Nodal Relapse-free Survival Research Articles

Effect analysis of 847 nasopharyngeal carcinoma cases treated with intensity modulated radiation: Experience and suggestions

ObjectivesTo identify the failure patterns and prognostic factors of nonmetastatic nasopharyngeal carcinoma (NPC) in the intensity-modulated radiotherapy (IMRT) era. MethodsData on 847 patients with newly diagnosed, non-disseminated NPC treated by IMRT between 2012 and 2016 were retrospectively reviewed. Survival outcome, failure patterns and prognosis factors were analyzed. ResultsThe 5-year local relapse-free survival, nodal relapse-free survival, distant metastasis-free survival, disease-free survival, and overall survival rates were 94.3%, 95.3%, 84.8%, 76.5% and 85.7%, respectively. The major local recurrence sites were the nasopharynx (91.5%, 43/47) and skull base (68.1%, 32/47); 39 patients had in-field failures, four had marginal failures, and four had out-field failures. Level IIb (62.2%, 23/37) was the most frequent regional recurrence site, followed by IIa (35.1%, 13/37) and retropharyngeal region (32.4%, 12/37); 35 cases had in-field failure alone, one had out-field failure alone, and one had both in- and out-field failure. TNM stage was the most significant factor for prognosis prediction. 402 (47.5%) patients had acute adverse events of grade 3 or 4; leukopenia (31.5%) and mucositis (26.7%) was the most common hematological and non-hematological event, respectively. Late complications were slight or moderate damages; xerostomia (647/847, 76.4%) and hearing impairment (422/847, 49.8%) remained the most troublesome. ConclusionNPC patients treated with IMRT obtained satisfactory survival outcomes. The key failure pattern was distant metastasis. The main pattern of local–regional failure was in-field failure. Screening high risk patients with distant metastases and optimizing radiotherapy targets should be studied.

Long-term outcomes of nasopharyngeal carcinoma treated with helical tomotherapy using simultaneous integrated boost technique: A 10-year result.

To evaluate the long-term survival and treatment-related toxicities of helical tomotherapy (HT) in nasopharyngeal carcinoma (NPC) patients. One hundred and ninety newly diagnosed non-metastatic NPC patients treated with HT from September 2007 to August 2012 were analyzed retrospectively. The dose at D95 prescribed was 70-74Gy, 60-62.7Gy and 52-56Gy delivered in 33 fractions to the primary gross tumor volume (pGTVnx) and positive lymph nodes (pGTVnd), the high risk planning target volume (PTV1), and the low risk planning target volume (PTV2), respectively, using simultaneous integrated boost technique. The statistical analyses were performed and late toxicities were evaluated and scored according to the Common Terminology Criteria for Adverse Events (version 3.0). The median follow-up time was 145 months. The 10-year local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 94%, 95%, 86%, and 77.8%; respectively. Fifty (26.3%) patients had treatment-related failures at the last follow-up visit. Distant metastasis, occurred in 25 patients, was the major failure pattern. Multivariate analysis showed that age and T stage were independent predictors of DMFS and OS, Concomitant chemotherapy improved overall survival, but anti-EGFR monoclonal antibody therapy failed. The most common late toxicities were mainly graded as 1 or 2. Helical tomotherapy with simultaneous integrated boost technique offered excellent long-term outcomes for NPC patients, with mild late treatment-related toxicities. Age and clinical stage were independent predictors of DMFS and OS. And, concurrent chemotherapy means better OS. Further prospective study is needed to confirm the superiority of this technology and to evaluate the roles of anti-EGFR monoclonal antibody treatment.

Treatment of Locally Advanced Nasopharyngeal Carcinoma by Helical Tomotherapy: An Observational, Prospective Analysis

Nasopharyngeal carcinoma (NPC) is endemic in southern China. Due to the unique anatomical and biological properties of NPCs, radiotherapy or combined modality based on radiotherapy is an effective treatment option. Helical tomotherapy (HT) is an emerging intensity modulated radiotherapy technology. The advantages of dose homogeneity, steepness of dose gradient, and protection of normal organs are reflected in the treatment of head and neck cancers. We present the preliminary (2-year) clinical outcomes of HT in 85 patients with locally advanced NPC (LA-NPC). Of these patients, 3 patients (3.5%) experienced treatment interruption due to severe pulmonary infection, and 82 (96.5%) completed radiation treatments. The 2-year estimate of progression-free survival, local relapse-free survival, nodal relapse-free survival, distant metastases-free survival, and overall survival rate were 90%, 96.3%, 98.8%, 96.3%, and 96.3%, respectively. Among the three patients that died, one had stage III disease and died from fatal nasopharyngeal bleeding after radiotherapy, while the other two patients succumbed to local recurrence. Our experience suggests that HT can achieve promising disease control and survival in the treatment of LA-NPC patients with mild acute and late toxicity profiles.

Prognostic impact of nodal relapse in definitive prostate-only irradiation.

Whole pelvic irradiation in prostate cancer patients might prevent metastatic spread of cancer cells through lymphatic drainages in patients eligible for definitive radiotherapy, but its use has declined in the last decades in favor of prostate-only irradiation (POI). The aim of our study is to assess the incidence of pelvic lymph nodal relapse and outcome in prostate cancer patients receiving POI. Data from 207 consecutive patients were collected. Clinical and treatment variables were collected. Biochemical relapse-free survival (BRFS), pelvic nodal relapse-free survival (PNRFS), distant metastasis-free survival (DMFS), disease-specific survival (DSS) and overall survival (OS) were calculated; analysis of prognostic variables was performed. Five-year BRFS, PNRFS, DMFS, DSS and OS were, respectively, 90, 98, 96, 97 and 91%. On multivariate analysis, independent negative predictors of BRFS were Gleason score ≥ 7 (HR: 3.25) and PSA nadir ≥ 0.08 (HR: 4.86). Pelvic nodal relapse was not correlated to impaired outcome. Lymph nodal pelvic relapse occurs in 2% of patients at 5years and does not correlate with impaired outcome, suggesting the lack of theoretical benefit of a prophylactic nodal irradiation. Tumor biology and response to treatment are the main determinants of outcome.

Additional Cervical Lymph Node Biopsy is Not a Significant Prognostic Factor for Nasopharyngeal Carcinoma in the Intensity-Modulated Radiation Therapy Era: A Propensity Score-matched Analysis from an Epidemic Area.

Introduction: This study aimed to evaluate the prognostic value of cervical lymph node biopsy and whether different biopsy methods would lead different outcomes in NPC in the intensity-modulated radiotherapy (IMRT) era.Material and Methods: 1492 patients with biopsy-proven, non-metastatic NPC, and treated by IMRT with or without chemotherapy were retrospectively reviewed. Cervical lymph node biopsy was performed in 183 (12.3%) patients: 61(4.1%) by needle puncture and 118(7.9%) by excision biopsy. Propensity-score matching was used to match patients in both arms at an equal ratio. Overall survival (OS), distant metastasis-free survival (DMFS), locoregional relapse-free survival (LRFS), and nodal relapse-free survival (NRFS) were assessed using the Kaplan-Meier method and compared using the log-rank test. Independent prognostic factors were identified using the Cox proportional hazards model.Results: In the original cohort of 1492 patients, patients receiving cervical lymph node biopsy had comparable survival (OS: P = 0.736, DMFS: P = 0.749, LRFS: P = 0.538, NRFS: P = 0.093,) with patients receiving isolated napharynx biopsy. The results for the propensity-match cohort of 316 patients were similar. Interestingly, compared with the control group and needle puncture biopsy group, a slightly lower nodal recurrence rate was observed in the excision biopsy group (P = 0.082 and P = 0.072, respectively). Adjusting for the known prognostic factors in multivariate analysis, cervical biopsy did not cause a higher risk of death, distant metastasis, or nodal relapse.Conclusions: Pretreatment cervical lymph node biopsy is not associated with impaired survival in NPC, suggesting the resist of the biopsy and more aggressive treatment after the biopsy may be unnecessary.

The feasibility of contralateral lower neck sparing intensity modulation radiated therapy for nasopharyngeal carcinoma patients with unilateral cervical lymph node involvement

ObjectivesTo investigate the feasibility of contralateral lower neck sparing intensity modulation radiated therapy (IMRT) for nasopharyngeal carcinoma patients (NPC) with unilateral cervical lymph node metastasis. Materials and methodsRetrospective review of 546 patients with unilateral cervical lymph node metastasis treated between November 2009 and February 2012 at one institution. All patients were staged using magnetic resonance imaging and received radical IMRT. Patients were classified into two groups: the inferior border of the negative neck irradiation field only covered Levels III to Va in Group 1; the inferior border covered entire neck down to Levels IV to Vb in Group 2. ResultsMedian follow-up was 49.9months (range, 1.3–69.2months). Four-year overall survival (OS:89.3% vs. 88.9%, P=0.91), disease-free survival (DFS:81.7% vs. 81.0%, P=0.91), distant metastasis-free survival (DMFS:88.2% vs. 87.9%, P=0.95), local relapse-free survival (LRFS:96.7% vs. 94.7%, P=0.70) and nodal relapse-free survival (NRFS: 96.1% vs. 95.9%, P=0.94) were not significantly different between Group 1 and Group 2. Twenty-two patients developed cervical lymph node relapse; of whom 20/22 (91.0%) developed unilateral relapse within pretreatment positive neck. Only one patient developed out-of-field relapse, though this patient also relapsed within the neck irradiation field (Level II). No clinicopathological feature tested had significant prognostic value for NRFS in multivariate analysis. ConclusionsIn the IMRT and MRI era, contralateral lower neck sparing IMRT seems to be feasible for NPC patients with unilateral cervical lymph node metastasis.

Prognostic factors and failure patterns in non-metastatic nasopharyngeal carcinoma after intensity-modulated radiotherapy.

BackgroundThe prognostic values of staging parameters require continual re-assessment amid changes in diagnostic and therapeutic methods. This study aimed to identify the prognostic factors and failure patterns of non-metastatic nasopharyngeal carcinoma (NPC) in the intensity-modulated radiotherapy (IMRT) era.MethodsWe reviewed the data from 749 patients with newly diagnosed, biopsy-proven, non-metastatic NPC in our cancer center (South China, an NPC endemic area) between January 2003 and December 2007. All patients underwent magnetic resonance imaging (MRI) before receiving IMRT. The actuarial survival rates were estimated using the Kaplan–Meier method, and survival curves were compared using the log-rank test. Multivariate analyses with the Cox proportional hazards model were used to test for the independent prognostic factors by backward eliminating insignificant explanatory variables.ResultsThe 5-year occurrence rates of local failure, regional failure, locoregional failure, and distant failure were 5.4, 3.0, 7.4, and 17.4%, respectively. The 5-year survival rates were as follows: local relapse-free survival, 94.6%; nodal relapse-free survival, 97.0%; distant metastasis-free survival, 82.6%; disease-free survival, 75.1%; and overall survival, 82.0%. Multivariate Cox regression analysis revealed that orbit involvement was the only significant prognostic factor for local failure (P = 0.011). Parapharyngeal tumor extension, retropharyngeal lymph node involvement, and the laterality, longest diameter, and Ho’s location of the cervical lymph nodes were significant prognostic factors for both distant failure and disease failure (all P < 0.05). Intracranial extension had significant prognostic value for distant failure (P = 0.040).ConclusionsThe key failure pattern for NPC was distant metastasis in the IMRT era. With changes in diagnostic and therapeutic technologies as well as treatment modalities, the significant prognostic parameters for local control have also been altered substantially.

Neoadjuvant and Concurrent Chemotherapy Have Varied Impacts on the Prognosis of Patients with the Ascending and Descending Types of Nasopharyngeal Carcinoma Treated with Intensity-Modulated Radiotherapy.

PurposeTo compare the outcomes of patients with ascending type (T4&N0-1) and descending type (T1-2&N3) of nasopharyngeal carcinoma (NPC) treated with concurrent chemoradiotherapy (CCRT), neoadjuvant chemotherapy (NACT) + intensity-modulated radiotherapy (RT) or NACT + CCRT.MethodsRetrospective analysis of 839 patients with ascending or descending types of NPC treated at a single institution between October 2009 to February 2012. CCRT was delivered to 236 patients, NACT + RT to 302 patients, and NACT + CCRT to 301 patients.ResultsThe 4-year overall survival rate, distant metastasis-free survival rate, local relapse-free survival rate, nodal relapse-free survival rate, loco-regional relapse-free survival rate, and progression free survival rate were 75.2% and 73.4% (P = 0.114), 85.7% and 74.1% (P = 0.008), 88.8% and 97.1% (P = 0.013), 96.9% and 94.1% (P = 0.122), 86.9% and 91.2% (P = 0.384), 73.7% and 66.2% (P = 0.063) in ascending type and descending type. Subgroup analyses indicated that NACT + RT significantly improved distant metastasis-free survival rate and progression-free survival rate when compared with CCRT in the ascending type, and there were no significant differences between the survival curves of NACT +RT and NACT + CCRT. For descending type, there were no significant differences among the survival curves of NACT +RT, CCRT, and NACT + CCRT groups, and the survival benefit mainly came from CCRT.ConclusionsCompared with NACT + CCRT or CCRT, NACT + RT may be a reasonable approach for ascending type. Although concurrent chemotherapy was effective in descending type, NACT + CCRT may be a more appropriate strategy for descending type.

Prognostic Model of Death and Distant Metastasis for Nasopharyngeal Carcinoma Patients Receiving 3DCRT/IMRT in Nonendemic Area of China.

Few studies were conducted to explore the prognostic factors for nonendemic nasopharyngeal carcinoma (NPC) in the era of 3-dimensional conformal radiation therapy (3DCRT)/intensity-modulated radiation therapy (IMRT). The aim of this study was to evaluate the potential prognostic factors for nonendemic NPC.Between January 2004 and December 2011, a total of 393 nonendemic NPC patients receiving 3DCRT/IMRT were reviewed according to the inclusion and exclusion criteria. The prognostic factors we analyzed included age, T stage, N stage, lymph node diameter, primary tumor volume, WHO histology types, and cranial nerve related symptoms. All patients were staged according to the 7th edition of the American Joint Committee on Cancer (AJCC) system. The factors found to be associated with the endpoints by univariate analyses were then entered into multivariate Cox proportional hazards regression analysis.The median follow-up time was 61.4 months (range: 4–130 months). The 5-year local recurrent-free survival (LRFS), nodal relapse-free survival (NRFS), distant metastasis free survival (DMFS), and disease-specific survival (DSS) for all patients were 89.3%, 96.4%, 73.5%, and 74.3%, respectively. Multivariate analysis indicated that N stage (N2–3), WHO pathologic type II, and primary tumor volume (>23 mL) were 3 independent prognostic factors for DSS and DMFS. According to the number of prognostic factors, patients were divided into 3 risk groups: low-risk group (patients without any risk factors); intermediate-risk group (patients with only 1 risk factor); and high-risk group (patients with more than 2 risk factors). The 5-year DSS for low, intermediate, and high-risk groups were 91.5%, 75.2%, and 49.3%, respectively (P < 0.001). The 5-year DMFS for low, intermediate, and high-risk groups were 89.4%, 77.9%, and 49.4%, respectively (P < 0.001).Advanced N stage (N2–3), larger tumor volume (>23 mL), and histological WHO type II are independently prognostic factors for nonendemic NPC patients in China.

Treatment of nasopharyngeal carcinoma using simultaneous modulated accelerated radiation therapy via helical tomotherapy: a phase II study.

BackgroundThe aim of the study was to evaluate short-term safety and efficacy of simultaneous modulated accelerated radiation therapy (SMART) delivered via helical tomotherapy in patients with nasopharyngeal carcinoma (NPC).MethodsBetween August 2011 and September 2013, 132 newly diagnosed NPC patients were enrolled for a prospective phase II study. The prescription doses delivered to the gross tumor volume (pGTVnx) and positive lymph nodes (pGTVnd), the high risk planning target volume (PTV1), and the low risk planning target volume (PTV2), were 67.5 Gy (2.25 Gy/F), 60 Gy (2.0 Gy/F), and 54 Gy (1.8 Gy/F), in 30 fractions, respectively. Acute toxicities were evaluated according to the established RTOG/EORTC criteria. This group of patients was compared with the 190 patients in the retrospective P70 study, who were treated between September 2004 and August 2009 with helical tomotherapy, with a dose of 70-74 Gy/33F/6.5W delivered to pGTVnx and pGTVnd.ResultsThe median follow-up was 23.7 (12–38) months. Acute radiation related side-effects were mainly problems graded as 1 or 2. Only a small number of patients suffered from grade 4 leucopenia (4.5%) or thrombocytopenia (2.3%). The local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), local-nodal relapse-free survival (LNRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 96.7%, 95.5%, 92.2%, 92.7% and 93.2%, at 2 years, respectively, with no significant difference compared with the P70 study.ConclusionsSmart delivered via the helical tomotherapy technique appears to be associated with an acceptable acute toxicity profile and favorable short-term outcomes for patients with NPC. Long-term toxicities and patient outcomes are under investigation.

Long-term efficacy of intensity-modulated radiotherapy with or without chemotherapy in treatment of nasopharyngeal carcinoma and its influencing factors: an analysis of 454 patients

Objective To analyze the long-term efficacy of intensity-modulated radiotherapy (IMRT) with or without chemotherapy in treatment of 454 patients with nasopharyngeal carcinoma (NPC) and its influencing factors. Methods A retrospective analysis was performed on the clinical data of 454 patients with non-metastatic NPC who received IMRT with or without chemotherapy in our center from 2007 to 2012. Prescribed doses of 69.96-73.92 Gy in 33 fractions, 69.96 Gy in 33 fractions, 60.06 Gy in 33 fractions, and 50.96 Gy in 28 fractions were applied to nasopharyngeal gross tumor volume, cervical metastatic lymph nodes, high-risk drainage area, and low-risk drainage area, respectively. In all patients, 438 received induction chemotherapy, 420 concurrent chemotherapy, and 216 adjuvant chemotherapy, most of which were based on cisplatin and taxol. The Kaplan-Meier method was used for calculating survival rates and the log-rank test was used for survival difference analysis and univariate prognostic analysis. The Cox model was used for the multivariate prognostic analysis. Results The 3-year sample size was 210. The 3-year overall survival (OS), local recurrence-free survival, nodal relapse-free survival, progression-free survival, and distant metastasis-free survival (DMFS) rates were 88.1%, 91.0%, 90.7%, 80.5%, and 85.1%, respectively. Age, T stage, and N stage were influencing factors for the OS rate (P=0.011; P=0.005; P=0.033); T stage and N stage were influencing factors for the disease progression-free survival (P=0.017; P=0.005) and DMFS (P=0.012; P=0.019). The grade ≥3 acute and late adverse reactions included hematological toxicity, oral mucositis, xerostomia, dysphagia, and brain injury. Conclusions IMRT promotes the long-term survival rates in patients with NPC. The distant metastasis is the major reason for treatment failure. The adverse reactions induced by IMRT combined with chemotherapy are tolerable. Key words: Nasopharyngeal neoplasms/radiotherapy; Radiotherapy, intensity-modulated; Prognosis

Intensity-modulated radiotherapy prolongs the survival of patients with nasopharyngeal carcinoma compared with conventional two-dimensional radiotherapy: A 10-year experience with a large cohort and long follow-up

BackgroundTo evaluate the survival benefit of intensity-modulated radiotherapy (IMRT) compared with conventional two-dimensional radiotherapy (2D-CRT) in nasopharyngeal carcinoma (NPC) using a large cohort with long follow-up. MethodsWe retrospectively analysed 7081 non-metastatic NPC patients who received curative IMRT or 2D-CRT from February 2002 to December 2011. ResultsOf the 7081 patients, 2245 (31.7%) were administered IMRT, while 4836 (68.3%) were administered 2D-CRT. At 5years, the patients administered IMRT had significantly higher local relapse-free survival (LRFS), loco-regional relapse-free survival (LRRFS), progression-free survival (PFS) and overall survival (OS) (95.6%, 92.5%, 82.1% and 87.4%, respectively) than those administered 2D-CRT (90.8%, 88.5%, 76.7% and 84.5%, respectively; p<0.001). The distant metastasis-free survival (DMFS) was higher for IMRT than 2D-CRT, with borderline significance (87.6% and 85.7%, respectively; p=0.056). However, no difference was observed between IMRT and 2D-CRT in nodal relapse-free survival (NRFS; 96.3% and 97.4%, respectively; p=0.217). Multivariate analyses showed that IMRT was an independent protective prognostic factor for LRFS, LRRFS and PFS, but not NRFS, DMFS or OS. ConclusionsIMRT provided an improved LRFS, LRRFS and PFS in both the early and advanced T classifications and overall stage for non-disseminated NPC compared with 2D-CRT. However, no significant advantage was observed in NRFS, DMFS or OS when IMRT was used.

Clinical outcomes and toxicity after exclusive versus postoperative radiotherapy in supraglottic cancer: new solutions for old problems? The case of stage I and II disease.

To compare acute and late toxicities, survival, and laryngeal preservation after radiotherapy alone (RR) or radiotherapy after partial laryngectomy (PLR) in early supraglottic laryngeal cancer. From 1984 to 2012, 172 patients were treated in our department. We analyzed and compared toxicities (CTCAE v 4.0), overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), metastasis-free survival (MFS), and the number of salvage total laryngectomies. Patients in the RR group were older (p = 0.05) and had more often comorbidities (p = 0.025); those in the PLR group had mostly T2 disease (p = 0.014). No difference in number of local, nodal, and distant recurrences was found. A higher incidence of late mild dry mouth in patients treated with RR (38 vs. 4 %, p = 0.000) was reported. At univariate analysis, only a younger age, a better performance status, and the absence of comorbidities favorably impacted on OS and DSS. No differences were found in DFS, LRFS, NRFS, MFS, and the number of rescue laryngectomies between the two groups. Younger age and a good performance status persisted as a predictive factor of better survival (OS and DSS) at multivariate analysis. Radical radiotherapy appears to be a viable alternative to conservative surgery, even in elderly patients with poor performance status and comorbidities. Salvage laryngectomy in the RR group was compared favorably with those reported in other conservative surgery series and in the group treated postoperatively of our series.

Risk stratification of metastatic neck nodes by CT and PET in patients with head and neck cancer receiving definitive radiotherapy.

The aim of this study was to investigate the prognostic impact of CT and (18)F-FDG PET/CT on the outcome of metastatic neck node (MNN) in patients with head and neck cancer receiving definitive radiotherapy or chemoradiotherapy. This patient-based study included 91 patients diagnosed with pharyngeal cancers with MNN (N1, 15; N2, 70; N3, 6). All had pretreatment CT and PET/CT before definitive chemoradiotherapy/radiotherapy. Parameters of MNNs for each patient, including maximal diameter, nodal volume, radiologic central necrosis, maximum standardized uptake value, metabolic tumor volume, and total lesion glycolysis (TLG), were retrieved for the analysis. Nodal relapse-free survival (NRFS) and survivals were calculated using the Kaplan-Meier method. Independent predictors were identified using Cox regression analysis. After a median follow-up of 18 mo, 64 patients remained nodal relapse-free, and 27 experienced neck recurrence. Multivariate analysis showed that the application of 40% of the maximal uptake of nodal TLG (N-TLG40%) 38 g or greater (P = 0.03; hazard ratio, 2.63; 95% confidence interval, 1.10-6.30) and radiologic necrosis on CT scan (P = 0.001; hazard ratio, 10.99; 95% confidence interval, 2.56-47.62) were 2 adverse features for NRFS. Patients who had an N-TLG40% 38 g or greater and central radiologic necrosis had a significantly inferior 2-y NRFS (53% vs. 77% and 45% vs. 95%, respectively). The outcome of MNNs in patients with head and neck cancer receiving chemoradiotherapy/radiotherapy can be predicted according to radiologic necrosis and N-TLG40% value. The 2 adverse features should be validated in future trials. In this way, patients can be treated alternatively or aggressively.

Interim FDG PET/CT for predicting the outcome in patients with head and neck cancer.

The study aimed to investigate the prognostic effects of interim (18) fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (PET/CT) during definitive radiotherapy (RT) or chemoradiotherapy (CRT) in patients with head and neck cancer. This is a prospectively treatment study. The pretreatment and interim PET/CT images of 51 patients with advanced pharyngeal cancers receiving definitive RT/CRT were evaluated prospectively. The interim PET/CT images were taken at a cumulative RT dose ranging from 41.4 to 46.8 Gy. The maximum standardized uptake value (SUVm) of the interim PET/CT and the reduction ratio of the SUVm (SRR) between the two images were measured. The differences between patients with or without local failures were examined using the Mann-Whitney test. Overall survival (OS), disease-free survival (DFS), and primary and nodal relapse-free survival rates were calculated using the Kaplan-Meier method. Independent prognosticators were identified using Cox regression analysis. After a median follow-up duration of 23 months, a higher interim SUVm was associated with local failures. Conducting a multivariate analysis revealed that a SUVmax reduction ratio of primary tumor (SRR-P) < 0.64 was associated with the inferior OS (hazard ratio 2.64; P =0.035) and DFS (hazard ratio 2.33; P = 0.045). Patients who had tumors with an SRR-P < 0.64 had a considerably lower 2-year OS and DFS compared with those who had SRR-P ≥ 0.64 (47% vs. 66%; 41% vs. 64%). A higher interim SUVm was associated with local recurrence. In addition, patients with a lower SRR-P should be considered to be at risk of primary failure. 4.

Clinical study of nasopharyngeal carcinoma treated by helical tomotherapy in China: 5-year outcomes.

Background. To evaluate the outcomes of nasopharyngeal carcinoma (NPC) patients treated with helical tomotherapy (HT). Methods. Between September 2007 and August 2012, 190 newly diagnosed NPC patients were treated with HT. Thirty-one patients were treated with radiation therapy as single modality, 129 with additional cisplatin-based chemotherapy with or without anti-EGFR monoclonal antibody therapy, and 30 with concurrent anti-EGFR monoclonal antibody therapy. Results. Acute radiation related side effects were mainly grade 1 or 2. Grade 3 and greater toxicities were rarely noted. The median followup was 32 (3–38) months. The local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were 96.1%, 98.2%, 92.0%, and 86.3%, respectively, at 3 years. Cox multivariate regression analysis showed that age and T stage were independent predictors for 3-year OS. Conclusions. Helical tomotherapy for NPC patients achieved excellent 3-year locoregional control, distant metastasis-free survival, and overall survival, with relatively minor acute and late toxicities. Age and T stage were the main prognosis factors.

A prospective, randomized study comparing outcomes and toxicities of intensity-modulated radiotherapy vs. conventional two-dimensional radiotherapy for the treatment of nasopharyngeal carcinoma

Background and PurposeTo compare clinical outcomes and toxicities of two-dimensional conventional radiation therapy (2D-CRT) and intensity modulated radiation therapy (IMRT) for the treatment of nasopharyngeal carcinoma (NPC). Materials and methodsBetween July 2003 and October 2008, 616 patients with non-metastatic stage I to IVb NPC were prospectively randomized to receive 2D-CRT (n=310; mean age, 44.8±13.6years) or IMRT (n=306; mean age, 46.7±12.5years). Clinical outcomes and acute and late toxicities were determined and compared. ResultsThe 2 groups were comparable with respect to all parameters of demographics and disease characteristics (all, p>0.05). Median follow-up was 42months (range, 1–83months). The 5-year actuarial local control rate was 90.5% in the IMRT group and 84.7% in the 2D-CRT group. The local control rates were 91% for stage T3 and 81.5% for stage T4 disease in the IMRT group and 80% and 62.2% in the 2D-CRT group, respectively. The 5-year actuarial nodal relapse-free survival (NRFS) rate was 92.4% in the IMRT and 92.9% in the 2D-CRT group (p>0.05). The NRFS was 93.9% for N2 disease in the IMRT group and 91.4% in the 2D-CRT group (p=0.02). The 5-year overall survival (OS) rate was 79.6% for the IMRT group and 67.1% for the 2D-CRT group (p=0.001). When stratified for stage, a significant difference was only noted for stage III disease. In terms of radiation-induced toxicities, patients in IMRT group had significantly lower radiation-induced toxicities than those in 2D-CRT group. ConclusionIMRT provides improved local-recurrence free survival, especially in late-stage NPC patients and is associated with a lower incidence of toxicities.

Clinic results of 121 nasopharyngeal carcinoma patients treated by helical tomotherapy

Objective To summarize the outcome of nasopharyngeal carcinoma ( NPC) treated by helical tomotherapy in the Chinese PLA general hospital. Methods Between September 2007 and August 2010, 121 newly diagnosed NPC patients were treated by radiotherapy with Tomotherapy system, with ( n =90) or without ( n = 31) concurrent chemotherapy or molecular target therapy. The prescription dose was 70 - 74 Gy/33f to primary tumor and positive lymph node planning target volume,60. 0 - 62. 7 Gy/33f to high risk planning target volume, and 52 -56 Gy/33f to low risk planning target volume. Acute side-effects were evaluated with RTOG/EORTC criteria. Results The remission rate of primary lesion and positive lymph nodes was 95. 0％ and 99. 0％ , respectively. The follow-up rate was 100％ . The number of patients with 1 ,2 and 3 years followed-up were 99 , 49 , and 7. The 1-, 2-and 3-year local relapse-free survival rates were 97. 30％ , 97. 3％ and 97. 3％ , respectively. The 1-,2-and 3-year nodal relapse-free survival rates were 100％ , 100％ and lOO％, respectively. The 1-, 2-and 3-year distant metastasis-free survival rates were 98. 4％ , 96. 3％ and 96. 3％ , respectively. The 1-, 2-and 3-year overall survival rates were 96. 5％ ,92. 6％ and 86. 8％ , respectively. Acute toxicities of skin, oral mucosa and xerostomia with grade 0,1,2 and 3 were 5. 0％ , 74. 4％ , 15. 7％ and 4. 9％ ; 0. 8％ , 37. 2％ , 57. 9％ and 4. 1％ ; 3. 3％ , 53. 7％ ,43. 0％ and 0％ , respectively. Xerostomia restored with time, no grade 2 or more xerostomia was observed 1 year after radiation therapy. Concurrent chemotherapy significantly increased incidence of mucositis,esophagitis and tracheitis. Conclusion Helical tomotherapy is efficient, secure and effective modality for the treatment of nasopharyngeal carcinoma. Key words: Nasopharyngeal neoplasms/radiotherapy; Radiotherapy,helical tomotherapy; Toxicities; Prognosis

Promising treatment outcomes of intensity-modulated radiation therapy for nasopharyngeal carcinoma patients with N0 disease according to the seventh edition of the AJCC staging system

BackgroundIntensity-modulated radiation therapy (IMRT) provides excellent locoregional control for nasopharyngeal carcinoma (NPC), and has gradually replaced two-dimensional conventional radiotherapy as the first-line radiotherapy technique. Furthermore, in the new seventh edition of the American Joint Committee on Cancer (AJCC) staging system, retropharyngeal lymph nodes were upgraded from N0 to N1 disease as a result of their negative impact on the distant metastasis-free survival (DMFS) rates of NPC. This retrospective study was conducted in order to review the treatment outcomes and patterns of failure in NPC patients with N0 disease after IMRT in order to effectively guide treatment in the future.MethodsWe retrospectively reviewed data from 506 biopsy-proven nonmetastatic NPC patients. There were 191 patients with negative cervical lymph node involvement. According to the seventh edition of the American Joint Committee on Cancer (AJCC) staging system, 110 patients (21.7%) were staged with N0 disease, and 81 patients (16.0%) were reclassified with N1 disease due to the presence of RLN metastasis. All patients received IMRT as the primary treatment.ResultsIn patients with negative cervical lymph node involvement, distant metastasis-free survival (DMFS) was significantly higher in patients without retropharyngeal lymph node (RLN) metastasis than those with RLN metastasis (95.9% vs. 88.1% respectively, P = 0.04). For N0 disease, the 5-year overall survival (OS), local relapse-free survival (LRFS), nodal relapse-free survival (NRFS) and DMFS rates were 93.8%, 97.1%, 99.1% and 95.9%, respectively. For T1N0, T2N0, T3N0 and T4N0, OS was 97.8%, 100%, 93.8% and 76.9%, LRFS was 100%, 92.9%, 100% and 88.9% and DMFS was 96.6%, 90.9%, 100% and 93.3%, respectively. OS and LRFS were higher in T1-3 N0 patients than T4N0 patients (P < 0.01 and P = 0.01, respectively).ConclusionsThe seventh edition of the AJCC N-staging system improves prognostic accuracy by upgrading RLN metastasis to N1 disease. IMRT produces excellent survival rates in T1-3 N0 disease; however, T4N0 disease remains a challenge and additional improvements are required to achieve a favorable prognosis for these NPC patients.

MiR-218 Suppresses Nasopharyngeal Cancer Progression through Downregulation of Survivin and the SLIT2-ROBO1 Pathway

Nasopharayngeal carcinoma (NPC) is an Epstein-Barr virus-associated malignancy most common in East Asia and Africa. Here we report frequent downregulation of the microRNA miR-218 in primary NPC tissues and cell lines where it plays a critical role in NPC progression. Suppression of miR-218 was associated with epigenetic silencing of SLIT2 and SLIT3, ligands of ROBO receptors that have been previously implicated in tumor angiogenesis. Exogenous expression of miR-218 caused significant toxicity in NPC cells in vitro and delayed tumor growth in vivo. We used an integrated trimodality approach to identify targets of miR-218 in NPC, cervical, and breast cell lines. Direct interaction between miR-218 and the 3'-untranslated regions (UTR) of mRNAs encoding ROBO1, survivin (BIRC5), and connexin43 (GJA1) was validated in a luciferase-based transcription reporter assay. Mechanistic investigations revealed a negative feedback loop wherein miR-218 regulates NPC cell migration via the SLIT-ROBO pathway. Pleotropic effects of miR-218 on NPC survival and migration were rescued by enforced expression of miR-218-resistant, engineered isoforms of survivin and ROBO1, respectively. In clinical specimens of NPC (n=71), ROBO1 overexpression was significantly associated with worse overall (P=0.04, HR=2.4) and nodal relapse-free survival (P=0.008, HR=6.0). Our findings define an integrative tumor suppressor function for miR-218 in NPC and further suggest that restoring miR-218 expression in NPC might be useful for its clinical management.