Treatment outcomes after reduction of the target volume of intensity-modulated radiotherapy following induction chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: A prospective,multi-center,randomized clinical trial

Purpose

To investigate whether reducing the target volume of intensity-modulated radiotherapy (IMRT) after induction chemotherapy (IC) improves the quality of life (QOL) in locoregionally advanced nasopharyngeal carcinoma (NPC) without decreasing the local control and survival rate.

Prognostic implication of pulmonary function at the beginning of postoperative radiotherapy in non-small cell lung cancer

PurposeThe purpose of this study was to investigate the prognostic effect of pulmonary function at the beginning of postoperative radiotherapy (PORT) in non-small cell lung cancer (NSCLC).Materials and methodsFrom January 2002 to December 2012, 115 patients with NSCLC who underwent PORT and took the forced expiratory volume in 1 second (FEV1) at the beginning of PORT were analysed. PORT began within 4–6 weeks following surgery, and the 3-dimensional conformal technique was used with conventional fractionation. The high and low FEV1 groups were divided by the median absolute value of FEV1 at the beginning of PORT, and we compared the clinical factors and survival between two groups.ResultsThe median absolute value of FEV1 at the beginning of PORT was 1.68 L (range, 0.83–3.89), and patients were divided into low and high FEV1 groups (<1.68 L versus ⩾1.68 L). Patients in the low FEV1 group showed a lower preoperative FEV1 (mean, 1.94 L versus 2.73 L, p < 0.001) and received more pneumonectomy (36.8% versus 8.6%, p < 0.001) compared to the high FEV1 group. The overall median follow-up time was 31 months (range, 3–110), and 5-year locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 52.4%, 48.9%, and 45.9%, respectively. Five-year OS of the low FEV1 group was significantly lower than that of the high FEV1 group (35.4% versus 56.9%, p = 0.002), and no significant differences were found in LRRFS and DMFS. In a multivariate analysis, the difference of OS between the low and high FEV1 groups remained significant (Hazard Ratio = 2.04, CI, 1.18–3.55, p = 0.011).ConclusionsThe FEV1 at the beginning of PORT was an independent significant prognostic factor in patients with NSCLC who received PORT. Considering this analysis was limited to only patients receiving PORT, further studies are warranted to compare the survival effect of postoperative pulmonary function between groups with/without PORT.     

Survival comparision of three-dimensional radiotherapy alone with concurrent chemoradiotherapy for non-surgical esophageal carcinoma

PurposeRadiotherapy is the main treatment method for patients with locally advanced, unresectable esophageal cancer. The aim of this study is to compare overall survival (OS) using 3D radiotherapy (3DRT) alone with concurrent chemoradiotherapy (CCRT) in 296 non-surgical esophageal carcinoma patients.Patents and methodsOver 10 years, of the 480 patients with esophageal carcinoma treated with 3DRT with or without chemotherapy, 148 patients each comprised 3DRT and CCRT groups after propensity score matching.ResultsThe 5- and 10-year OS (P = 0.337) and PFS (P = 0.715) rates for 3DRT alone were 22.0%, 14.4% and 26.1%, 23.2%, respectively, compared with 28.8%, 18.6% and 34.7%, 29.1% for CCRT, respectively. CCRT did not improve 5-year and 10-year OS or PFS in 60–70 Gy group (OS: 27.5% and 25.2%; 17.9% and 17.0%, P = 0.938; PFS: 38.3% and 31.8%; 31.9% and 27.8%, P = 0.890) nor reduce 10-year hematogenous metastasis (31.7% and 28.3%, P = 0.698). CCRT improved 5-year OS and PFS of 50.0–59.9 Gy group (OS: 33.3% and 12.0%, P = 0.029; PFS: 33.1% and 10.6%, P = 0.081). For 3DRT, the 5-year OS and PFS rates were significantly better in the 60–70 Gy group (P = 0.017) compared with 50.0–59.9 Gy group (P = 0.002). For CCRT group, 5-year OS and PFS favored the 50.0–59.9 Gy group, but the difference was insignificant. Major toxicities were greater with CCRT compared with 3DRT.ConclusionFor non-surgical esophageal carcinoma patients, 3DRT combined with CCRT was effective in prolonging both OS and PFS.     

Prognostic value of parapharyngeal extension in nasopharyngeal carcinoma treated with intensity modulated radiotherapy

Background and purpose

The development of improved diagnostic and therapeutic techniques has revolutionized the management of nasopharyngeal carcinoma (NPC). The purpose of this study is to revaluate the prognostic value of parapharyngeal extension in NPC in the IMRT era.

Material and methods

We retrospectively reviewed data from 749 biopsy-proven non-metastatic NPC patients. All patients were examined with magnetic resonance imaging (MRI) and received intensity-modulated radiotherapy (IMRT) as the primary treatment.

Results

The incidence of parapharyngeal extension was 72.1%. A significant difference was observed in the disease-free survival (DFS; 70.3% vs. 89.1%, P < 0.001), distant metastasis-free survival (DMFS; 79.3% vs. 92.0%, P < 0.001), and local relapse-free survival (LRFS; 92.8% vs. 99.0%, P = 0.002) of patients with and without parapharyngeal extension. Parapharyngeal extension was an independent prognostic factor for DFS and DMFS in multivariate analysis (P = 0.001 and P = 0.015, respectively), but not LRFS. The difference between DMFS in patients with or without parapharyngeal space extension was statistically significant in patients with cervical lymph node metastasis (P < 0.001).

Conclusions

In the IMRT era, parapharyngeal extension remains a poor prognosticator for DMFS in NPC, especially in patients with positive lymph node metastasis. Additional therapeutic improvements are required to achieve a favorable distant control in NPC with parapharyngeal extension.     

Treatment of nasopharyngeal carcinoma with intensity-modulated radiotherapy: the Hong Kong experience

PURPOSE: To evaluate the efficacy of using intensity-modulated radiotherapy (IMRT) in the primary treatment of nasopharyngeal carcinoma (NPC), including the role of dose escalation above 66 Gy level. METHODS AND MATERIALS: Between July 2000 and September 2002, 63 newly diagnosed NPC patients were treated with IMRT. The disease was Stage I in 9 (14%), Stage II in 18 (29%), Stage III in 22 (35%), and Stage IV in 14 (22%). The prescribed dose was 66 Gy to the gross tumor volume (GTV) and positive neck nodes, 60 Gy to the planning target volume (PTV), and 54-60 Gy to the clinically negative neck. All 20 (100%) patients with T1-2a tumors received intracavitary brachytherapy (ICB) boost, and 15/42 (36%) patients with T2b-T4 tumors received conformal boost (8 Gy/4 fractions). Nineteen patients with advanced stage disease also received either neoadjuvant or concurrent chemotherapy. Acute and late normal tissue effects were graded according to the Radiation Therapy Oncology Group (RTOG) radiation morbidity scoring criteria. Local relapse-free survival (LRFS), nodal relapse-free survival (NRFS), distant metastasis-free survival (DMFS), and overall survival (OS) were estimated using the Kaplan-Meier method. RESULTS: With a median follow-up of 29 months (range 8-45 months), 4 patients developed local in-field failure, 1 patient developed regional relapse, and 13 patients developed distant metastases. All 4 patients with local failure had either T3 or T4 disease before primary treatment and did not have ICB or conformal boost. The 3-year actuarial LRFS, NRFS, DMFS, and OS were 92%, 98%, 79%, and 90%, respectively. Multivariate analysis showed that dose escalation above 66 Gy was significantly associated with better PFS and DMFS, whereas GTV size was a significant adverse factor for OS. The worst acute mucositis was Grade 1 or 2 in 36 (59%), and Grade 3 in 25 (41%) patients. Acute dysphagia requiring tube feeding occurred in 5 (8%) patients. The proportion of patients with Grade 2-3 xerostomia was 57% at 3 months, and 23% at 2 years after IMRT. Within the subset of patients with a mean parotid dose of <31 Gy, the proportions with Grade 2-3 xerostomia were 30% and 17% at 3 months and 2 years, respectively. CONCLUSION: Our experience of using IMRT in the primary treatment of NPC showed a very high rate of locoregional control and favorable toxicity profile. Furthermore, we found that dose escalation above 66 Gy of IMRT-based therapy was a significant determinant of progression-free survival and distant metastasis-free survival for advanced T-stage tumors. Distant metastases represent the predominant mode of treatment failure.     

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

PurposeTo evaluate the long-term treatment outcome in patients with recurrent nasopharyngeal carcinoma (NPC) treated with salvage intensity modulated radiotherapy (IMRT).Materials and methodsOne 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.ResultsAll patients completed the planned IMRT. The median volume of the recurrent gross target volume of nasopharynx (rGTVnx) was 42.2 cm³ (range 1.5–146.3 cm³). The median mean re-irradiation dose to the rGTVnx was 70.4 Gy (range 62.1–77.6 Gy). 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.ConclusionRe-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.     

基于MRI和IMRT的鼻咽癌鼻窦侵犯的预后研究

目的探讨基于MRI和IMRT的鼻咽癌鼻窦侵犯在鼻咽癌分期中的意义。方法 回顾分析2005—2010年基于MRI诊断的接受IMRT的1197例初诊鼻咽癌患者资料。根据AJCC第7版分期重新分期。鼻窦侵犯分为伴有鼻窦侵犯T₃、T₄期。Kaplan-Meier法计算LRFS、DMFS、OS率并Logrank法检验。Cox模型多因素预后分析及T分期各亚组局部复发风险比。结果 鼻窦侵犯率为14.2%。鼻窦侵犯不是影响鼻咽癌OS、LRFS、DMFS的因素(P=0.677、0.485、0.211)。T₂期、伴鼻窦侵犯T₃期及不伴鼻窦侵犯T₃期局部复发风险比接近(HR=1.927、2.030、2.283)。LRFS、OS曲线在T₂期、伴鼻窦侵犯T₃期及不伴鼻窦侵犯T₃期接近(P>0.05),与伴鼻窦侵犯T₄期及不伴鼻窦侵犯T₄期明显分开(P<0.05)。结论 鼻窦侵犯不是IMRT鼻咽癌OS、LRFS和DMFS的预后因素,但伴鼻窦侵犯的T₃期OS、LRFS与T₂、T₃期相似,预后较T₄期好。     

Volumes tumoraux avant et après chimiothérapie : de nouveaux facteurs pronostiques dans les carcinomes nasopharyngés

PurposeThe pre- and post-induction chemotherapy tumor volumes of nasopharyngeal carcinomas may be prognostic indicators for adapting the therapeutic strategy. The objective of our study is to assess the prognostic impact of pre- and post-induction chemotherapy volumes in patients treated for locally advanced nasopharyngeal carcinomas.Patients and methodsThis is a retrospective study including 52 patients with locally advanced nasopharyngeal carcinoma treated with 3 courses of induction chemotherapy (TPF) followed by intensity modulated radiotherapy associated with concomitant chemotherapy.ResultsThe median initial and post induction chemotherapy total volumes were 92.3 and 41.5 mL, respectively. At 3 years, the LRFS, DMFS, DFS and OS were respectively 85.9%, 63.5%, 56.8% and 67.8%. In multivariate study, the combination of a high initial volume (> 100 mL) and post-chemotherapy volume (> 35 mL) was an independent factor for LRFS, DMFS, DFS and OS. The total baseline volume had a better predictive prognostic value for DFS and OS than the TNM classification (8th edition 2017).ConclusionThe prognostic weight of tumor and nodal volumes was greater than the TNM classification (8th edition). The pre- and post-chemotherapy tumor volumes allow selecting a high-risk patients’ subgroup “high initial and post chemotherapy volumes” in which it would be advisable to offer more intensive treatment regimens.     

Effect of adaptive replanning in patients with locally advanced nasopharyngeal carcinoma treated by intensity-modulated radiotherapy: a propensity score matched analysis

Purpose

Limited data have been published regarding the effect of adaptive radiotherapy (ART) on clinical outcome in patients with nasopharyngeal carcinoma (NPC). We compared the long-term outcomes in patients with locally advanced NPC treated by adaptive intensity-modulated radiotherapy (IMRT) replanning versus IMRT.

Methods

200 NPC patients with stage T3/T4 were included between October 2004 and November 2010. Patients in both treatment groups were matched using propensity score matching method at the ratio of 1:1. Clinical outcomes were analyzed with Kaplan–Meier method, log-rank test and Cox regression.

Results

After matching, 132 patients (66 patients in each group) were included for analysis. The median follow-up for the IMRT replanning group was 70 months, while the IMRT group was 69 months. The 5-year local–regional recurrence-free survival (LRFS) rate was higher in IMRT replanning group (96.7 vs. 88.1 %, P = 0.022). No significant differences in distant metastasis-free survival (DMFS), progression-free survival (PFS) and overall survival (OS) were observed between the two groups. 21.2 % patients in IMRT replanning group and 28.8 % patients in IMRT group had distant metastasis. In multivariable analysis, IMRT replanning was identified as an independent prognostic factor for LRFS (hazard ratio 0.229; 95 % CI 0.062–0.854; P = 0.028), but not for DMFS, PFS and OS.

Conclusions

IMRT replanning provides an improved LRFS for stage T3/T4 NPC patients compared with IMRT. Distant metastasis remains the main pattern of treatment failure. No significant advantage was observed in DMFS, PFS and OS when adaptive replanning was used.

     

Prognostic factors for 495 nonoperative esophageal squamous cancer patients receiving IMRT plus chemotherapy: A retrospective analysis

PurposeChemoradiotherapy is regarded as a standard scheme for inoperable and unresectable esophageal cancers. Our aims were to explore the prognostic factors relevant to esophageal squamous cell carcinoma (ESCC) following intensity-modulated radiation therapy (IMRT) plus chemotherapy.Material and methodsTotally 495 ESCC patients undergoing IMRT combined with chemotherapy in our hospital between 2011 and 2020 were retrospectively analyzed. Potential clinical prognosis-related factors were assessed by uni- and multivariate analyses.ResultsThe median overall survival (OS) and progression-free survival (PFS) of the ESCC patients were 2.25 and 1.24 years, respectively. Uni- and multivariate analyses demonstrated the relevant independent prognostic factors of OS and PFS were gender, T stage, N stage, clinical stage, and tumor location (P < 0.05), but not chemotherapy or radiotherapy dose. We further compared the 5-year OS rates among different T stages, N stages, clinical stages, genders, and tumor locations. The survival rate at the higher clinical stage was significantly lower (P < 0.001). The 5-year OS in the upper thorax of the tumor was 46.0% and exceeded other tumor locations (P < 0.05). The 5-year OS was 56.1% among females and 33.3% among males (P = 0.001).ConclusionsFor ESCC patients receiving IMRT combined with chemotherapy, their long-term curative effects are influenced by T stages, N stages, clinical stages, genders, and tumor locations. ESCC patients who are females, or have upper thoracic tumor, or are at early clinical stage own better prognosis.     

T1-2N1M0期鼻咽癌IMRT同期化疗疗效分析

目的 回顾性成组配对分析早期鼻咽癌单纯IMRT与IMRT同期化疗疗效及不良反应。方法 2009—2010年共98例T_1-2N₁M₀期鼻咽癌患者行单纯放疗或同期放化疗,筛选出39对患者进行疗效及不良反应对比分析。Kaplan-Meier法计算生存率且Logrank法检验。结果 3年随访率为95%。单纯IMRT组和同期放化疗组3年OS率分别为97%、95%(P=0.411),PFS率分别为97%、92%(P=0.301),LRFS率分别为97%、97%(P=0.606),DMFS率分别为100%、92%(P=0.082)。白细胞减少、贫血、血小板减少发生率同期放化疗组大于单纯IMRT组(P=0.000、0.000、0.000),单纯IMRT组与同期放化疗组3级口腔口咽黏膜炎发生率分别为26%和36%(P=0.093),听力下降发生率分别为41%、62%(P=0.100)。结论 同期化疗联合IMRT未能提高早期鼻咽癌T_1-2N₁期患者OS、PFS、LRFS率,亦未能降低DMFS率;且血液毒性、3级黏膜炎、听力下降发生率较单纯IMRT组高。     

High pretreatment serum lactate dehydrogenase level correlates with disease relapse and predicts an inferior outcome in locally advanced nasopharyngeal carcinoma

PurposeHere, we evaluate the prognostic effect of pretreatment serum lactate dehydrogenase (LDH) in locally advanced nasopharyngeal carcinoma (NPC).Methods and materialsPretreatment serum samples from a randomized controlled trial, which contained 199 neoadjuvant chemoradiotherapy patients and 201 neoadjuvant-concurrent chemoradiotherapy cases with locally advanced NPC, were collected and examined for LDH. With 5-year follow-up, the prognostic effect of pretreatment serum LDH was analysed by Kaplan–Meier analysis and multivariate Cox regression model.ResultsThree hundred and sixty-seven patients (91.75%) had a normal (109.0–245.0 U/L) pretreatment LDH level, compared to 33 cases (8.25%) that had a higher (?245.0 U/L) LDH level. The mean and median pretreatment LDH levels of these 400 patients were 186.6 and 174.0 U/L (range, 83.0–751.0 U/L), respectively. Compared with the normal subset, elevated LDH level predicted an inferior 5-year overall survival (56.9% versus 76.8%, P = 0.004), disease-free survival (DFS, 45.4% versus 64.7%, P = 0.001), local relapse-free survival (76.1% versus 89.6%, P = 0.019) and distant metastasis-free survival (DMFS, 54.3% versus 72.2%, P = 0.001). Multivariate analysis confirmed that the LDH level was an independent prognostic factor to predict death, disease progression, local relapse and distant metastasis. For the subgroup with normal LDH (median point of 177.0 U/L), we detected an evident 5-year DFS (68.8% versus 59.5%, P = 0.047) and DMFS advantage (77.3% versus 65.3%, P = 0.016) in 109.0–177.0 U/L subset than that of 178.0–245.0 U/L subgroup.ConclusionsSerological LDH level was an independent prognostic factor for locally advanced NPC. Combining pretreatment LDH with TNM staging might lead to more accurate risk definition.     

Correlation of progression-free and post-progression survival with overall survival in advanced colorectal cancer

BackgroundPolychemotherapy and biological drugs have increased therapeutic options and outcomes of advanced colorectal cancer (CRC). We examined the relation between progression-free survival (PFS), post-progression survival (PPS) and overall survival (OS) in trials of modern (oxaliplatin- and irinotecan-based) chemotherapy alone or with targeted therapies for advanced CRC. We also evaluated surrogacy of PFS and OS.Patients and methodsA PubMed search identified 34 randomized trials. We split the OS, PFS and PPS and evaluated the correlation between OS and either PFS or PPS.ResultsThe median PPS and PFS were 10.75 and 8.4 months, respectively. For all trials, PPS was strongly associated with OS [regression coefficient (R²) = 0.8; Spearman's rank correlation coefficient (r) = 0.88], whereas PFS was moderately associated with OS (R² = 0.43; r = 0.64). In trials with targeted therapies, the correlation of PPS with OS was 0.88. However, across all trials, correlation between differences in median PFS (ΔPFS) and median OS (ΔOS) is 0.59 (P = 0.0007), confirming PFS/OS surrogacy.ConclusionOur findings indicate that in recent first-line, phase III, trials, OS becomes more associated with PPS than PFS. However, improvements in PFS are strongly associated with improvements in OS. In this setting so, PFS may be an appropriate surrogate for OS.     

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...     

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.     

Is replacement of the supraclavicular fossa with the lower level classification based on magnetic resonance imaging beneficial in nasopharyngeal carcinoma?

Purpose and objectivesTo investigate the pattern of lymph node metastasis and treatment outcome after intensity-modulated radiotherapy (IMRT) in nasopharyngeal carcinoma (NPC), and assess the possibility of replacing Ho’s supraclavicular fossa (SCF) with the lower level (LL; cervical extension below caudal edge of cricoid cartilage) based on magnetic resonance imaging (MRI) as a criterion for N3 disease.Methods and materialsWe retrospectively reviewed 749 patients with biopsy-proven non-metastatic NPC treated with IMRT. Lymph node metastasis was mapped using the 2013 International Consensus Guidelines.ResultsCervical lymph node (CLN) laterality, CLN greatest dimension (>60 vs. ⩽60 mm) and Ho’s SCF were independent prognostic factors for disease-free survival (DFS) and distant metastasis-free survival (DMFS; P < 0.01) in multivariate analysis. Replacing Ho’s SCF with the LL was also predictive for DFS and DMFS (P < 0.01). Compared to the 7th UICC/AJCC, N-categories based on the LL provided more satisfactory distinction between hazard ratios for distant and disease failure for each N-category. N3a and N3b as defined by the 7th UICC/AJCC had similar DMFS (P = 0.31) and DFS (P = 0.21).ConclusionsReplacing Ho’s SCF with the LL is simple and practical. The N-category staging system could be further simplified by merging N3 subcategories.     

鼻咽癌调强放疗后长期生存结果及失败模式分析

目的 回顾分析IMRT治疗鼻咽癌的10年生存结果及失败模式,为鼻咽癌的优化治疗提供参考。方法 收集2001-2008年间865例采用IMRT的鼻咽癌患者的临床资料。生存分析采用Kaplan-Meier法,Logrank检验和单因素分析,Cox模型多因素预后分析。结果 中位随访时间为132.0个月,全组患者10年无局部复发生存(LRFS)、无远处转移生存(DMFS)、无进展生存(PFS)、肿瘤特异生存(DSS)分别为92.0%、83.4%、75.7%、78.6%。共210例死亡,其中124例(124/210,59.0%)死于远处转移, 47例(41/210,22.3%)死于局部区域复发。DSS的独立不良预后因素包括年龄>50岁(P=0.00)、LDH≥245 IU/L (P=0.00)、Hb<120 g/L (P=0.01)、T2-T4期(P=0.00)、N1-N3期(P=0.00)和GTV-nx>20 cm³(P=0.00)。Ⅱ期鼻咽癌患者单纯放疗组与联合化疗组10年LRFS、DMFS、DSS均相近(P=0.83、0.22、0.23),Ⅲ期鼻咽癌患者联合化疗组10年LRFS、DSS均优于单纯放疗组(P=0.01、0.01)但10年DMFS相近(P=0.14),Ⅳ a+Ⅳ b期患者总体预后较差。结论 IMRT改善了鼻咽癌患者的远期生存,远处转移成为最主要的失败模式;而Ⅰ-Ⅱ期患者采用单纯IMRT可取得满意生存结果,联合化疗可进一步提高Ⅲ期患者LRFS及DSS,而Ⅳ a+Ⅳ b期患者治疗模式仍需更多探讨。     

Postprogression survival for first-line chemotherapy in patients with advanced gastric cancer

BackgroundWith the increasing availability of active agents, the importance of postprogression survival (PPS) has been recognised for several malignancies. However, little is known of PPS in advanced gastric cancer.Patients and methodsA literature search identified 43 randomised trials in chemotherapy-naive patients with advanced gastric cancer. We partitioned overall survival (OS) into progression-free survival (PFS) and PPS, and then examined the correlation between median OS and either median PFS or median PPS. The correlation between differences in OS (ΔOS) and those in PFS (ΔPFS) between trial arms was also investigated.ResultsThe average median OS was significantly longer in recent (2006 and later) trials than in older (2005 and earlier) trials (10.60 versus 8.64 months, P < 0.001), as was the average median PPS (5.34 versus 3.74 months, P = 0.001). Median PPS was correlated with median OS for all trials (r = 0.732), and this correlation was more pronounced in recent trials (r = 0.850). By contrast, the correlation between median PFS and median OS was less pronounced in recent trials (r = 0.282), as was that between ΔPFS and ΔOS (r = 0.365).ConclusionAn increase in median PPS was found in accordance with an increase in median OS in recent trials compared with older trials for patients with advanced gastric cancer.     

Cancer stem cell enrichment marker CD98: A prognostic factor for survival in patients with human papillomavirus-positive oropharyngeal cancer

PurposeSeveral hypotheses have been proposed to explain the relatively good prognosis of patients with a human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) and one of these is a higher sensitivity to (chemo)radiation. Previous studies have suggested that treatment failure in OPSCC patients is caused by resistance of cancer stem cells (CSCs). The purpose of this study was to evaluate the association between the number of CSCs and prognosis in HPV-positive OPSCC patients.Experimental designAll OPSCC patients (n = 711) treated between 2000 and 2006 in two Dutch university hospitals were included. Presence of HPV in a tumour tissue specimen was tested by p16-immunostaining followed by HPV DNA GP5+/6+polymerase chain reaction (PCR). The presence and intensity of tumour CSC markers CD44 and CD98 were determined by immunohistochemistry and semiquantitative scoring was performed. Overall survival (OS) and progression-free survival (PFS) rates were compared between patients with low and high CD44/CD98 expression in relation to HPV status.ResultsHPV-positive tumours showed a lower percentage of cells with CD44 and CD98 expression than HPV-negative tumours (p < 0.001, χ²-test). Within the group of patients with HPV-positive OPSCC, a high percentage of CD98-positive tumour cells was associated with a significantly worse 5-year OS and PFS (OS: 36.4% and PFS: 27.3%) compared to patients with a low percentage of CD98-positive cells (OS: 71.9% and PFS: 70.5%, respectively) (p < 0.001).ConclusionsHPV-positive OPSCCs harbour fewer cells expressing the CSC enrichment markers CD44 and CD98. Furthermore, OS and PFS were significantly worse for patients with HPV-positive OPSCC with a high percentage of CD98-positive cells.     

Accelerated partial breast irradiation using intensity-modulated radiotherapy versus whole breast irradiation: 5-year survival analysis of a phase 3 randomised controlled trial

BackgroundAccelerated partial breast irradiation (APBI) has been introduced as an alternative treatment method for selected patients with early stage breast cancer (BC). Intensity-modulated radiotherapy (IMRT) has the theoretical advantage of a further increase in dose conformity compared with three-dimensional techniques, with more normal tissue sparing. The aim of this randomised trial is to compare the local recurrence and survival of APBI using the IMRT technique after breast-conserving surgery to conventional whole-breast irradiation (WBI) in early stage BC.MethodsThis study was performed at the University of Florence (Florence, Italy). Women aged more than 40 years affected by early BC, with a maximum pathological tumour size of 25 mm, were randomly assigned in a 1:1 ratio to receive either WBI or APBI using IMRT. Patients in the APBI arm received a total dose of 30 Gy to the tumour bed in five daily fractions. The WBI arm received 50 Gy in 25 fractions, followed by a boost on the tumour bed of 10 Gy in five fractions. The primary end-point was occurrence of ipsilateral breast tumour recurrences (IBTRs); the main analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT02104895.FindingsA total of 520 patients were randomised (260 to external WBI and 260 to APBI with IMRT) between March 2005 and June 2013. At a median follow-up of 5.0 years (Interquartile Range (IQR) 3.4–7.0), the IBTR rate was 1.5% (three cases) in the APBI group (95% confidence interval (CI) 0.1–3.0) and in the WBI group (three cases; 95% CI 0.0–2.8). No significant difference emerged between the two groups (log rank test p = 0.86). We identified seven deaths in the WBI group and only one in the APBI group (p = 0.057). The 5-year overall survival was 96.6% for the WBI group and 99.4% for the APBI group. The APBI group presented significantly better results considering acute (p = 0.0001), late (p = 0.004), and cosmetic outcome (p = 0.045).InterpretationTo our knowledge, this is the first randomised study using the IMRT technique for APBI delivery. No significant difference in terms of IBTR and overall survival was observed between the two arms. APBI displayed a significantly better toxicity profile.