Timing of biochemical failure and distant metastatic disease for low-, intermediate-, and high-risk prostate cancer after radiotherapy

BACKGROUND: The relation of prostate cancer risk-group stratification and the timing of biochemical failure (BF) and distant metastasis (DM) is not well defined. The authors hypothesized that early failures due to subclinical micrometastasis at presentation could be differentiated from late failures due to local persistence. METHODS: A total of 1833 men with clinically localized prostate cancer treated with 3D-conformal radiotherapy with or without short-term androgen deprivation were retrospectively analyzed. By using American Society for Therapeutic Radiology and Oncology (ASTRO) and Phoenix (Nadir+2) definitions (developed at the ASTRO-RTOG [Radiation Therapy Oncology Group] consensus meeting, Phoenix, Arizona, January 21, 2005), the interval hazard rates of BF and DM were determined for men with low-risk, intermediate-risk, and high-risk disease. RESULTS: Median follow-up was 67 months. Multivariate analysis showed that increasing risk group was independently associated with higher ASTRO BF (P < .0001) and Nadir+2 BF (P < .0001). The preponderance (87%) of ASTRO BF occurred 4 years. The hazard of Nadir+2 BF persisted in Years 8-12 in all risk groups. The interval hazard function for DM appeared to be biphasic (early peak followed by a drop and late increase) for intermediate-risk and high-risk patients, but no distinct early wave was evident for low-risk patients. CONCLUSIONS: Because of backdating, ASTRO BF underestimates late BF. Local persistence of disease is suggested by delayed Nadir+2 BF and subsequent late DM in every risk group. The paucity of early DM among those with low-risk tumors supports the hypothesis that occult micrometastases contributed to the early wave.     

Prognostic model for survival of local recurrent nasopharyngeal carcinoma with intensity-modulated radiotherapy

Background:

Intensity-modulated radiotherapy (IMRT) is the main salvage treatment for advanced locally recurrent nasopharyngeal carcinoma (NPC); however, survival outcomes vary. We aimed to construct a prognostic-score model to identify patients who could benefit from salvage IMRT.

Methods:

This retrospective study involved 251 patients with locally recurrent NPC. The following parameters were analysed following IMRT: patient performance status, age, gender, late complications, T-stage of recurrence, synchronous nodal recurrence, primary gross tumour volume (GTV-nx), disease-free interval, re-irradiation dose and chemotherapy. The model was based on the hazard ratio coefficients of six significantly negative prognostic factors for survival.

Results:

Significantly negative prognostic factors included Karnofsky Performance Status ⩽70, age >50 years, late complications, recurrent T_3–4 stage, synchronous nodal recurrence and GTV-nx >30 cm³. Three subgroups were defined according to model scores: low risk (0–4), intermediate risk (5–8) and high risk (9–15). The 5-year overall survival rates were 64.3%, 32.2% and 7.7%, respectively. The main cause of death was radiation-induced complications.

Conclusion:

The prognostic-score model demonstrated that re-irradiation with IMRT is suitable for low-risk and intermediate-risk patients but may be unsuitable for high-risk patients. Further research into the protection of critical adjacent organs to reduce late complications in these patients is warranted.     

鼻咽癌调强放疗疗效及预后影响因素分析(附691例)

目的:回顾性分析我院采用调强放疗(intensity-modulated radiotherapy,IMRT)治疗鼻咽癌的疗效及预后影响因素.方法:收集2009年01月至2015年08月691例鼻咽癌患者的临床资料进行生存分析.结果:中位随访时间为62.8个月,全组患者5年总生存(overall survival,OS...     

454例鼻咽癌IMRT±化疗远期疗效及影响因素分析

目的 对454例鼻咽癌IMRT±化疗的远期疗效及影响因素分析。方法 回顾分析本中心2007—2012年采用IMRT±化疗的454例无远处转移鼻咽癌患者资料。放疗处方剂量:鼻咽大体肿瘤69.96~73.92 Gy分33次, 颈部转移淋巴结69.96 Gy分33次, 高危引流区60.06 Gy分33次, 低危引流区50.96 Gy分28次。诱导化疗438例, 同期化疗420例, 辅助化疗216例, 顺铂、紫杉醇为主。Kaplan-Meier法计算生存并Logrank 法检验和单因素预后分析, Cox法多因素预后分析。结果 3年样本数为210例, 3年OS、LRFS、NRFS、PFS、DMFS分别为88.1%、91.0%、90.7%、80.5%、85.1%。影响OS因素有年龄(P=0.011)、T分期(P=0.005)、N分期(P=0.033);T、N分期对DPFS (P=0.017、 0.005)、DMFS (P=0.012、0.019)均有影响。≥3级急性及晚期不良反应主要为血液学、口腔黏膜反应, 口干、吞咽困难和脑损伤。结论 IMRT提高了鼻咽癌患者长期生存, 远处转移是主要失败原因, IMRT联合化疗不良反应能耐受。     

High-risk endometrial cancer may be benefit from adjuvant radiotherapy plus chemotherapy

Objective:To present patterns of practice and outcomes in the adjuvant treatment of intermediate-and high-risk endometrial cancer.Methods:Retrospective data on 224 women with intermediate-risk and high-risk endometrial cancer from 1999 to 2006 were reviewed.All patients underwent surgical staging.Patterns of adjuvant treatment,consisting of pelvic radiotherapy,chemotherapy,and radiotherapy plus chemotherapy,were assessed.The 3and 5-year disease-specific survival(DSS) rates were calculated using the Kaplan-Meier method.Results:The difference in 5-year DSS rate was statistically significant between adjuvant group and non-adjuvant group(80.65% vs.63.80%,P=0.040).In 110 high-risk patients who underwent adjuvant treatment,both 5-year DSS rate and recurrent rate were significantly different in combined radiotherapy and chemotherapy group compared with radiotherapy alone and chemotherapy alone groups(DSS rate,P=0.049;recurrent rate,P=0.047).In 83 intermediate-risk women who underwent adjuvant treatment,there was no significant difference in 5-year DSS rate and recurrence rate among the combined radiotherapy and chemotherapy,radiotherapy alone and chemotherapy alone groups(DSS rate,P=0.776;recurrent rate,P=0.937).Conclusions:Adjuvant radiotherapy plus chemotherapy is associated with a higher 5-year DSS rate and lower recurrence rate compared with radiotherapy alone and chemotherapy alone in high-risk endometrial cancer patients.Patients with intermediate-risk endometrial cancer may be not likely to benefit from adjuvant combined radiotherapy and chemotherapy.     

Primary bone lymphoma--treatment and outcome

AimsA retrospective review of patients with histologically confirmed primary bone lymphoma (PBL) diagnosed and treated at a single tertiary referral centre between 1985 and 2003.Materials and methodsThe medical records of all patients treated for histologically primary bone lymphoma were identified using the hospital data base. Data was obtained on patient demographics, stage, treatment and outcome.ResultsTwenty-two patients with PBL were identified. Seventeen had localised disease and five had multifocal bone involvement. The median age was 50 years. Of the patients who could be graded according to the International Prognostic Index (IPI), 12 cases were classified as low risk, seven as intermediate risk and one as high risk. All patients received chemotherapy; 19 with an anthracycline-containing regimen. Eighteen patients were treated with radiotherapy to a median total dose of 40 Gy (range 30–50 Gy). Three patients had surgery instead of radiotherapy as local treatment (one fibulectomy and two endoprosthetic replacements). The median follow-up was 84.5 months (range 3–206 months). The overall 10-year survival was 74%; 92% for low-risk IPI vs 73% for intermediate-risk IPI (P = 0.27). The 10-year relapse-free survival was 85% overall and 83% for both low- and intermediate-risk IPI (P = 0.87). Local relapse was seen in one patient. Orthopaedic complications occurred in two patients — one developed a pathological fracture after biopsy before radiotherapy and the other developed avascular necrosis outside the irradiated area.ConclusionsCombined modality treatment for PBL results in good local control and survival rates with acceptable toxicity.     

鼻咽癌调强放疗后感音神经性听力下降的临床分析

目的 分析鼻咽癌患者调强放疗后感音神经性听力下降(SNHL)的影响因素。方法 比较2012— 2013年间接受单纯放疗和同期放化疗的 29例鼻咽癌患者声导抗测听、纯音听阈测定及耳蜗放射剂量,所有患者均接受调强放疗。采用前瞻性分析方法分析耳蜗放射剂量对鼻咽癌患者SNHL的影响,同时了解放疗后时间、化疗、T分期、年龄等因素对结果的影响。结果 58只耳中6只(10%)发生了低频SNHL,17只(29%)发生高频SNHL。放疗后发生感音神经性耳聋患者和未发生听力下降患者耳蜗剂量不同(左耳46、1 Gy∶35、5 Gy,P=0、006;右耳45、0 Gy∶35、8 Gy,P= 0、009)。当耳蜗平均剂量限制到44 Gy以下时只有15%(6/38)耳发生SNHL。颅底骨质破坏对听力有影响(P=0、047)。结论耳蜗的平均剂量和颅底骨质的侵犯是鼻咽癌患者放疗后SNHL的重要影响因素。建议耳蜗的平均剂量限制在44 Gy是合理的。     

Intensity-modulated radiation therapy leads to survival benefit only in patients with high-risk prostate cancer: a population-based study

BackgroundDuring the last years, there has been a rapid adoption of intensity-modulated radiation therapy (IMRT) in patients with prostate cancer (PCa), despite the lack of randomized trials evaluating its effectiveness. The aim of our study was to evaluate the survival benefit associated with IMRT in patients with PCa.Patients and methodsOverall, 42 483 patients with PCa treated with IMRT or initial observation between 2001 and 2007 within the Surveillance, Epidemiology, and End Results (SEER)-Medicare were evaluated. Patients in both treatment arms were matched using propensity-score methodology. After propensity-score matching, 19 064 patients remained in our analyses. Eight-year cancer-specific mortality (CSM) rates were estimated, and the number needed to treat (NNT) was calculated. Competing risks regression analyses tested the relationship between treatment type and CSM.ResultsOverall, the 8-year CSM rates were 3.4% and 4.1% for patients treated with IMRT versus initial observation, respectively (P < 0.001). The corresponding 8-year NNT was 142. In patients with low/intermediate-risk disease, IMRT was not associated with lower CSM rates compared with observation (P = 0.7). In patients with high-risk disease, the 8-year CSM rates for IMRT versus observation were 5.8% versus 10.5%, respectively (P < 0.001). The corresponding NNT was 21. When high-risk patients were stratified according to age (<73 versus ≥73), and Charlson comorbidity index (≤1 versus >1) the 8-year CSM rates for IMRT versus observation were 4.3% versus 9.4% and 6.9% versus 11.9% and 5.3% versus 11.4% and 6.1% versus 10.1%, respectively (all Ps < 0.001). The corresponding NNTs were 19, 21, 16, and 25, respectively. In multivariate analyses, the protective effect of IMRT was more evident in high-risk patients with younger age and lower comorbidities.ConclusionsIMRT leads to a survival advantage only in patients with high-risk disease. Conversely, patients with low/intermediate-risk disease did not benefit from IMRT at 8-year follow-up.     

高危因素联合分层法在预测N2-3M0期鼻咽癌预后的临床价值分析

目的 分析高危因素联合分层法在预测N2-3M0期鼻咽癌预后的临床价值。方法 2013-2015年间226例N2-3M0期首程鼻咽癌病例被纳入研究,分析肿瘤体积、颈部转移淋巴结特征(坏死、融合)和T、N分期等与生存的关系,分析影响生存的高危因素,探讨高危因素联合分层法在预测预后的价值。结果 N3期、Vn≥47.15cm³和淋巴结融合是N2-3M0期鼻咽癌患者远处转移的高危因素,根据高危因素分为低危、中危、高危、极高危组。生存分析显示低危、中危、高危、极高危组3年总生存率分别为84.2%、76.7%、58.7%、36.4%(P<0.001),无远处转移生存率分别为87.3%、85.2%、54.5%、12.1%(P<0.001),无进展生存率分别为76.8%、74.3%、49.2%、12.1%(P<0.001),无局部区域复发生存率分别为89.2%、88.5%、91.5%、88.3%(P=0.914)。比较N分期、Vn分组、淋巴结融合分组和高危因素联合分层法的无远处转移生存曲线发现:高危因素联合分层法将组间曲线分离的更开,明显优于其他三组(P<0.05)。结论 高危因素联合分层法在预测N2-3M0期鼻咽癌患者预后的临床价值更高。     

高危因素联合分层法在预测N2-3M0期鼻咽癌预后的临床价值分析

目的 分析高危因素联合分层法在预测N2-3M0期鼻咽癌预后的临床价值。方法 2013-2015年间226例N2-3M0期首程鼻咽癌病例被纳入研究,分析肿瘤体积、颈部转移淋巴结特征(坏死、融合)和T、N分期等与生存的关系,分析影响生存的高危因素,探讨高危因素联合分层法在预测预后的价值。结果 N3期、Vn≥47.15cm³和淋巴结融合是N2-3M0期鼻咽癌患者远处转移的高危因素,根据高危因素分为低危、中危、高危、极高危组。生存分析显示低危、中危、高危、极高危组3年总生存率分别为84.2%、76.7%、58.7%、36.4%(P<0.001),无远处转移生存率分别为87.3%、85.2%、54.5%、12.1%(P<0.001),无进展生存率分别为76.8%、74.3%、49.2%、12.1%(P<0.001),无局部区域复发生存率分别为89.2%、88.5%、91.5%、88.3%(P=0.914)。比较N分期、Vn分组、淋巴结融合分组和高危因素联合分层法的无远处转移生存曲线发现:高危因素联合分层法将组间曲线分离的更开,明显优于其他三组(P<0.05)。结论 高危因素联合分层法在预测N2-3M0期鼻咽癌患者预后的临床价值更高。     

Risk-adapted androgen deprivation and escalated three-dimensional conformal radiotherapy for prostate cancer: Does radiation dose influence outcome of patients treated with adjuvant androgen deprivation? A GICOR study.

PURPOSE: Multicenter study conducted to determine the impact on biochemical control and survival of risk-adapted androgen deprivation (AD) combined with high-dose three-dimensional conformal radiotherapy (3DCRT) for prostate cancer. Results of biochemical control are reported. PATIENTS AND METHODS: Between October 1999 and October 2001, 416 eligible patients with prostate cancer were assigned to one of three treatment groups according to their risk factors: 181 low-risk patients were treated with 3DCRT alone; 75 intermediate-risk patients were allocated to receive neoadjuvant AD (NAD) 4-6 months before and during 3DCRT; and 160 high-risk patients received NAD and adjuvant AD (AAD) 2 years after 3DCRT. Stratification was performed for treatment/risk group and total radiation dose. RESULTS: After a median follow-up of 36 months (range, 18 to 63 months), the actuarial biochemical disease-free survival (bDFS) at 5 years for all patients was 74%. The corresponding figures for low-risk, intermediate-risk, and high-risk disease were 80%, 73%, and 79%, respectively (P = .847). Univariate analysis showed that higher radiation dose was the only significant factor associated with bDFS for all patients (P = .0004). When stratified for treatment group, this benefit was evident for low-risk patients (P = .009) and, more interestingly, for high-risk patients treated with AAD. The 5-year bDFS for high-risk patients treated with AAD was 63% for radiation doses less than 72 Gy and 84% for those > or = 72 Gy (P = .003). CONCLUSION: The results of combined AAD plus high-dose 3DCRT are encouraging. To our knowledge, this is the first study showing an additional benefit of high-dose 3DCRT when combined with long-term AD for unfavorable disease.     

局部晚期鼻咽癌吉西他滨和顺铂联合调强放疗Ⅱ期临床试验

目的 评价吉西他滨和顺铂与调强放疗序贯治疗局部晚期鼻咽癌的疗效和不良反应。方法 71例局部晚期鼻咽癌(Ⅲ期 41例、Ⅳ_A期 30例)患者接受新辅助化疗、调强放疗、辅助化疗,新辅助化疗、辅助化疗各2个疗程\[吉西他滨1000 mg/m²,第1、8天静脉滴注(>30 min);顺铂 25 mg/m²,第 1~3天,静脉滴注;21 d为1个疗程\]。调强放疗鼻咽大体肿瘤体积 66.0~70.4 Gy,颈部淋巴结大体肿瘤体积66 Gy, 临床高危靶体积60 Gy,临床低危靶体积54 Gy。结果 新辅助化疗后的有效率为91.2%,主要急性不良反应为 1~2级骨髓抑制。所有患者随访满 3年,3年鼻咽局部控制率、区域控制率、无远处转移率、总生存率分别为93%、99%、91%、90%。3级晚期不良反应中张口困难 1例、听力下降 2例、颅神经损伤 2例。结论 吉西他滨和顺铂联合调强放疗局部晚期鼻咽癌有效、方便、耐受性良好,值得进一步探索药物最适当的治疗周期。     

305例鼻咽癌调强放疗预后因素分析

背景与目的:放疗是鼻咽癌治疗的有效手段。本研究目的是分析大样本量调强放疗(intensity-modulated radiation therapy,IMRT)治疗鼻咽癌的效果、不良反应并探索其预后因素。方法:分析从2003年9月到2006年9月在福建省肿瘤医院接受IMRT的305例鼻咽癌患者临床资料并作生存分析。肿瘤靶区的处方剂量为66～69.75Gy/30～33次。Ⅲ～Ⅳa期患者接受了以铂类为基础的化疗。结果:中位随访时间35个月(5～61个月)。分别有16、8和39例出现局部﹑颈部淋巴结复发及远处转移。3年局控率﹑区域淋巴结控制率﹑无远处转移率﹑无瘤生存率及总生存率分别为94.3%﹑97.7%﹑86.1%﹑80.3%和89.1%。多因素分析表明T分期并不影响局控率及总生存率(P>0.05),N分期是影响总生存率(P=0.000)、无远处转移率(P=0.000)及无瘤生存率(P=0.003)的独立预后因素。同步和辅助化疗不改善Ⅲ～Ⅳa期患者预后(P>0.05)。严重的急性不良反应包括Ⅲ度皮肤反应14例(4.6%)、Ⅲ度口腔黏膜反应90例(29.5%)及Ⅲ～Ⅳ度骨髓抑制20例(6.5%);IMRT治疗两年后...     

IMRT同期化疗在Ⅲ期鼻咽癌中作用分析

目的 探讨IMRT同期化疗对Ⅲ期鼻咽癌患者预后的影响和作用。方法 回顾性分析2001-2008年间中山大学肿瘤防治中心接受单纯IMRT和IMRT同期铂类药物化疗的 251例Ⅲ期鼻咽癌患者,分析相关预后因子和探讨IMRT同期化疗作用。采用Kaplan-Meier法计算生存率,组间差异比较采用log-rank检验,Cox模型预后因素分析。结果 全组 10年无局部区域复发生存(LRFS)、无远处转移生存(DMFS)、无进展生存(PFS)和总生存(OS)率分别为88.6%、81.1%、68.8%和75.1%。单因素和多因素分析显示N分期和鼻咽肿瘤体积是最重要的预后影响因素,同期化疗有助于改善患者PFS和OS (均 P<0.05)。T3N0-1期患者单纯放疗组和同期放化疗组各生存指标均相近(10年LRFS为93.8%∶93.2%,P=0.933;10年DMFS为80.9%∶86.8%,P=0.385;10年PFS为70.6%∶77.7%,P=0.513;10年OS为71.8%∶83.6%,P=0.207);T1-3N2期患者同期放化疗的LRFS、PFS和OS优于单纯放疗(10年LRFS为87.3%∶66.7%,P=0.016;10年PFS为70.2%∶41.0%,P=0.003;10年OS为78.5%∶51.7%,P=0.008),DMFS有提高趋势(10年DMFS为80.3%∶66.4%,P=0.103)。结论 IMRT中同期化疗的加入有助于改善Ⅲ期鼻咽癌患者预后,在N2期组获益较为明显,需要根据患者治疗失败风险予以个体化治疗方案。     

The role of concurrent chemotherapy in intensity-modulated radiotherapy for patients with stage Ⅲ nasopharyngeal carcinoma

Objective To investigate the clinical efficacy of concurrent chemotherapy in intensity-modulated radiotherapy (IMRT) for patients with stage Ⅲ nasopharyngeal carcinoma (NPC). Methods Clinical data of 251 patients with stage Ⅲ NPC treated with IMRT alone or concurrent chemoradiotherapy (CCRT) at Sun Yat-sen University Cancer Center from February 2001 to December 2008 were retrospectively analyzed. The prognostic factors of NPC were analyzed and the efficacy of CCRT was assessed. The survival rate was calculated by Kaplan-Meier method. The differences between two groups were analyzed by log-rank test. The prognostic factors were analyzed by Cox model. Results The 10-year locoregional-free survival (LRFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) for NPC patients were 88.6%, 81.1%, 68.8% and 75.1%, respectively. Univariate and multivariate analyses demonstrated that N staging and nasopharyngeal tumor volume were the most important prognostic factors, and concurrent chemotherapy significantly improved PFS and OS (both P<0.05). In T3N0-1 patients, there was no significant difference in survival indexes between IMRT alone and CCRT (10y-LRFS:93.8% vs. 93.2%, P=0.933;10y-DMFS:80.9% vs. 86.8%, P=0.385;10y-PFS:70.6% vs. 77.7%, P=0.513;10y-OS:71.8% vs. 83.6%, P=0.207). For T1-3N2 patients, CCRT was significantly better than radiotherapy alone in LRFS, PFS, and OS (10y-LRFS:87.3% vs. 66.7%, P=0.016;10y-PFS:70.2% vs. 41.0%, P=0.003;10y-OS:78.5% vs. 51.7%, P=0.008), whereas there was an increasing trend in DMFS (10y-DMFS:80.3% vs. 66.4%, P=0.103). Conclusions Concurrent chemotherapy can improve clinical prognosis of stage Ⅲ NPC patients, and the most survival benefits are obtained in the N2 group. Individualized treatment options should be delivered based on the risk of treatment failure.     

Intensity-Modulated Radiotherapy for Nasopharyngeal Carcinoma: Penang General Hospital Experience

Purpose: To study the overall treatment time (OTT) and acute toxicity of intensity-modulated radiotherapy(IMRT) treatment for nasopharyngeal carcinoma (NPC). Methods: This retrospective study covered all NPCpatients who underwent radical IMRT treatment at the Penang General Hospital from June 2011 to February2012. Patients of any age and stage of disease with histologically proven diagnosis were included. Informationwas collected on patient demographics, clinical stage, treatment received, including any neoadjuvant and/orconcurrent chemotherapy, acute toxity and completion of IMRT within the OTT. Results: A total of 26 NPCpatients were treated with IMRT during the study period; 88.5% had stage III/IV disease. 45.2% receivedneo-adjuvant chemotherapy while 50.0% were given concurrent chemo-irradiation. All patients completed thetreatment and 92.3% within the 7 weeks OTT. Xerostomia was present in all patients with 92.3% having grade2. Severe grade III/IV acute toxicity occurred in 73.1% of patients, the commonest of which was oral mucositis(57.6%). This was followed by dysphagia which occurred in 53.8%, skin reactions in 42.3% and weight loss in19.2%. However, haematological toxicity was mild with only one patient having leucopaenia. Conclusion: IMRTtreatment for NPC is feasible in our center. More importantly, it can be delivered within the 7 weeks OTT inthe majority of patients. Severe grade 3/4 toxicity is very common (73.1%) and thus maximal nutritional andanalgesic support is required throughout the treatment.     

Propensity score matching analysis of cisplatin-based concurrent chemotherapy in low risk nasopharyngeal carcinoma in the intensity-modulated radiotherapy era

Background

Patients with stage II nasopharyngeal carcinoma were reported to benefit from adding cisplatin-based concurrent chemotherapy to two-dimensional conventional radiotherapy. But this benefit becomes uncertain in the intensity-modulated radiotherapy (IMRT) era, owing to its significant advantage.

Methods

We enrolled 661 low risk (T1N1M0, T2N0-1M0 or T3N0M0, the 2010 UICC/AJCC staging system) patients who underwent IMRT with or without concurrent chemotherapy. Particularly, patients with IMRT alone or IMRT plus cisplatin-based concurrent chemotherapy were equally matched using propensity-score matching method. Overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRFS) were assessed with Kaplan-Meier method, log-rank test and Cox regression.

Results

Among 661 patients, IMRT alone achieved parallel OS (P = 0.379), DMFS (P = 0.169) and LRFS (P = 0.849) to IMRT plus concurrent chemotherapy. In the propensity-matched cohort of 482 patients, similar survival were observed between both arms (4-years OS 97.4% vs 96.1%, P = 0.134; DMFS 96.5% vs 95.1%, P = 0.763; LRFS 93.8% vs 91.5%, P = 0.715). In multivariate analysis, cisplatin-based concurrent chemotherapy did not lower the risk of death, distant metastasis or locoregional relapse. And this association remained unchanged in subgroups by age, sex, histology and stage.

Conclusions

In this study, low risk nasopharyngeal carcinoma patients who underwent IMRT could not benefit from cisplatin-based concurrent chemotherapy.     

Risk subset of the survival for nasopharyngeal carcinoma patients with bone metastases: who will benefit from combined treatment?

Bone metastasis from nasopharyngeal carcinoma (NPC) is the most frequent type of distant metastasis (DM). The purpose of this study was to elucidate survival, prognostic factors, and significant of treatment in NPC patients with bone metastasis. A total of 221 patients who developed single type of DM from NPC at the first failure after primary treatment were retrospectively recruited from January 1998 to October 2000. The correlation between disease-free interval (DFI) and clinicopathologic features was assessed by the Chi-square test. Univariate and multivariate analyses of clinicopathologic variables were performed using Cox proportional hazards regression models. Actuarial survival rates were plotted against time using the Kaplan-Meier method, and log-rank testing was used to compare the differences between the curves. The median overall survival (OS) of the whole cohort and bone metastatic NPC patients were 38.5 and 33.3months, respectively. After univariate and multivariate analyses of clinicopathologic variables, age, local recurrence, subsequent metastasis, DFI and treatment modality were independently significant prognostic factors. The outcomes of bone metastatic NPC patients in low- and high-risk subset were significantly different (49.5 vs. 19.4months, P<0.001). In stratified survival analysis, compared to chemotherapy alone, chemoradiotherapy (CRT) could benefit the patients in low-risk subset (P<0.001), but not those in high-risk subset (P=0.135). Our findings indicated that clinicopathologic variables could provide easily available prognostic factors for survival in NPC patients with bone metastasis. A subset of bone metastatic NPC patients would benefit from aggressive combined treatment and receive a long-term survival.     

OPTIMA: a phase II dose and volume de-escalation trial for human papillomavirus-positive oropharyngeal cancer

BackgroundPatients with HPV+ oropharyngeal squamous cell carcinoma were assigned to dose and volume de-escalated radiotherapy (RT) or chemoradiotherapy (CRT) based on response to induction chemotherapy in an effort to limit treatment-related toxicity while preserving efficacy.Patients and methodsPatients were classified as low-risk (≤T3, ≤N2B, ≤10 pack-year history) or high-risk (T4 or ≥N2C or >10 PYH). After three cycles of carboplatin/nab-paclitaxel, response was assessed using Response Evaluation Criteria in Solid Tumors 1.1. Low-risk patients with ≥50% response received 50 Gray (Gy) RT (RT50) while low-risk patients with 30%–50% response or high-risk patients with ≥50% response received 45 Gy CRT (CRT45). Patients with lesser response received standard-of-care 75 Gy CRT (CRT75). RT/CRT was limited to the first echelon of uninvolved nodes. The primary end point was 2-year progression-free survival compared with a historic control of 85%. Secondary end points included overall survival and toxicity.ResultsSixty-two patients (28 low risk/34 high risk) were enrolled. Of low-risk patients, 71% received RT50 while 21% received CRT45. Of high-risk patients, 71% received CRT45. With a median follow-up of 29 months, 2-year PFS and OS were 95% and 100% for low-risk patients and 94% and 97% for high-risk patients, respectively. The overall 2-year PFS was 94.5% and within the 11% noninferiority margin for the historic control. Grade 3+ mucositis occurred in 30%, 63%, and 91% of the RT50, CRT45, and CRT75 groups, respectively (P = 0.004). Rates of any PEG-tube use were 0%, 31%, and 82% for RT50, CRT45, and CRT75 groups, respectively (P < 0.0001).ConclusionsInduction chemotherapy with response and risk-stratified dose and volume de-escalated RT/CRT for HPV+ OPSCC is associated with favorable oncologic outcomes and reduced acute and chronic toxicity. Further evaluation of induction-based de-escalation in large multicenter studies is justified.Clinical trial registrationClinical trials.gov identifier: NCT02258659.     

Long-term outcomes of intensity-modulated radiotherapy for 868 patients with nasopharyngeal carcinoma: An analysis of survival and treatment toxicities

Background and purpose

To evaluate the long-term survival outcomes and toxicity of NPC patients treated with intensity-modulated radiotherapy (IMRT).

Materials and methods

From May 2001 to October 2008, 868 non-metastatic NPC patients treated by IMRT were analyzed retrospectively. The Radiation Therapy Oncology Group (RTOG) criteria were used to assess toxicity.

Results

With a median follow-up of 50 months (range, 5–115 months), the 5-year estimated disease specific survival (DSS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS) and distant metastasis-free survival (DMFS) were 84.7%, 91.8%, 96.4% and 84.6%, respectively. Of the 868 patients, 186 (21.3%) developed failure after treatment. Distant metastasis was the major failure pattern after treatment. The 5-year OS rate in patients with stage I, II, III, and IVa–b were 100.0%, 94.3%, 83.6%, and 70.5%, respectively. The 5-year LRFS rate in patients with stage T1, T2, T3, and T4 disease were 100.0%, 96.0%, 90.4%, and 83.3%, respectively (χ² = 26.32, P < 0.001). The 5-year DMFS for N0, N1, N2, and N3 patients were 96.1%, 85.6%, 73.7%, and 62.1%, respectively (χ² = 65.54, P < 0.001). Concurrent chemotherapy failed to improve survival rates for patients with advanced locoregional disease. The most common acute toxicities were mainly in grade 1 or 2. Compared with IMRT alone, IMRT plus concurrent chemotherapy increased the severity of acute toxicities. The incidence of brain radiation damage was relatively high (5.5%, 48/868 cases), and was not observed in patients with stage T1–2.

Conclusion

IMRT for NPC yielded excellent survival outcomes, and distant metastasis was the most commonly seen failure pattern after treatment. The role of concurrent chemotherapy for advanced locoregional stage NPC patients needs to be further investigated. Treatment-related toxicities were well tolerable. However, the incidence of brain radiation damage was relatively high, especially for patients with advanced T-stage.