Elective nodal irradiation (ENI) vs. involved field radiotherapy (IFRT) for locally advanced non-small cell lung cancer (NSCLC): A comparative analysis of toxicities and clinical outcomes

Background

Elective nodal irradiation (ENI) and involved field radiotherapy (IFRT) are definitive radiotherapeutic approaches used to treat patients with locally advanced non-small cell lung cancer (NSCLC). ENI delivers prophylactic radiation to clinically uninvolved lymph nodes, while IFRT only targets identifiable gross nodal disease. Because clinically uninvolved nodal stations may harbor microscopic disease, IFRT raises concerns for increased nodal failures. This retrospective cohort analysis evaluates failure rates and treatment-related toxicities in patients treated at a single institution with ENI and IFRT.

Methods

We assessed all patients with stage III locally advanced or stage IV oligometastatic NSCLC treated with definitive radiotherapy from 2003 to 2008. Each physician consistently treated with either ENI or IFRT, based on their treatment philosophy.

Results

Of the 108 consecutive patients assessed (60 ENI vs. 48 IFRT), 10 patients had stage IV disease and 95 patients received chemotherapy. The median follow-up time for survivors was 18.9 months. On multivariable logistic regression analysis, patients treated with IFRT demonstrated a significantly lower risk of high grade esophagitis (Odds ratio: 0.31, p = 0.036). The differences in 2-year local control (39.2% vs. 59.6%), elective nodal control (84.3% vs. 84.3%), distant control (47.7% vs. 52.7%) and overall survival (40.1% vs. 43.7%) rates were not statistically significant between ENI vs. IFRT.

Conclusions

Nodal failure rates in clinically uninvolved nodal stations were not increased with IFRT when compared to ENI. IFRT also resulted in significantly decreased esophageal toxicity, suggesting that IFRT may allow for integration of concurrent systemic chemotherapy in a greater proportion of patients.     

DIBH技术对纵隔淋巴瘤累及部位放疗靶区与OAR受量影响

目的 探讨深吸气屏气(DIBH)技术对纵隔淋巴瘤放疗靶区和正常组织受量影响。方法 前瞻性采集连续收治的5例Ⅰ、Ⅱ期纵隔淋巴瘤病例。采用受累部位照射和蝴蝶野设野原则,对比DIBH和自由呼吸(FB)扫描时靶区绝对体积变化、重要OAR绝对剂量体积和相对剂量-体积差别。配对t检验差异。结果 5例中位年龄30岁。与FB相比DIBH时靶区绝对体积化疗前GTV缩减29.4 cm³(P=0.006),PTV缩减322 cm³(P=0.005);肺绝对体积平均增大1456 cm³(P=0.001),心脏宽度缩小1.3 cm (P=0.012)。DIBH时心脏和肺D_mean显著降低(心脏为8.5 Gy∶11.6 Gy,P=0.022;肺为7.6 Gy∶11.6 Gy,P=0.000)。比较受一定水平照射的绝对体积时,心脏在高剂量水平V₁₅及以上显著降低(P均<0.05)。DIBH时肺和心脏相对百分比在所有剂量水平(V₅—V₃₅)均显著小于FB (P均<0.05)。结论 纵隔淋巴瘤放疗,DIBH技术能显著缩小PTV,增加肺体积,且显著降低心肺D_mean和V₅—V₃₅水平的相对剂量-体积参数。     

Potential Benefit of Involved-Field Radiotherapy for Patients With Relapsed-Refractory Hodgkin's Lymphoma With Incomplete Response Before Autologous Stem Cell Transplantation

IntroductionWe investigated for a possible role for peritransplantation involved-field radiotherapy (IFRT) by comparing patients who received IFRT before after autologous stem cell transplantation (ASCT) and patients who received salvage chemotherapy (CT) alone.Patients and MethodsWe retrospectively evaluated 73 consecutive patients with Hodgkin lymphoma treated with ASCT between 2003 and 2014. Twenty-one patients (28.8%) received peritransplantation radiotherapy. A Cox regression analysis (multivariate analysis; MVA) was performed to evaluate the prognostic role of any risk factor. Overall survival (OS) and progression-free survival (PFS) were calculated from the date of ASCT. Response to CT and ASCT were evaluated with positron emission tomography (PET) scan.ResultsMedian follow-up was 41 months (range, 1-136 months). Overall, no significant difference appeared between patients who received IFRT and patients treated with CT alone; however, patients who were treated with IFRT had worse prognostic factors. In the MVA, advanced stage at relapse and persistent disease before ASCT (evident on PET scan [PET+]) were related to worse PFS and OS. In patients with limited stage disease at relapse and PET+, peritransplantation radiotherapy showed higher 3-year OS rates (91.7% vs. 62.3%) and PFS rates (67.5% vs. 50%) compared with patients treated with CT alone, although this difference was not significant (P = .14 and P = .22, respectively).ConclusionIFRT used before or after ASCT might partially compensate for worse prognostic factors among the overall population; subgroup analysis showed a trend for survival benefit at 3 years in patients with limited stage disease at relapse and PET+ before ASCT.     

食管鳞癌术后局部区域复发患者接受不同照射方式获益人群的初步分析

目的 探讨胸段食管鳞癌患者术后局部区域复发接受放疗患者不同照射方式的人群获益情况。方法 回顾性分析2009-2014年间河北医科大学第四医院 344例食管癌术后复发接受了调强适形放疗或同步化放疗患者的病历资料,分析患者的复发部位分布的情况、预后影响因素,并对接受选择性淋巴结照射(ENI)和累及野照射(IFI)两种方式的获益人群进行分层分析。结果 术后单区域复发 276例(80.2%),其中≥2个区域复发 68例(19.8%)。随访率96.2%。全组患者1、3、5年总生存率分别为53.6%、22.6%、16.4%,中位生存期12.8个月(95%CI为 11.3~14.3个月);1、3、5年无局部复发生存率分别为46.5%、16.9%、12.0%,中位生存期11.0个月(95%CI为 9.6~12.4个月);1、3、5年无进展生存率分别为39.8%、11.3%、6.7%,中位生存期7.9个月(95%CI为 5.8~10.0个月)。全组多因素分析结果显示患者性别、阳性淋巴结对数比(LODDS)、化疗周期数均为患者预后的独立影响因素(P=0.003、<0.001、<0.001)。亚组单因素分析结果显示对食管病变长度<5.0cm、N0期、手术清扫淋巴结≤9个、术后阳性淋巴结转移区域数为0个、LODDS≤0.030患者进行ENI可使其受益(P=0.032、0.012、0.001、0.012、0.014);而对手术清扫淋巴结≥16个患者进行IFI可使其获益(P=0.035)。结论 放疗为食管癌术后局部区域复发患者的有效治疗模式,对于术前食管造影显示食管病变较短、术后病理N分期较早、LODDS评分较低和清扫淋巴结数目较少者可能应用ENI较IFI更能使其获益;而术中清扫淋巴结数目较多患者可能应用IFI较ENI更能使其获益。     

胸段食管鳞癌根治性放化疗IFI和ENI前瞻性多中心随机对照临床研究

目的 比较胸段食管鳞癌根治性放化疗采用IFI和ENI照射的不良反应、失败模式和长期生存。方法 符合入组条件胸段食管鳞癌采用随机数字表法分为IFI或ENI组。主要观察终点为急性放化疗不良反应,次要观察终点为失败模式、PFS和OS。Kaplan-Meier法计算生存率,Logrank法检验差异。结果 2012—2016年9个试验中心共筛选食管鳞癌患者 228例,最终可分析的患者ENI组 101例,IFI组 104例。IFI组≥2级急性放射性食管炎和放射性肺炎的发生率明显低于ENI组(P=0.018,0.027)。ENI组和IFI组在总失败率、局部区域失败率、远处转移率、野内和野外淋巴结复发率等均相近(P=0.401、0.561、0.510、0.561、0.681)。ENI组与和IFI组1、2、3、4年OS率和中位OS期分别为84.1%、57.3%、39.4%、31.6%和28个月与83.6%、62.1%、44.5%、31.5%和32个月(P=0.654);1、2、3年PFS率和中位PFS期分别为71.9%、42.3%、32.7%和20个月与70.1%、45.0%、35.9%和22个月(P=0.885)。结论 与ENI相比,胸段食管鳞癌采用IFI照射可减少急性放射性食管炎和肺炎发生率,而不会降低局部-区域淋巴结和肿瘤控制率及远期生存。临床试验注册 临床试验注册中心,注册号:NCT01551589。     

临床T1~2N0~1M0食管癌放疗长期疗效、治疗失败原因和选择性淋巴结照射结果分析

目的 明确和评价临床可手术切除食管癌放射治疗的疗效,分析其治疗失败的原因,同时对选择性淋巴结照射的可行性进行分析。方法　对可能影响入组食管癌患者预后的生存因素进行分析,并对其死亡原因进行详细分析。同时对进行了选择性淋巴结照射的21例患者的生存相关情况与其他102例患者进行了比较研究。疾病治疗失败原因分为复发、远处转移和淋巴结转移。结果 全组患者1、3、5年总生存率及局部控制率分别为87.8%、47.2%、36.5%和89.7%、67.7%、49.0%。多因素分析显示病变X线长度、临床N分期及近期疗效是其独立的预后因素。选择性淋巴结照射并未给患者生存及局控率上带来益处,但对纵膈淋巴结转移和（或）远处转移患者有益（χ2=5.778,P=0.016）。结论 三维适形放射治疗可作为早期食管癌有效的治疗方式之一;选择性淋巴结照射可能会降低淋巴结转移率,但需要后续进一步研究证实,是否能提高患者的生存率也有待进一步研究。     

Reduction of the treated volume to involved node radiation therapy as part of combined modality treatment for early stage aggressive non-Hodgkin’s lymphoma

Background and purpose

This retrospective study investigated whether focused involved node radiation therapy (INRT) can safely replace involved field RT (IFRT) in patients with early stage aggressive NHL.

Patients and methods

We included 258 patients with stage I/II aggressive NHL who received combined modality treatment (87%) or primary RT alone (13%). RT consisted of a total dose of 30–40 Gy in 15–20 fractions IFRT or INRT. We compared survival, relapse pattern, radiation-related toxicity and quality of life for both RT techniques.

Results

Type of RT was not related to the outcome in either the uni- or multivariate survival analysis. Relapses developed in 59 of 252 patients (23%) of which 47 (80%) were documented as distant recurrence only. Failure of the INRT technique was noted in one patient. There was no significant difference in acute radiation-related toxicity between RT-groups but IFRT showed a significantly higher incidence of higher grade toxicities. Patients treated with INRT had a significantly better physical functioning and global quality of life compared to the IFRT group.

Conclusions

Given the retrospective nature of this study, no solid conclusions can be drawn. However, in view of the equivalent efficacy and more favorable toxicity profile, the replacement of IFRT by INRT in combination with chemo-(immuno)-therapy looks very attractive for patients with early stage aggressive NHL.     

Cancer of the oesophagus and lymph nodes management in the neoadjuvant or definitive radiochemotherapy setting

Despite representing a 1% of diagnosed cancer cases in the USA and up to 5% in eastern Asia and Africa, oesophageal cancer still holds numerous questions concerning the best therapeutic management. For squamous cell carcinoma, while radiochemotherapy has proven itself to be the gold standard as part of the trimodality or alone as a definitive treatment, radiotherapy modalities are still debated especially regarding lymph node irradiation. Involved nodes irradiation was developed with the aim of maintaining clinical outcomes and enhancing quality of life but lacks grade 1 evidence. In this article, we aim to summarize the state of art regarding lymph node irradiation, discuss the impact of target definition, delivery techniques, concomitant treatment and the perspectives. Being highly connected to the lymph vessels, lymphatic metastases are frequent and can locate from the neck to the coeliac area with each node having a different prognostic significance. Regarding the comparison between elective nodal irradiation and involved nodes irradiation, evidence-based medicine mostly relies on retrospective studies. Pooled, it suggests similar clinical outcomes with lower acute toxicities in favour of involved nodes irradiation. However, delivery techniques, doses and concomitant treatment were not consensual. Studies are ongoing evaluating the impact of radiation delivery techniques and the choice of concomitant treatment, i.e. immunotherapy. Modern techniques of imaging, radiation therapy progressing each day and alternative treatment modalities being tested, the need of randomized controlled trials has never been so high. Elective nodal irradiation should remain the standard of care while phase 3 trials explore the safety of involved nodal irradiation.     

Involved-field, low-dose chemoradiotherapy for early-stage anal carcinoma

PURPOSE: To report the results of patients with early-stage anal cancer treated using a low-dose, reduced-volume, involved-field chemoradiotherapy protocol. METHODS AND MATERIALS: Between June 2000 and June 2006, 21 patients were treated with external beam radiotherapy (30 Gy in 15 fractions within 3 weeks) and concurrent chemotherapy (bolus mitomycin-C 12 mg/m(2) on Day 1 to a maximum of 20 mg followed by infusion 5-fluorouracil 1,000 mg/m(2)/24 h on Days 1-4). Of the 21 patients, 18 underwent small-volume, involved-field radiotherapy and 3 were treated with anteroposterior-posteroanterior parallel-opposed pelvic fields. Of the 21 patients, 17 had had lesions that were excised with close (<1 mm) or involved margins, 1 had had microinvasive disease on biopsy, and 3 had had macroscopic tumor <2 cm in diameter (T1). All were considered to have Stage N0 disease radiologically. RESULTS: After a median follow-up of 42 months, only 1 patient (4.7%) had experienced local recurrence and has remained disease free after local excision. No distant recurrences or deaths occurred. Only 1 patient could not complete treatment (because of Grade 3 gastrointestinal toxicity). Grade 3-4 hematologic toxicity occurred in only 2 patients (9.5%). No significant late toxicity was identified. CONCLUSION: The results of our study have shown that for patients with anal carcinoma who have residual microscopic or very-small-volume disease, a policy of low-dose, reduced-volume, involved-field chemoradiotherapy produces excellent local control and disease-free survival, with low rates of acute and late toxicity.     

Hitting a Moving Target: Successful Management of Diffuse Large B-cell Lymphoma Involving the Mesentery With Volumetric Image-guided Intensity Modulated Radiation Therapy

Introduction

We report successful treatment of mesenteric diffuse large B-cell lymphoma (DLBCL) using localized involved site radiation therapy (ISRT), intensity modulated radiation therapy (IMRT), and daily computed tomography (CT)-image guidance.

Breast conserving therapy after neoadjuvant chemotherapy; data from the Dutch Breast Cancer Audit

IntroductionNAC has led to an increase in breast conserving surgery (BCS) worldwide. This study aims to analyse trends in the use of neoadjuvant chemotherapy (NAC) and the impact on surgical outcomes.MethodsWe reviewed all records of cT1-4N0-3M0 breast cancer patients diagnosed between July 2011 and June 2016 who have been registered in the Dutch National Breast Cancer Audit (NBCA) (N = 57.177). The surgical outcomes of 'BCS after NAC′ were compared with 'primary BCS′, using a multivariable logistic regression model.ResultsBetween 2011 and 2016, the use of NAC increased from 9% to 18% and 'BCS after NAC' (N = 4170) increased from 43% to 57%. We observed an involved invasive margin rate (IMR) of 6,7% and a re-excision rate of 6,6%. As compared to 'primary BCS′, the IMR of 'BCS after NAC′ is higher for cT1 (12,3% versus 8,3%; p < 0.005), equal for cT2 (14% versus 14%; p = 0.046) and lower for cT3 breast cancer (28,3% versus 31%; p < 0.005). Prognostic factors associated with IMR for both 'primary BCS′ as for 'BCS after NAC′ are: lobular invasive breast cancer and a hormone receptor positive receptor status (all p < 0,005).ConclusionThe use of NAC and the incidence of 'BCS after NAC′ increased exponentially in time for all stages of invasive breast cancer in the Netherlands. This nationwide data confirms that 'BCS after NAC′ compared to 'primary BCS′ leads to equal surgical outcomes for cT2 and improved surgical outcomes for cT3 breast cancer. These promising results encourage current developments towards de-escalation of surgical treatment.     

Toxicities and effects of involved-field irradiation with concurrent cisplatin for unresectable carcinoma of the pancreas

PURPOSE: To evaluate local effects and acute toxicities of involved field irradiation with concurrent cisplatin (CDDP) for unresectable pancreatic carcinoma. MATERIALS AND METHODS: Thirty-three patients with unresectable pancreatic carcinoma were treated with chemoradiotherapy. Sixteen were Stage IVA; 17 were Stage IVB. The total prescribed dose of radiotherapy was 50 Gy/25 fractions or 50.4 Gy/28 fractions, using a three-dimensionally determined involved-field that included only the primary tumor and clinically enlarged lymph nodes. Twelve patients received a daily i.v. infusion of CDDP; 21 patients received a combination of CDDP and 5-fluorouracil either i.v. or through the proper hepatic artery. RESULTS: Twenty-seven (82%) patients completed planned chemoradiotherapy. Nausea was the most frequent complaint. No patient experienced Grade 4 toxicities. More than half achieved pain relief. As for the primary site, only 4 patients (12%) achieved a partial response at 4 weeks; however, 3 additional patients attained >50% tumor reduction thereafter. The most frequent site of disease progression was the liver, and only 3 patients developed local progression alone. No regional lymph nodal progression outside the treatment field was seen. Median survival time and survival at 1 year were 7.1 months and 27%, respectively, for the entire group. Difference in overall survival between patients with and without distant metastases was significant (p = 0.01). CONCLUSIONS: Involved-field irradiation with concurrent daily CDDP was well tolerated without compromising locoregional effects.     

Organ motion in image-guided radiotherapy: lessons from real-time tumor-tracking radiotherapy

External radiotherapy using imaging technology for patient setup is often called image-guided radiotherapy (IGRT). The most important problem to solve in IGRT is organ motion. Four-dimensional radiotherapy (4DRT), in which the accuracy of localization is improved – not only in space but also in time – in comparison to 3DRT, is required in IGRT. Real-time tumor-tracking radiotherapy (RTRT) has been shown to be feasible for performing 4DRT with the aid of a fiducial marker near the tumor. Lung, liver, prostate, spinal/paraspinal, gynecological, head and neck, esophagus, and pancreas tumors are now ready for dose escalation studies using RTRT.