, minor subcapsular bleeding occurred without clinical significance, and 1 patient was diagnosed with a pneumothorax that was not clinically significant. Brachytherapy HDR with CT imaging is an effective and safe method of local treatment of liver metastases. The effectiveness of the treatment is probably dose-dependent, and increases with increasing dosage.

Triple Negative Apocrine Carcinomas as a Distinct Subtype of Triple Negative Breast Cancer: A Case-control Study

BackgroundInvasive triple negative apocrine carcinoma (TNAC) of the breast is a rare type of triple negative breast cancer. Several studies reported significantly distinct prognosis for TNAC when compared with most of the non-apocrine triple negative (NATN) tumors. This is a case-control study reporting onoutcomes from our long-term single-center experience. Patients and MethodsWe analyzed the clinicopathologic features of a series of 46 TNAC tumors treated in a 15-year period. Tumor characteristics and outcomes have been compared with a homogeneous control series of 43 NATN tumors treated during the same follow-up period. Local relapse-free survival (LRFS), distant metastases-free survival (DMFS), and overall survival (OS) have been evaluated. ResultsLRFS in the TNAC group was 85% and 78% at 5 and 10 years, respectively. LRFS in the NATN group was 90% and 79% at 5 and 10 years, respectively (hazard ratio [HR], 1.14; 95% confidence interval [CI], 0.41-3.19; P = .80). DMFS in the TNAC group was 85% and 85% at 5 and 10 years, respectively. DMFS in the NATN group was 85% and 75% at 5 and 10 years, respectively (HR, 0.39; 95% CI, 0.14-1.08; P = .071). OS in the TNAC group was 86% and 83% at 5 and 10 years, respectively. OS in the NATN group was 86% and 63% at 5 and 10 years, respectively. OS was significantly better in the TNAC group (HR, 0.45; 95% CI, 0.20-0.99; P = .049). ConclusionsTNAC seems to represent a distinct group of triple negative breast cancer, characterized by a favorable long-term outcome when compared with NATN tumors.

Abstract P6-09-07: Triple negative apocrine carcinomas as a distinct subtype of triple negative breast cancer: A case-control study

Abstract Introduction. Invasive apocrine carcinoma of the breast is a rare type of breast cancer (BC), pure apocrine carcinoma constitutes &amp;lt;1% of all BC. Mammary apocrine epithelium has a characteristic steroid receptor profile that is negative for full length estrogen receptor-alpha and progesterone receptor and is androgen receptor positive. Conflicting data are available on the outcome of this type of disease: few studies reported significantly different prognosis of triple negative (TN) apocrine carcinomas when compared to most non-apocrine triple negative (NA-TN) tumors. The aim of this study is to report our long-term experience in a single-center series of TN apocrine tumors. Methods. We analyzed clinical and pathological features of a series of TN apocrine carcinomas treated at our Centre in a 15-year period. Clinical and pathological characteristics and outcomes have been compared with a control series of NA-TN tumors treated during the same follow up period. Local relapse-free survival (LRFS), distant metastases-free survival (DMFS), and overall survival (OS) have been evaluated and compared between groups of patients. Results. Forty-five TN apocrine carcinomas were analyzed. The mean age at diagnosis was 60 years (range 34-83 years). The proportions of apocrine tumor grades varied, with G1 being seen in 6.8% of patients, G2 in 51.1%, and G3 in 40.1%. The majority of apocrine carcinomas had small tumor size (T1: 72.7%; T2: 27.3%), and negative axillary nodal status (66.7%). The series was compared to a homogenous control group of 45 NA-TN patients. The mean age was 54 years (range 32-79 years), affected by high grade (G3: 53.7%), small tumor size (T1: 87.5%; T2: 12.5%), and mostly negative axillary nodal status (82.9%). LRFS in the apocrine group was 85% and 78% at 5- and 10-year, respectively. LRFS in the NA-TN group was 90% and 79% at 5- and 10-year, respectively. No difference was evidenced between groups (HR 1.44 95%CI 0.62-3.79; p=0.39). DMFS in the apocrine group was 85% and 85% at 5- and 10-years, respectively. DMFS in the NA-TN group was 85% and 75% at 5- and 10-year, respectively. DMFS was significantly better in the apocrine group (HR 0.69 95%CI 0.28-1.62). OS in the apocrine group was 86% and 83% at 5- and 10-year, respectively. OS in the NA-TN group was 86% and 63% at 5- and 10-years, respectively. OS was significantly better in the apocrine group (HR 0.57 95%CI 0.26-1.18). Conclusions. Apocrine carcinomas represent a clinic-pathological distinct group of triple-negative BC, characterized by significantly more favorable clinical prognosis in terms of long-term disease-related morbidity or mortality when compared to NA-TN tumors. Citation Format: Meattini I, Pezzulla D, Carta GA, Becherini C, Perna M, Grassi R, Garlatti P, Desideri I, Scotti V, Bernini M, Sanchez LJ, Orzalesi L, Nori J, Bianchi S, Livi L. Triple negative apocrine carcinomas as a distinct subtype of triple negative breast cancer: A case-control study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-09-07.

Robotic surgery for rectal cancer: Short-term and oncological outcomes for 607 consecutive patients.

756 Background: Conventional laparoscopic surgery (CLS) for rectal cancer has several inherent technical difficulties, including a limited range of motion of the instruments.Robot-assisted laparoscopic surgery (RALS) has some technical advantages over CLS because it improves dexterity with an increased range of movements at the tips of the instruments. The purpose of this study was to evaluate the short-term and oncological outcomes of RALS for rectal cancer, including robotic, autonomic nerve-preserving, lateral lymph node dissection (RALLD), a new, technically challenging procedure. Methods: Between December 2011 and August 2017, 607 consecutive patients underwent RALS for rectal cancer. Surgical outcomes, pathological results, and oncological results were investigated retrospectively. Results: There were 403 males and 204 females; 577 patients had adenocarcinoma, 19 had carcinoid tumor, 8 had GIST, and 2 had other malignant tumor. The types of procedures performed were: 453 anterior resections, 93 intersphincteric resections, and 61 abdominoperineal resections. RALLD was performed in 202 patients (33.3%). Preoperative chemoradiotherapy was performed in 34 patients. The overall median operative time was 257(109-683) min. In cases without RALLD, the median operative time was 217 (109-545) min, while median operative time was 420 (162-683) min with RALLD. None of the cases was converted to an open or laparoscopic procedure.There was no surgical mortality. The overall complication rate for Clavien-Dindo classification grade III-IV was 3.0%. The oncological results for 279 patients with primary rectal adenocarcinoma, operated before December 2014 was also investigated (Stage I/II/III 115/48/116). The 5-year overall survival was 96.6%, the 3-year relapse free survival was 88.3%, and 3-year local relapse free survival was 98.5%. The 3-year RFS of pStage I/II/III was 96.2/89.6/79.6% respectively. Conclusions: RALS for rectal cancer is a feasible procedure with low morbidity and a low conversion rate, and acceptable oncological results.

The significance and long-term clinical outcome of preoperative chemoradiotherapy using S-1 plus Irinotecan for locally advanced rectal cancer.

819 Background: Preoperative chemoradiotherapy regimen using S-1 plus Irinotecan is still under clinical investigation. The aim of this study was to investigate the significance and the long-term outcomes of this regimen for locally advanced rectal cancer. Methods: Between 2009 and 2016, 81 patients underwent radical surgery after preoperative chemoradiotherapy. Radiotherapy was administered in total 45Gy with 1.8Gy/day for 25 days. S-1 was administered orally in a fixed daily dose of 80mg/m2 on days 1 to 5, 8 to 12, 22 to 26, and 29 to 33. Irinotecan was infused with dose of 80 mg/m2 on days 1, 8, 22, and 29. 6-9 weeks after the completion of the treatment, radical surgery was performed. The median follow-up was 35.3 months. Results: Of the 81 patients, 76 (93.8%) completed treatment of chemoradiotherapy. Relative dose intensity of CPT-11 was 92.8%, S-1 was 90.1%. 79 (97.5%) patients completed the radiotherapy. 18 patients (22.2%) had ≧Grade 3 hematologic toxicity (leukopenia; 15 patients, neutropenia; 16 patients ). 23 patients (28.3%) had ≧Grade 3 nonhematologic toxicity (diarrhea). In terms of the surgical procedure, 73 of 81 patients (90.1%) underwent sphincter-preserving surgery including 42 patients intersphincteric resection, and 8 patients (9.9%) underwent abdominoperineal resection. The tumor regression grade of 1/2/3(pCR) was 30/39/12(14.8%). In terms of long-term survival, 3-year local relapse-free survival rate was 96.7%, the recurrence-free survival rate was 71.6% and 3-year overall survival rate was 94.9%. Conclusions: Preoperative chemoradiotherapy using combined with Irinotecan as secondary drugs may result safe and feasible and accomplished favorable downstaging. This regimen was considered to be effective in patients with locally advanced rectal cancer.

Prognostic analysis of patients with locally advanced nasopharyngeal carcinoma following intensity modulated radiation therapy.

The present study retrospectively analyzed the prognostic factors of 135 patients with locally advanced nasopharyngeal carcinoma (NPC) who received intensity modulated radiation therapy between August 2008 and January 2012 at Xiangya Hospital of Central South University. Patients were staged from III-IVA according to the 7th American Joint Committee on Cancer staging system. Using Statistical Analysis System 9.3 software, the present study demonstrated that, among these 135 patients, the 5-year overall survival, the 5-year local relapse-free survival, and the 5-year disease metastasis-free survival were 84, 82, and 78%, respectively. Multivariate Cox regression analysis identified that targeted treatment [hazard ratio (95% confidence interval), 2.642 (1.001, 6.972); P=0.0497] served as an independent negative prognostic factor in locally advanced NPC. The results of immunostaining revealed that the staining intensity of the radiation-resistant group was increased compared with that of the radiation-sensitive group. These results demonstrate that a high expression of EGFR may be associated with radiation resistance, and targeted treatment may not be effective in patients with locally advanced nasopharyngeal carcinoma with low expression of EGFR.

Neoadjuvant Chemotherapy with Fluorouracil plus Nedaplatin or Cisplatin for Locally Advanced Nasopharyngeal Carcinoma: a Retrospective Study

The present study aimed to evaluate the efficacy, toxicity and long-term outcome of nedaplatin or cisplatin combined with 5-fluorouracil neoadjuvant chemotherapy (NF or PF regimen) followed by concurrent chemoradiotherapy (CCRT) for treatment of locally advanced nasopharyngeal carcinoma (NPC). In this study, a total of 186 patients with locally advanced NPC between January 2009 and November 2011 in our center were retrospectively analyzed. 103 cases were received NF neoadjuvant chemotherapy followed by nedaplatin concurrent intensity-modulated radiotherapy (IMRT), and 83 cases were received PF neoadjuvant chemotherapy followed by cisplatin concurrent IMRT. Overall survival (OS), progression-free survival (PFS), local relapse-free survival (LRFS), regional relapse-free survival (RRFS) and distant metastasis-free survival (DMFS), as well as acute toxicities were monitored. Results showed that there were no significant differences in 5-year OS, PFS, LRFS, RRFS and DMFS between NF and PF groups. NF group had a higher incidence of grade 3-4 neutropenia (46.6% vs. 31.3%, P=0.035) and thrombocytopenia (17.5% vs. 7.3%, P=0.042) compared with PF group. However, NF group was less common to suffer from grade 3-4 nausea (1.9% vs. 24.1%, P<0.001), vomiting (0% vs. 13.3%, P<0.001) and weight loss (0% vs. 4.8%, P=0.025). In multivariate analysis, N stage was an independent factor for OS, PFS, RRFS and DMFS. In conclusion, neoadjuvant chemotherapy with fluorouracil plus nedaplatin followed by nedaplatin concurrent with IMRT exhibited similar efficacy but more tolerable toxicity than cisplatin setting, which might be an effective and safe choice for treatment of locally advanced NPC.

Accelerated Hyper Fractionated Radiotherapy in Localized Ewing’s Sarcoma with or without Surgery: What’s New? A Phase II Study

Background and aim of work: We aimed from this study to determine the response and local relapse free survival (RFS) of pediatric patients with localized Ewing’s sarcoma treated with accelerated hyper-fractionated RT. Patient and methods: This study was a nonrandomized uncontrolled phase II study and was conducted at clinical oncology department and south Egypt cancer institute; it involved 28 patients with histologically confirmed Ewing’s sarcoma; all of them were subjected to PET/CT whenever possible or MRI with contrast of the primary site, MSCT chest, bone scan, and LDH to ensure absence of metastasis followed by the protocol of accelerated hyper fractionated RT. Results: The overall response rate (ORR) was 92.9% by MRI with significant effect of the type of response on local RFS (P 0.002). The median local RFS of 28 patients with localized Ewing’s sarcoma was 30 ± 8.599 months with 95% CI = 13.147 - 46.853; the 3-year local control was 35%. Conclusion: Accelerated hyper fractionated RT didn’t achieve better results than standard fractionation RT, but it is recommended to be done on a large sample size, and multiple centers, and continued follow up is also recommended to evaluate 5-year LRFS, 5-year OS.

Once-Weekly Hypofractionated Radiotherapy for Breast Cancer in Elderly Patients: Efficacy and Tolerance in 486 Patients

Purpose Radiation therapy is a key treatment of breast cancer. Elderly patients with associated diseases that modify their performance status do not tolerate long periods of daily irradiation. The objective of this study is to analyze the results of weekly hypofractionated treatment in these patients. Material and Methods Between 1992 and 2016, we included 486 elderly patients presenting concomitant pathology or sociofamilial problems in which it was not feasible to propose conventional treatment. They were treated with conservative surgery or mastectomy and then adjuvant hypofractionated irradiation, administering 5 Gy or 6.25 Gy in 6 fractions, once a week (total dose 30–37.5 Gy) over 6 weeks. Results Breast cancer overall survival according to the Kaplan-Meier method at 5 years was 74.2% ± 2.3%; breast cancer disease-free survival was 90% ± 1.6%; local relapse-free survival was 96.5% ± 1% showing that patients die more from other causes and not from their neoplasia. Acute dermatitis was mild (75.6% of the patients grades I–III) and 30.6% had moderate chronic fibrosis. Conclusions The once-weekly hypofractionated radiotherapy is a feasible and convenient option for elderly patients with breast cancer. It is a safe treatment modality with similar survival and local control results compared to standard fractionation, while the side effects are acceptable.

Efficacy and tolerance of high-dose-rate brachytherapy boost after external radiotherapy in the treatment of squamous cell carcinoma of the anal canal.

PurposeThe aim of this study was to evaluate the efficacy and toxicity of high-dose-rate brachytherapy (HDR-BT) boost in anal squamous cell carcinoma (ASCC).Material and methodsThis was a monocentric retrospective study involving patients treated by external irradiation (± chemotherapy), with HDR-BT boost, for a localized ASCC. Clinical evaluation was performed every six months. Oncological results were analyzed with: local relapse-free survival (LRFS), colostomy-free survival (CFS), metastatic-free survival (MFS), disease-free survival (DFS), and overall survival (OS). Acute and late toxicities were collected (CTCV4.0) and LENT/SOMA score was performed.ResultsFrom May 2005 to January 2018, 46 patients (pts) were analyzed. The median follow-up was 61 months (10-145 months), the median age was 65 years (34-84 years), with a sex ratio M/F = 0.24. The TNM classification was as follows: T1 – 13 pts (21.7%), T2 – 34 pts (73.9%), T3 – 2 pts (4.3%), N+ – 6 pts (13.1%). External beam radiotherapy (EBRT) delivered a median dose of 45 Gy (36-50.4 Gy) in 25 fractions, and HDR-BT 12 Gy (10-18 Gy) in 3 fractions. The median overall treatment time (OTT) was 58 days (41-101 days), with a median EBRT/brachytherapy interval of 17 days (4-60 days). Oncological findings showed 5-year rates of LRFS 81.2%, MFS 88.7%, DFS 70%, and OS 90%. All abdominoperineal amputations were performed in case of local relapse (4 pts, 8.7%), leading to a 5-year CFS of 79.5%. Acute urinary toxicities were frequent (G1 41.3%, G2 4.3%). The acute digestive toxicities were: G1 71.7%, G2 6.5%, and G3 2.2%. The late urinary toxicities were: G1 4.3%, G2 2.2%, and G3 2.2%. Late digestive toxicities were: G1 56.5%, G2 8.7%, G3 2.2%, and G4 2.2%.ConclusionsIn ASCC management, HDR-BT boost appears to be a treatment with a long-term acceptable toxicity profile, shorter than EBRT boost, with a reduction of side effects.

Effectiveness and Safety of Simultaneous Integrated Boost-Proton Beam Therapy for Localized Pancreatic Cancer.

Purpose:To evaluate the clinical effectiveness and feasibility of simultaneous integrated boost-proton beam therapy in patients with localized pancreatic cancer.Methods:Thirty-seven patients with localized pancreatic cancer underwent simultaneous integrated boost-proton beam therapy, and 8 (21.6%) patients received induction chemotherapy. The internal target volume was obtained by summing the gross tumor volumes in exhalation phase computed tomography images. Planning target volume 1 included internal target volume plus 3 to 5 mm margins, excluding the 5 mm expanded volume of gastrointestinal structures, and planning target volume 2 included the internal target volume plus 7 to 12 mm margins. The prescribed doses to planning target volume 1 and planning target volume 2 were 45 GyE (equivalent dose in 2 Gy, 54.4 GyE10) and 30 GyE (equivalent dose in 2 Gy, 32.5 GyE10) in 10 fractions, respectively.Results:Overall, treatment was well tolerated, with no grade of toxicity ≥3. Median overall survival was 19.3 months, and 1-year local progression-free survival, relapse-free survival, and overall survival rates were 64.8%, 33.2%, and 75.7%, respectively. Patients treated with simultaneous integrated boost-proton beam therapy after induction chemotherapy had a significantly higher median overall survival time compared to those with simultaneous integrated boost-proton beam therapy alone (21.6 months vs 16.7 months, P = .031). Multivariate analysis showed that induction chemotherapy was a significant factor for overall survival (P < .05).Conclusions:Simultaneous integrated boost-proton beam therapy could be feasible and promising for patients with localized pancreatic cancer.

Prospective matched study on comparison of volumetric-modulated arc therapy and intensity-modulated radiotherapy for nasopharyngeal carcinoma: dosimetry, delivery efficiency and outcomes.

Background: The purpose of this study is to assess the feasibility of volumetric-modulated arc therapy (VMAT) for nasopharyngeal carcinoma (NPC) patients by comparing the physical dosimetry, delivery efficiency and clinical outcomes with intensity-modulated radiotherapy (IMRT).Methods: A prospective matched study was performed for patients with newly diagnosed NPC who underwent VMAT or IMRT. The patients in two groups were equally matched in terms of gender, age, tumor stage and chemotherapy. The target coverage, homogeneity index (HI) and conformity index (CI) of the planning target volume (PTV), organs at risk (OARs) sparing, average treatment time and clinical outcomes were analyzed.Results: From June 2013 to August 2015, a total of 80 patients were enrolled in this study, with 40 patients in each group. The coverage of PTV was similar for both groups. D2 was observed slight difference only in early stage disease (T1-2) (VMAT vs. IMRT, 7494±109 cGy vs. 7564±92 cGy; p=0.06). The HI of VMAT group was better than that of IMRT group (p=0.001), whereas CI was slightly worse (p=0.061). The maximum doses received by the brain stem, spinal cord, and optic nerve of VMAT were higher than those of IMRT (p<0.05). But the irradiation volumes in healthy tissue were generally lower for VMAT group, with significant differences in V20, V25 and V45 (p<0.05). With regard to the delivery efficiency compared with IMRT (1160 ± 204s), a 69% reduction in treatment time was achieved by VMAT (363 ± 162s). Both groups had 5 cases of nasopharyngeal residual lesions after radiotherapy. The 2-year estimated local relapse-free survival, regional relapse-free survival and locoregional relapse-free survival, distant metastasis-free survival, disease-free survival and overall survival were similar between two groups, with the corresponding rates of 100%, 97.4%, 97.4%, 90.0%, 90.0% and 92.4% in VMAT group, and 100%, 100%, 100%, 95.0%, 95.0% and 97.5% in IMRT group, respectively.Conclusions: Both VMAT and IMRT can meet the clinical requirements for the treatment of NPC. The short-term tumor regression rates and 2-year survival rates with the two techniques are comparable. The faster treatment time benefits of VMAT will enable more patients to receive precision radiotherapy.

Optimal time of tumour response evaluation and effectiveness of hypofractionated proton beam therapy for inoperable or recurrent hepatocellular carcinoma

ObjectiveTo evaluate the optimal time of tumour response and effectiveness of hypofractionated proton beam therapy (PBT) for hepatocellular carcinoma (HCC).ResultsOverall, treatment was well tolerated with no grade toxicity ≥3. Of 71 patients, 66 patients (93%) eventually reached complete response (CR) after PBT: 93.9% (62 of 66) of patients who reached CR within 12 months, and the remaining 4 patients (6.1%) reached CR at 12.5, 16.2, 19.1 and 21.7 months, respectively. The three-year local progression-free survival (LPFS), relapse-free survival (RFS) and OS rates were 89.9%, 26.8%, and 74.4%, respectively. Multivariate analysis revealed that the tumour response was an independent prognostic factor for LPFS, RFS, and OS.ConclusionMost CR was achieved within 1 year after PBT and further salvage treatments in PBT field might be postponed up to approximately 18–24 months. Hypofractionated PBT could be good alternative for HCC patients who are unsuitable for surgical or invasive treatments with curative intent.Materials and MethodsSeventy-one inoperable or recurrent HCC patients underwent hypofractionated PBT using 66 GyE in 10 fractions. The tumour responses were defined as the maximal tumour response observed during the follow-up period using the modified Response Evaluation Criteria in Solid Tumors criteria.

Accelerated partial breast irradiation for suitable elderly women using a single fraction of multicatheter interstitial high-dose-rate brachytherapy: Early results of the Single-Fraction Elderly Breast Irradiation (SiFEBI) Phase I/II trial

Purpose/ObjectiveTo evaluate feasibility and early clinical outcomes of a single fraction of multi-catheter interstitial high-dose rate brachytherapy for accelerated partial breast irradiation (APBI) in the elderly. Material/MethodsFrom November 2012 to September 2014, 26 patients (≥70) with early breast cancer were enrolled in a prospective phase II trial (NCT01727011). After lumpectomy, intra-operative catheter implant was performed for post-operative APBI (single fraction 16 Gy). Surveillance was achieved at 1, 3 and 6 months after APBI, then twice a year. Acute toxicity was investigated. Early cosmetic outcome was analyzed (patient, radiation oncologist, 2 observers). Local and regional relapse-free survival, cancer specific survival and overall survival were analyzed. ResultsMedian age was 77 years [69–89]. Median CTV was 41 cc [22-95]. Acute toxicity was observed in 18 pts (70%) with a total of 44 events: G1: 75.7%; G2: 22.8%; G3: 4.5%. Breast fibrosis (31.8%), puncture site inflammation (13.6%) and skin hyperpigmentation (11.4%) were the most frequent side effects. Cosmetic evaluation at 6 months was excellent/good in 88%, 92%, 85% and 88% for patient, radiation oncologist, observer #1 and #2 respectively. With a median follow-up of 37.2 months [35.6-42.3], side effects were G1: 4 pts (15%) and G2: 1 pt (4%). Three-year Local and regional relapse-free survival, cancer specific survival and overall survival rates were 100%, 100%, 100% and 95.2% respectively. ConclusionsFor elderly early breast cancer, a post-operative multi-catheter interstitial high-dose rate brachytherapy single dose (16 Gy) appears feasible. Acute toxicity is acceptable as well as early cosmetic outcome. Oncologic outcome seems encouraging and allows going forward with new clinical trials focusing on single fraction APBI.

Relationship between positive lymph nodes and distant metastasis after intensity-modulated radiotherapy in patients with nasopharyngeal carcinoma

Objective To explore the relationship between positive cervical lymph nodes and distant metastasis after intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). Methods A retrospective analysis was performed on the clinical data of 474 patients who were newly diagnosed with NPC but no distant metastasis and received IMRT from 2010 to 2012. The survival rates were calculated by the Kaplan-Meier method. The log-rank test was used for comparison of survival rates and univariate prognostic analysis. The multivariate analysis was made by the Cox regression model. Results In the 474 patients, 400 had positive cervical lymph nodes and 122 had residual masses in the neck after IMRT. The four-year distant metastasis, overall survival, disease-free survival, local relapse-free survival, and distant metastasis-free survival (DMFS) rates were 13.71%(65/474), 82.9%, 81.4%, 93.5%, and 86.3%, respectively. The univariate and multivariate analyses showed that treatment approach, lymph node metastases in lower neck Ⅳ/Ⅴb/Ⅴc regions, the greatest diameter of the positive cervical lymph nodes, the diameter of residual lymph nodes, and time to lymph node recession were independent prognostic factors for DMFS (all P<0.05). Conclusions Chemoradiotherapy can reduce the distant metastasis rate after IMRT for NPC. The larger the cervical lymph nodes are, the more likely there are residual masses; the larger the residual cervical lymph nodes are, the higher risk of distant metastasis there is. Large cervical lymph nodes (≥6 cm), residual masses larger than 1 cm, and residual masses at 3 months after IMRT are negative prognostic factors for DMFS after IMRT for NPC. Better intervention treatment approaches need to be explored. Key words: Nasopharyngeal neoplasms/intensity-modulated radiotherapy; Distant metastasis; Lymph node

Suggestions for surveillance and radiation strategy in nasopharyngeal carcinoma treated with IMRT: Based on hazard-rate and patterns of recurrence

ObjectiveThe study was designed to appraise the locoregional recurrence patterns using conventional two-dimensional radiotherapy (2D-RT) and intensity modulated radiation therapy (IMRT) in nasopharyngeal carcinoma (NPC) in order to better establish the scenario of the modern radiotherapy and the duration of surveillance. Materials and MethodsWe reviewed the institutional database to identify patients with pathologically confirmed, non-metastatic NPC who completed radical 2D-RT or IMRT at our center from 2000 to 2011. We collected data on clinicopathologic features, treatments and outcomes. Statistical analyses were performed using SPSS 20.0 or STATASE 14.0. ResultsThe median follow-up was 60.1 months. Of 2315 patients, 1289 (53%) were treated with 2D-RT and 1026 (47%) with IMRT. IMRT group achieved better locoregional control rate, with the 5-year locoregional relapse-free survival (LRRFS) were 84.9% and 87.7% among patients received 2D-RT and IMRT, respectively (P = 0.050). IMRT was superior to 2D technique in terms of local relapse-free survival (LRFS) (88.4% vs 91.1%, P = 0.047) and the advantage was only significant in T3-4 subgroup (81.6% vs 90.2%, P = 0.000). Similar neck control rates were observed using different RT techniques. And the recurrence time appeared to be postponed by IMRT, with peaks accounting for the year 1.5 and year 3–4 compared to which was predominant at the first two years using 2D-RT in nature. ConclusionsIMRT provided an improved LRRFS in overall stage and LRFS in advanced T stage for NPC compared with 2D-RT. Annual hazard of recurrence also changed with RT techniques.