5-year Locoregional Failure-free Survival Research Articles

Implications of Image-Defined Risk Factors and Primary-Site Response on Local Control and Radiation Treatment Delivery in the Management of High-Risk Neuroblastoma: Is There a Role for De-escalation of Adjuvant Primary-Site Radiation Therapy?

The predictive value of Image-Defined Risk Factors (IDRFs) developed by the International Neuroblastoma Risk Group Task Force as it relates to primary-site management is undefined and may aid patient selection for de-escalation of adjuvant radiation therapy to the primary site in high-risk neuroblastoma. Patients (N=76) with high-risk neuroblastoma treated on prospective trials at our institution from 1997 to 2014 were eligible for inclusion. IDRFs were defined based on pretherapy imaging. Overall survival, progression-free survival, and locoregional failure-free survival (LRFFS) were described using the Kaplan-Meier estimator and tested across strata by using the log-rank test. Twenty of 76 patients (26%) experienced local (n=6), regional (n=6), or combined locoregional failure (n=8) with or without distant failure. Ten (50%) of the locoregional failures had concurrent distant relapse. Of patients who completed all therapy, both those with no IDRFs and those with >90% resection had a 3-year LRFFS of 100%, with or without radiation therapy. Patients with either ≥1 IDRF or<Gross Total Resection (GTR) or the inability to complete all therapy had inferior 3-year LRFFS of 77.8% and 14.4% with or without radiation therapy, respectively (P<.04). Patients treated with a dose ≥30.6Gy as part of therapy for residual disease had an 83.3% locoregional control rate. Patients with >90% tumor resection and no primary site IDRFs at diagnosis may be candidates for de-escalation of adjuvant primary-site radiation therapy, although validation of these findings in future studies is required.

Locoregional Recurrence of De-escalated Radiation Dose in Selected Nasopharyngeal Carcinoma: Experience from a Single Center Institution

In the era of intensity modulated radiotherapy (IMRT), nasopharyngeal carcinoma (NPC), especially in stage T1-3, could achieve excellent locoregional control rate higher than 90% after definitive radiotherapy. The outstanding locoregional controlling may lead to dose de-escalation in highly selected patients. In order to assess the locoregional recurrence and long-term outcome of de-escalated dose in T1-3 NPCs treated with IMRT, a retrospective propensity score analysis was conducted. A total of 264 patients diagnosed with T1-3NanyM0 nasopharyngeal carcinoma between June 2011 and June 2015 were retrospective analyzed. With a median age of 50 years old, 66 patients were female and 198 were male. All the patients were treated with IMRT. The prescription IMRT dose, namely the standard dose, in our institution is 69.96Gy/2.12Gy/33F or 70Gy/2Gy/35F to primary tumor and cervical metastatic lymph nodes, 60.06Gy/1.82Gy/33F or 59.5Gy/1.7Gy/35F to high risk target and 50.96Gy/1.82Gy/28F or 51Gy/1.7Gy/30F to low risk target. About 74% of these patients were treated with induction chemotherapy, 67% were treated with concurrent chemotherapy. With a median follow-up time of 48 months. The 5-year locoregional failure free survival (LRFS), distant metastasis free survival (DMFS), disease free survival (DFS), and overall survival (OS) were 90.0%, 81.2%, 76.1% and 83.5%, respectively. Thirty patients received IMRT dose less than prescription dose, categorized as dose de-escalation group, with a median dose of 64Gy (60-68Gy). Of the 30 patients in dose de-escalation group, 24 were treated with induction chemotherapy and 21 were treated with concurrent chemotherapy. Other 234 patients received exactly prescription dose were categorized as standard dose group, with irradiation dose of 70Gy. Propensity scores were computed (30 patients for dose de-escalation group and 60 patients in standard dose group), and there is no significant difference in 5-year LRFS and 5 year OS between two groups (90.1% and 82.5% in standard dose group; 92.0% and 80.1% in dose de-escalation group, p=0.354 for LRFS and 0.879 for OS). No independent prognostic factor, including age, gender, T stage, N stage and RT dose, was associated with loco-regional failure in multivariate analysis. In our results, highly selected T1-3 nasopharyngeal carcinoma, especially those with response to induction chemotherapy, a moderate de-escalation dose delivered with IMRT are with comparable outcomes to those of standard dose.

The efficacy of induction chemotherapy in the treatment of stage II nasopharyngeal carcinoma in intensity modulated radiotherapy era

PurposeTo evaluate the efficacy of induction chemotherapy in the treatment of stage II nasopharyngeal carcinoma (NPC) in era of intensity modulated radiotherapy (IMRT). Methods and materialsA total of 173 patients with American Joint Committee on Cancer (AJCC) 7th stage II NPC from two institutions were included. All patients were divided into two groups: induction chemotherapy + concurrent chemoradiotherapy group (ICRT) group and concurrent chemoradiotherapy group (CCRT). Induction chemotherapy was consisted of one to three cycles of cisplatin plus fluorouracil (PF) or paclitaxel plus cisplatin (TP). Concurrent chemotherapy included one to three cycles of cisplatin. We retrospectively assessed overall survival (OS), progression-free survival (PFS), locoregional failure free survival (LRFFS) and distant metastasis free survival (DMFS) in patients of both groups. T-test, Chi-square test, Kaplan–Meier methodology and Cox proportional hazards model were used to analyze. ResultsWith a median follow up of 64.7 months, no significant difference was found in grade 3–4 hematologic toxicity, liver dysfunction and renal impairment between ICRT and CCRT group. Univariable analyses shown adding induction chemotherapy to CCRT significantly decreased 5-year OS (87.9% vs 95.5%, P = 0.033), 5-year PFS (74.0% vs 86.1%, P = 0.035), 5-year LRFFS (80.0% vs 91.2%, P = 0.016), but there was no statistically significant difference in 5-year DMFS (87.1% vs 94.7%, P = 0.095). In multivariable analyses, we found the consistent results that induction chemotherapy was a negative factor associated with OS (HR of death = 3.768, 95% CI = 1.117–12.709; P = 0.032), PFS (HR of progression = 2.156, 95% CI = 1.060–4.386; P = 0.034), LRFFS (HR of locoregional relapse = 2.435, 95% CI = 1.009–5.874; P = 0.048) and also DMFS (HR of metastasis = 2.873, 95% CI = 1.005–8.211; P = 0.049), in stage II NPC patients. ConclusionIn present study, we found that induction chemotherapy caused deleterious effect on stage II NPC patients. However, this is a retrospective study and the adverse effects of induction chemotherapy has not been previously reported. It warrants further investigation.

Delayed clinical complete response to intensity-modulated radiotherapy in nasopharyngeal carcinoma

ObjectiveTwelve weeks after radiotherapy is the recommended time-point for assessing tumor response in nasopharyngeal carcinoma (NPC); however, regression after 12 weeks remains unclear. We explored NPC regression and the prognosis of patients with delayed clinical complete response (cCR). Materials and methodsMRI images of 556 NPC patients treated with intensity-modulated radiotherapy (IMRT) between 2009 and 2012 were retrospectively reviewed. Clinical tumor response was assessed at 3–4 (assessment 1) and 6–9 months (assessment 2) after IMRT, and survival rates were compared. ResultsOf the 556 patients, 463 (83.3%) had cCR at assessment 1 (early cCR). Of the 93 patients with partial response at assessment 1, 45 (48.4%) achieved cCR at assessment 2 (delayed cCR), and 48 did not have cCR at assessment 2 (non-cCR). Locoregional failure rate was lower in patients with a cCR than those without a cCR at assessment 1 (7.1% vs. 26.9%, P < .001) and assessment 2 (7.1% vs. 45.8%, P < .001). Multivariate analysis showed cCR was a favorable prognostic factor for locoregional failure-free survival (LRFFS), failure-free survival (FFS), and overall survival (OS). Early and delayed cCR groups had better 5-year LRFFS (92.6% vs. 93.3% vs. 54.2%), FFS (83.8% vs. 84.4% vs. 48.5%) and OS (92.1% vs. 90.6% vs. 65.4%) than the non-cCR group (all P < .001). ConclusionsNearly half of the patients with partial response at 3–4 months achieve cCR by 6–9 months; delayed cCR is not a poor prognosticator. We suggest later assessment of cCR at 6–9 months after IMRT is acceptable in responding NPC.

Salvage EBRT and HDR Brachytherapy for Isolated Vaginal Recurrence of Endometrial Cancer in Patients with No Prior Adjuvant Therapy

The goal of the study was to evaluate clinical outcomes for women with isolated vaginal recurrence of endometrial cancer after hysterectomy without adjuvant radiation or chemotherapy, who received salvage treatment with both external beam radiation therapy (EBRT) and high dose rate (HDR) brachytherapy. 30 women with recurrences treated between 2000 and 2010 were included in this single institution retrospective study. Median time to recurrence from surgery was 16.7 months, range 3.2 to 170.7 months. Median age at recurrence was 73 years, range 57 to 94 years. Initial histology was endometrioid adenocarcinoma in 25 patients (83%); others were papillary serous, clear cell, or adenosquamous. Initial disease was known to be grade 1 or 2 in 19 patients (63%), and 2009 FIGO stage IA in 19 patients. All patients received pelvic EBRT in 1.8 Gy daily fractions to a total of 45 or 50.4 Gy. Interstitial brachytherapy was used in 27 patients (90%) and 3 received intracavitary brachytherapy only. CT-based inverse planning was used for all patients. The median brachytherapy EQD2 dose was 24 Gy, range 16 to 33.3 Gy. The median total EQD2 dose was 68.3 Gy, range 63 to 77.6 Gy. Three patients received concurrent hormonal or cytotoxic systemic therapy with salvage radiation. Kaplan-Meier estimates of overall survival (OS), cause specific survival (CSS), progression free survival (PFS), locoregional failure free survival (LRFFS), and distant failure free survival (DFFS) were calculated. Univariate Cox proportional hazard ratio models were used to identify features prognostic for outcomes. Median follow-up for vital status was 76.4 months, range 10.8 to 149.2 months. Median follow-up for disease status was 57.7 months, range 0 to 103.3 months. At last follow-up, 12 patients (40%) had died of which 7 (23%) were due to endometrial cancer progression. At last follow-up for disease status, 8 patients (27%) had known disease recurrence after salvage, with 3 patients (10%) recurring locoregionally and 5 patients (17%) recurring with distant metastases. Of the 3 patients with locoregional failure, 2 had died. Of the 5 patients with distant failure, all 5 had died. The 5-year Kaplan-Meier estimated OS, CSS, and PFS were 77%, 83%, and 75% respectively. The 5-year LRFFS and DFFS were 87% and 86%. Initial grade of disease (1-2 vs. 3) was prognostic for OS, CSS, and DFFS (5-year OS 95% vs. 29%, p = 0.005). Initial stage of disease (IA vs. >IA) was prognostic for CSS, PFS, and DFFS (5-year CSS 93% vs. 74%, p = 0.025). Initial stage remained prognostic for DFFS when restricted to 23 patients with stage IA or IB disease only (5-year DFFS 100% vs. 50%, p = 0.043). There was one treatment related death, otherwise no reported grade ≥ 3 toxicity. Salvage EBRT and HDR brachytherapy resulted in a high rate of long-term locoregional control. Initial higher grade and higher stage disease were associated with distant failure and cancer related mortality.

Impact of Smoking on Outcomes in HPV+ Oropharynx Cancer: It′s More Than Pack-Years

We sought to examine the impact of smoking status on clinical outcomes in human papillomavirus positive (HPV+) squamous-cell carcinoma (SCC) of the oropharynx. Smoking status and outcomes for 484 pts with HPV+ SCC of the oropharynx from 2001-2015 were determined from an institutional review board approved database. Stage I-IVB pts were included. Smoking status was coded on each patient as never, former (quit > 3 months before diagnosis), or active smoking (quit within 3 months of diagnosis or continued smoking during and/or after treatment). Pack-years (pk-yrs) were also captured for smokers. Co-morbidities were scored according to the Charlson comorbidity index. Kaplan-Meier plots were generated for overall survival (OS), progression-free survival (PFS), locoregional failure free survival (LRFFS), and distant metastasis-free survival (DMFS). Cox proportional hazard regressions were used for univariate (UVA) and multivariate analysis (MVA). Separate MVA were performed to assess the relative impact of pk-yrs and smoking status. Active smokers included 94 pts (19%), 226 pts (47%) were former smokers, and 164 (34%) were never smokers. Of smokers, 247 pts (51%) had >10 pk-yrs and 179 (37%) had >20 pk-yrs. Median follow-up for the entire cohort was 36.3 months (range = 1-162.6 months). Active smokers had significantly worse outcomes compared to never/former smokers for 5-year OS (56.8% vs. 89.6%, P<0.0001), PFS (60.1% vs. 80.4%, P<0.0001), and DMFS (78.1% vs. 90.9%, P = 0.002). There was no difference in the rate of 5-year LRFFS for active vs. never/former smokers (88.4% vs. 92.8%, P = 0.12). On UVA, all smoking parameters (any smoker, >10 pk-yrs, >20 pk-yrs, active smokers) were significantly associated with inferior OS. On MVA, active smoking was the smoking related variable most strongly associated with inferior OS and PFS respectively (HR = 3.4, P<0.0001; HR 2.2, P = 0.0004). Other parameters significantly associated with inferior OS and PFS respectively included higher Charlson scores (HR = 4.2, P<0.0001; HR = 4.0, P<0.0001), and T4 stage (HR = 2.9, P = 0.006; HR = 3.0, P = 0.0008). When smoking was analyzed by pk-yrs in a separate MVA, ≥20 pk-yrs was significantly associated with worse OS and PFS (HR = 3.1, P<0.0001; HR = 1.6, P = 0.03), in addition to higher Charlson scores and T4 disease. Active smoking at diagnosis or continuing to smoke during and/or after treatment is the most powerful smoking related predictor of PFS and OS. While less strongly correlated, >20 pk-yrs was also associated with inferior outcomes, perhaps driven by the active smoking subpopulation within that group. These findings should be incorporated into future risk stratification schemes and clinical trial design.

Induction Chemotherapy plus Concurrent Chemoradiotherapy vs Concurrent Chemoradiotherapy in Elderly Patients with Advanced Nasopharyngeal Carcinoma

Objective This study aimed to compare survival and toxicity between induction chemotherapy followed by concurrent chemoradiotherapy (IC + CCRT) and concurrent chemoradiotherapy (CCRT) alone in elderly patients with advanced nasopharyngeal carcinoma (NPC). Study Design Propensity-matched analysis of survival and toxicity in a retrospective elderly cohort. Setting Department of Medical Oncology, Jingzhou Hospital, Tongji Medical College, Huazhong University of Science and Technology, China. Subjects and Methods In total, 193 patients with stage III to IVb NPC who were treated with IC + CCRT or CCRT alone were enrolled. A cohort with suitable propensity scores was created (82 patients in the IC + CCRT group and 82 patients in the CCRT group). Survival and toxicity were compared between the 2 groups. Results For the IC + CCRT group and the CCRT group, the 5-year locoregional failure-free survival (LRFFS) rate was 80.4% and 77.2% ( P = .53), the 5-year distant failure-free survival (DFFS) rate was 80% and 76.9% ( P = .517), the 5-year overall survival (OS) rate was 71.8% and 60.5% ( P = .26), and the 5-year cancer-specific survival (CSS) rate was 75.3% and 66.7% ( P = .144), respectively. There was a significant difference in the cumulative incidence of all grade 3 to 4 toxicities between the 2 groups (29.9% vs 17.7%, P = 4.8 × 10-6). Conclusions IC + CCRT had a high cumulative incidence of grade 3 to 4 toxicities in elderly patients with advanced NPC, while there were no improvements in 5-year LRFFS rate, DFFS rate, OS rate, or CSS rate between patients who underwent the IC + CCRT vs CCRT alone. Concurrent chemoradiotherapy alone is still the standard of treatment.

Clinical outcomes and prognostic factors of salivary gland adenoid cystic carcinomas: a case control study

To determine whether there was any difference in the clinical and pathologic features, management, and survival outcomes based on tumor site for salivary adenoid cystic carcinoma (ACC). This study is a retrospective chart review of 63 salivary ACC patients. These patients were subclassified into 2 groups, the minor salivary glands group (MiSGG) and the major salivary glands group (MaSGG). With a median follow-up time of 69.6months, the overall 5-year locoregional failure-free survival, distant metastasis-free survival, overall survival (OS), and cancer-specific survival (CSS) rates were 83.1%, 74.9%, 84.7%, and 89.1%, respectively. Compared with MaSGG patients, MiSGG patients were characterized by a trend toward higher T classification (P=.054). In multivariate analysis, age, T classification, and radiotherapy were independent factors for OS, whereas N classification, margin status, and tumor site (minor or major salivary glands) were observed to be independent prognostic factors for CSS. Compared with MaSGG patients, MiSGG patients were characterized by a trend toward higher T classification. Tumor site (minor or major salivary glands) was observed to be an independent prognostic factor for CSS of salivary ACC.

Identification of surrogate endpoints in patients with locoregionally advanced nasopharyngeal carcinoma receiving neoadjuvant chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone.

BackgroundIn the era of intensity-modulated radiotherapy (IMRT), the efficacy of additional neoadjuvant chemotherapy (NACT) to concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) is currently being investigated in ongoing trials. Overall survival (OS) is the gold standard endpoint in NPC trials. We performed this analysis to identify surrogate endpoints for OS, which could shorten follow-up duration and speed up assessment of treatment effects.MethodsWe retrospectively analysed 208 matched-pair patients with locoregionally advanced NPC receiving NACT+CCRT or CCRT. Progression-free survival (PFS), failure-free survival (FFS), distant failure-free survival (D-FFS) and locoregional failure-free survival (LR-FFS) at 2 and 3 years were assessed as surrogates for 5-year OS according to Prentice’s criteria. The strength of the associations were assessed using Spearman’s rank correlation coefficient.ResultsNo significant differences were observed between treatment arms for any surrogate endpoint at 2 years, which rejected Prentice’s second criterion. In contrast, 3-year LR-FFS, PFS, FFS and D-FFS were consistent with all four of Prentice’s criteria; the rank correlation coefficient (0.730) between 3-year PFS and 5-year OS was highest.Conclusions3-year PFS, FFS and D-FFS could be valid surrogate endpoints for 5-year OS; 3-year PFS may be the most accurate.

Excellent Outcomes and Orbital Preservation for Advanced T4 Sino-Nasal Cancers Using Combined Chemotherapy, Intensity Modulated Radiation Therapy, and Surgery

inhibitor that may potentiate the efficacy of concurrent radiation therapy (RT) and docetaxel (D). A Phase 2 trial was conducted to determine the efficacy and toxicities of the combination in patients with LA-SCCHN. Materials/Methods: Patients (pts) with previously untreated Stage III-IVb SCCHN received daily RTwith IMRT using dose painting: 70 Gy at 2 Gy/ fx to the primary tumor and gross nodes, 63 Gy at 1.8 Gy/fx to the highrisk nodal levels, and 56 Gy at 1.6 Gy/fx to the elective neck. Daily E (150 mg) was started 2 weeks prior to beginning RT. Elrotinib and D (20 mg/ m/week) were given concurrently with RT and pts were maintained on daily E for up to two years following the completion of RT. Data was collected on site of failures and HPV status, RT schedules, and toxicities. Toxicity was scored using CTCAE v3. Probabilities of survivals were estimated by the Kaplan-Meier method. Differences in outcomes according to HPV status, were evaluated using the log-rank test. Results: 43 pts (33 male), median age 57 years (range 35-75), with Stage III or IV (81%) were enrolled. Median follow-up is now 29.1 months (range 1.4 60.5). The primary site of disease was as follows: oropharynx (28), larynx (11) and oral cavity (4). Mean RT dose was 69.9 Gy to the primary site (range 61.2-72.4 Gy) and the mean duration of RT was 53 days. One pt died during chemoRT from a narcotic overdose. HPV status was available for 36 pts (23 HPV+). For all pts, 3-year locoregional failure-free survival (LFFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) were 81.1%, 76.8%, 64.6%, 73.7% respectively. HPV positive status showed a trend toward improved LFFS at 3 yrs (95.7% vs 71.6%, pZ0.06), PFS (82.6% vs 43.6%, pZ0.06), and OS (77.0% vs 66.1%, pZ0.36). Grade 3 leukopenia was noted in a majority of pts. Grade 4 hematologic toxicity was observed in 13 pts and Grade 4 GI toxicity was noted in 2 pts. Conclusions: Erlotinib in combination with RT and docetaxel is an active and tolerable treatment regimen for pts with LA-SCCHN with acceptable toxicities. HPV positive status was associated with a trend toward improved LFFS, PFS, and OS. Acknowledgment: This reseach was supported in part by Genentech, NIH grants P30 CA43703 and M01 RR-000080. Author Disclosure: M. Yao: None. C. Woods: None. P. Savvides: None. P. Lavertu: None. R. Rezaee: None. C. Zender: None. P. Fu: None. M. Gibson: None. J. Wasman: None. M. Machtay: Q. Leadership; RTOG.

The effects of ECE on the benefits of PMRT for breast cancer patients with positive axillary nodes

BackgroundThe purpose of the present study was to retrospectively evaluate the effects of extracapsular extension (ECE) on the benefits of post-mastectomy radiation therapy (PMRT) for groups of patients with varying numbers of positive axillary nodes (1–3, 4–9 and ≥10 positive axillary nodes). Methods: A total of 1220 axillary node-positive patients who had received mastectomy were involved in this study. Patients were grouped as ‘Radio + /ECE + ’, ‘Radio–/ECE + ’, ‘Radio + /ECE–’ or ‘Radio–/ECE–’ according to status of ECE and whether receiving PMRT or not, and were evaluated in terms of local region relapse (LRR) rate. The 5-year and 10-year Kaplan-Meier disease-free survival and overall survival (OS) rates were analyzed. Results: ECE-positive differed from ECE-negative groups with statistical significance for all comparisons in favor of the ECE-negative group: 5-year locoregional failure-free survival (LRFFS) (82.69% vs 91.83%, P < 0.001), 10-year LRFFS (75.39% vs 90.02%, P < 0.001); 5-year OS (52.12% vs 74.46%, P < 0.001), 10-year OS (35.17% vs 67.63%, P < 0.001). There were no significant effects of ECE on the benefits of PMRT for patients with 1–3 (P = 0.5720), ≥10(P = 0.0614) positive axillary nodes. However, for the group of patients with 4–9 positive axillary nodes, ECE status had a significant effect on the benefits of PMRT with respect to 5-year and 10-year LRFFS (P < 0.05). Conclusion: In our study, regardless of the ECE status, PMRT didn't significantly improve the LRFFS for patients with 1–3 or ≥10 positive axillary nodes. However, for patients with 4–9 positive axillary nodes, ECE could be an important criterion to consider when deciding whether to receive PMRT.

Concurrent Weekly Docetaxel Chemotherapy in Combination with Radiotherapy for Stage III and IVA-B Nasopharyngeal Carcinoma

Cisplatin is the most common chemotherapeutic agent for loco-regionally advanced nasopharyngeal carcinoma (NPC); however, toxicity is a limiting factor for some patients. We retrospectively compared the efficacy and toxicity of weekly docetaxel-based and cisplatin-based concurrent chemoradiotherapy in loco-regionally advanced NPC. Eighty-four patients with Stage III and IVA-B NPCs, treated between 2007 and 2008, were retrospectively analyzed. Thirty received weekly docetaxel-based concurrent chemotherapy, and 43 were given weekly cisplatin-based concurrent chemotherapy. Radiotherapy was administered using a conventional technique (seven weeks, 2.0 Gy per fraction, total dose 70-74 Gy) with 6-8 Gy boosts for some patients with locally advanced disease. Median follow-up time was 42.3 months (range, 8.6-50.8 months). There were no significant differences in the 3-year loco-regional failure-free survival (85.6% vs. 92.3%; p=0.264), distant failure-free survival (87.0% vs. 92.5%; p=0.171), progression-free survival (85.7% vs. 88.4%; p=0.411) or overall survival (86.5% vs. 92.5%, p=0.298) of patients treated concurrently with docetaxel or cisplatin. Severe toxicity was not common in either group. Weekly docetaxel-based concurrent chemoradiotherapy is potentially effective and has a tolerable toxicity; however, further investigations are required to determine if docetaxel is superior to cisplatin for advanced stage NPC.

Treatment of Stage IV(A–B) nasopharyngeal carcinoma by induction-concurrent chemoradiotherapy and accelerated fractionation: Impact of chemotherapy schemes

The aim of this study was to evaluate the impact of different chemotherapy regimens in patients with advanced nasopharyngeal carcinoma (NPC) treated by induction-concurrent chemoradiotherapy. Between 1998 and 2003, 75 Stage IV(A-B) NPC patients were treated with 3 cycles of induction chemotherapy with cisplatin plus 5-fluorouracil (PF) (n = 41) or cisplatin plus gemcitabine (PG) (n = 34), followed by accelerated radiotherapy in concurrence with 2 cycles of cisplatin. In 18 (24%) patients, cisplatin was completely replaced by carboplatin in both concurrent cycles, mainly because of borderline renal functions. The median follow-up was 3.6 years. The 3-year locoregional failure-free survival, progression-free survival, and overall survival of the whole group were 80%, 68%, and 80% respectively. No significant difference was found between patients treated with either induction regimens. However, patients with only carboplatin in the 2 concurrent cycles had significantly inferior 3-year locoregional failure-free survival (56% vs. 86%, p = 0.014), progression-free survival (39% vs. 72%, p = 0.001), and overall survival (61% vs. 87%, p = 0.046) when compared with the rest of the group. In multivariate analysis, the complete replacement of cisplatin by carboplatin during concurrent chemoradiotherapy was still an independent adverse factor in locoregional failure-free survival (hazard ratio, 3.662; 95% CI, 1.145-11.765; p = 0.029) and progression-free survival (hazard ratio, 3.390; 95% CI, 1.443-7.937; p = 0.005). The more convenient PG regimen is as effective as the PF regimen as induction chemotherapy for patients with advanced NPC. Replacing cisplatin with carboplatin in the concurrent phase carries a poor prognosis.