Chunying Shen

Treatment outcomes and prognostic features in adenoid cystic carcinoma originated from the head and neck

Surgery is the main treatment modality for adenoid cystic carcinoma (ACC) originated from the head and neck. However, the extensive local infiltrative and perineural spread related to this malignancy often cause difficulty to achieve high tumor control. The aim of this study is to evaluate the efficacy of postoperative radiotherapy (RT) in ACC, and to identify prognostic variables associated with treatment outcomes. A retrospective review of 101 patients diagnosed with ACC in the head and neck region was performed. T stage distribution was T1, 25; T2, 35; T3, 18; and T4, 23 patients. All patients were grouped into two arms: surgery alone or combined with postoperative radiotherapy. The 5-year local-regional control (LRC), overall survival (OS) and disease-free survival (DFS) rates for all the patients were 70.5%, 91.7% and 63.2%, respectively. On univariant analysis, postoperative radiotherapy did improve the 5-year LRC and DFS compared to surgery alone (81.0% vs. 53.4%, p=0.0003 and 71.3% vs. 50.0%, p=0.0052, respectively). And patients with T1-T2 lesions achieved better treatment outcomes, whereas stage T3-T4 was associated with high local failure and poor disease-free survival. Furthermore, multivariate analysis revealed that the addition of radiotherapy and early lesions were both favorite predictors for local control and survival rates. The prognosis for ACC of the head and neck was excellent. Surgery combined with postoperative radiotherapy significantly reduced the local failure, and further improved disease-free survival. Nevertheless, the relatively high distant metastasis was an obstacle of curing the ACC patients.

Prognostic Impact of Primary Tumor Volume in Patients With Nasopharyngeal Carcinoma Treated by Definitive Radiation Therapy

Objectives/Hypothesis: Tumor burden has been confirmed as one of the important indicators in disease control after treatment for various types of malignancies. This report aims to document the value of the primary tumor volume of nasopharyngeal carcinoma [gross tumor volume of the primary site (GTV‐P)] in predicting the treatment outcome after high‐dose definitive radiation therapy.

Effect of dosimetric factors on occurrence and volume of temporal lobe necrosis following intensity modulated radiation therapy for nasopharyngeal carcinoma: A case-control study

PURPOSE To determine dosimetric risk factors for the occurrence of temporal lobe necrosis (TLN) among nasopharyngeal carcinoma (NPC) patients treated with intensity modulated radiation therapy (IMRT) and to investigate the impact of dose-volume histogram (DVH) parameters on the volume of TLN lesions (V-N). METHODS AND MATERIALS Forty-three NPC patients who had developed TLN following IMRT and 43 control subjects free of TLN were retrospectively assessed. DVH parameters included maximum dose (Dmax), minimum dose (Dmin), mean dose (Dmean), absolute volumes receiving specific dose (Vds) from 20 to 76 Gy (V20-V76), and doses covering certain volumes (Dvs) from 0.25 to 6.0 cm(3) (D0.25-D6.0). V-Ns were quantified with axial magnetic resonance images. RESULTS DVH parameters were ubiquitously higher in temporal lobes with necrosis than in healthy temporal lobes. Increased Vds and Dvs were significantly associated with higher risk of TLN occurrence (P<.05). In particular, Vds at a dose of ≥70 Gy were found with the highest odds ratios. A common increasing trend was detected between V-N and DVH parameters through trend tests (P for trend of <.05). Linear regression analysis showed that V45 had the strongest predictive power for V-N (adjusted R(2) = 0.305, P<.0001). V45 of <15.1 cm(3) was relatively safe as the dose constraint for preventing large TLN lesions with V-N of >5 cm(3). CONCLUSIONS Dosimetric parameters are significantly associated with TLN occurrence and the extent of temporal lobe injury. To better manage TLN, it would be important to avoid both focal high dose and moderate dose delivered to a large area in TLs.

Treatment outcomes and late toxicities of 869 patients with nasopharyngeal carcinoma treated with definitive intensity modulated radiation therapy: new insight into the value of total dose of cisplatin and radiation boost

This study was to report the long-term outcomes and toxicities of nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). From 2009 to 2010, 869 non-metastatic NPC patients treated with IMRT were retrospectively enrolled. With a median follow-up of 54.3 months, the 5-year estimated local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) were 89.7%, 94.5%, 85.6%, 76.3%, 84.0%, respectively. In locally advanced NPC, gender, T, N, total dose of cisplatin more than 300 mg/m2 and radiation boost were independent prognostic factors for DMFS and DFS. Age, T, N and total dose of cisplatin were independent prognostic factors for OS. Radiation boost was an adverse factor for LRFS, RRFS, DMFS and DFS. Concurrent chemotherapy was not an independent prognostic factor for survival, despite marginally significant for DMFS in univariate analysis. Concurrent chemotherapy increased xerostomia and trismus, while higher total dose of cisplatin increased xerostomia and otologic toxicities. In conclusion, IMRT provided satisfactory long-term outcome for NPC, with acceptable late toxicities. Total dose of cisplatin was a prognostic factor for distant metastasis and overall survival. The role of concurrent chemotherapy and radiation boost in the setting of IMRT warrants further investigation.

Involvement of both Cervical Lymph Nodes and Retropharyngeal Lymph Nodes has prognostic value for N1 patients with Nasopharyngeal Carcinoma

BackgroundThe N1 definition of 2010 UICC/AJCC staging system for nasopharyngeal carcinoma (NPC) covers quite a large range of nodal pattern. The objective of this research is to investigate prognostic value of lymph nodes related factors including involvement of both cervical lymph nodes (CLNs) and retropharyngeal lymph nodes (RLNs) or not, size and number of cervical lymph nodes (CLNs) in N1 patients with NPC.Methods142 newly diagnosed non-metastatic N1 patients with NPC, staged according to the 2010 AJCC staging system for NPC were retrospectively enrolled. All patients had undergone contrast-enhanced magnetic resonance imaging (MRI), and received radiotherapy, with or without chemotherapy as their primary treatment.ResultsThe median follow-up was 48 months. The 5-year local recurrence-free survival (LFS), nodal recurrence-free survival (NFS), local-regional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) of the whole group were 82.3%, 83.0%, 81.0%, 82.1%, 75.3% and 89.8%, respectively. In univariate analysis, patients with both CLNs and RLNs involvement showed a significant lower DMFS, PFS and LRFS than the rest patients (p = 0.004 p = 0.003 and p = 0.034, respectively). Neither size nor number of CLNs affected the survival. In multivariate analysis, involvement of both CLNs and RLNs was an independent prognostic factor for DMFS and PFS (p = 0.019, p = 0.019), but there was no enough evidence confirming its prognostic value for LRFS (p = 0.051).ConclusionsFor N1 patients with NPC, involvement of both RLNs and CLNs may be a potentially prognostic factor for distant metastasis and disease progression. The N stage for N1 patients with involvement of both cervical lymph nodes and retropharyngeal lymph nodes might need to be deliberated.

Treatment outcome of nasopharyngeal carcinoma with retropharyngeal lymph nodes metastasis only and the feasibility of elective neck irradiation

OBJECTIVE To investigate the outcome of nasopharyngeal carcinoma (NPC) with retropharyngeal lymph nodes (RLNs) metastasis only and evaluate the feasibility of elective neck irradiation. MATERIALS AND METHODS This is a retrospective study of 119 newly diagnosed non-metastatic NPC patients with RLNs metastasis only. All of them received definitive radiotherapy. Eighty nine patients received elective neck irradiation to levels II, III, VA and the rest received whole neck irradiation, including levels II-V. RESULTS The median follow-up was 36.6 months. The 5-year local recurrence-free survival (LFS), nodal recurrence-free survival (NFS), distant metastasis-free survival (DMFS) and overall survival (OS) was 81.4%, 92.7%, 91.8%, and 93.6%, respectively. Four patients developed nodal relapse and only one was out-of-field relapse. No significant difference of nodal recurrence was observed between elective neck irradiation and whole neck irradiation. IMRT or three-dimensional conformal radiotherapy (3D-CRT) showed a trend of improving regional control, compared with conventional two-dimensional radiotherapy (2D-RT) (p=0.074). In 2D-RT, a higher dose (>5600 cGy) to the upper neck showed a benefit of regional control(p=0.006). Multivariate analysis demonstrated that only the dose of upper neck was an independent prognostic factor of NFS. CONCLUSIONS Elective irradiation to levels II, III, VA was not inferior to whole neck irradiation for NPC patients with RLNs metastasis only. However, more evidences are needed to confirm the result. IMRT showed a trend of improving regional control. A higher dose of prophylactic radiation may be required for upper neck region in patients with RLNs metastasis.

Salvage Intensity-Modulated Radiation Therapy (IMRT) for Locally Recurrent Nasopharyngeal Cancer after Definitive IMRT: A Novel Scenario of the Modern Era.

Locally recurrent nasopharyngeal carcinoma (rNPC) after definitive IMRT occurs in 10% of all cases and represents a distinct clinical entity that has been selectively enriched by radio-resistant cancer cells. Therefore, we report of the outcomes of 77 patients who had repeat salvage-IMRT for rNPC after only a definitive course of IMRT. Various clinical outcomes were measured. Log-rank tests were used to detect differences in the survival outcomes between factor-defined subgroups. Multivariable analysis was performed using the Cox proportional hazard model. The median follow-up time was 25.7 months (range 3.0–75.7 months), measured from the time of recurrence. The median OS time and PFS time of the entire cohort was 37.0 and 20.5 months, respectively. Thirty-four patients (44.2%) died. Approximately 35% of these patients died from disease progression, but 53% were from treatment-induced severe adverse effects (SAEs) without evidence of disease progression. Higher T-classification of the recurrent tumor and the development of SAEs were found to be the only independent and significant adverse prognostic factors on multivariable analysis. These outcomes underscore the particularly virulent characteristics of rNPC after definitive IMRT. Concerning is the impact of re-irradiation toxicity on patient mortality.

Omission of chemotherapy in early stage nasopharyngeal carcinoma treated with IMRT a paired cohort study

AbstractThe objective of this study was to evaluate the necessity of concurrent chemotherapy in T1-2N1 nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiation therapy (IMRT).The retrospective analysis was conducted using the paired comparison method. We matched cases to controls using the greedy matching algorithm with 1:1 control to case ratio. Controls were matched to cases by factors including age, gender, T stage, and duration of RT. The control group included patients received IMRT alone. In another group, concurrent chemotherapy (DDP 40 mg/m2/w) was administrated to each paired patient.From Jan 2009 to Dec 2011, a total of 86 well-balanced T1-2N1 (2002 UICC staging system) NPC patients were retrospectively analyzed. Half of them (43 patients) received radical IMRT alone and another 43 received concurrent chemotherapy with IMRT (CCRT). Median follow-up is 37.4 months (4.8–66.2 months). All patients received a radiation dose of 66Gy/30Fx. In the CCRT group, all patients received a cumulative dose of ≥200 mg/m2. The differences of 3-year overall survival (OS), 3-year progression-free survival (PFS), 3-year relapse-free survival (RFS), and 3-year metastasis-free survival (MFS) between 2 groups were not significant (P > 0.05). The most frequently increased toxicities related to chemotherapy were mild to moderate leukopenia (P = 0.003) and mild anemia (P = 0.008).Omission of weekly cisplatin chemotherapy resulted in comparable survival outcomes to CCRT in IMRT populations. More data from future randomized trials are warranted to further confirm it.

The role of adjuvant chemotherapy in nasopharyngeal carcinoma with bulky neck lymph nodes in the era of IMRT

Nasopharyngeal carcinoma (NPC) patients with N2–3 diseases are prone to develop distant metastasis even treated with standard concurrent chemoradiotherapy (CCRT). Our study is aim to determine the optimal treatment strategy of these patients. Patients with histologically proven NPC were retrospectively analyzed according to the AJCC 2002 stage classification system. A total of 547 patients who had N2–3 diseases were enrolled. They were all treated with Intensity-modulated radiation therapy (IMRT) combined with systemic treatments, including radiotherapy alone (RT alone), neoadjuvant chemotherapy followed by radiotherapy (NACT+RT), CCRT, NACT+CCRT, NACT followed by radiotherapy and adjuvant chemotherapy (NACT+RT+AC), CCRT+AC and NACT+CCRT+AC. A subgroup analysis was also conducted. With a median follow-up time of 53.8 months, adjuvant chemotherapy significantly decreased the risk of distant metastasis (HR 0.413, 95% CI 0.194–0.881, p = 0.022) as well as significantly increased the OS (HR 0.398, 95% CI 0.187–0.848, p = 0.017) in patients with N3 disease. The addition of adjuvant chemotherapy seemed to provide benefits to patients with N3 stage NPC and the current study may indicate the need for further randomized investigation.

Cetuximab in combination with chemoradiotherapy in the treatment of recurrent and/or metastatic nasopharyngeal carcinoma

The aim of the study was to assess the efficacy and toxicity of cetuximab in the combined treatment for patients with recurrent and/or metastatic nasopharyngeal carcinoma (R/M NPC). Between March 2007 and November 2011, a total of 30 R/M NPC patients treated with comprehensive therapy including cetuximab were retrospectively enrolled. Intensity-modulated radiation therapy was delivered in recurrent disease with a median dose of 60 Gy. Chemotherapy regimens included TP/TPF (docetaxel 60–75 mg/m2 d1+DDP 25 mg/m2 d1–3±5-FU 500 mg/m2/day with 120-h infusion), GP (gemcitabine 1.0 g/m2 d1, d8+DDP 25 mg/m2 d1–3), and PC (paclitaxel 60 mg/m2/week d1+carboplatin AUC 2/week d1). Acute and late toxicities were documented by the radiation oncologists. The median age of the patients was 44 years (range 26–62). A total of 21 patients (70%) achieved response (CR+PR). The median survival time, time to progression, and 2-year overall survival were 23.6, 12.2 months, and 53.3%, respectively. Cetuximab appears to be effective and well tolerated when combined with chemoradiation therapy for the treatment of R/M NPC.