A Systematic Review and Meta-Analysis of Prognostic Biomarkers in Anal Squamous Cell Carcinoma Treated With Primary Chemoradiotherapy

Recent studies suggest that the treatment response and survival from head and neck tumours can be stratified according to biomarker status, particularly human papillomavirus (HPV) status and p16 expression, but the evidence for predictive biomarkers in anal squamous cell carcinoma (ASCC) remains limited. The aim of this study was to determine which biomarkers were associated with locoregional recurrence (LRR), overall survival and disease-free survival (DFS) in ASCC. A systematic search was undertaken of the MEDLINE, Embase, Cochrane Library, CINAHL and Web of Science databases using validated terms for ASCC, biomarkers and prognosis. Biomarkers were included in the meta-analysis if they were reported by at least four studies and provided sufficient data to permit the calculation of survival effect estimates. HPV status, p16, p53 and epidermal growth factor receptor (EGFR) met the inclusion criteria for meta-analysis and were reported by 17 retrospective cohort studies describing 1635 patients. When compared with HPV-negative tumours, HPV-positive tumours were associated with reduced LRR (pooled hazard ratio = 0.27 [95% confidence interval 0.16–0.48]; P < 0.001), improved overall survival (hazard ratio =0.26 [0.12–0.59]; P = 0.001) and DFS (hazard ratio = 0.33 [0.16–0.70]; P = 0.003). Likewise, p16-positive tumours were associated with reduced LRR (hazard ratio = 0.26 [0.13–0.52]; P < 0.001), improved overall survival (hazard ratio = 0.44 [0.24–0.81]; P = 0.009) and DFS (hazard ratio = 0.44 [0.23–0.83]; P = 0.012) when compared with p16-negative tumours. HPV-positive/p16-positive tumours had improved overall survival when compared with HPV-negative/p16-negative tumours (hazard ratio = 0.27 [0.15–0.48], P < 0.001), but not HPV-negative/p16-positive tumours (hazard ratio = 0.64 [0.21–1.90]; P = 0.421). p53 mutation was associated with worse DFS (hazard ratio = 1.63 [1.33–2.01]; P = 0.003). There was no association between EGFR status and any survival outcome. HPV status, p16 and p53 expression are of prognostic utility in ASCC. Future studies should prospectively validate these findings with a view to conducting subsequent randomised controlled trials where patients are stratified according to biomarker status and randomised to different treatment regimens.     

血清鳞状细胞癌抗原在宫颈鳞状细胞癌中的变化及意义

[目的]探讨血清鳞状细胞癌抗原水平在宫颈鳞状细胞癌中的变化及其临床意义。[方法]应用微粒子酶免分析（MEIA）对2000年3月～2000年7月在浙江省肿瘤医院收治的宫颈鳞癌（包括5例鳞腺癌）165例患者进行血清鳞状细胞癌抗原水平检测并分析其与临床分期、肿瘤大小、病理分级、淋巴结转移之间关系,其中放射治疗的93例患者进行治疗前后的血清鳞状细胞癌抗原水平的自身比较,以及与近期疗效的关系。[结果]165例宫颈鳞癌患者血清鳞状细胞癌抗原阳性率为64.2％（106/165）。鳞状细胞癌抗原水平与临床分期、肿瘤大小有关（P<0.05）;与病理分级、淋巴结转移之间无统计学差异（P>0.05）;放射治疗前后患者血清鳞状细胞癌抗原水平变化有统计学意义（P<0.05）,且与疗效相关（P<0.05）。[结论]血清鳞状细胞癌抗原是宫颈鳞癌的相关的肿瘤标记物,在监测宫颈鳞癌的发生和评价疗效等方面具有重要价值,对判断宫颈鳞癌的预后具有一定的临床意义。     

Squamous cell carcinoma of the anal canal at The Queen Elizabeth Hospital: A local experience

Aim: Concurrent chemoradiotherapy is the standard treatment for squamous cell carcinoma of anal canal. We describe our experience of treating such patients at our center. Methods: Patients with anal squamous cell carcinoma were treated with a uniform sphincter preserving protocol at The Queen Elizabeth Hospital, South Australia. Standard radiotherapy along with 5‐fluorouracil (750 mg/m² on days 1–5 and days 29–32) and mitomycin C (12 mg/m² on day 1 only) was given to eligible patients. Results: Of the 34 patients included in this study, nearly 60% were women. Most (89.3%) had T1‐2 disease. One‐third had nodal involvement. Twenty‐seven had chemoradiotherapy, six had local excision alone and one had radiotherapy alone. Among those who had chemoradiation, 71.5% had a complete response and remained colostomy free until the last follow‐up. Most completed the treatment without major side‐effects. The 3 and 5‐year disease free survival rate was 62% and 53%, respectively. All patients who failed chemoradiation underwent salvage surgery with a median survival time of 32.5 months. Conclusion: Sphincter preservation is the goal for anal cancers. Chemoradiotherapy is an important modality to achieve this goal.     

三维适形放射治疗在非小细胞肺癌综合治疗中的价值

[目的]探讨三维立体定向放射治疗在非小细胞肺癌综合治疗中的价值。[方法]研究组52例采用前胸后背相对野常规放射治疗,剂量36Gy,18次,2Gy/次,3.6周完成;然后进行三维适形放射治疗,剂量30～42Gy,3Gy/次,10～14次。对照组52例采用常规放射治疗,剂量60～62Gy,2Gy/次,30～31次。两组患者放射治疗结束后,均进行化疗。[结果]研究组放射性食管炎和放射性肺炎发生率显著低于对照组(P<0.05,P<0.01)。研究组近期有效率(CR PR)(86.5%,45/52)显著高于对照组(51.9%,27/52)(P<0.05)。研究组1、2年局部控制率(78.8%,51.9%)显著高于对照组(46.2%,15.4%)(P<0.01)。研究组1、2年生存率(63.46%,38.46%)显著高于对照组(53.85%,17.31%)(P<0.01)。[结论]三维适形放射治疗可用于非小细胞肺癌的综合治疗,其毒副反应轻,有较好的近期疗效。     

Definitive Chemoradiotherapy for Oesophageal Cancer — A Promising Start on an Exciting Journey

Despite many advances in the management of oesophageal cancer, survival rates remain poor. Currently there is no clear consensus on the optimum management modality for localised disease. Surgery alone or combined with neoadjuvant chemotherapy or chemoradiotherapy and definitive chemoradiotherapy are all treatment options used for treating selected patient groups throughout the world. This overview discusses the evidence for definitive chemoradiotherapy, its role for certain patient groups and compared with other treatment options and how it has evolved with emerging technologies over recent decades. It highlights some key areas of research for future trials, including more precise treatment delivery, treatment intensification and a possible randomised controlled trial comparing radiation and surgical-based treatment.     

外科手术在治疗病变局限期小细胞肺癌中的地位

近年对外科手术在治疗局限期小细胞肺癌中的地位有了重新的认识。现有资料认为采用综合治疗力争根治性切除是使患者长期存活的重要治疗模式。化、放疗仍是小细胞肺癌的主要治疗手段 ,手术应掌握适应证。总的策略是在术前诱导化疗的基础上手术 ,辅以必须的术后化疗。手术能够完全切除的 ,术后应进行预防性颅脑照射。对于术中发现肺门和纵隔淋巴结转移的 ,建议术后纵隔放疗     

Patterns of Failure Following Dose-escalated Chemoradiotherapy for Fluorodeoxyglucose Positron Emission Tomography Staged Squamous Cell Carcinoma of the Oesophagus

Aims

To analyse outcomes and patterns of failure following dose-escalated definitive chemoradiotherapy (CRT) for oesophageal squamous cell carcinoma using fluorodeoxyglucose positron emission tomography for staging and treatment planning.

多西他赛单药用于晚期食管鳞癌二线治疗的疗效分析

[目的]探讨多西他赛在晚期食管鳞癌患者二线治疗中的疗效及不良反应.[方法]回顾性分析85例晚期食管鳞癌患者,所有患者均为一线治疗进展后采用二线多西他赛治疗.Kaplan-Meier法进行生存分析.Cox法对影响患者预后的因素进行多因素分析.[结果]患者中位无进展生存期为3.5个月,中位生存期为5.5个月.一线化疗达到部分缓解的患者多西他赛治疗疗效优于一线治疗后稳定及进展的患者(4.0个月vs 3.2个月,P=0.015).多数患者能够耐受不良反应,发生Ⅲ～Ⅳ度不良反应的患者比例为25.8％.[结论]多西他赛在二线食管鳞癌患者中有一定的疗效.一线治疗中疗效好的患者采用多西他赛二线治疗疗效较好.     

喉咽鳞癌不同治疗方案对喉功能保留及预后的影响

目的：回顾性分析初治的97例喉咽鳞癌患者应用不同治疗方法后的生存率、喉功能保留率和复发与转移情况等,探索更合理的处理方法。方法：采用SPSS10．0统计软件Kaplan—Meier法和PearsonY。检验／Fisher’s确切概率比较单纯放疗组30例,新辅助化疗＋放疗组17例,单纯手术组11例,手术＋术后放疗组33例,姑息化疗组6例的治疗效果。结果：97倒喉咽鳞癌总的3、5年累计生存率分别为46．43％和31．88％,中位生存时间是28个月。单纯放疗组、新辅助化疗＋放疗组、单纯手术组、手术＋术后放疗组5年生存率分则是18．33％、23．53％、36．36％和53．65％,5年复发率分别是70．00％、52．94％、36．36％和27．27％。接受原发灶手术共41例,喉功能部分或全部保留的手术患者与全喉切除术不保留喉功能的患者的5年生存率分别是57．14％、39．16％,P=0．3574;两组的5年局部复发率分剐是21．05％、13．64％,差异均无统计学意义,P=0．4140。结论：喉咽鳞癌患者接受单纯放疗或新辅助化疗＋放疗生存率较低,单纯手术治疗也不能明显提高生存率,手术＋放疗的治疗模式可使患者生存率有明显提高,部分喉咽鳞癌肿瘤局限,可考虑行保留喉功能的喉部分切除术,并不增加复发的风险。     

Differential Relapse Patterns for Non-small Cell Lung Cancer Subtypes Adenocarcinoma and Squamous Cell Carcinoma: Implications for Radiation Oncology

AimsCurative-intent (radical) radiotherapy aims to control local disease and cure non-small cell lung cancer (NSCLC). The predominant subtypes of NSCLC are adenocarcinoma and squamous cell carcinoma (SCC). The radiotherapy paradigm offered to patients does not differ according to these two subtypes. Relapse patterns and disease control rates for adenocarcinoma and SCC treated with radical radiotherapy were determined.Materials and methodsA radical radiotherapy database covering the period from 2004 to June 2016 was examined to determine the first sites of relapse and the actuarial local and distant control rates.ResultsIn total, 537 patients with known pathological subtype were treated over the period. In 39 (7%), the site of first relapse was uncertain. Of the remainder, 203 (41%) had adenocarcinoma and 295 (59%) had SCC. At a median follow-up of 16.4 months, 58% had relapsed. There was a difference in relapse patterns (chi-squared test P < 0.0005), with a higher rate of first relapse locally in SCC (42% of all patients versus 24%) and a higher rate of first relapse in the brain for adenocarcinoma (14% versus 3%). The actuarial local control rate was worse for SCC (hazard ratio 0.6, 95% confidence interval 0.5–0.9, P = 0.002). The brain metastasis-free survival was worse for adenocarcinoma (hazard ratio 4.1, 95% confidence interval 2.2–7.5, P < 0.0001).ConclusionThere is a difference in relapse patterns between NSCLC histological subtypes, indicating that these are distinct entities. This may have implications for follow-up policy and strategies to improve disease control.     

紫杉醇脂质体联合奈达铂同步放化疗治疗中晚期宫颈鳞癌

[目的]探讨紫杉醇脂质体联合奈达铂同步放化疗治疗中晚期宫颈鳞癌患者的疗效及不良反应。[方法]对26例病理确诊的Ⅱb～Ⅳa期宫颈鳞癌患者采用盆腔外照射+高剂量率腔内后装放疗及同期化疗,化疗方案为:紫杉醇脂质体40mg/m2+奈达铂20mg/m2,每周1次,共6次。观察近期疗效、1、2、3年生存率及化疗、放疗不良反应。[结果]完全缓解(CR)20例(76.9%),部分缓解(PR)5例(19.2%),稳定(SD)1例(3.8%),进展(PD)0例,有效率(RR)为96.2%(25/26)。1、2、3年生存率分别为96.2%、88.5%、84.6%。不良反应主要为骨髓抑制、脱发及胃肠道反应,但均能耐受;放疗远期并发症发生率低且较轻。[结论]紫杉醇脂质体联合奈达铂同步放化疗治疗中晚期宫颈鳞癌的疗效好,不良反应可耐受,患者依从性高。     

The Impact of Radiotherapy Dose in Patients with Locally Advanced Esophageal Squamous Cell Carcinoma Receiving Preoperative Chemoradiotherapy

Objective: For patients with esophageal squamous cell carcinoma, preoperative chemoradiotherapy followed by planned esophagectomy is used as a curative treatment modality. However, the impact of radiotherapy dose remains undefined. Method: A total of 141 patients with stage III esophageal squamous cell carcinoma (ESCC; as defined by the 7th American Joint Committee on Cancer), receiving preoperative chemoradiotherapy followed by esophagectomy between 2000 and 2015 at Kaohsiung Chang Gung Memorial Hospital, Taiwan, were retrospectively reviewed. The radiotherapy dose of preoperative chemoradiotherapy (36 Gy before 2009 and 50–50.4 Gy after 2009) and other clinicopathological parameters were collected and correlated with the response to chemoradiotherapy and treatment outcome. Result: Of these 141 patients, the radiotherapy dose was 36 Gy in 59 (42%) patients and 50 Gy in 82 (58%) patients. A complete pathological response was noted in 12 (20%) of 59 patients receiving 36 Gy radiotherapy, and 37 (45%) of 82 patients receiving 50 Gy radiotherapy (p = 0.002). The three-year overall survival and disease-free survival rates were 31% and 25% in patients receiving 36 Gy radiotherapy, and 54% and 46% in patients receiving 50–50.4 Gy radiotherapy, respectively (p = 0.023 for overall survival; p = 0.047 for disease-free survival). Multivariate analysis showed that a higher radiotherapy dose was associated with increased pathological complete response (p = 0.003, hazard ratio: 3.215), better overall survival (p = 0.024, hazard ratio: 1.585), and superior disease-free survival (p = 0.049, hazard ratio: 1.493). However, higher radiotherapy doses revealed more surgical complications, including acute respiratory distress syndrome (p = 0.048) and anastomosis leaks (p = 0.004). Conclusion: For patients with locally advanced ESCC, preoperative chemoradiotherapy with higher radiotherapy doses led to increased pathologic complete response rates and improved survival.     

40例晚期非小细胞肺癌放射治疗为主的综合治疗结果

目的　报告放射治疗为主综合治疗 40例 (NSCLC)的近期疗效。方法　从 1993年 2月至 1999年 8月 ,经病理组织学或细胞学确诊的 40例不能手术的Ⅲ期NSCLC分为两组 :A组辅助化疗 +白细胞介素 -2 +放射治疗 :B组单纯放射治疗。结果　治疗后 ,A组病人CR 3例 (16 7% ) ,PR 13 (72 2 % ) ,有效率为 88 9% ;B组病人CR 2例 (10 5 % ) ,PR 9例 (4 7 4% ) ,有效率为 5 7 9%。有效率比较有显著差异 (P <0 .0 5 )。放、化疗反应均可耐受。结论　综合治疗能加快肿瘤消散 ,增强机体抗瘤能力 ,提高不能手术的NSCLC的近期疗效 ,急性反应可耐受     

肺鳞癌靶向治疗研究现状

随着肺癌驱动基因研究的逐步深入,肺癌靶向治疗已取得较大进展。与肺腺癌相比,肺鳞癌的靶向治疗进展明显滞后。对肺腺癌临床疗效确切的靶向药物,如：表皮生长因子受体-酪氨酸激酶抑制剂（epidermal growth factor receptor-tyrosine kinase inhibitor, EGFR-TKI）、棘皮类微管相关样蛋白-4（echinodern microtubule-associated-protein-like 4, EML4）-间变型淋巴瘤激酶（anaplastic lymphoma kinase, ALK）融合基因抑制剂等,均对肺鳞癌疗效欠佳,目前肺鳞癌缺少有效的靶向治疗药物。因此,迫切需要对肺鳞癌的驱动基因和靶向治疗进行更深入的研究。本文将对肺鳞癌靶向治疗的研究现状作一综述。     

Chemoradiotherapy of nonsmall cell lung cancer

The efficacy of radiotherapy in locally advanced unresectable non-small cell lung cancer is low. This method does not provide effective eradication of bulky disease in the thorax, neither does it prevent uncontrolled systemic disease. The addition of chemotherapy to radiation results in increased cure rate by both improving tumor control in the thorax and by eliminating or delaying the emergence of metastatic disease. The two most frequently tested strategies of combining chemotherapy and radiation include primary chemotherapy followed by radiation and concurrent application of both methods. This review provides the rationale for this strategy and presents the results of major Phase III studies. Discussed are advantages of chemoradiation, its limitations in clinical practice and prospects for the future.     

The Place of Radiation Therapy in the Treatment of Squamous Cell Carcinoma of the Nasal Vestibule

Radiation therapy and limited resection give equally good results in early squamous cell carcinomas of the nasal vestibule, each producing local control rates of 90% or more. For more extensive disease, primary radiation therapy with surgery reserved for residual or recurrent carcinoma is recommended in view of the significant cosmetic defects which generally follow major resection. Small and superficial lesions can be treated by external beam therapy or interstitial implants. Large or infiltrative lesions are best managed by external beam therapy. Serious late morbidity following irradiation is uncommon and has been reported in fewer than 5% of patients. Regional nodal metastases are diagnosed at the time of first presentation in about 5% of patients and signal a very poor prognosis. However, the data available do not support elective treatment of clinically uninvolved regional nodes. Fewer than 5% of patients manifest late nodal metastases when the primary tumor area remains free of recurrence, and most of these metastases can be controlled by neck dissection and/or irradiation.     

Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma: A Review

Research indicates that a small population of cancer cells is highly tumorigenic, endowed with the capacityfor self-renewal, and has the ability to differentiate into cells that constitute the bulk of tumors. These cells areconsidered the ‘‘drivers’’ of the tumorigenic process in some tumor types, and have been named cancer stemcells (CSC). Epithelial-mesenchymal transition (EMT) appears to be involved in the process leading to theacquisition of stemness by epithelial tumor cells. Through this process, cells acquire an invasive phenotype thatmay contribute to tumor recurrence and metastasis. CSC have been identified in human head and neck squamouscell carcinomas (HNSCC) using markers such as CD133 and CD44 expression, and aldehyde dehydrogenase(ALDH) activity. Head and neck cancer stem cells reside primarily in perivascular niches in the invasive frontswhere endothelial-cell initiated events contribute to their survival and function. Clinically, CSC enrichment hasbeen shown to be enhanced in recurrent disease, treatment failure and metastasis. CSC represent a novel targetof study given their slow growth and innate mechanisms conferring treatment resistance. Further understandingof their unique phenotype may reveal potential molecular targets to improve therapeutic and survival outcomesin patients with HNSCC. Here, we discuss the state-of-the-knowledge on the pathobiology of cancer stem cells,with a focus on the impact of these cells on head and neck tumor progression, metastasis and recurrence due totreatment failure.     

不同剂量顺铂和5-氟脲嘧啶联合化疗合并放疗治疗中晚期食管癌临床研究

目的 :评价不同剂量顺铂 5 FU联合放疗治疗中晚期食管癌的疗效及毒副作用。方法 :1993年 2月～ 1994年 9月我科收治中晚期食管鳞癌 83例 ,随机分成大剂量组、小剂量组、单放组。结果 :①近期疗效 :大剂量组 85.7% ,小剂量组 75.0 % ,单放组 37.0 % ;② 1、3、5年生存率 :大剂量组 71.4 %、35 7%、2 1.4 % ;小剂量组 67.9%、39.3%、2 5.0 % ;单放组 4 0 .7%、2 2 .2 %、11.1% ;③毒副反应 (Ⅲ～Ⅳ级 ) :骨髓抑制及胃肠道反应 ,大剂量组 4 6.4 %、39.3% ;小剂量组 10 .7%、3.6%。结论 :①大、小剂量组的近、远期疗效均优于单放组 ,P <0 .0 5;大、小剂量组之间疗效无显著差异 ,P <0 .0 5;②大剂量组的毒副反应明显高于小剂量组 ,P <0 .0 5。因此认为小剂量组治疗中晚期食管癌疗效确切、毒副反应低、治疗连贯 ,值得临床应用