Tai Xiang Lu

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 Survival After Cisplatin-Based Induction Chemotherapy and Radiotherapy for Nasopharyngeal Carcinoma: A Pooled Data Analysis of Two Phase III Trials

5524 Background: To evaluate the long-term treatment outcome in patients with advanced stage nasopharyngeal carcinoma (NPC) treated by cisplatin-based induction chemotherapy and radiotherapy (CRT) versus radiotherapy alone (RT). METHODS The updated records of two previously reported phase III studies (the Asian-Oceania Clinical Oncology Association trial and the Guangzhou trial). testing the benefit of adding induction chemotherapy to radiotherapy in NPC were reviewed and the data were pooled together for analysis. A total of 784 patients were included for analysis, with equal number of patients in both the CRT and RT arms. The induction chemotherapy consisting of 2-3 cycles of cisplatin 100 mg/m2 day 1, bleomycin 10 mg/m2 day 1 & 5, and fluorouracil 800 mg/m2 day 1-5, or cisplatin 60 mg/m2 day 1 and epirubicin 110 mg/m2 day 1. Radiotherapy was given to the nasopharynx and neck using megavoltage radiation, with a median dose of 70 Gy. Treatment compliance was 92.6% in the CRT arm and 98% in the RT arm. The median follow-up time for surviving patients was 67 months. Analysis was done by intention to treat. RESULTS The addition of induction chemotherapy to radiotherapy was associated with a decrease in relapse by 14.3% and cancer deaths by 12.9% at 5 years. The 5-year relapse-free survival rate was 50.9% in the CRT arm and 42.7% in the RT arm (p=0.014), and the 5-year disease-specific survival rate was 63.5% in the CRT arm and 58.1% in the RT arm (p=0.029). The median disease-specific survival was not yet reached in the CRT arm and it was 82 months in the RT arm. The incidence of loco-regional failure and distant metastases were reduced by 18.3% and 13.3% at 5 years respectively with induction chemotherapy. There was no significant difference in the failure patterns between the 2 arms. CONCLUSIONS The addition of cisplatin-based induction chemotherapy to radiotherapy was associated with a modest but significant improvement in survival in advanced stage NPC. No significant financial relationships to disclose.

Initial experience using intensity-modulated radiotherapy for recurrent nasopharyngeal carcinoma

PURPOSE To report our initial experience on the feasibility, toxicity, and tumor control using intensity-modulated radiotherapy (IMRT) for retreatment of recurrent nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS A total of 49 patients with locoregional recurrent carcinoma in the nasopharynx were treated with IMRT between January 2001 and February 2002 at the Sun Yat-Sen University Cancer Center, Guangzhou, China. The average time to the nasopharyngeal recurrence was 30.2 months after initial conventional RT. The median isocenter dose to the nasopharynx was 70 Gy (range 60.9-78.0) for the initial conventional RT. All patients were restaged at the time of recurrence according to the 1992 Fuzhou, China staging system on NPC. The number of patients with Stage I, II, III and IV disease was 4, 9, 10, and 26, respectively. T1, T2, T3, and T4 disease was found in 4, 9, 11, and 25 patients, respectively. N0, N1, N2, and N3 disease was found in 46, 2, 0, and 1 patient, respectively. Invasion of the nasal cavity, maxillary sinus, ethmoid sinus, sphenoid sinus, and cavernous sinus and erosion of the base of the skull was found in 8, 1, 3, 8, 15, and 20 patients, respectively. The gross tumor volume (GTV) was contoured according to the International Commission on Radiation Units and Measurements (ICRU) Report 62 guidelines. The critical structures were contoured, and the doses to critical structures were constrained according to ICRU 50 guidelines. The GTV in the nasopharynx and positive lymph nodes in the neck received a prescription dose of 68-70 Gy and 60 Gy, respectively. All patients received full-course IMRT. Three patients who had positive lymph nodes were treated with five to six courses of chemotherapy (cisplatin + 5-fluorouracil) after IMRT. RESULTS The treatment plans showed that the percentage of GTV receiving 95% of the prescribed dose (V(95-GTV)) was 98.5%, and the dose encompassing 95% of GTV (D(95-GTV)) was 68.1 Gy in the nasopharynx. The mean dose to the GTV was 71.4 Gy. The average doses of the surrounding critical structures were much lower than the tolerable thresholds. At a median follow-up of 9 months (range 3-13), the locoregional control rate was 100%. Three cases (6.1%) of locoregional residual disease were seen at the completion of IMRT, but had achieved a complete response at follow-up. Three patients developed metastases at a distant site: two in the bone and one in the liver and lung at 13 months follow-up. Acute toxicity (skin, mucosa, and xerostomia) was acceptable according to the Radiation Therapy Oncology Group criteria. Tumor necrosis was seen toward the end of IMRT in 14 patients (28.6%). CONCLUSION The improvement in tumor target coverage and significant sparing of adjacent critical structures allow the feasibility of IMRT as a retreatment option for recurrent NPC after initial conventional RT. This is the first large series using IMRT to reirradiate local recurrent NPC after initial RT failed. The treatment-related toxicity profile was acceptable. The initial tumor response/local control was also very encouraging. In contrast to primary NPC, recurrent NPC reirradiated with high-dose IMRT led to the shedding of tumor necrotic tissue toward the end of RT. More patients and longer term follow-up are warranted to evaluate late toxicity and treatment outcome.

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

PURPOSE Reports 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. METHODS AND MATERIALS Between 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. RESULTS At 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. CONCLUSIONS IMRT 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.

Preliminary results of trial NPC-0501 evaluating the therapeutic gain by changing from concurrent-adjuvant to induction-concurrent chemoradiotherapy, changing from fluorouracil to capecitabine, and changing from conventional to accelerated radiotherapy fractionation in patients with locoregionally advanced nasopharyngeal carcinoma

A current recommendation for locoregionally advanced nasopharyngeal carcinoma (NPC) is conventional fractionated radiotherapy with concurrent cisplatin plus adjuvant cisplatin and fluorouracil (PF). In this randomized trial, the authors evaluated the potential therapeutic benefit from changing to an induction‐concurrent chemotherapy sequence, replacing fluorouracil with oral capecitabine, and/or using accelerated rather than conventional radiotherapy fractionation.

A randomized trial on addition of concurrent-adjuvant chemotherapy and/or accelerated fractionation for locally-advanced nasopharyngeal carcinoma

BACKGROUND AND PURPOSE To evaluate the therapeutic benefits by adding chemotherapy (+C) and/or accelerated-fractionation (AF) for patients with T3-4N0-1M0 nasopharyngeal carcinoma. MATERIALS AND METHODS From 1999 to 2004, 189 eligible patients were randomized to one of four treatment groups (CF/CF+C/AF/AF+C). The number of fractions/week was 5 for the CF groups and 6 for the AF groups. Patients in the +C groups were given concurrent cisplatin plus adjuvant cisplatin and fluorouracil. RESULTS The AF+C group achieved significantly higher failure-free rate (88% at 5-year) than the CF group (63%; p=0.013), the AF group (56%; p=0.001) and the CF+C group (65%; p=0.027). As compared with CF alone, the increase in late toxicity was statistically insignificant (36% vs. 20%; p=0.25). Deaths due to cancer progression decreased (7% vs. 33%; p=0.011) but deaths due to incidental causes increased (9% vs. 2%; p=0.62). Improvement in overall survival reached borderline significance (85% vs. 66%; p=0.058). CONCLUSIONS Concurrent-adjuvant chemotherapy combined with AF significantly reduced failure and cancer-specific deaths. Although the increase in major late toxicity and incidental deaths were statistically insignificant, a subtle increase in non-cancer deaths narrowed the overall survival gain.

Long-term treatment outcome of recurrent nasopharyngeal carcinoma treated with salvage intensity modulated radiotherapy.

PURPOSE To evaluate the long-term treatment outcome in patients with recurrent nasopharyngeal carcinoma (NPC) treated with salvage intensity modulated radiotherapy (IMRT). MATERIALS AND METHODS One hundred and fifty one previously irradiation NPC patients with recurrent disease and re-irradiated by IMRT between 2001 and 2006 had been reviewed. The disease was re-stage I in 7, re-stage II in 21, re-stage III in 50 and re-stage IV in 73. Thirty-seven patients received concurrent chemotherapy, 39 had induction chemotherapy and 75 had radiotherapy alone. RESULTS All patients completed the planned IMRT. The median volume of the recurrent gross target volume of nasopharynx (rGTVnx) was 42.2 cm(3) (range 1.5-146.3 cm(3)). The median mean re-irradiation dose to the rGTVnx was 70.4Gy (range 62.1-77.6Gy). The median follow-up time after re-irradiation was 40.0 months (range 1.9-116.9 month). The 5-year local control rate (LCR) and overall survival rate (OS) for re-stage I, II, III, IV were 80.0%, 85.0%, 80.0%, 78.7% and 71.4%, 62.9%, 35.5%, 30.2%, respectively. Multivariate analysis indicated that rT classification (hazard ratio (HR), 2.02; 95%confidence interval (CI), 1.03-3.97; P=0.04) and the volume of rGTVnx (HR, 2.05; 95%CI, 1.31-3.22; P<0.01) were independent predictors for OS. Patients (39.0%) with re-stage III or IV disease experienced Grade 3 or 4 late toxicities. CONCLUSION Re-irradiation by IMRT for recurrent NPC resulted in encouraging local control. The clinical outcome for patients with early re-stage diseases was satisfactory. Further investigations, focus on optimising radiation dose and establishing effective treatment strategies, are warranted for advanced recurrent disease in order to improve overall survival and minimise late toxicity.

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

PURPOSE To 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. METHODS AND MATERIALS The 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. RESULTS The 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). CONCLUSION RT 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 PURPOSE To 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. MATERIALS AND METHODS Forty of 870 patients were diagnosed with TLI after IMRT, the clinical and dosimetric characteristics of these TLI were analyzed. RESULTS A 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. CONCLUSIONS The 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.