Comparison of radiotherapy combined with nimotuzumab vs. chemoradiotherapy for locally recurrent nasopharyngeal carcinoma.

BACKGROUND: The present study compared the effectiveness and toxicity of two treatment modalities, namely radiotherapy combined with nimotuzumab (N) and chemoradiotherapy (CRT) in patients with locally recurrent nasopharyngeal carcinoma (LR-NPC). METHODS: Patients with LR-NPC who were treated with radiotherapy were retrospectively enrolled from January 2015 to December 2018. The treatment included radiotherapy combined with N or platinum-based induction chemotherapy and/or concurrent chemotherapy. The comparison of survival and toxicity between the two treatment modalities was evaluated using the log-rank and chi-squared tests. Overall survival (OS) was the primary endpoint. RESULTS: A total of 87 patients were included, of whom 32 and 55 were divided into the N group and the CRT group, respectively. No significant differences were noted in the survival rate between the N and the CRT groups (4-year OS rates, 37.1% vs. 40.7%, respectively; P = 0.735). Mild to moderate acute complications were common during the radiation period and mainly included mucositis and xerostomia. The majority of the acute toxic reactions were tolerated well. A total of 48 patients (55.2%) demonstrated late radiation injuries of grade ≥ 3, including 12 patients (37.5%) in the N group and 36 patients (66.5%) in the CRT group. The CRT group exhibited significantly higher incidence of severe late radiation injuries compared with that of the N group (P = 0.011). CONCLUSION: Radiotherapy combined with N did not appear to enhance treatment efficacy compared with CRT in patients with LR-NPC. However, radiotherapy combined with N may be superior to CRT due to its lower incidence of acute and late toxicities. Further studies are required to confirm the current findings.

Failure patterns and individualized treatment plans of reirradiation for inoperable locally recurrent nasopharyngeal carcinoma.

Re-irradiation with intensity-modulated radiotherapy (IMRT) remains the primary treatment modality for inoperable locally recurrent nasopharyngeal carcinoma (NPC). However, the rate of radiation-related late adverse effects is often substantially high. Therefore, we aimed to explore failure patterns and individualized treatment plans of re-irradiation for inoperable locally recurrent NPC. Ninety-seven patients who underwent IMRT were retrospectively analyzed. Sixty-two patients had clinical target volume of recurrence (rCTV) delineated, and thirty-five patients had only gross tumor volume of recurrence (rGTV) delineated. Twenty-nine patients developed second local failures after re-irradiation with IMRT (28 cases available). Among those patients, 64.3% (18/28) of patients and 35.7% (10/28) developed in-field or out-field, respectively. No statistical correlation was observed between target volume (rGTV or rCTV) and the local recurrence rate, local failure patterns, grade ≥ 3 toxicity, and survival. Multivariate analysis showed that recurrent T (rT) stage (HR 2.62, P = 0.019) and rGTV volume (HR 1.73, P = 0.037) were independent prognostic factors for overall survival (OS). Risk stratification based on rT stage and rGTV volume revealed that low risk group had a longer 3-year OS rate (66.7% vs. 23.4%), lower total grade ≥ 3 toxicity (P = 0.004), and lower re-radiation associated mortality rates (HR 0.45, P = 0.03) than high risk group. This study demonstrates that the delineation of rCTV may not be beneficial for re-irradiation using IMRT in locally recurrent NPC. Patients with low risk were most suitable for re-irradiation, with maximizing local salvage and minimizing radiation-related toxicities. More precise and individualized plans of re-irradiation are warranted.

Prioritizing sufficient dose to gross tumor volume over normal tissue sparing in intensity-modulated radiotherapy treatment of T4 nasopharyngeal carcinoma.

BACKGROUND: In intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC), priority is often given minimize dose to the critical organs at risk (OARs) to avoid potential morbid sequelae. However, in T4 NPC, dosimetric inadequacy enforced by dose constraints on OARs may significantly impact tumor control. METHODS: This was a single-institute cohort that patients diagnosed between July 2005 and December 2010 with T4 NPC treated with IMRT. All patients were re-classification according to the 7th-AJCC stage. RESULTS: Overall, the average doses such as Dmax , D1% , D2% and D1cc for various Central nervous system (CNS) OARs including brainstem, optic nerve, chiasm, temporal lobes and spinal cord were found to exceed published guidelines as RTOG0225. However, no clinical toxicities were seen during the follow-up period except for 13% patients with temporal lobe necrosis. CONCLUSION: Our retrospective review showed that its feasible to maximize gross tumor volume dose coverage while exceeding most CNS OAR constraint standards, with ideal local control and no obvious increase of craniocerebral toxicity.

Administration of oral maintenance chemotherapy for 1 year following definitive chemoradiotherapy may improve the survival of patients with stage N3 nasopharyngeal carcinoma.

OBJECTIVES: This study aims to evaluate the effectiveness and the optimal maintenance period of oral chemotherapy using S1 following definitive chemoradiotherapy in patients with stage N3 nasopharyngeal carcinoma (N3-NPC). MATERIALS AND METHODS: A retrospective review was performed for N3-NPC treatment with maintenance chemotherapy (MC) [chemoradiotherapy (CRT)-MC] or without MC (CRT-non-MC) following definitive CRT between May 2014 and December 2017. Toxicities during MC were recorded. Overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS) were compared between CRT-MC and CRT-non-MC cohorts. The optimal duration of using maintenance S1 (MC-S1) was also analyzed. RESULTS: A total of 304 patients with stage N3-NPC were identified, of whom 56 were treated with CRT-MC and 248 with CRT-non-MC. After a median follow-up of 48 months, significant differences in OS (74.9 vs. 91.7%; P = 0.003), PFS (60.7 vs. 83.7%; P = 0.001) and DMFS (68.8 vs. 85.5%; P = 0.015) were observed between the CRT-non-MC and CRT-MC groups. Skin hyperpigmentation, leukopenia and fatigue were common but not severe (grade 1-2) side effects of MC. The OS, DMFS and PFS were significantly higher for patients who received S1 administration over a period of ≥12 cycles compared with those who received <12 cycles (3-year OS, 100 vs. 87.5%, P = 0.018; 3-year PFS, 93.9 vs. 67.9%, P = 0.006; 3-year DMFS, 97.1 vs. 67.9%, P = 0.002). CONCLUSIONS: Using MC-S1 in patients with N3-NPC following definitive chemoradiotherapy achieved superior survival rate compared with the patients with non-MC. The side effects of MC-S1 were mild and tolerable. S1 should be maintained for ≥12 cycles.

Modified reduced-volume intensity-modulated radiation therapy in non-metastatic nasopharyngeal carcinoma: A prospective observation series.

BACKGROUND AND PURPOSE: Although the efficacy of "reduced-volume intensity-modulated radiation therapy (IMRT)" in nasopharyngeal carcinoma (NPC) has been confirmed, two issues regarding the necessity of clinical target volume 1(CTV1) delineation and the optimal margin of CTV2 remained undetermined. The current series, utilized de-intensification technique that omitted the contouring of CTV1 and narrowed the margin of CTV2 from 10 mm to 8 mm, namely "modified reduced-volume IMRT" was initiated to evaluate the efficacy and feasibility of this renew technique in a prospective series. PATIENTS AND MATERIALS: Dosimetric analysis was performed in 40 non-metastatic NPC cases to evaluate whether our modification is feasible. Then this de-intensification technique was applied in non-metastatic NPC patients treated in our attending group since late 2014. Survival outcomes focused on local recurrence-free survival (LRFS) and local failure pattern were analyzed. RESULTS: Preliminary dosimetric evaluation of "modified reduced-volume IMRT" showed that the 60 Gy isodose curve generated naturally by this technique could well wrap the target area of CTV1. Subsequent observation series, which included a total of 471 patients and had a median follow-up time of 46.2 months(range,3.7-70.8 months), reported that 4-year estimated LRFS, regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 96.6%, 97.7%, 87.7% and 92.4%, respectively. All local recurrence lesions occurred within 95% isodose lines and were considered in-field failures. CONCLUSIONS: Our de-intensification technique "modified reduced-volume IMRT" was feasible and did not compromise therapeutic efficacy, well-designed multicenter prospective trials are needed for further research.

Interobserver variability in target volume delineation in definitive radiotherapy for thoracic esophageal cancer: a multi-center study from China.

PURPOSE: To investigate the interobserver variability (IOV) in target volume delineation of definitive radiotherapy for thoracic esophageal cancer (TEC) among cancer centers in China, and ultimately improve contouring consistency as much as possible to lay the foundation for multi-center prospective studies. METHODS: Sixteen cancer centers throughout China participated in this study. In Phase 1, three suitable cases with upper, middle, and lower TEC were chosen, and participants were asked to contour a group of gross tumor volume (GTV-T), nodal gross tumor volume (GTV-N) and clinical target volume (CTV) for each case based on their routine experience. In Phase 2, the same clinicians were instructed to follow a contouring protocol to re-contour another group of target volume. The variation of the target volume was analyzed and quantified using dice similarity coefficient (DSC). RESULTS: Sixteen clinicians provided routine volumes, whereas ten provided both routine and protocol volumes for each case. The IOV of routine GTV-N was the most striking in all cases, with the smallest DSC of 0.37 (95% CI 0.32-0.42), followed by CTV, whereas GTV-T showed high consistency. After following the protocol, the smallest DSC of GTV-N was improved to 0.64 (95% CI 0.45-0.83, P = 0.005) but the DSC of GTV-T and CTV remained constant in most cases. CONCLUSION: Variability in target volume delineation was observed, but it could be significantly reduced and controlled using mandatory interventions.

Update report of nasopharyngeal carcinoma treated with reduced-volume intensity-modulated radiation therapy and hypothesis of the optimal margin.

BACKGROUND AND PURPOSE: To establish the minimally required margins in different directions measured from GTV in the definitive treatment of nasopharyngeal carcinoma (NPC) using IMRT based on the 5-year results. METHODS AND MATERIALS: Between November 2003 and May 2007, 414 patients with non-metastatic NPC were treated with IMRT according to our institutional protocol. Treatment outcomes at 5 years were analyzed. Distances from GTV-T to CTV2 (i.e., CTV 59.4 Gy) in 6 directions (anterior, posterior, superior, inferior, and bilateral) were measured and analyzed. RESULTS: The 5-year estimated overall survival (OS), disease free survival (DFS), local control (LC) were 80%, 77% and 95%, respectively. For the margins measured from GTV-T to CTV2, margins used with T4 disease were significantly and uniformly smaller than the whole group in all the 6 directions (P=0.000, 0.000, 0.000, 0.000 and 0.046, respectively). However, no increase of local recurrence was associated to this limited margins used. CONCLUSIONS: Our 5-years' experience showed a very high LC rate. The strategy we used for CTV delineation was safe and reliable. Determined CTV through GTV expansion to a minimally required margin, using GTV+margin (used in our T4 patients)+the whole nasopharyngeal mucosa, especially for the patients with early T disease, might be feasible.