Wei Wei Xiao

Local control, survival, and late toxicities of locally advanced nasopharyngeal carcinoma treated by simultaneous modulated accelerated radiotherapy combined with cisplatin concurrent chemotherapy

The aim of this phase 2 study was to determine the long‐term local control, survival, and late toxicities among patients with locally advanced nasopharyngeal carcinoma (NPC) treated with intensity‐modulated radiotherapy (IMRT) with the simultaneous modulated accelerated radiation therapy (SMART) boost technique and concurrent chemotherapy.

Long-Term Outcomes of Early-Stage Nasopharyngeal Carcinoma Patients Treated With Intensity-Modulated Radiotherapy Alone

PURPOSEnReports of intensity-modulated radiotherapy (IMRT) for early-stage nasopharyngeal carcinoma (NPC) have been limited. The present study evaluated the long-term survival outcomes and toxicity of early-stage NPC patients treated with IMRT alone.nnnMETHODS AND MATERIALSnBetween February 2001 and January 2008, 198 early-stage (T1-T2bN0-N1M0) NPC patients had undergone IMRT alone. The data from these patients were retrospectively analyzed. The patients were treated to 68 Gy at 2.27 Gy/fraction prescribed to the planning target volume of the primary nasopharygeal gross tumor volume. The Radiation Therapy Oncology Group scoring system was used to assess the toxicity.nnnRESULTSnAt a median follow-up of 50.9 months (range, 12-104), the 5-year estimated disease-specific survival, local recurrence-free survival, and distant metastasis-free survival rate was 97.3%, 97.7%, and 97.8%, respectively. The 5-year local recurrence-free survival rate was 100% for those with Stage T1 and T2a and 94.2% for those with Stage T2b lesions (p = 0.252). The 5-year distant metastasis-free survival rate for Stage T1N0, T2N0, T1N1, and T2N1 patients was 100%, 98.8%, 100%, and 93.8%, respectively (p = .073). All local recurrence occurred in patients with T2b lesions. Five patients developed distant metastasis. Of these 5 patients, 4 had had Stage T2bN1 disease and 1 had had Stage T2bN0 disease with retropharyngeal lymph node involvement. The most common acute toxicities were mainly Grade 1 or 2. At 24 months after IMRT, no Grade 3 or 4 xerostomia had developed, and 62 (96.9%) of 64 evaluated patients were free of trismus; only 2 patients (3.1%) had Grade 1 trismus. Radiation encephalopathy and cranial nerve injury were not observed.nnnCONCLUSIONSnIMRT alone for Stage T1N0, T2N0, T1N1, and T2N1 yielded satisfactory survival outcomes with acceptable toxicity, and no differences were found in survival outcomes among these four subgroups. Patients with Stage T2b lesions might have relatively greater risk of local recurrence and those with T2bN1 disease mighth have a greater risk of distant metastasis.

Treatment Outcomes After Radiotherapy Alone for Patients With Early-Stage Nasopharyngeal Carcinoma

PURPOSEnTo analyze the treatment outcomes of patients with early-stage nasopharyngeal carcinoma after radiotherapy (RT) alone and discuss the effects of different T and N stages on the prognosis.nnnMETHODS AND MATERIALSnThe clinical data from 362 early-stage (T1-T2N0-N1M0, 1992 Fuzhou, China staging system) nasopharyngeal carcinoma patients who had undergone RT alone between January 1999 and December 2001 and were hospitalized in the Cancer Center of Sun Yat-Sen University were collected and reviewed.nnnRESULTSnThe median follow-up was 70 months. The 5-year overall survival rate for the whole group was 85%. The 5-year overall survival rate of those with T1N0, T2N0, and T1N1 was 96.6%, 91.3%, and 85.8%, respectively, with no statistically significant difference detected among the three groups (p > .05). However, the 5-year overall survival rate of 73.1% for those with Stage T2N1 was significantly different from that of the former three groups. The 5-year local recurrence-free survival and 5-year regional recurrence-free survival rates among the four groups was not significantly different (p < .05). The 5-year distant metastasis-free survival rate of those with Stage T1N0, T2N0, and T1N1 was 94.9%, 97.5%, and 95.6%, respectively, without any significant differences (p > .05); however, the 81.2% rate for those with Stage T2N1 was significantly different (p < .05).nnnCONCLUSIONnRT alone for Stage T1N0, T2N0, and T1N1 yielded satisfactory results. The outcome for those with T2N1 was obviously poorer than that for the other three groups. The main reason for treatment failure in this group was distant metastasis. Patients who have a high risk of distant metastasis in the T2N1 group may need combined treatment instead of RT alone.

Treatment outcomes for different subgroups of nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy

Although many studies have investigated intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC), sample sizes in the reported studies are usually small and different in outcomes in different T and N subgroups are seldom analyzed. Herein, we evaluated the outcomes of NPC patients treated with IMRT and further explored treatment strategy to improve such outcome. We collected clinical data of 865 NPC patients treated with IMRT alone or in combination with chemotherapy, and classified all cases into the following prognostic categories according to different TNM stages: early stage group (T1–2N0–1M0), advanced local disease group (T3–4N0–1M0), advanced nodal disease group (T1–2N2–3M0), and advanced locoregional disease group (T3–4N2–3M0). The 5-year overall survival (OS), local relapse-free survival (LRFS), and distant metastases-free survival (DMFS) were 83.0%, 90.4%, and 84.0% respectively. The early disease group had the lowest treatment failure rate, with a 5-year OS of 95.6%. The advanced local disease group and advanced nodal disease group had similar failure pattern and treatment outcomes as well as similar hazard ratios for death (4.230 and 4.625, respectively). The advanced locoregional disease group had the highest incidence of relapse and death, with a 5-year DMFS and OS of 62.3% and 62.2%, respectively, and a hazard ratio for death of 10.402. Comparing with IMRT alone, IMRT in combination with chemotherapy provided no significant benefit to locoregionally advanced NPC. Our results suggest that the decision of treatment strategy for NPC patients should consider combinations of T and N stages, and that IMRT alone for early stage NPC patients can produce satisfactory results. However, for advanced local, nodal, and locoregional disease groups, a combination of chemotherapy and radiotherapy is recommended.

Clinical and dosimetric characteristics of temporal lobe injury following intensity modulated radiotherapy of nasopharyngeal carcinoma

BACKGROUND AND PURPOSEnTo evaluate the temporal lobe injury (TLI) in nasopharyngeal carcinoma (NPC) patients who had received intensity modulated radiotherapy (IMRT) and to assess the dosimetric parameters associated with TLI.nnnMATERIALS AND METHODSnForty of 870 patients were diagnosed with TLI after IMRT, the clinical and dosimetric characteristics of these TLI were analyzed.nnnRESULTSnA total of 4.6% (40/870) patients have developed TLI. However, TLI is not observed in T1-2 patients, the incidences are 3.1% and 13.4% in T3 and T4 patients respectively. The Dmax (maximum point dose, Gy) and D1 cc (the dose delivered to the 1 cubic centimeter volume, Gy) in injured temporal lobes (TLs) are greater than that in normal TLs (P<0.01). TLI is not observed in TLs with Dmax<64 Gy or D1 cc<52 Gy, and the 5-year incidence of TLI in patients with Dmax 64-68 Gy or D1 cc 52-58 Gy is <5.0%. A linear regression demonstrates a 2.6% augment of TLI per Gy of Dmax exceeding 64 Gy and a 2.5% augment of TLI per Gy of D1 cc exceeding 52 Gy; TLI is correlated with Dmax (r=0.89, P<0.01) and D1 cc (r=0.87, P<0.01) respectively.nnnCONCLUSIONSnThe incidence of TLI is relatively high, especially for patients with advanced T-stage NPC, and correlated with Dmax and D1 cc. IMRT with Dmax<68 Gy or D1 cc<58 Gy in TLs is relatively safe.

Analysis of late toxicity in nasopharyngeal carcinoma patients treated with intensity modulated radiation therapy

PurposeTo observe the late toxicities in nasopharyngeal carcinoma (NPC) patients who achieved long-term survival after intensity modulated radiation therapy (IMRT).Methods208 untreated NPC patients who received IMRT and survived more than five years with locoregional disease control and no metastasis were evaluated in this study. The prescription dose to the gross target volume of nasopharynx (GTVnx), positive neck lymph nodes (GTVnd), clinical target volume 1 (CTV1) and 2 (CTV2) was 68Gy/30f, 60-66Gy/30f, 60xa0Gy/30f and 54Gy/30f, respectively. The nasopharynx and upper neck targets were irradiated using IMRT, and the lower neck and supraclavicular fossae targets were irradiated using the half-beam technique with conventional irradiation. The late toxicities were evaluated according to the LENT/SOMA criteria of 1995.ResultsThe median follow-up time was 78xa0months (60–96 months). The occurrence rates of cervical subcutaneous fibrosis, hearing loss, skin dystrophy, xerostomia, trismus, temporal lobe injury, cranial nerve damage, cataract, and brain stem injury induced by radiotherapy were 89.9%, 67.8%, 47.6%, 40.9%, 7.21%, 4.33%, 2.88%, 1.44%, and 0.48%, respectively. No spinal cord injury and mandible damage were found. Grade 3–4 late injuries were observed as follows: 1 (0.48%) skin dystrophy, 4 (1.92%) cervical subcutaneous fibrosis, 2 (0.96%) hearing loss, 2 (0.96%) cranial nerve palsy, and 1 (0.48%) temporal lobe necrosis. No grade 3–4 late injuries occurred in parotid, temporomandibular joints and eyes. Xerostomia decreased gradually over time and then showed only slight changes after 4xa0years. The change in the incisor distance stabilised by 1xa0year after RT, however, the incidence of hearing loss, skin dystrophy, subcutaneous fibrosis and nervous system injuries increased over time after RT.ConclusionThe late injuries in most NPC patients who had long-term survivals after IMRT are alleviated. Within the 5xa0years of follow-up, we found xerostomia decreased gradually; The change in the incisor distance stabilised by 1xa0year after RT; while hearing loss, nervous system injuries increased over time after RT.

Long-term outcomes of a phase II randomized controlled trial comparing intensity-modulated radiotherapy with or without weekly cisplatin for the treatment of locally recurrent nasopharyngeal carcinoma

AbstractBackgroundnSalvage treatment for locally recurrent nasopharyngeal carcinoma (NPC) is complicated and relatively limited. Radiotherapy, combined with effective concomitant chemotherapy, may improve clinical treatment outcomes. We conducted a phase II randomized controlled trial to evaluate the efficacy of intensity-modulated radiotherapy with concomitant weekly cisplatin on locally recurrent NPC.MethodsnBetween April 2002 and January 2008, 69 patients diagnosed with non-metastatic locally recurrent NPC were randomly assigned to either concomitant chemoradiotherapy group (nxa0=xa034) or radiotherapy alone group (nxa0=xa035). All patients received intensity-modulated radiotherapy. The radiotherapy dose for both groups was 60xa0Gy in 27 fractions for 37xa0days (range 23–53xa0days). The concomitant chemotherapy schedule was cisplatin 30xa0mg/m2 by intravenous infusion weekly during radiotherapy.ResultsThe median follow-up period of all patients was 35xa0months (range 2–112xa0months). Between concomitant chemoradiotherapy and radiotherapy groups, there was only significant difference in the 3-year and 5-year overall survival (OS) rates (68.7% vs. 42.2%, Pxa0=xa00.016 and 41.8% vs. 27.5%, Pxa0=xa00.049, respectively). Subgroup analysis showed that concomitant chemoradiotherapy significantly improved the 5-year OS rate especially for patients in stage rT3–4 (33.0% vs. 13.2%, Pxa0=xa00.009), stages III–IV (34.3% vs. 13.2%, Pxa0=xa00.006), recurrence interval >30xa0months (49.0% vs. 20.6%, Pxa0=xa00.017), and tumor volume >26xa0cm3 (37.6% vs. 0%, Pxa0=xa00.006).ConclusionCompared with radiotherapy alone, concomitant chemoradiotherapy can improve OS of the patients with locally recurrent NPC, especially those with advanced T category (rT3–4) and stage (III–IV) diseases, recurrence intervals >30xa0months, and tumor volume >26xa0cm3.

Analysis of dosimetric factors associated with temporal lobe necrosis (TLN) in patients with nasopharyngeal carcinoma (NPC) after intensity modulated radiotherapy

BackgroundThe radiation tolerance dose-volume in brain remains unclear for nasopharyngeal carcinoma (NPC) patients treated with intensity modulated radiotherapy (IMRT). We performed this study to investigate dosimetric factors associated with temporal lobe necrosis (TLN) in NPC patients treated with IMRT.MethodsFrom 2001 to 2008, 870 NPC patients were treated with IMRT. For the whole group, 40 patients have developed MRI-diagnosed TLN, and 219 patients were followed-up more than 60u2009months. Predictive dosimetric factors for TLN were identified by using univariate and multivariate analysis in these 259 patients.ResultsBy univariate analyses, rVX ( percent of temporal lobes receivingu2009≥u2009X Gy) and aVX ( absolute volumes of temporal lobes receivingu2009≥u2009X Gy, values of X considered were 10, 20, 30, 40, 50, 60, 66 and 70) were all significantly associated with TLN. Multivariate analysis by logistic regression showed that rV40 and aV40 were significant factors for TLN. All dosimetric factors in current serials were highly correlated one another (pu2009<u20090.001). The 5-year incidence of TLN for rV40 <10% or aV40 <5u2009cc is less than 5%. The incidence for rV40u2009≥u200915% or aV40cu2009≥u200910c is increased significantly and more than 20%.ConclusionsIn this study, all dosimetric factors were highly correlated, rV40 and aV40 were independent predictive factors for TLN, IMRT with rV40 <10% or aV40 <5u2009cc in temporal lobe is relatively safe.

Impact of primary tumor volume and location on the prognosis of patients with locally recurrent nasopharyngeal carcinoma

IntroductionThe properties of a tumor itself were considered the main factors determining the survival of patients with locally recurrent nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). However, recurrent tumors were mainly evaluated by using the American Joint Committee on Cancer staging system, which was modeled on primary tumors and did not incorporate the tumor volume. This study aimed to investigate the prognostic values of the primary tumor location and tumor volume, and to determine whether evaluating these parameters could improve the current staging system.MethodsMagnetic resonance (MR) images for 229 patients with locally recurrent NPC who underwent IMRT were analyzed retrospectively.ResultsThe skull base, parapharyngeal space, and intracranial cavity were the most common sites of tumors. There was a difference in the survival between patients with T1 and T2 diseases (77.6xa0% vs. 50.0xa0%, Pu2009<u20090.01) and those with T3 and T4 diseases (33.0xa0% vs. 18.0xa0%, Pu2009=u20090.04) but no difference between patients with T2 and T3 diseases (50.0xa0% vs. 33.0xa0%, Pu2009=u20090.18). Patients with a tumor volume ≤38xa0cm3 had a significantly higher survival rate compared with those with a tumor volume >38xa0cm3 (48.7xa0% vs. 15.2xa0%, Pu2009<u20090.01).ConclusionsA new staging system has been proposed, with T3 tumors being down-staged to T2 and with the tumor volume being incorporated into the staging, which may lead to an improved evaluation of these tumors. This new system can be used to guide the treatment strategy for different risk groups of recurrent NPC.

Risk factors and prediction-score model for distant metastasis in nasopharyngeal carcinoma treated with intensity-modulated radiotherapy

The objective of this study is to identify the risk factors and construct a prediction-score model for distant metastasis (DM) in nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT). A total of 520 nonmetastatic NPC patients were analysed retrospectively. The independent risk factors for DM were tested by multivariate Cox regression analysis. The prediction-score model was established according to the regression coefficient. The median follow-up was 88.4xa0months. The 5-year DM rate was 15.1xa0%. N2–3, primary tumour volume of nasopharynx (GTVnx) >24.56xa0cm3, haemoglobin change after treatment (ΔHGB) >25.8xa0g/L, albumin-globulin ratio (AGR) ≤1.34, pretreatment neutrophil-lymphocyte ratio (NLR) >2.81 and pretreatment serum lactate dehydrogenase (LDH) >245xa0U/L were significantly adverse independent predictive factors for DM. Three subgroups were defined based on the prediction-score model: low risk (0–2), intermediate risk (3–4) and high risk (5–8). The 5-year DM rates were 4.6, 21.8 and 50.8xa0%, respectively (Pu2009<u20090.001). The areas under the curve for DM in the prediction-score model and the UICC/AJCC staging system seventh edition were 0.748 and 0.627, respectively (Pu2009<u20090.001). The scoring model is useful in evaluating the risk of DM in IMRT-treated NPC patients and guiding future therapeutic trials. Further prospective study is needed.