Local-regional Relapse-free Survival Research Articles

Endostar combined with concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone for locoregionally advanced nasopharyngeal carcinoma (LA-NPC): A phase III, prospective, randomised-controlled, multicenter clinical trial.

6002 Background: Cisplatin-based concurrent chemoradiotherapy (CCRT) has long been regarded as standard treatment for LA-NPC. However, approximately 30% of patients still fail to obtain a satisfactory effect. Endostar (Rh-endostatin), an anti-angiogenesis inhibitor, is well-tolerated and has been reported as a promising complement to CCRT. This trial aimed to evaluate the efficacy and safety of adding Endostar to CCRT for LA-NPC. Methods: In this prospective, randomized phase III study, patients with LA-NPC (stage III-IVb, 7th edition) were enrolled at 6 centers in China, and randomly assigned (1:1) to receive Endostar plus CCRT (CCRT+E group, n=150) or CCRT alone (CCRT group, n=150). Endostar (7.5 mg/m2/day, days 1-10, 15 days/cycle) was given continuously intravenously for 5 cycles (3 concurrent from 5 days before radiotherapy, and 2 adjuvant from the first day after the completion of radiotherapy). The primary endpoint was the progress-free survival (PFS) rate. The secondary endpoints included overall survival (OS), distant metastasis-free survival (DMFS), local-regional relapse-free survival (LRRFS), the rate of complete response (CR) at 3 months after RT, and safety. Results: Between November 2016 and July 2020, 300 patients with LA-NPC were randomized (CCRT+E group, 150; CCRT group, 150). As of the data cutoff (December 2023), the median follow-up was 66 months. Intention-to-treat analysis showed that patients in the CCRT+E group achieved better CR rate at 3 months after RT (90.0% vs 80.7%, P=0.022). The 3-year PFS was 84.8% in the CCRT+E group, and 75.1% in the CCRT group (HR, 0.544; 95% CI, 0.336-0.879; Plog-rank=0.011). The 3-year OS was 89.2% vs. 85.3% (HR, 0.595; 95% CI, 0.361-0.982; Plog-rank=0.039). The 3-year DMFS was 89.7% vs. 80.5% (HR, 0.468; 95% CI, 0.266-0.821; Plog-rank=0.007). The 3-year LRRFS was 91.5% vs. 90.8% (HR, 0.808; 95% CI, 0.407-1.604; Plog-rank=0.541). Patients in the CCRT+E group and in the CCRT group had similar Grade 3-4 acute and late toxicity profile (61.7% vs. 65.3%, p=0.519 and 8.0% vs.7.3%, p=0.815). Conclusions: The addition of Endostar to standard CCRT significantly improved the 3-year PFS of LA-NPC patients with good safety profile. Clinical trial information: NCT02907710 .

The value of intravoxel incoherent motion model-based diffusion-weighted imaging for predicting long-term outcomes in nasopharyngeal carcinoma.

The aim of this study was to evaluate the prognostic value for survival of parameters derived from intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in patients with nasopharyngeal carcinoma (NPC). Baseline IVIM-DWI was performed on 97 newly diagnosed NPC patients in this prospective study. The relationships between the pretreatment IVIM-DWI parametric values (apparent diffusion coefficient (ADC), D, D*, and f) of the primary tumors and the patients' 3-year survival were analyzed in 97 NPC patients who received chemoradiotherapy. The cutoff values of IVIM parameters for local relapse-free survival (LRFS) were identified by a non-parametric log-rank test. The local-regional relapse-free survival (LRRFS), LRFS, regional relapse-free survival (RRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) rates were calculated by using the Kaplan-Meier method. A Cox proportional hazards model was used to explore the independent predictors for prognosis. There were 97 participants (mean age, 48.4 ± 10.5 years; 65 men) analyzed. Non-parametric log-rank test results showed that the optimal cutoff values of ADC, D, D*, and f were 0.897 × 10-3 mm2/s, 0.699 × 10-3 mm2/s, 8.71 × 10-3 mm2/s, and 0.198%, respectively. According to the univariable analysis, the higher ADC group demonstrated significantly higher OS rates than the low ADC group (p = 0.036), the higher D group showed significantly higher LRFS and OS rates than the low D group (p = 0.028 and p = 0.017, respectively), and the higher D* group exhibited significantly higher LRFS and OS rates than the lower D* group (p = 0.001 and p = 0.002, respectively). Multivariable analyses indicated that ADC and D were the independent prognostic factors for LRFS (p = 0.041 and p = 0.037, respectively), D was an independent prognostic factor for LRRFS (p = 0.045), D* and f were the independent prognostic factors for OS (p = 0.019 and 0.029, respectively), and f acted was an independent prognostic factor for DMFS (p = 0.020). Baseline IVIM-DWI perfusion parameters ADC and D, together with diffusion parameter D*, could act as useful factors for predicting long-term outcomes and selecting high-risk patients with NPC.

Patterns of Local-Regional Relapse Following Intensity-Modulated Radiotherapy for Patients With Nasopharyngeal Carcinoma

<h3>Purpose/Objective(s)</h3> Despite definite radiotherapy, post-treatment recurrence remains a major challenge for patients with nasopharyngeal carcinoma (NPC). This study aimed to evaluate risk factors for local-regional relapse in patients with non-metastatic NPC treated with intensity-modulated radiation therapy (IMRT). <h3>Materials/Methods</h3> We retrospectively analyzed data from 1040 patients with newly diagnosed, non-metastatic, biopsy-proven NPC from 2013 to 2019 (including 7, 133, 475, and 425 cases of stage I, II, III, and IVA disease, respectively, according to the 8th edition of the American Joint Committee on Cancer staging system). All patients received IMRT at a single institution in China (with or without concurrent chemotherapy). Recurrent sites were delineated on imaging and coregistered with the initial treatment planning computed tomography. The recurrences were classified as "in-field failure" if 95% of GTVr (gross tumor volume of recurrence) was within the 95% isodose; "marginal failure" if 20%–95% of GTVr was within the 95% isodose, or "out-field failure" if less than 20% of GTVr was inside the 95% isodose. Univariate and multivariate analyses with the Cox proportional hazards model were performed to identify the independent risk factors. <h3>Results</h3> With a median follow-up of 44 months, 76 patients (7.3%) developed a recurrence. The median interval of relapse was 20.5 months (range: 7–109 months). The 2-year overall survival, local relapse-free survival and regional relapse-free survival were 95.8%, 96.4% and 98.4%, respectively. Local-alone, regional-alone and synchronous local-regional failures accounted for 57.9% (44/76), 32.9% (25/76), and 9.2% (7/76) of recurrent NPC cases, respectively. In these patients, the male:female ratio was 2.4:1 and the median age was 50 years (range: 21–74 years). Among the 62 local-regional failures with available diagnostic images, 53 cases (85.4%) were "in-field", 5 cases (8.1%) had "marginal", 4 cases (6.5%) were as "out-field". Multivariate analysis showed that the non-keratinizing differentiated subtype and the absence of concurrent chemotherapy (CCT) were independent factors for local recurrence after IMRT (differentiated NPC versus undifferentiated NPC HR = 1.987, 95% CI 1.056–3.738, <i>P</i> = 0.033; non-CCT versus CCT HR = 2.098, 95% CI 1.134–3.884, <i>P</i> = 0.018). The rate of lymph nodes associated with liquefaction was 12.4% by the primary tumors but 46.7% at regional recurrence (liquefaction versus non-liquefaction HR = 11.031, 95% CI 4.992–24.372, <i>P</i><0.001). <h3>Conclusion</h3> The major recurrence patterns were in-field failures. The poor local control rates may be associated with the absence of CCT and differentiated carcinoma of NPC. Lymph node with liquefaction was an independent prognostic factor for regional recurrence.

High-dose rate brachytherapy in localized penile cancer: 5-Year clinical outcome analysis

PurposeTo analyze the oncological outcome and toxicity profile after conservative treatment based on multicatheter interstitial high-dose rate brachytherapy (MHB) for patients presenting a localized penile cancer. Materials and methodsPatients with histologically proven, non-metastatic (T1-T2 N0-N2 M0) localized penile cancer were treated with MHB. Needles were placed under general anesthesia into the target volume using a dedicated template. Treatment planning was performed using a post-implant CT-scan to deliver 35 Gy or 39 Gy (9f, 5d) for adjuvant or definitive treatment respectively. Five-year oncological outcome was evaluated with local relapse-free (LRFS), regional relapse-free (RRFS), and metastasis-free survival (MFS), specific (SS) and overall survival (OS). In pre-treatment and follow-up consultations, skin, urinary and sexual toxicities were investigated using CTCAEv4.0 classification, International Prostate Symptom Score (IPSS) and International Index of Erectile Function 5-items (IIEF-5). Dosimetry data were also analyzed. ResultsFrom 03/2006 to 05/2020, with a median follow-up of 72.4 months [3–174], 29 pts, mainly T1 (75.9%) and N0 (89.7%), underwent MHB. Eleven (38%) and 18 pts (62%) received MHB as adjuvant or definitive treatment respectively. Five-year LRFS, RRFS, MFS, SS and OS were 82%, 82%, 89%, 88% and 73% respectively. Six patients (20.7%) experienced local relapse and underwent salvage penectomy leading to a penile preservation rate of 79.3%. Acute skin toxicity was reported 1 month after MHB, with 28% G1, 66% G2 and 6% G3. Late skin complications were telangiectasia for 5 pts (17%) and necrosis for 3 pts (10.3% requiring hyperbaric oxygen therapy). Comparing pre- and post-treatment status, no significant change was observed for skin appearance, IPSS and IIEF-5. ConclusionMHB represents an efficient first line conservative treatment option for early penile cancers. Oncological outcome and late toxicity profile appear encouraging. However, larger-scale cohorts with longer follow-up are needed to more accurately precise the features of the best candidate to MHB.

Myasthenia Gravis Is Not an Independent Prognostic Factor of Thymoma: Results of a Propensity Score Matching Trial of 470 Patients.

ObjectiveThe association between the prognosis of thymoma and MG remains controversial. Differences in clinical characteristics and treatments between patients with and without MG may affect the findings of those studies. We designed this propensity score matching trial to investigate whether MG is an independent prognostic predictor in thymoma.MethodsPatients with pathologically diagnosed thymoma and MG were enrolled in the MG group. Moreover, the propensity score matching method was used to select patients who were diagnosed with thymoma without MG from the database of two participating centers. Matched factors included sex, age, Masaoka stage, pathological subtypes, and treatments. Matched patients were enrolled in the non-MG group. Chi-squared test was used to compare the characteristics of the two groups. Overall survival, local-regional relapse-free survival, distant metastasis-free survival, progression-free survival, and cancer-specific survival were calculated from the diagnosis of thymoma using the Kaplan–Meier method.ResultsBetween April 1992 and October 2018, 235 patients each were enrolled in the MG and non-MG groups (1:1 ratio). The median ages of patients in the MG and non-MG groups were 46 years old. The World Health Organization pathological subtypes were well balanced between the two groups (B2 + B3: MG vs. non-MG group, 63.0 vs. 63.4%, p = 0.924). Most patients in both groups had Masaoka stages I–III (MG vs. non-MG group, 90.2 vs. 91.5%, p = 0.631). R0 resections were performed in 86.8 and 90.2% of the MG and non-MG groups, respectively (p = 0.247). The median follow-up time of the two groups was 70.00 months (MG vs. non-MG group, 73.63 months vs. 68.00 months). Five-year overall survivals were 92.5 and 90.3%, 8-year overall survivals were 84.2 and 84.2%, and 10-year overall survivals were 80.2 and 81.4% (p = 0.632) in the MG and non-MG groups, respectively. No differences were found in the progression-free survival, distant metastasis-free survival, and local-regional relapse-free survival between the two groups.ConclusionMG is not an independent or direct prognostic factor of thymoma, although it might be helpful in diagnosis thymoma at an early stage, leading indirectly to better prognosis.

Combined neat model for the prognosis of postoperative stage III-N2 non-small cell lung cancer.

BackgroundLung cancer serum tumor markers including carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21‐1), and carbohydrate antigen 125(CA125) as prognostic predictors is controversial. Therefore, this study aimed to evaluate the association between these markers and the survival of patients with postoperative stage III‐N2 non‐small cell lung cancer (NSCLC).MethodsWe enrolled 1011 patients with pathologically confirmed stage III‐N2 NSCLC who underwent resection and whose pretreatment serum tumor marker levels were available. Patients were categorized according to their serum levels into low‐, medium‐, and high‐risk groups. Overall survival (OS), progression‐free survival (PFS), local regional relapse‐free survival (LRFS), and distant metastasis‐free survival (DMFS) were calculated from the date of resection. Their association with each serum tumor marker was assessed using the log‐rank test.ResultsAbnormal CEA levels were associated with worse five‐year OS, PFS and DMFS; abnormal CYFRA21‐1 levels were associated with worse five‐year OS and LRFS; and abnormal CA125 levels were associated with worse five‐year OS, PFS, LRFS and DMFS. Among the risk groups, there were significant differences in five‐year OS, PFS, LRFS and DMFS (P = 0.000). In propensity score matching analysis, the model also achieved prognostic significance for all four survival classifications (P = 0.001–0.004) among the three risk groups.ConclusionsThe combined model achieved prognostic significance for all survival outcome types. The serum tumor markers tested are useful prognostic predictors for postoperative NSCLC patients but not for all survival outcomes. The combination of the three indices is more reliable in predicting all four of the survival outcomes.Key pointsSignificant findings of the studySerum CEA, CYFRA21‐1, and CA125 levels can be used as prognostic factors of postoperative N2 non‐small cell lung cancer patients but not for all survival outcomes, suggesting that combinative detection of all three indices would be more reliable.What this study addsOur model utilizes available technology, with conventional cutoff values, inexpensive costs, and simple mathematics methods and, thus, can be feasibly employed by clinicians or oncologists.

TTF-1 Expression is Correlated with Necessity of Postoperative Radiotherapy in Stage IIIA-N2 Lung Adenocarcinoma

The role of postoperative radiotherapy (PORT) in patient with stage IIIA-N2 non-small cell lung cancer is still controversial. It is urgent to explore the prognostic factor which might be helpful to make treatment choice. Thyroid transcription factor-1 (TTF-1) is overexpressed in up to 95% of primary lung adenocarcinoma. Several studies stated that TTF-1 is a prognostic factor in NSQ-NSCLC with conflicting results by reasons of different stages and treatments. Here, we conducted this study to gain a better insight into the association between TTF-1 expression and the necessity of postoperative radiotherapy in patients with stage IIIA-N2 lung adenocarcinoma after R0 resection. Patients with pathologically confirmed inoperable stage IIIA-N2 lung adenocarcinoma and underwent R0 resection with or without PORT in our institution were eligible. Data on demographics, histology, invasion, radiotherapy, chemotherapy, and survival were collected.TTF-1 expressions were determined by immunohistochemistry using available specimen after resection. Patients were classified into the TTF-1 overexpression group (TTF-1 : 3+) and TTF-1 not overexpression group (TTF-1 score 0-2+). Overall survival(OS), progression free survival(PFS), local regional relapse free survival(LRFS) and distant metastasis free survival(DMFS) were calculated from the date of resection. The necessity of PORT is assessed by log-rank test. From October 2006 to April 2015，101 patients fulfilled the enrollment criteria. Fifty-seven patients were male and 44 patients were female. The median age was 56 years old (34-74 years old). Negative, score 1+, score 2+ and score 3+ TTF-1 expression were in 8, 8,17, 68 patients, respectively. Median follow up time was 26.8 months. In patients with TTF-1 overexpression, 19 patients received PORT and 49 did not. For these patients, none of the OS(82.9% vs.81.8%,P=0.731), PFS(57.9% vs. 51.5%P=0.518), LRFS(100% vs.97.6%P=0.513) and DMFS(63.2% VS.62.4%P=0.910) were associated with PORT .In patients without TTF-1 expression, patients who received PORT got more favorable OS (50.0% vs.20.8%P=0.137)and PFS(83.3%VS.22.0%,p=0.028) compared with who did not. Moreover, there is no significant differences in LRFS (100% VS 86.5%p=0.395) and DMFS (66.7%vs 47.1%P=0.442) between patients with and without PORT. This retrospective study demonstrates that patients with TTF-1 score 0-2+ might benefit more from postoperative radiotherapy.

Characteristics and Treatment Outcomes of Primary Mediastinal Seminomas: A Report of 30 Cases from a Single Center

The low incidence primary mediastinal seminoma has precluded the development of clinical trials, and present knowledge is based on case reports and tiny studies. We performed this single-center retrospective analysis to evaluate the clinical characteristics, treatments, and prognosis in patients with pathologically confirmed primary mediastinal seminoma. Data regarding clinicopathologic characteristics, treatment protocols, toxicities, and survival were collected from 30 patients who attended our institution between December 2000 and December 2018. Survival was assessed using the Kaplan-Meier method. Univariate analysis was performed using the log-rank test. The 30 patients were with a median age of 30 years old (13-63 years). Chest pain, stuffiness and cough were the most common symptoms (22.2%,22.2%, 13.9%). The medium maximum diameter of primary tumor was 10.2 centimeters. Eighteen patients were with invasion of adjacent structures such as lung and superior vena vessel. Three and two patients were diagnosed as lymph node metastasis and distant metastasis. R0 resection and debulking resection were performed in 12(40.0%) and 2(6.7%) patients, respectively. Treatment comprised radiotherapy in 15(50.0%) patients and chemotherapy in 27(90.0%). The median radiation dose was 45Gy and the most widely used chemotherapy regimens were bleomycin, etoposide and cisplatin. The median follow-up time was 25.1months(1.8 -198.2 months). At the last follow up, two patients died. Both two patients lived more than ten years after treatment and neither of them died of seminomas or treatment induced toxicities. Local recurrence and distant metastasis were observed in 3 patients each. At 5 years and 10 years, local-regional relapse free survivals were 86.7% and 86.7%, overall survivals were 100% and 100%, progression-free survivals were77.4% and 77.4%, and distant metastasis–free survivals were 85.6% and 85.6%, respectively. In univariate analysis, there is a marginal differences of local regional relapse free survival between patients who received radiotherapy and who did not (100% vs. 74.3%, p=0.081). Primary mediastinal seminoma was frequently diagnosed with invasion of adjacent structures. Chemotherapy is the most widely used treatment and radiotherapy may increase local-regional relapse free survival.

Prognostic Value of the Pretreatment Primary Lesion Quantitative Dynamic Contrast-Enhanced Magnetic Resonance Imaging for Nasopharyngeal Carcinoma

Early identifying the long-term outcome of chemoradiotherapy is helpful for personalized treatment in nasopharyngeal carcinoma (NPC). This study aimed to investigate the prognostic significance of pretreatment quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for NPC. The relationships between the prognosis and pretreatment quantitative DCE-MRI (Ktrans, Kep, Ve, and fpv) values of the primary tumors were analyzed in 134 NPC patients who received chemoradiotherapy. Kaplan-Meier analysis was performed to calculate the local-regional relapse-free survival (LRRFS), local relapse-free survival (LRFS), regional relapse-free survival, distant metastasis-free survival (DMFS), progression-free survival, and overall survival rates. Cox proportional hazards model was used to explore the independent predictors for prognosis. The local-failure group had significantly higher Ve (p = 0.033) and fpv values (p = 0.005) than the non-local-failure group. The Ve-high group showed significantly lower LRRFS (p = 0.015) , LRFS (p = 0.013) , DMFS (p = 0.027) and progression-free survival (p = 0.035) rates than the Ve-low group. The fpv-high group exhibited significantly lower LRRFS (p = 0.004) and LRFS (p = 0.005) rates than the fpv-low group. Ve was the independent predictor for LRRFS (p = 0.008), LRFS (p = 0.007), DMFS (p = 0.041), and overall survival (p = 0.022). fpv was the independent indicator for LRRFS (p = 0.003) and LRFS (p = 0.001). Baseline quantitative DCE-MRI may be valuable in predicting the prognosis for NPC.

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.

Impact of Neoadjuvant Chemotherapy on the Administration of Concurrent Chemoradiation for Locally Advanced Nasopharyngeal Carcinoma

ObjectivesThe standard of care for locally advanced nasopharyngeal carcinoma (NPC) is concurrent cisplatin chemoradiotherapy. Neoadjuvant chemotherapy can be administered to downsize tumors before concurrent treatment to optimize radiation volumes. Our hypothesis was that the use of cisplatin in the neoadjuvant phase could limit the amount of cisplatin that patients could tolerate in the concurrent phase of treatment.MethodsThis is a retrospective analysis of Canadian NPC patients who received neoadjuvant chemotherapy with the intention to downsize locally advanced tumors prior to concurrent cisplatin plus radiation. Baseline demographic and treatment data were obtained from institutional databases and chart review; all data were analyzed with SPSS (SPSS Inc. Released 2005. SPSS for Windows, Version 14.0. Chicago: SPSS Inc.) Overall survival (OS), disease-specific survival (DSS), and local/regional relapse-free survival (LRRFS) were analyzed using Kaplan-Meier survival functions. Univariate and multivariate models were used to determine factors associated with the total dose of concurrent chemotherapy.ResultsForty-six patients were identified as receiving neoadjuvant chemotherapy before concurrent chemoradiotherapy. In the univariate and multivariate analyses of patients who received concurrent chemotherapy, receiving over 200 mg/m2 concurrent cisplatin with radiation was associated with a higher neoadjuvant dose of chemotherapy received. The median follow-up time was 2.6 years (range, 0.17 years to 10.6 years). At three years, the OS was 83%, DSS was 86%, and LRRFS was 74%.ConclusionsNPC patients have been treated with neoadjuvant chemotherapy at this center with favorable outcomes. Most patients could tolerate concurrent chemotherapy after radiotherapy. Receiving higher doses of concurrent chemotherapy was associated with also having higher doses of neoadjuvant cisplatin. This suggests that neoadjuvant cisplatin is not a limiting factor in the delivery of full-dose concurrent chemotherapy.

Adjuvant radiotherapy after curative surgery for oral cavity squamous cell carcinoma and treatment effect of timing and duration on outcome-A Taiwan Cancer Registry national database analysis.

Conduct an accurate risk assessment of resected oral cavity squamous cell carcinoma (OSCC) patients by accessing a nationwide systemic investigation is pivotal to improve treatment outcomes. In this article, we tried to determine the impact of different prognostic factors for OSCC patients who received adjuvant radiotherapy (RT) after curative surgery, using Taiwan's national cancer registry database (TCR). A nationwide, large population‐based study was conducted using TCR with patients identified from 2007 to 2015. The study variables included age, gender, cancer subsites, stage, histology grade, margin and extra‐nodal extension (ENE) status, treatment type, surgery to RT interval (ORI), total RT treatment time (RTT), and RT dose. Univariate and multivariate analysis were performed to identify predictors of the variables associated with overall survival (OS), cause‐specific survival (CSS), local‐regional relapse‐free survival (LRFS), and distant metastasis‐free survival (DMFS). 8986 OSCC patients treated with surgery and adjuvant RT were analyzed. In multivariate analysis, worse outcomes were associated with males, older age, subsite in the oral tongue, advanced stage, higher histologic grade, involved margin, and positive ENE. ORI only showed an adverse trend in LRFS, when exceeding 7 weeks (P = .06). RTT >8 weeks was a significant poor predictor in OS, CSS and LRFS (P < .001). Extreme RT dose (>70 Gy or ≤50 Gy) also demonstrated an adverse impact on the outcomes. Prolonged RT treatment time and extreme RT doses were identified as significantly poor prognostic predictors in OSCC patients who received adjuvant RT after curative surgery.

Failure patterns and prognostic factors of patients with primary mucosal melanoma of the nasal cavity and paranasal sinuses

Objectives: To analyse the failure patterns and prognostic factors influencing survival in patients with primary mucosal melanoma of the nasal cavity and paranasal sinuses.Materials and methods: Fifty-one patients were analysed retrospectively. Forty-eight, 33, 10, and 13 patients underwent surgery, radiotherapy, chemotherapy, and immunotherapy, respectively. Failure events, including local recurrence, regional relapse, distant metastases, and death, were examined.Results: During follow-up (median: 59.0 months), 36 patients experienced failure after treatment, including local (n = 17), regional (n = 8), and distant organ (n = 23) metastases. The median failure times for local, regional, and distant metastases were 13.0, 14.0, and 8.0 months, respectively. The median survival times from local, regional, and distant failure to death were 10.5, 8.0, and 4.0 months, respectively. The 5-year overall survival rates of patients with and without distant organ metastases were 14.4% and 72.6%, respectively (p < .001). Multivariate analyses showed that radiotherapy increased local recurrence-free and regional relapse-free survival. Patients with stage IV tumours had reduced distant metastasis-free and overall survival compared to patients with stage I–III tumours.Conclusions: Distant metastasis was mainly owing to failure. Radiotherapy and the disease stage were prognostic factors for survival.

Systematic review and meta-analysis of the efficacy of breast conservation therapy followed by radiotherapy in four breast cancer subtypes.

The different molecular subtypes of breast cancer are associated with distinct outcomes. We assessed the efficacy of breast conservation therapy (BCT) followed by radiotherapy for patients with different breast cancer subtypes. We searched the MEDLINE, EMBASE, and Cochrane Library databases to identify studies published prior to April 30, 2016 that assessed the efficacy of BCT followed by radiotherapy in breast cancer patients with different molecular subtypes. A meta-analysis of seven studies that included 3,798 luminal A, 770 luminal B, 344 human epidermal growth factor receptor 2 (Her-2), and 767 triple-negative breast cancer (TNBC) patients was performed. The pooled odds ratio [OR] for local relapse-free survival in luminal A compared to Her-2 patients was 0.1960 (95% confidence interval [CI]: 0.0440–0.8728, p = 0.0325) at 5 years and 0.2592 (95% CI: 0.1301–0.5167, p = 0.0001) at 10 years. The pooled OR for local-regional relapse-free survival in luminal A compared to TNBC patients was 0.1381 (95% CI: 0.0565–0.3374, p = 0.0000) at 5 years and 0.1221 (95% CI: 0.0182–0.8192, p = 0.0304) at 10 years. Thus, the rate of local-regional control is higher in luminal A patients than in Her-2 or TNBC patients.

Tratamiento no quirúrgico en cáncer epidermoide de orofaringe avanzado. Análisis de resultados oncológicos en función del subsitio tumoral y fraccionamiento de radioterapia

ObjectiveTo report results of our concomitant radiochemotherapy protocol for advanced oropharyngeal cancer. Materials and methodsRetrospective study. Concomitant radiochemotherapy was performed with weekly cisplatin. Conventional fractionation (CF), hyperfractionation (Hfx) or accelerated fractionation with concomitant boost (FABC) were accepted. Overall survival (OS), Disease-free survival (RFS), Local relapse-free survival (LRFS) and Regional relapse-free survival (RRFS) were calculated, according subsite and radiotherapy fractionation. ResultsWe found 87 patients. Median follow-up: 120 months. 53%, 30% and 17% received FC, FABC, Hfx respectively. OS at 2, 5 and 10 years was 73%, 61% and 43% respectively. The 5-year OS was, by anatomic subsite: Tonsillar 74%, 33% soft palate, base of tongue 33%, and 33% for posterior pharyngeal wall. By comparing the OS in tonsil versus other subsites we found statistically significant difference in favor of tonsillar cancer (P<.001). Median OS for tonsillar cancer was not achieved, while in other subsites was 22 months.DFS was different in different subsites, better for amygdala and different among different fractionations, better for Hfx, reaching significant differences. The same trends were demonstrated in LRFS and RRFS.We observed a 23% of second cancers, being lung the most common site. ConclusionConcomitant radiotherapy with weekly cisplatin is an appropriate treatment for oropharyngeal cancer. It provides excellent outcomes in tonsillar cancer, especially with modified fractionation and Hfx type. For other subsites it seems advisable to explore a new treatment approach.

The efficacy and toxicity of individualized intensity-modulated radiotherapy based on the tumor extension patterns of nasopharyngeal carcinoma.

BackgroundTo evaluate the efficacy and toxicity of intensity-modulated radiotherapy (IMRT) using individualized clinical target volumes (CTVs) based on the loco-regional extension patterns of nasopharyngeal carcinoma (NPC).MethodsFrom December 2009 to February 2012, 220 patients with histologically-proven, non-disseminated NPC were prospectively treated with IMRT according to an individualized delineation protocol. CTV1 encompassed the gross tumor volume, entire nasopharyngeal mucosa and structures within the pharyngobasilar fascia with a margin. CTV2 encompassed bilateral high risk anatomic sites and downstream anatomic sites adjacent to primary tumor, bilateral retropharyngeal regions, levels II, III and Va, and prophylactic irradiation was gave to one or two levels beyond clinical lymph nodes involvement. Clinical outcomes and toxicities were evaluated.ResultsMedian follow-up was 50.8 (range, 1.3–68.0) months, four-year local relapse-free, regional relapse-free, distant metastasis-free, disease-free and overall survival rates were 94.7%, 97.0%, 91.7%, 87.2% and 91.9%, respectively. Acute severe (≥ grade 3) mucositis, dermatitis and xerostomia were observed in 27.6%, 3.6% and zero patients, respectively. At 1 year, xerostomia was mild, with frequencies of Grade 0, 1, 2 and 3 xerostomia of 27.9%, 63.3%, 8.3% and 0.5%, respectively.ConclusionsIMRT using individualized CTVs provided high rates of local and regional control and a favorable toxicity profile in NPC. Individualized CTV delineation strategy is a promising one that may effectively avoid unnecessary or missed irradiation, and deserve optimization to define more precise individualized CTVs.

The association of clinical-pathologic factors and Oncotype Dx recurrence score (RS) in the outcome of early stage breast cancer.

55 Background: Oncotype Dx recurrence score (RS) is routinely used to guide systemic therapy based on the estimated risk for distant relapse. Patients with early stage disease are also at risk for locoregional recurrence, and in some instances local relapse is the only site of failure. The objective of this study is to evaluate patient outcomes in association with known clinical-pathologic risk factors and RS. Observations in context of known clinical-pathologic features and RS may have important clinical implications relative to adjuvant locoregional therapy. Methods: This is an IRB approved retrospective study that includes patients with unilateral breast cancer and in whom the RS was reported. A total of 716 patients met this defined criteria. Seventy two percent underwent breast conserving therapy (BCS) and 28% underwent mastectomy; 68% had stage I and the remaining had &gt; Stage II disease.The clinical-pathologic variables including age, stage, BRCA mutation, extent of surgery, and RS were studied in evaluating patient outcomes. Results: The median age was 56 years (27 to 84 years). The overall distribution of RS reported as low (18), intermediate (19-30), and high ( &gt; 31) was 59%, 31%, and 10%, respectively. This distribution ratio was no different among patients treated with BCS and mastectomy. However, among BRCA mutation carriers there was a higher incidence of the high RS.Overall, the median follow up was over 3 years, and 25% of the patients have been followed over 5 years. The 3-year and 5-year any relapse-free survival was 93% and 89%, respectively. Age was significantly associated with observed inferior any relapse-free survival; 85% and 91% in women &lt; 40 years vs &gt; 40 years, respectively (p = 0.018). On univariate analysis, RS had no significant association with local regional relapse free survival. Further, associations between the clinical-pathologic features and RS using multivariate analysis will be presented. Conclusions: Observations with early follow up do not suggest a select role of RS in guiding risk tailored local regional therapy. Longer follow will further our understanding of patients at risk for local regional relapse.

Concurrent erlotinib and radiotherapy for chemoradiotherapy-intolerant esophageal squamous cell carcinoma patients: results of a pilot study

Concurrent chemoradiotherapy is the standard treatment for patients with locally advanced esophageal squamous cell carcinoma. However, a number of patients present intolerance to chemoradiotherapy because of advanced age or malnutrition. Erlotinib, an inhibitor of epidermal growth factor receptor tyrosine kinase, was shown to be effective in treating esophageal carcinoma, with mild toxicities. In this pilot study, we investigated the safety and efficacy of concurrent erlotinib and radiotherapy as an alternative treatment modality for esophageal carcinoma patients who are intolerant to chemoradiotherapy. Pathologically diagnosed esophageal squamous cell carcinoma patients who could not tolerate concurrent chemoradiotherapy were enrolled. All patients were treated with concurrent erlotinib and intensity-modulated radiation therapy. Erlotinib was given orally for 60 days (150 mg per day). Radiotherapy (total dose, 60 Gy) was given at dosages of 2 Gy for a total of 30 times. Immunohistochemical staining was performed to assess epidermal growth factor receptor expression. Toxicities were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0). The overall survival, progression-free survival, and local-regional relapse-free survival were calculated using the Kaplan-Meier method. Between December 2007 and March 2011, 18 patients were enrolled. The median age was 71.5 years. Primary disease was stages II, III, and IV in 3, 8, and 4 patients, respectively. There were three patients with recurrent disease after radical surgery. The median follow-up time was 17.2 months. Grade 3 esophagitis and skin rash were observed in five (27.8%) and two (11.1%) patients, respectively. Radiation pneumonitis of grades 2 and 5 was observed in one patient each. No grade 3/4 impaired liver function or hematological toxicity was observed. At 1 month after radiotherapy, two (11.1%) patients achieved complete response, 11 (61.1%) patients achieved partial response, and 5 (27.8%) patients had stable disease. The median time of overall survival and progression-free survival was 21.1 and 12 months, respectively. Two-year overall survival, progression-free survival, and local-regional relapse-free survival were 44.4%, 38.9%, and 66.7%, respectively. Five of six patients examined for epidermal growth factor receptor had high expression levels (3+). The relationship between epidermal growth factor receptor expression and treatment outcomes could not be concluded. For esophageal squamous cell carcinoma patients who cannot tolerate chemoradiotherapy, concurrent erlotinib and radiotherapy are tolerable and effective. Valuable markers to predict the effect of erlotinib should be exploited in future studies.

Concurrent radiochemotherapy in locally-regionally advanced oropharyngeal squamous cell carcinoma: analysis of treatment results and prognostic factors.

BackgroundConcurrent radiochemotherapy is a recommended treatment option for patients with locally advanced squamous cell head and neck carcinomas with recent data showing the most significant absolute overall and event-free survival benefit achieved in patients with oropharyngeal tumours. The aim of this study was to analyse the results of three-dimensional conformal radiotherapy given with concomitant weekly cisplatin in patients with advanced oropharyngeal carcinoma and to identify prognostic factors influencing outcomes of this patients category.MethodsSixty-five patients with stage III or IV squamous cell carcinoma of the oropharynx who underwent concurrent radiochemotherapy between January 2005 and December 2010 were retrospectively analyzed. All patients received radiotherapy to 70 Gy/35 fractions/2 Gy per fraction/5 fractions per week. Concurrent chemotherapy consisted of weekly cisplatin (30 mg/m2) started at the first day of radiotherapy.ResultsMedian age was 57 years (range, 36 to 69 years) and 59 (90.8%) patients were male. Complete composite response was achieved in 47 patients (72.3%). Local and/or regional recurrence was the most frequent treatment failure present in 19 out of 25 patients (76.0%). At a median follow-up of 14 months (range, 5 to 72 months), 2-year local relapse-free, regional relapse-free, locoregional relapse-free, disease-free, and overall survival rates were 48.8%, 57.8%, 41.7%, 33.2% and 49.7%, respectively.On multivariate analysis the only significant factor for inferior regional relapse-free survival was the advanced N stage (p = 0.048). Higher overall stage was independent prognostic factor for poorer local relapse-free survival, locoregional relapse-free survival and disease-free survival (p = 0.022, p = 0.003 and p = 0.003, respectively). Pre-treatment haemoglobin concentration was an independent prognostic factor for local relapse-free survival, regional relapse-free survival, locoregional relapse-free survival, disease-free survival, and overall survival (p = 0.002, p = 0.021, p = 0.001, p = 0.002 and p = 0.002, respectively).ConclusionsPoor treatments results of this study suggested that introduction of intensity-modulated radiotherapy, use of induction chemotherapy followed by concurrent radiochemotherapy, accelerated radiotherapy regimens, and molecular targeted therapies could positively influence treatment outcomes. The incorporation of reversal of anaemia should be also expected to provide further improvement in locoregional control and survival in patients with advanced squamous cell carcinoma of the oropharynx.

Age &lt;40 Years is an Independent Prognostic Factor Predicting Inferior Overall Survival in Patients Treated with Breast Conservative Therapy

To evaluate the effect of age at diagnosis on the treatment outcome after breast conservative therapy (BCT), retrospective analysis was done for 378 patients undergoing BCT for early breast cancer. Patients were divided into two groups according to their age: 'younger' (<40years, n=108) and 'older' (≥40years, n=270). Multivariate analysis was performed on the variables including tumor characteristics, the use of systemic therapy, and age to assess risk factors for local-regional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), and overall survival rates (OS). The median follow-up duration was 94months. The 8-year LRRFS, DMFS, and OS for younger and older groups were 88.1% and 96.5% (p=0.0022); 85.7% and 93.7% (p=0.0310); 89.2% and 95.9% (p=0.0205), respectively. On multivariate analysis, younger age was the only significant predictor of poor LRRFS (p=0.0022). Younger age and ER negativity showed borderline significance for DMFS (p=0.0828 and 0.0618, respectively). Younger age had trend toward inferior OS (p=0.0702). In conclusion, age younger than 40years was associated with inferior LRRFS in early breast cancer patients treated with BCT. There was also a trend for inferior DMFS and OS in younger patients. Age at diagnosis should be considered for individualized patient management.