头颈部骨肉瘤治疗现状

头颈部骨肉瘤为少见肿瘤,临床特点与复发模式不同于其他部位骨肉瘤。头颈部骨肉瘤发病年龄晚,局部复发率高,远处转移率低,局部复发为死亡主要原因。手术为主要治疗手段。手术切缘阳性、近切缘及手术切缘不确定者推荐术后放疗。化疗的作用尚有争议。针对复发转移、不可手术切除的骨肉瘤,有效的分子靶向治疗药物有待于继续探索。     

Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) as neoadjuvant chemotherapy for patients with muscle-invasive transitional cell carcinoma of the bladder

BACKGROUND:

Meta‐analysis data demonstrate a 5% absolute survival benefit for neoadjuvant chemotherapy (NAC) using cisplatin‐based combination regimens in the radical treatment of muscle‐invasive bladder cancer (MIBC). However, there are no randomized, controlled trial data on the optimum regimen. Accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) is a dose‐intense regimen that has the potential to minimize delays to definitive, potentially curative therapy. A retrospective analysis is presented of the efficacy and toxicity of AMVAC as NAC in patients with MIBC and its impact on the patient pathway.

METHODS:

Eighty consecutive patients with MIBC were treated with AMVAC as NAC by 2 UK multidisciplinary uro‐oncology teams. Three or 4 cycles of AMVAC (methotrexate 30 mg/m², vinblastine 3 mg/m², doxorubicin 30 mg/m², and cisplatin 70 mg/m²) were given at 2‐week intervals, with granulocyte colony‐stimulating factor support, prior to either radical surgery or radical radiotherapy.

RESULTS:

All planned cycles of chemotherapy were completed, without dose reduction or delay in 84% of patients. All 80 patients subsequently received their planned definitive therapy. Grade 3/4 toxicities were seen in 26% of the 42% of patients for whom toxicity data are available, including 12% grade 3/4 neutropenia. Pathological complete response to AMVAC was seen in 43% of 60 surgical patients. Objective radiological local response was seen in 83% of 57 evaluable patients. Two‐year disease‐free and overall survival were 65% and 77%, respectively.

CONCLUSIONS:

AMVAC is safe and appears to be a well‐tolerated and effective NAC regimen for MIBC. It minimizes delays to definitive treatment and produces excellent pathological and radiological response rates. It is an appropriate comparator for future randomized trials. Cancer 2012. © 2012 American Cancer Society.     

Current status of neoadjuvant and adjuvant chemotherapy for muscle-invasive bladder cancer

Muscle-invasive transitional cell carcinoma occurs in approximately 30% of patients and is associated with a high risk of distant metastasis. Radical local therapy in the form of cystectomy or radiotherapy is curative in a portion of patients. Systemic therapy to treat occult micrometastasis at the time of local control is necessary to improve outcomes. Neoadjuvant chemotherapy is associated with a 5–6% improvement in overall survival at 5 years, and adjuvant chemotherapy may achieve similar results, although this remains unproven. Operative complications are not increased with neoadjuvant therapy. Perioperative treatment strategies remain underutilized, and many patients are not offered treatment to reduce the risk of relapse. Neoadjuvant strategies are a potent tool for research and should be employed to test new agents for the treatment of transitional cell carcinoma.     

Neoadjuvant therapy for gastric cancer: current evidence and future directions

Although surgical resection remains the only potentially curative treatment for gastric cancer (GC), poor long-term outcomes with resection alone compel a multimodality approach to this disease. Multimodality strategies vary widely; while adjuvant approaches are typically favored in Asia and the United States (USA), a growing body of evidence supports neoadjuvant and/or perioperative strategies in locally advanced tumors. Neoadjuvant approaches are particularly attractive given the morbidity associated with surgical management of GC and the substantial risk of omission of adjuvant therapy. The specific advantages of chemoradiotherapy (CRT) compared to chemotherapy have not been well defined, particularly in the preoperative setting and trials aimed at determining the optimal elements and sequencing of therapy are underway. Future studies will also define the role of targeted and biologic therapies.     

Lymph node status after neoadjuvant radiotherapy for rectal cancer is a biologic predictor of outcome

BACKGROUND:

Lymph node (LN) status after surgery for rectal cancer is affected by preoperative radiotherapy. The purpose of this study was to perform a population‐based evaluation of the impact of pathologic LN status (ypN) after neoadjuvant radiotherapy on survival.

METHODS:

Patients undergoing radical resection for rectal adenocarcinoma were identified from the Surveillance Epidemiology and End Results registry (1991‐2004). Patient characteristics, overall survival, and cancer‐specific survival (CSS) by ypN stage after surgery and use of preoperative or postoperative radiotherapy were compared.

RESULTS:

Of the 23,809 patients identified, 12,513 received preoperative (n = 5367) or postoperative (n = 7146) radiotherapy and resection. Preoperative patients were more likely to be younger (P < .001) and histopathologically free of detectable nodal metastasis (ypN0) than postoperative (51.8% vs 31.7%, P < .001). Median total numbers of LNs (6 vs 10) and positive LNs (2 vs 3) were lower among preoperative than postoperative (P < .001 for both). OS and CSS were similar among pN0 patients. However, on proportional hazards regression, ypN+ stage was associated with an increase in relative risk for death by 21% overall (hazard ratio [HR] = 1.21; 95% confidence interval 1.09‐1.35, P < .001) and 23% cancer‐specific (HR = 1.23; P = .001) for preoperative compared with postoperative.

CONCLUSIONS:

Pathologic LN status after neoadjuvant radiotherapy for rectal cancer is a biologic marker of prognosis. Patients who are ypN+ after preoperative are a subgroup of LN positive patients with adverse outcome. These high‐risk patients should be targeted for studies of novel multidisciplinary approaches, including expanded chemo‐ and biologic therapies. Cancer 2009. © 2009 American Cancer Society.     

Combining surgery and chemotherapy for invasive bladder cancer: current and future directions

More than 13,000 patients died from invasive bladder cancer in 2005 alone. Radical cystectomy is the most commonly prescribed treatment for patients with muscle-invasive bladder cancer, or for those with a nonmuscle-invasive disease that is refractory to intravesical therapy. Despite advances in surgical technique and improved understanding of the role of pelvic lymphadenectomy, 5-year survival probabilities suggest that improvements in treatment are necessary. The maturation of several randomized clinical trials on perioperative chemotherapy, and particularly neoadjuvant chemotherapy, clearly suggest that an integrated treatment program of systemic chemotherapy and definitive locoregional therapy may improve the outcome for bladder cancer patients. The next frontier is the molecular characterization of this spectrum of diseases that make up invasive bladder cancer and targeted therapeutics. Prospective validation of molecular markers and evaluation of novel therapeutic agents, alone or in combination with established cytotoxic agents, provide hope of better outcomes for bladder cancer patients.     

A comparison of the outcomes of neoadjuvant and adjuvant chemotherapy for clinical T2-T4aN0-N2M0 bladder cancer

BACKGROUND:

Despite evidence supporting perioperative chemotherapy, few randomized studies compare neoadjuvant and adjuvant chemotherapy for bladder cancer. Consequently, the standard of care regarding the timing of chemotherapy for locally advanced bladder cancer remains controversial. We compared patient outcomes following neoadjuvant or adjuvant systemic chemotherapy for cT2‐T4aN0‐N2M0 bladder cancer.

METHODS:

In a retrospective review of a single institutional database from 1988 through 2009, we identified patients receiving neoadjuvant or adjuvant multiagent platinum‐based systemic chemotherapy for locally advanced bladder cancer. Survival analysis was performed comparing disease‐specific survival (DSS) and overall survival (OS).

RESULTS:

A total of 146 patients received systemic perioperative chemotherapy (73 neoadjuvant, 73 adjuvant). Of these, 84% (122/146) received cisplatin‐based chemotherapy compared with carboplatin‐based chemotherapy (24/146, 16.4%). Most patients receiving cisplatin‐based chemotherapy were treated with methotrexate/vinblastine/adriamycin/cisplatin (79/122, 64.8%), whereas the remaining patients received gemcitabine/cisplatin (GC) (43/122, 35.2%). In multivariable analysis, there was no significant difference in DSS (P = .46) or OS (P = .76) between neoadjuvant or adjuvant chemotherapy groups. There was statistically significant improvement in DSS when patients received neoadjuvant GC rather than adjuvant GC (P = .049, hazard ratio, 10.6; 95% confidence interval, 1.01‐112.2).

CONCLUSION:

In this study, there was no statistically significant difference in OS and DSS between patients receiving neoadjuvant versus adjuvant systemic platinum‐based chemotherapy for locally advanced bladder cancer. In addition, there was no significant difference between neoadjuvant and adjuvant cisplatin‐ or carboplatin‐based chemotherapy. Chemotherapy sequence relative to surgery appeared less important than whether or not a patient actually received perioperative chemotherapy. Cancer 2011;. © 2011 American Cancer Society.     

Current and future therapeutic approaches for the treatment of follicular lymphoma

Introduction: Recent advances in prognostication as well as management of Follicular Lymphoma (FL) are moving to personalized approach.

Areas covered: Prognostic scores as well as consolidated and innovative therapeutic approaches are evaluated according to the various presentation modalities. For asymptomatic, low-tumor burden FL, a ‘watch and wait’ policy is currently the first-choice approach, although possible alternatives are discussed. Early stage FL may be treated with local radiotherapy although the role of minimal residual disease in possible additional agents should be determined. The first line treatment for symptomatic FL is chemo-immunotherapy followed by two years maintenance therapy with anti-CD20 monoclonal antibodies. A deeper knowledge of FL biology has opened new perspectives regarding the timing of therapy and has offered new targets for the development of novel agents that aim to change the therapeutic scenario of FL management.

Expert commentary: The introduction of novel agents could question the incurability of FL and change the therapeutic goal from prolonging the complete remission state to eradicating the disease in young/fit patients, as well as improving quality of life in elderly/unfit patients. In the near future, combining new biologic agents and adoptive cell therapies could help in achieving these aims.     

Current treatment approaches for diffuse large B-cell lymphoma

There have been two major developments over the last decade that has led to improvements in outcome and longer survival for patients with diffuse large B-cell lymphoma (DLBCL). These developments have been firstly to increase the dose of active cytotoxic drugs and shorten the time between cycles, resulting in dose-dense and/or dose-intense regimens and secondly the addition of the anti-CD20 monoclonal antibody rituximab to chemotherapy. Both strategies have been associated with higher response rates, lower relapse rates, longer event-free survival (EFS) and improved overall survival (OS), particularly in better prognostic groups. A combination of dose-dense and dose-intense chemotherapy regimens plus rituximab is currently being tested to confirm that the use of both approaches confers survival advantage. High-risk, poorer-prognosis DLBCL remains a challenge, and new treatment strategies are required for these patients. Improvements in outcome may potentially be achieved through a greater understanding of the genetic abnormalities specifically associated with poorer-prognosis disease, and factors that lead to unresponsiveness to chemotherapy. The role of radiotherapy is currently less clearly defined than at anytime in the management of DLBCL and the current evidence for using radiotherapy in this disease is therefore rigorously reviewed.     

Current update of treatment strategies for borderline resectable pancreatic cancer: a narrative review

Background and ObjectiveBorderline resectable pancreatic cancer (BRPC) is a tumor that infiltrates into the large blood vessels, with a high probability that the tumor will remain after surgical resection. To date, there has been no confirmed treatment strategy for BRPC. However, high-level studies, such as those using the intention-to-treat analysis, have recently been published. This review aimed to update the current status of treatment strategies for BRPC.MethodsWe searched for studies, including those investigating patients with BRPC, either treated by upfront surgery or with neoadjuvant treatment and reported the R0 resection rate and overall survival using an intention-to-treat analysis.Key Content and FindingsConsequently, 22 articles were identified. Twelve were prospective studies. Six studies compared neoadjuvant therapy with upfront surgery, and both the R0 resection rate and overall survival in patients who underwent upfront surgery were significantly worse than in those who underwent neoadjuvant treatment in all studies. Six studies evaluated neoadjuvant chemotherapy, while 15 studies neoadjuvant chemoradiation. No reports showed the superiority or inferiority of the two methods, and the optimal regimen was not determined in either treatment. The high-precision radiation therapy techniques have been studied, but the optimal method and dose fractionation were unclear.ConclusionsThe current standard of care for the BRPC is neoadjuvant therapy. Although the optimal regimen of neoadjuvant therapy was not determined, several prospective trials are underway to identify the optimal neoadjuvant treatment.     

AQP1在骨肉瘤中的表达和意义

目的探讨骨肉瘤中AQP1的表达和临床意义。方法对39例骨肉瘤和22例骨良性疾病对照组标本采用免疫组化法观察AQP1的表达并用人工计数和自动图像分析两种方法检测其表达差别,同时行CD34抗体染色标记肿瘤微血管,计算所有标本MVD。结果①AQP1表达于肿瘤微血管和小血管内皮细胞及绝大多数骨肉瘤的肿瘤细胞,尤其见于骨肉瘤的肿瘤巨细胞上;②人工计数AQP1阳性细胞百分比（YP）、AQP1人工计数分级、自动图像分析所得平均光密度（MD）,均表明AQP1在骨肉瘤中高表达（P均〈0.01）;③骨肉瘤中AQP1的YP与MVD呈明显正相关（r=0.341,P〈0.05）。结论大多数骨肉瘤肿瘤细胞高表达AQP1的原因不明;AQP1在骨肉瘤生物学行为及肿瘤微血管生成中占有重要作用;提示AQP1有可能作为骨肉瘤治疗的新靶点。     

Prognostic value and clinicopathological correlation of the tumor regression grade in neoadjuvant chemotherapy for gastric adenocarcinoma: a retrospective cohort study

BackgroundNeoadjuvant chemotherapy (NACT) and radical gastrectomy are the gold standard treatments for resectable advanced gastric cancer (GC). However, the prognostic value of the pathological tumor regression grade (TRG) of NACT remains controversial. This retrospective study aimed to investigate the correlation between the TRG after NACT and clinicopathological features as well as its prognostic value in advanced GC.MethodsIn total, 551 patients with GC who received NACT combined with surgical resection at the Zhejiang Cancer Hospital from April 2004 to December 2019 were included. The demographic characteristics, treatment response, tumor characteristics, treatment regimens, and survival data were reviewed from the medical records of all patients. The Chi-square test was used to analyze the correlation between TRG and clinicopathological factors. Kaplan-Meier univariate analysis and Cox regression multivariate analysis were used to determine the independent risk factors affecting the prognosis of GC patients.ResultsAmong the 551 patients with advanced GC who accepted NACT treatment, 14 were determined to be in TRG 0, 98 in TRG 1, 257 in TRG 2, and 182 in TRG 3. Also, TRG was significantly correlated with the cT stage (P=0.015), ypT stage (P<0.001), ypN stage (P<0.001), ypTNM stage (P<0.001), vascular tumor thrombus (P<0.001), Borrmann classification (P=0.042), and lymph node ratio (LNR) (P<0.001). Furthermore, patients who had a good pathological response to NACT had a better prognosis, with a 3-year overall survival (OS) of 70.9% versus 48.8% in patients who had a poor pathological response. We also found that TRG (P=0.042, HR =1.65) was an independent prognostic factor affecting the OS of GC patients.ConclusionsTRG plays a significant role in the prognostic value in neoadjuvant chemotherapy for gastric adenocarcinoma. Patients with higher cT stage, higher levels of pre-CA199 and pre-CA125 may have worse pathological response.     

Current and future therapeutic approaches for the treatment of small cell lung cancer

Introduction: Small-cell lung cancer (SCLC) is a very aggressive disease characterized by a high response rate to first-line chemotherapy, but most patients relapse within 1 year with disappointing results to second-line treatments. Chemotherapy has reached a plateau of effectiveness and new therapeutic strategies are needed to change the natural history of SCLC.

Areas covered: This review will focus on the current results and the future development of the therapeutic approaches for the treatment of SCLC.

Expert commentary: Immunotherapy is becoming a new frontier for the management of SCLC with preliminary interesting results. To date, no targeted drugs have been approved for clinical practice but several novel agents are in an advanced stage of clinical development in SCLC.     

Intra-arterial induction high-dose chemotherapy with cisplatin for oral and oropharyngeal cancer: long-term results

Intra-arterial (IA) chemotherapy for curative treatment of head and neck cancer experienced a revival in the last decade. Mainly, it was used in concurrent combination with radiation in organ-preserving settings. The modern method of transfemoral approach for catheterisation, superselective perfusion of the tumour-feeding vessel, and high-dose (150 mg x m(-2)) administration of cisplatin with parallel systemic neutralisation with sodium thiosulphate (9 g x m(-2)) made preoperative usage feasible. The present paper presents the results of a pilot study on a population of 52 patients with resectable stage 1-4 carcinomas of the oral cavity and the oropharynx, who were treated with one cycle of preoperative IA chemotherapy executed as mentioned above and radical surgery. There have been no interventional complications of IA chemotherapy, and acute side effects have been low. One tracheotomy had to be carried out due to swelling. The overall clinical local response has been 69%. There was no interference with surgery, which was carried out 3-4 weeks later. Pathological complete remission was assessed in 25%. The mean observation time was 3 years. A 3-year overall and disease-free survival was 82 and 69%, respectively, and at 5 years 77 and 59%, respectively. Survival results were compared to a treatment-dependent prognosis index for the same population. As a conclusion, it can be stated that IA high-dose chemotherapy with cisplatin and systemic neutralisation in a neoadjuvant setting should be considered a feasible, safe, and effective treatment modality for resectable oral and oropharyngeal cancer. The low toxicity of this local chemotherapy recommends usage especially in stage 1-2 patients. The potential of survival benefit as indicated by the comparison to the prognosis index should be controlled in a randomised study.     

Comparison of neoadjuvant regimens for resectable gastroesophageal junction cancer: a systematic review of randomized clinical trials across three decades

BackgroundThe optimal perioperative treatment for adenocarcinoma of gastroesophageal junction (GEJ) tumor remains uncertain. The systematic review aims to assess the best neoadjuvant modality, namely chemotherapy (CT) versus chemoradiotherapy (CRT) based on randomized controlled trials (RCTs) for resectable gastric, esophageal and GEJ tumors.MethodsWe performed a comprehensive PubMed database and Cochrane Library search to identify relevant RCTs related to neoadjuvant treatment for resectable GEJ adenocarcinoma. We included all published RCTs (phase 2 or 3) that tested specific neoadjuvant therapies (CT or CRT) if the patient population included GEJ tumors. We applied the Version 2 Cochrane risk-of-bias tool (RoB 2) to all the eligible studies. Outcomes examined included R0 resection and pathological response based on intention-to-treat (ITT) analysis, surgical outcomes, notable adverse events, and overall survival (OS). Each randomized group of every study was noted to be neoadjuvant CRT, CT, or surgery alone in order to compare the outcomes among these treatment approaches.ResultsWe identified 25 RCTs with 7,855 patients published from 1996 to 2019. Seven studies tested preoperative CT versus surgery alone, 7 tested preoperative radiotherapy (RT) or CRT versus surgery alone, 4 tested preoperative RT or CRT versus preoperative CT, and 7 tested other combinations. The R0 resection ranged 47–100% and the 3-year OS ranged 6–66.1% in all the study arms. In an exploratory analysis, CRT strategies showed a superior R0 resection rate [80.2%; 95% confidence interval (CI): 79.8–80.6%] to surgery alone (60.9%; 95% CI: 60.4–61.3%; P<0.01) and to preoperative CT (63.9%; 95% CI: 63.6–64.2%; P<0.01). When comparing 3- and 5-year OS, improvement was noted when comparing CRT to surgery alone (P<0.01), and perioperative CT to surgery alone (P<0.01), but no definite difference was noted between CRT versus CT.DiscussionPreoperative CRT showed improvement in R0 resection rate to surgery alone and preoperative CT. However, there is no significant difference in OS between CRT and CT. Both neoadjuvant strategies remain clinically meaningful options for patients with resectable GEJ tumors. Lack of patient-level data and inconsistent reporting of key outcomes across studies were the main limitations of our study.     

Neoadjuvant gemcitabine and cisplatin chemotherapy for locally advanced urothelial cancer of the bladder

BACKGROUND:

The purpose of this study was to investigate the effect of neoadjuvant chemotherapy with gemcitabine and cisplatin (GC) on pathologic down‐staging of patients with locally advanced urothelial cancer (UC) of the bladder.

METHODS:

This was a retrospective cohort study of patients treated with radical cystectomy (RC) for clinical stage cT2‐T4, N any, M0 bladder UC at Strong Memorial Hospital from 1999 to 2009. The primary exposure variable was use of neoadjuvant chemotherapy (GC vs none). The primary outcome was stage pT0 at RC. Secondary outcomes included other down‐staging end points in the bladder ( RESULTS: A total of 160 eligible patients were identified, of whom 25 were treated with neoadjuvant GC before RC (GC + RC) and 135 without neoadjuvant chemotherapy (RC only). Stage pT0 at cystectomy was found in 20% of patients in the GC + RC group and in 5% of patients in the RC group (adjusted risk difference [aRD] = 16%, P = .03). For other down‐staging end points, the estimated treatment effect was as follows (all point estimates favoring chemotherapy): P = .005); P = .004); P = .008); margins aRD = 8% (P = .41); nodes aRD = 4% (P = .74).

CONCLUSIONS:

Neoadjuvant GC was found to be capable of down‐staging UC in the bladder; however, no effect on disease in nodes was seen in this study. Cancer 2012;. © 2011 American Cancer Society.     

Long-term follow-up of patients treated with neoadjuvant chemotherapy and radiotherapy for large, extremity soft tissue sarcomas

BACKGROUND:

Patients with large, high‐grade, extremity soft tissue sarcomas (STS) are at significant risk for distant recurrence and death. A regimen of preoperative chemotherapy consisting of mesna, Adriamycin (doxorubicin), ifosfamide, and dacarbazine (MAID), interdigitated with radiotherapy (RT) and followed by resection and postoperative chemotherapy with or without RT, has demonstrated high rates of local and distant control. We report the long‐term follow‐up data on 48 patients treated with this regimen compared to an historical matched‐control patient population.

METHODS:

Adult patients with high‐grade extremity STS ≥ 8 cm were treated with 3 cycles of preoperative chemotherapy combined with 44 Gy of RT followed by surgery. Three cycles of postoperative MAID were planned. For patients with positive surgical margins, 16 Gy of RT was delivered postoperatively.

RESULTS:

Patients received the MAID/RT regimen from 1989 through 1999. After a median follow‐up of 9.3 years in surviving patients in the MAID group and 13.2 years in surviving patients in the control group, the 7‐year disease‐specific and overall survival rates were 81% and 50% (P = .004) and 79% and 45% (P = .003) for the MAID and control patients, respectively. Five of 11 patients in the MAID group and 7 of 25 control patients died of sarcoma ≥5 years after treatment. One patient in the MAID group developed a fatal myelodysplasia at 53 months.

CONCLUSIONS:

For patients with high‐risk, extremity STS, the significant survival benefits conferred by an intense regimen of neoadjuvant chemoradiotherapy and surgery are sustained even with long‐term follow‐up. Cancer 2012. © 2011 American Cancer Society.