IGF-1R expression predicts clinical outcome in patients with locally advanced oral squamous cell carcinoma

To assess the expression of IGF-1R in oral cavity squamous cell carcinoma patients, to explore its relation with clinical and pathologic prognostic factors and its role in predicting clinical outcome. One hundred and thirty-one consecutive patients suffering from oral cavity squamous cell carcinoma were included in this study from July 1989 to April 2005. Follow-up was closed in May 2010. The mean follow-up for survivors was 110.26±47.42 months. Patients were staged following the TNM classification. Patients in tumour stages I and II were referred to surgery. Patients in stages III-IV were referred to postoperative radiotherapy. Radiation therapy was administered up to a mean dose of 62.13±7.74 Gy in 1.8-2 Gy fractions. IGF-1R expression was studied by immunohistochemistry in paraffin-embedded tumour tissue. IGF-1R was expressed in 101 patients (77.1%). IGF-1R expression was related to tumour grade (P=0.012). Tumour stage was the most important prognostic factor for survival. Low (negative and fairly) IGF-1R tumour expression was correlated to better long-term Local Disease Free Survival (P=0.016), Disease-Free Survival (P=0.029), and Survival (P=0.009) in patients achieving tumour stages III-IV. Low IGF-1R expression was related to better long-term control in patients suffering locally advanced oral carcinoma.     

Predictors and impact of microsurgical complications in patients with locally advanced oral squamous cell carcinoma

Microvascular free flap transfer for post‐oncologic reconstructive surgery in oral cancer is considered to be a challenge due to the complexity of the anatomy and function of the region. We sought to identify possible factors associated with microsurgical complications and to assess the impact of these complications in relation to patient survival. Following the inclusion and exclusion protocol, 142 patients with stage III and IV oral squamous cell carcinoma (OSCC) who underwent immediate free flap reconstruction after tumor ablation were included in the study. Clinical and surgical procedural‐related factors were retrieved from a database and analyzed retrospectively; survival data were evaluated using the Kaplan–Meier method. Major complications that required re‐anastomosis of the flap vessels occurred in 23 patients (16.2%); total necrosis of the flaps, regardless of salvage treatment, occurred in seven cases, with 95.1% of full flap survival. The American Society of Anesthesiologists classification, types of neck dissection, and number of flaps were regarded as strong predictors for surgical complications. Patients with these complications appeared to have a shortened survival (5‐year cancer‐specific survival of approximately 60%, both in stage III and IV OSCC). However, the impact of surgical complications on survival was significant only in stage III OSCC (P = 0.037). Strategies to minimize surgical complications should be used to ensure better prognoses for these patients.     

Posttreatment cut-off levels of squamous cell carcinoma antigen as a prognostic factor in patients with locally advanced cervical cancer treated with radiotherapy

Objective

The aim of the present study was to assess prognostic factors for patients with locally advanced cervical cancer treated with radiotherapy as the primary treatment and to assess the posttreatment cut-off levels of squamous cell carcinoma antigen (SCC-Ag) to predict three-year overall survival (OS) rates.

Methods

One hundred and twenty-eight patients with cervical squamous cell carcinoma (International Federation of Gynecology and Obstetrics [FIGO] stage IIB-IVA) treated using radiotherapy or concurrent chemoradiotherapy were identified. Of these patients, 116 who had SCC-Ag levels >1.5 ng/mL prior to treatment were analyzed retrospectively.

Results

Median age was 68 years (range, 27 to 79 years). The complete response rate was 70.7% and the three-year OS rate was 61.1%. The median levels of pretreatment and posttreatment SCC-Ag were 11.5 ng/mL (range, 1.6 to 310.0 ng/mL) and 0.9 ng/mL (range, 0.4 to 41.0 ng/mL), respectively. Multivariate analysis showed that pretreatment anemia (p=0.041), pelvic lymph node metastasis (p=0.016) and posttreatment SCC-Ag levels (p=0.001) were independent prognostic factors for three-year OS. The SCC-Ag level cut-off point for three-year OS rates, calculated using a receiver operating characteristic curve, was 1.15 ng/mL (sensitivity, 80.0%; specificity, 74.0%).

Conclusion

Pretreatment anemia and pelvic lymph node metastasis are poor prognostic factors in locally advanced cervical cancer. Furthermore, posttreatment SCC-Ag levels <1.15 ng/mL predicted better three-year OS rates.     

Risk stratification of patients with advanced squamous cell carcinoma of cervix treated by radiotherapy alone

PURPOSE: To identify prognostic factors for local and distant relapse and perform risk stratification for patients with advanced cervical cancer treated with radiotherapy (RT) alone. METHODS AND MATERIALS: A total of 1031 patients with Stage IB-IVA squamous cell carcinoma of the cervix treated with full-course RT but without any chemotherapy were included for analysis. Of these, 311 patients with nonbulky Stage IB-IIA disease were designated the reference group and the other 720 patients were the study group. The associations of stage, squamous cell carcinoma antigen (SCC-ag) level, hemoglobin level, age, cell differentiation, and pelvic lymph node status with treatment failure were evaluated. The independent prognostic factors were identified by multivariate analysis. The study group was further stratified into subgroups using combinations of these risk factors. RESULTS: In the study group, independent risk factors for local relapse were advanced stage and age <45 years. The 5-year local relapse-free survival rate was 86% for patients > or =45 years with bulky Stage IB-IIA or IIB disease, and was even greater, up to 90% if the SCC-ag level was <2. In contrast, it was 65% for patients with Stage IIIB who were <45 years old. The independent risk factors for distant failure were advanced stage, SCC-ag level >2, and positive pelvic lymph nodes. The 5-year distant relapse-free survival rate was 83% for patients with bulky Stage IB-IIA and IIB disease, SCC-ag level <2, and negative lymph nodes and 43% for patients with Stage III, SCC-ag level >2, and positive lymph nodes. CONCLUSION: The risk of treatment failure in advanced-stage cervical cancer patients treated by RT alone can be more precisely predicted by risk stratification. A certain subgroup of patients had better control than the others. The benefit of treating these relatively low-risk patients with additional treatment such as concurrent chemotherapy should be further evaluated in prospective studies or meta-analyses.     

局部晚期及转移性食管鳞癌免疫治疗现状分析

  目的  免疫治疗被批准用于晚期食管鳞癌（esophageal squamous cell carcinoma,ESCC）的二线治疗,但临床研究由于其严格的入排标准不能完全反映真实世界的情况。本研究旨在分析局部晚期和转移性ESCC免疫治疗现状,并探索可能影响预后的因素。  方法  纳入2018年1月至2020年11月在北京大学肿瘤肿瘤医院接受免疫治疗的局部晚期及转移性ESCC患者,分析临床病理资料、治疗情况、疗效、不良反应和无进展生存期（progression-free survival,PFS）。  结果  本研究纳入33例ESCC患者,其中1例合并强制性脊柱炎。患者均接受程序性细胞死亡抑制剂治疗,最常用的药物为信迪利单抗（17/33,52%）。25例（76%）接受免疫联合治疗,包括联合化疗或抗血管靶向治疗。接受一线、二线和三线及以上治疗的ESCC患者分别为19例（58%）、10例（30%）和4例（12%）。1~2级和3~4级治疗相关不良反应发生率分别为64%（21/33）和27%（9/33）。11例（33%）发生免疫相关性不良反应（immune-related adverse events,irAEs）,包括皮疹5例,甲状腺功能减退4例,免疫性肝炎2例,免疫性肠炎2例,反应性毛细血管增生症2例,免疫性肺炎1例。4例irAEs影响免疫治疗使用,其中3例采用类固醇激素治疗。总体客观缓解率为36%（12/33）。中位PFS为9.17个月（95%CI8.23~ 10.11）。多因素分析显示基线白细胞计数（P=0.010）、免疫治疗线数（P=0.004）、免疫治疗疗效（P=0.049）是PFS的独立影响因子。  结论  免疫治疗在晚期ESCC的临床实践中,药物选择和治疗模式更加多样,但是依然产生良好的疗效。早期应用免疫治疗有效患者可以获得更长的PFS,而白细胞计数升高可能为不良预后因素,未来需扩大人群进一步验证。      

局部中晚期鼻咽癌IMRT同步化疗后急性放射性口腔黏膜炎的预测因素分析

目的 通过前瞻性分析资料齐全的同期放化疗局部晚期鼻咽癌患者的剂量学及临床相关因素,寻找急性放射性口腔黏膜炎的预测因子。方法 对2015—2016年间连续入组的92例局部晚期鼻咽癌IMRT同步化疗患者采用RTOG评分标准进行急性放射性黏膜炎评分,定义评分≥3为重度放射性黏膜炎。获取临床资料,从IMRT计划系统获取患者的DVH剂量学参数信息。对可能预测重度黏膜炎的因素进行统计分析。结果 全组患者重度急性放射性口腔黏膜炎的发生率为21%(19/92),体重下降、口腔黏膜V₃₀是重度黏膜炎的相关因素(P=0.017、0.003)。ROC曲线分析显示口腔黏膜V₃₀诊断重度放射性口腔黏膜炎的阈值为73.16%(敏感性0.842,特异性0.671),ROC的AUC值0.753(P=0.001)。结论 体重下降和口腔黏膜V₃₀是重度黏膜炎的预测因素。     

Podoplanin expression predicts prognosis in patients with oral squamous cell carcinoma treated with neoadjuvant radiochemotherapy

Despite new therapeutic approaches patients with advanced oral squamous cell carcinoma still have a dismal prognosis. The main factor contributing to this problem is locoregional failure due to a lack of response to treatment. Several trials have proven the effect of neoadjuvant radiochemotherapy followed by radical surgery in comparison to primary surgery followed by adjuvant radiochemotherapy. No reliable parameters have been identified so far to predict response to radiochemotherapy. The aim of our study was to assess whether podoplanin expression in pretreatment biopsies could serve as a biomarker to predict the host response to neoadjuvant radiochemotherapy.In this retrospective study, podoplanin expression was examined in a set of 63 patients with oral squamous cell carcinoma by immunohistochemistry. We analyzed associations between the level of podoplanin expression and various clinicopathologic parameters, including response to radiochemotherapy, clinical and histological N-status. Furthermore we evaluated the effects of these parameters on overall survival and on locoregional control in univariate and multivariate analysis.The χ²-test revealed that high expression of podoplanin in pretreatment biopsy material was associated with non-regression of the tumor (p = 0.013) and poor overall survival (p < 0.001). Five-year survival rates of 92.9% for patients with weak expression and 15.0% for high expression were revealed. Podoplanin expression was also significantly associated with ypN status (p = 0.004) and ypUICC status (p < 0.001).We concluded that podoplanin might serve as a factor to predict treatment response in oral squamous cell carcinoma treated with neoadjuvant platin-based radiochemotherapy as well as a prognostic factor for overall survival and locoregional control.     

A phase I trial combining oral cisplatin (CP Ethypharm) with radiotherapy in patients with locally advanced head and neck squamous cell carcinoma

Purpose

To determine the maximum tolerated dose (MTD) of oral cisplatin (CP Ethypharm®) in combination with radiotherapy in head and neck squamous cell carcinoma (HNSCC) and the recommended dose for phase II trials.

Patients and methods

Phase I, multicenter, open-labelled, non-comparative and dose escalating trial. CP Ethypharm® was administered on five consecutive days every other week for 7 weeks (4 treatment cycles) in combination with radiotherapy. Eighteen patients with locally advanced HNSCC were allocated to four cisplatin dose levels: 10 mg/m²/day: 4 patients; 15 mg/m²/day: 4, 20 mg/m²/day: 5 and 25 mg/m²/day: 5. The inclusion of patients was dictated by occurrence of dose limiting toxicities (DLTs) at each dosing level.

Results

The most frequently experienced AEs were gastrointestinal (GI) disorders. Five DLTs were observed, including three at 25 mg/m² level (two grade 2 renal toxicities, one grade 3 GI and renal toxicities), one at 20 mg/m² level (grade 3 GI disorders), one at 10 mg/m² level (grade 4 mucositis). PK analysis showed no significant difference of C_max values between day 1 and day 5 of treatment at each dose level (total & ultrafilterable platinum).

Conclusion

Due to 3 DLTs experienced at 25 mg/m²/day, MTD was reached and the recommended dose for phase II studies was determined as 20 mg/m²/day.     

Decreased cognitive functioning in patients with advanced oral squamous cell carcinoma

Cognitive impairment causes a delay in diagnosis and treatment of the various cancer entities, resulting in reduced surgical outcomes and patient survival. However, no investigations have been carried out as to whether an association exists between cognitive functioning and tumour size in patients with oral squamous cell carcinoma (OSCC). In this study, 46 patients with OSCC were evaluated by using a screening test for dementia, consisting of a combination of the mini-mental state examination and the clock test (81% sensitivity and 90% specificity). Test scores were correlated with tumour size according to the TNM staging system, which was categorized as being either limited (T1, T2; n=24) or advanced (T3, T4; n=22). No difference in age (P=0.172), sex (P=0.330), the percentage of drinkers (P=0.090) or the percentage of smokers (P=0.484) was evident between the groups. Patients with advanced tumour size scored significantly lower (median 5.5 of 9 possible points) when compared with those having tumours of a limited size (median 9 of 9 possible points; P=0.005). The median score of patients with T3/T4 tumours suggested the need for comprehensive neuropsychological evaluations for dementia. In conclusion, this study has demonstrated the correlation of reduced cognitive functioning in patients with advanced OSCC. As a consequence, instructions for the identification of early signs and of symptoms of oral cancer are strongly recommended for relatives and nursing staff of patients with cognitive impairment. Such patients might need immediate treatment for oral cancer but might not be able to understand the significance of their symptoms and therefore present late, often too late.     

Downregulation of tapasin expression in primary human oral squamous cell carcinoma: association with clinical outcome

MHC class I peptide loading complex defects are frequently observed in tumor cells which facilitate tumor cells escaping from immune surveillance. Tapasin plays an important role in the assembly of MHC class I molecules with peptides in the endoplasmic reticulum. The aim of this study was to investigate the expression of tapasin in primary oral squamous cell carcinoma (OSCC) and its potential clinical implication. Formalin-fixed, paraffin-embedded tumor biopsies from 67 patients with primary OSCC were analyzed for tapasin expression using immunohistochemistry. Tapasin promoter methylation status in OSCC cell lines was determined using ethylation-specific polymerase chain reaction, bisulphate genomic sequencing, and expression reactivation assay. Lack of tapasin expression was observed in 30 of 67 (43%) tumors and was significantly associated with poor pathologic differentiation grade of OSCC (P = 0.028). The cumulative 5-year survival rate was also significantly correlated with pathologic differentiation grade (P = 0.001) and tapasin expression level (P = 0.015). Decreased tapasin expression was an indicator of poor survival (P = 0.048). Tapasin promoter methylation was observed in all three OSCC cell lines examined, and the mRNA and protein levels of tapasin increased markedly after treatment with 5-aza-2′-deoxycytidine. Downregulation of tapasin is associated with a poor clinical outcome for OSCC patients and may serve as a prognostic biomarker. The promoter methylation may contribute to the tapasin downregulation in OSCC.     

局部晚期食管鳞癌放射治疗中CT影像组学特征的变化

目的:通过提取和筛选食管癌计划CT和每周重复CT图像的影像组学特征,分析其特征变化与放射治疗响应的相关性。方法:共入组行放疗的局部晚期食管鳞癌患者15例,每周治疗结束后对患者重新行模拟CT扫描,由同一名医师在5次重复CT图像上勾画靶区。利用Python编程提取计划CT和重复扫描CT图像中靶区的影像组学变量特征并做统计分析,筛选出与放疗周数、靶区体积变化以及治疗结局(2年生存)因素强相关的组学特征,并用斯皮尔曼相关性和点双列相关性分析法对特征相关性进行统计学分析。结果:影像组学特征分析中,在靶区CTV1和CTV2中各提取了1 688个特征,并分别筛选出了10个与放疗周数、靶区体积变化以及治疗结局(2年生存)最强相关的特征。组学特征与治疗次数(放疗周数)呈强负相关(<-0.6),与体积变化呈强正相关(>0.6),与治疗结局(2年生存)呈弱相关,其相关系数分别为(-0.81～-0.67)、(0.72～0.99)和(-0.37～0.52)。结论:食管癌放疗过程中靶区CT影像组学变量特征与治疗时间、靶区体积大小以及治疗结局均存在相关性,基于CT影像组学变量特征变化可潜在地预测食管癌放...     

Management of dermatitis in patients with locally advanced squamous cell carcinoma of the head and neck receiving cetuximab and radiotherapy

Locally advanced squamous cell carcinoma of the head and neck is generally managed with a combination of surgery, RT, and/or chemotherapy or cetuximab. Appropriate management of radiation dermatitis associated with cetuximab and radiotherapy is necessary to allow adequate drug administration and to improve the quality of life and outcome. We generate a recommendation for radiation dermatitis on the basis of a systematic revision of the literature. Radiation dermatitis is experienced by the majority of patients undergoing radiotherapy for HNSCC, generally being mild to moderate (grades 1-2), showing about 25% severe toxicity (grade ≥ 3). Recommendations for prophylaxis and therapeutic interventions for each type of toxicity were proposed. This paper reviews comprehensive consensus guidelines to help manage the radiation dermatitis in order to make an optimal use of available therapeutic arsenal.     

Importance of tumor regression assessment in predicting the outcome in patients with locally advanced rectal carcinoma who are treated with preoperative radiotherapy

BACKGROUND: Locally advanced rectal carcinoma has a poor prognosis. However, since the introduction of preoperative radiotherapy, the outcome of patients with rectal carcinoma has been reported to have improved. Nevertheless, to the authors' knowledge few data are available regarding the histopathologic response to radiotherapy as assessed on surgical specimens as a potential predictive factor for outcome. METHODS: To estimate the effect of radiotherapy on rectal carcinoma, the authors retrospectively reviewed the surgical specimens of 102 patients with T3-4, N0 or > or = N1 rectal carcinoma and 1 patient with T2 but N1 rectal carcinoma. All patients were treated preoperatively with a hyperfractionated accelerated radiotherapy schedule in a prospective protocol (Trial 93-01). Using a standardized approach, tumor regression was graded using a system that varies from Grade 1 (tumor regression Grade [TRG] 1) when complete tumor regression is observed to Grade 5 (TRG5) when no tumor regression is observed. RESULTS: Radiotherapy resulted in tumor downstaging in 43% of the patients. There were 2 pT1 tumors (2%), 21 pT2 tumors (20%), 66 pT3 tumors (64%), and 14 pT4 tumors (14%) after treatment. Regional lymph nodes were involved in 55 patients (53%). None of the patients demonstrated a complete tumor regression after radiotherapy, but in 79% of the specimens a partial tumor regression was observed (TRG1: 0%; TRG2: 20%; TRG3: 39%; TRG4: 20%; and TRG5: 21%). The median actuarial overall survival (OS) and disease-free survival (DFS) were 52 months. Actuarial local recurrence rates at 2 years and 5 years were 6.4% and 7.6%, respectively. Univariate analysis showed the actuarial DFS to be significantly lower in patients with lymph node metastases (P = 0.0004) and advanced pT stages (pT3-4) (P = 0.03). A favorable outcome for OS, DFS, and local control was observed in patients with TRG2-4 (i.e., responders) compared with patients with TRG5 (i.e., nonresponders), but also in patients with low residual tumor cell density (TRG2, 3, and 4). On multivariate analysis, TRG remained an independent prognostic indicator for local tumor control. CONCLUSIONS: Tumor regression as well as residual tumor cell density were found to be predictive factors of survival in rectal carcinoma patients after preoperative radiotherapy. Even after preoperative radiotherapy, the pathologic stage of the surgical specimen remained a prognostic factor. The use of a standardized approach for pathologic evaluation must be implemented to allow comparison between the results of various treatment approaches.     

营养治疗对不可切除局部晚期食管鳞癌患者放化疗的影响

目的 探索营养治疗对不可切除局部晚期食管鳞癌放化疗患者临床疗效和免疫应答的影响.方法 回顾性纳入2018年5月至2019年5月就诊于南通大学附属如皋医院的100例局部晚期食管鳞癌患者,接受5-氟尿嘧啶和顺铂为基础化疗和同步放疗,患者分为常规治疗组(53例)和营养治疗组(47例),通过记录其一般临床信息、营养指标、免疫状...     

Intensity-modulated radiotherapy combined with paclitaxel and platinum treatment regimens in locally advanced esophageal squamous cell carcinoma

Purpose

This study was conducted to investigate the efficacy and toxicity of combination treatment with intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy with paclitaxel plus different platinum agents in locally advanced esophageal squamous cell carcinoma (ESCC).

Methods

This retrospective study enrolled 242 patients treated with paclitaxel (135 mg/m²) plus platinum regimens. According to the different platinum agents used, patients were classified into: cisplatin 80 mg/m² (CP), nidaplatinum 80 mg/m² (NP), lobaplatin 35 mg/m² (LP), and oxaliplatin 135 mg m² (OP) groups, and survival and toxicity rates between the four groups were compared. The median overall survival (OS) was 31.1 months.

Results

No significant differences were observed among the CP, NP, LP, and OP groups with regard to 3-year survival rates (46.2, 56.4, 45.7, and 29.0%, respectively). A stratified analysis indicated that 3-year survival rates were significantly lower in the OP group. Renal toxicities and gastrointestinal reactions were more frequent in the CP group than in the other three groups. Three-year survival rates were similar among patients receiving 2, 3, or ≥4 cycles of chemotherapy (40.1, 49.5, and 50.8%, respectively). Multivariate analysis indicated that tumor volume and maximum diameter of metastatic lymph nodes might be independent prognostic factors.

Conclusion

Paclitaxel plus nidaplatinum or lobaplatin is recommended in locally advanced ESCC due to their satisfying therapeutic effects and less toxicity. Tumor volume and maximum diameter of metastatic lymph nodes are independent prognostic factors in ESCC patients receiving IMRT and concurrent chemotherapy.

     

Impact of EGFR and p53 expressions on survival and quality of life in locally advanced oral squamous cell carcinoma patients treated with chemoradiation

EGFR and p53 are molecular markers which play important role in tumor progression and development. The objective of this study was to assess the association between EGFR and p53 expression and survival, and to determine whether EGFR and p53 expression levels were associated with differences quality of life in OSCC patients undergoing chemoradiation. A total of 120 OSCC patients aged 20–67 y and stage III/IV were recruited. Treatment response was assessed according to W.H.O. (1979). EGFR and p53 expression in tumor tissue was estimated by immunohistochemical (IHC) method and quantified as percentage positive nuclei. Molecular marker expressions of both EGFR and p53 were found significantly (P < 0.01 or P < 0.001) associated with overall response, survivals and quality of life. Neither EGFR nor p53 expression was associated with hematologic or non-hematologic toxicity. EGFR and p53 molecular marker expressions may have significant association with survival and QOL in OSCC patients undergoing chemoradiation.     

晚期食管鳞癌放疗联合口服替吉奥治疗的疗效

目的:评估口服替吉奥联合三维适形放疗治疗局部晚期食管癌的疗效和安全性.方法:48例局部晚期食管癌患者进入研究,随机分为单纯放疗组(24例)和放疗联合替吉奥化疗组(24例).比较两组患者的疗效、生存时间和不良反应.结果:单纯放疗组客观缓解率62.50%,放化疗联合组客观缓解率91.67%,有显著统计学差异(P<0.05).两组不良反应、生活质量无显著差异.单纯放疗组3年生存率32.33%,放化疗联合组3年生存率61.34%,有显著统计学差异(P<0.05).结论:三维适形放疗同步口服替吉奥化疗治疗晚期食管鳞癌可以有效提高患者的治疗效果,改善预后,不良反应可以耐受,是一种安全有效的治疗方案.