Impact of adjuvant treatment modalities on survival outcomes in curatively resected pancreatic and periampullary adenocarcinoma

Background

We examined the impact of adjuvant modalities on resected pancreatic and periampullary adenocarcinoma (PAC).

Methods

A total of 563 patients who were curatively resected for PAC were retrospectively analyzed between 2003 and 2013.

Results

Of 563 patients, 472 received adjuvant chemotherapy (CT) alone, chemoradiotherapy (CRT) alone, and chemoradiotherapy plus chemotherapy (CRT-CT) were analyzed. Of the 472 patients, 231 were given CRT-CT, 26 were given CRT, and 215 were given CT. The median recurrence-free survival (RFS) and overall survival (OS) were 12 and 19 months, respectively. When CT and CRT-CT groups were compared, there was no significant difference with respect to both RFS and OS, and also there was no difference in RFS and OS among CRT-CT, CT and CRT groups. To further investigate the impact of radiation on subgroups, patients were stratified according to lymph node status and resection margins. In node-positive patients, both RFS and OS were significantly longer in CRT-CT than CT. In contrast, there was no significant difference between groups when patients with node-negative disease or patients with or without positive surgical margins were considered.

Conclusions

Addition of radiation to CT has a survival benefit in patients with node-positive disease following pancreatic resection.     

乳癌术后辅助放化治疗对远期生存的影响

本文回顾总结我院内科１９７７至１９８７年收治９８例Ⅱ、Ⅲ期乳癌术后病人辅助化疗及辅助放化治疗的远期疗效，该组５、１０年生存率７１．４％与４２．９％，较同期手术组Ⅱ、Ⅲ期病人５、１０年生存率６６．４％与２９．６％提高。在Ⅱ期病人中辅助化疗组５、１０年生存率９４．１％与７３．５％明显高于Ⅱ期放化治疗组５、１０年生存率６９．６％与２６．１％。Ⅲ期病人辅助化疗组与辅助放化组生存率相近似。     

Simultaneous adjuvant radiotherapy and chemotherapy for stage I and II breast cancer

The purpose of the present paper was to evaluate treatment outcome after conservative breast surgery or mastectomy followed by simultaneous adjuvant radiotherapy and cyclophosphamide, methotrexate and fluorouracil (CMF) therapy. Two hundred and sixty eight (268) patients were treated at two Australian and two New Zealand centres between 1981 and July 1995. One hundred and sixty-nine patients underwent conservation surgery and 99 had mastectomies. Median follow-up was 53 months. Conventionally fractionated radiation was delivered simultaneously during the first two cycles of CMF, avoiding radiation on the Fridays that the intravenous components of CMF were delivered. In conservatively treated patients, 5-year actuarial rates of any recurrence, distant recurrence and overall survival were 34.5 ± 5.2%, 25.4 ± 4.5% and 75.5 ± 4.8%, respectively. Crude incidence of local relapse at 4 years was 6.3% and at regional/distant sites was 26.3%. Highest grades of granulocyte toxicity (< 0.5 × 10⁹/L), moist desquamation, radiation pneumonitis and persistent breast oedema were recorded in 10.7, 8.5, 8.9 and 17.2%, respectively. In patients treated by mastectomy, 5-year actuarial rates of any recurrence, distant recurrence and overall survival were 59.7 ± 7.3%, 56.7 ± 7.4% and 50.1 ± 7%. The crude incidence of local relapse at 4 years was 5.6% and at regional/distant sites it was 45.7%. The issue of appropriate timing of adjuvant therapies has become particularly important with the increasing acknowledgement of the value of anthracycline-based regimens. For women in lower risk categories (e.g. 1–3 nodes positive or node negative), CMF may offer a potentially better therapy, particularly where breast-conserving surgical techniques have been used. In such cases CMF allows the simultaneous delivery of radiotherapy with the result of optimum local control, without compromise or regional or systemic relapse rates. Further randomized trials that directly address the optimal integration of the two modalities, such as the one carried out in Boston, are clearly necessary.     

Adjuvant chemo-endocrine therapy for androgen-dependent mammary tumor in mice

Summary About 500 male DS mice grafted with androgen-dependent Shionogi carcinoma 115 (SC115) were used. When the tumor diameter reached about 20 mm (approximately 25 days after transplantation), excision of the tumor and/or castration were carried out. The injection of cyclophosphamide (80 mg/kg body weight × 3 at 7-day intervals) was started from the day after excision.In mice with excised tumor, adjuvant chemo-endocrine therapy was the most effective treatment examined; cumulative 120-day mortalities after transplantation of tumors in non-treated, adjuvant endocrine therapy, adjuvant chemotherapy and adjuvant chemo-endocrine therapy groups were 91%, 29%, 21% and 0%, respectively. Castration induced development of clusters of androgen-independent cancer cells in androgendependent SC115 tumor. In mice without tumor excision, the chemo-endocrine therapy was again the most effective treatment, though 86% of mice died by the 120th day after tumor transplantation. These findings suggest the usefulness of adjuvant chemo-endocrine therapy for achieving complete remission in hormonedependent tumors. Address for reprints: K. Matsumoto, M.D., Dept. of Pathology, Osaka University, Medical School, Kita-ku, Osaka 430, Japan.     

结直肠癌辅助治疗现状

在过去的20年结直肠癌辅助治疗有很大改进。辅助性放化疗已成为结直肠癌综合治疗的重要组成部分。本文综述了结直肠癌术后辅助化疗、术前、术后辅助放疗、免疫治疗、局部门静脉灌注化疗的现状。     

直肠癌新辅助化放疗

近年来的前瞻性研究已证实新辅助化放疗即术前化放疗可以明显提高直肠癌患者的局部控制率和保肛率,但直肠癌新辅助化放疗的理论基础、适应证、治疗方案、治疗时间等尚未明确.     

Role of chemotherapy and targeted therapy in early-stage non-small cell lung cancer

Introduction: Adjuvant platinum based chemotherapy is accepted as standard of care in stage II and III non-small cell lung cancer (NSCLC) patients and is often considered in patients with stage IB disease who have tumors ≥ 4 cm. The survival advantage is modest with approximately 5% at 5 years.

Areas covered: This review article presents relevant data regarding chemotherapy use in the perioperative setting for early stage NSCLC. A literature search was performed utilizing PubMed as well as clinical trial.gov. Randomized phase III studies in this setting including adjuvant and neoadjuvant use of chemotherapy as well as ongoing trials on targeted therapy and immunotherapy are also discussed.

Expert commentary: With increasing utilization of screening computed tomography scans, it is possible that the percentage of early stage NSCLC patients will increase in the coming years. Benefits of adjuvant chemotherapy in early stage NSCLC patients remain modest. There is a need to better define patients most likely to derive survival benefit from adjuvant therapy and spare patients who do not need adjuvant chemotherapy due to the toxicity of such therapy. Trials for adjuvant targeted therapy, including adjuvant EGFR-TKI trials and trials of immunotherapy drugs are ongoing and will define the role of these agents as adjuvant therapy.     

Prognostic factors affecting the outcome of early cervical cancer treated with radical hysterectomy and post-operative adjuvant therapy

The purpose of this study is to investigate the clinical and histological features that may affect the survival of the patients and to evaluate the impact of post-operative adjuvant therapy on the outcomes of patients with stage IB and IIA carcinoma of the cervix. From August 1998 to January 2005, 140 patients with International Federation of Gynecology and Obstetrics stage IB and IIA cervical cancer were treated with radical hysterectomy and post-operative pelvic radiation therapy with or without chemotherapy. The median age was 55 years (range, 29-86 years). Seventy-six patients had stage IB and 64 patients had stage IIA disease. Tumour size was <4 cm in 96 patients and > or = 4 cm in 44 patients. One hundred and eleven patients had histology of squamous cell carcinoma, 12 patients has adenocarcinoma and 17 patients had other histologic types. Depth of stromal invasion was <2/3 in 20 patients and > or = 2/3 in 120 patients. Twenty-three patients had parametrial invasion and 117 patients had no parametrial invasion. Thirteen patients had lymphovascular space invasion and 127 had no lymphovascular space invasion. Nine patients had positive surgical margin and 131 patients had negative margin. Twenty-seven patients had pelvic lymph node metastasis and 113 patients had no pelvic lymph node metastasis. Seventy-five patients received concurrent chemoradiotherapy and 65 patients received radiotherapy alone. The 5-year overall survival (OAS) and disease-free survival were 83% and 72% respectively. In the log rank test, tumour size (P = 0.0235), pararmetrial invasion (P = 0.0121), pelvic lymph node metastasis (P < 0.0001) and adjuvant chemotherapy + radiotherapy (P = 0.0119) were significant prognostic factors for OAS, favouring tumour size <4 cm, absence of parametrial invasion and pelvic lymph node metastasis, and those who received adjuvant chemoradiotherapy. The patients who received radiation with concomitant chemotherapy had a 5-year OAS rate of 90% versus those who received radiotherapy alone, with a rate of 76%. For patients with high-risk early stage cervical cancer who underwent a radical hysterectomy and pelvic lymphadenectomy, adjuvant chemoradiotherapy resulted in better survival than radiotherapy alone. The addition of weekly cisplatin to radiotherapy is recommended. The treatment-related morbidity is tolerable.     

食管癌术后辅助治疗的Meta分析

[目的]探讨食管癌术后辅助治疗的价值.[方法]收集1995年至2011年期间发表的关于食管癌术后辅助治疗的随机对照研究文章,利用Stata12.0软件进行Meta分析.[结果]与单纯手术相比,术后辅助化疗患者的3年无进展生存率相对危险度(RR)为1.225 (95％CI:1.012～1.482,P=0.037),差异有统计学意义.而3、5年总生存率的RR值分别为0.899(95％CI:0.797～1.016,P=0.087),1.183(95％CI:0.97～1.442,P=0.098),差异无统计学意义.同样,与单纯手术相比,术后辅助放疗患者的3年总生存率的RR值为0.935 (95％CI:0.879～0.994,P=0.033),差异有统计学意义.而5年总生存率的RR值为0.988(95％CI:0.821～1.188,P=0.897),差异无统计学意义.Begg's与Egger试验检测P值均大于0.05,不存在发表偏倚.[结论]术后辅助化疗能延长食管癌患者术后的3年无进展生存率,术后辅助放疗不利于延长食管癌患者的3年总生存率.     

Surgical adjuvant therapy of rectal carcinoma: a controlled evaluation of leucovorin, 5-fluorouracil and radiation therapy with or without interferon-alpha2b.

BACKGROUND: The aim of this study was to determine whether the efficacy of the combination of 5-fluorouracil (5-FU), leucovorin (LV) and radiation therapy (RT) could be improved by the addition of interferon-alpha2b (IFN-alpha) in patients who have had a 'curative' resection, for rectal adenocarcinoma (Dukes' B2/C; T3 N0, T4 N0, N1-3). PATIENTS AND METHODS: A total of 207 eligible patients with a performance status of 0 or 1 were randomized postoperatively between days 21 and 70 to one of the two treatment groups: group A, LV 20 mg/m2 i.v. bolus and 5-FU 425 mg/m2 i.v. days 1-5 and 29-33, LV 20 mg/m2 and 5-FU 400 mg/m2 days 57-60 and 85-88, LV 20 mg/m2 and 5-FU 380 mg/m2 days 1-5 and 29-33 with the second day 1 occurring 28 days after the completion of RT (45 Gy); group B, LV, 5-FU and RT as in group A, and IFN-alpha 5 x 10(6) IU s.c. three times during each week chemotherapy is given. RESULTS: 104 patients were randomized into group A and 103 into group B. There was no statistically significant difference in either disease-free survival or overall survival between the two groups. Toxicity was also the same, except for the flu-like syndrome associated with the IFN-alpha administration. CONCLUSIONS: There was no difference in efficacy between the two combinations. Toxicity was greater with the LV + 5-FU + IFN-alpha regimen because of the flu-like syndrome.     

Multigene tests for breast cancer: the physician’s perspective

Breast cancer is the most common tumour in women and the first cause of death for cancer in the female population. Preserving the quality of life has therefore become an important objective in the management of the disease. The benefits of adjuvant chemotherapy in patients with HR+ HER2- early breast cancer should always be balanced against its potential short and long-term adverse effects, and identifying the appropriate patients for whom chemotherapy can offer the highest clinical benefit is critical. Besides clinical and pathological factors, today four multigene tests able to guide the choice of the adjuvant therapy early breast cancer are available in Italy: Oncotype DX^®, EndoPredict^®, MammaPrint^® e Prosigna^®. This review evaluates the main characteristics of these diagnostic tests, the studies on clinical utility, their economic impact and their inclusion in international and national guidelines. The Oncotype DX Breast Recurrence Score^® test is the only multigene test validated, with level IA evidence, to guide the adjuvant therapy decisions: hormone therapy alone for most patients with RS results 0–25, and chemotherapy for patients with RS results 26–100. Clinical data demonstrate that the Oncotype DX test is able to significantly impact therapeutic decisions, reducing chemotherapy use up to 49% and supporting the use of chemotherapy (up to 12%) in potentially under-treated patients. Based on the level of clinical evidence and established clinical utility, several multigene tests have been included in the main international guidelines, with recommendations ranging from “strong” to “moderate”.     

局部晚期食管癌的新辅助治疗

新辅助治疗是指在成功的术后辅助治疗经验基础上提出的术前辅助治疗,其目的 在于增加手术切除肿瘤的可能性并提高患者的生存率,包括新辅助化疗、新辅助放疗和新辅助放化疗.新辅助放化疗在促进切除率和提高生存率上可能成为局部晚期食管癌新辅助治疗的首选方案.     

Updates in adjuvant systemic therapy for melanoma

There has been a rapid increase in adjuvant therapies approved for treatment following surgical resection of stages III/IV melanoma. We review current indications for adjuvant therapy, which currently includes a heterogenous group of stages III and IV patients with melanoma. We describe several pivotal clinical trials of systemic immune therapies, targeted immune therapies, and adjuvant vaccine strategies. Finally, we discuss the evidence for selecting the most appropriate treatment regimen(s) for the individual patient.     

A prospective phase 2 study of surgery followed by chemotherapy and radiation for superior sulcus tumors

BACKGROUND:

The optimal treatment for locally advanced superior sulcus tumors is not clear. The authors report long‐term results of a trial examining the safety and efficacy of surgery followed by concurrent chemoradiation therapy for this disease.

METHODS:

Thirty‐two patients with resectable or marginally resectable superior sulcus tumors at The University of Texas MD Anderson Cancer Center from 1994 to 2010 were enrolled in a prospective trial. Surgery involved segmentectomy or lobectomy with en bloc resection of the involved chest wall and complete nodal staging; radiation therapy (RT) began 14 to 42 days later to a dose of 60 grays (Gy) in 50 1.2‐Gy fractions if surgical margins were negative or 64.8 Gy in 54 1.2‐Gy fractions if margins were positive. Two cycles of etoposide (50 mg/m²) and cisplatin (50 mg/m²) were given during RT, and another 3 cycles were given after RT. Eleven patients underwent prophylactic cranial irradiation (PCI).

RESULTS:

The protocol completion rate was 78%. Gross total resection was accomplished in all 32 patients; 28% underwent R1 resection. Operative mortality was 0%. The most common surgical complication was postoperative pneumonia (25%). At a median follow‐up time of 53.4 months (range, 2‐154 months), the 2‐year, 5‐year, and 10‐year rates of locoregional control were 84%, 76%, and 76%; distant metastasis‐free survival, 52%, 48%, and 48%; disease‐free survival, 49%, 45%, and 45%; and overall survival, 72%, 50%, and 45%, respectively. The brain was the most common site of distant failure (n = 5), but no patient who received PCI experienced brain metastasis.

CONCLUSIONS:

Surgery followed by postoperative chemoradiation is safe and effective for the treatment of marginally resectable superior sulcus tumors. Cancer 2011;. © 2011 American Cancer Society.     

The accuracy of transrectal ultrasound in predicting the pathological stage of low-lying rectal cancer after preoperative chemoradiation therapy

Purpose: There has been a growing interest in the use of preoperative radiation therapy in rectal cancer treatment in the last years. The need for accurate preoperative staging is important so as to avoid overtreatment in stage I patients, and to select patients who require downstaging prior to surgery as they are technically inoperable. While transrectal ultrasound (TRUS) has been reported to accurately stage preoperative patients, its efficacy postradiation has been questioned. The authors report a series studied by TRUS to contribute to the discussion on the role of this method.

Methods and Materials: Twenty-eight patients with rectal cancer were accrued. Twenty-six patients, clinically staged T2-T4 or/and N1-N3 between March 1990 to October 1993, underwent preoperative chemoradiation. Two patients (T2N0) were treated by local excision and postoperative radiotherapy. Following therapy and just before surgery, each patient was restaged by TRUS. These results were subsequently compared with a pathological stage of resected specimen for both the primary tumor (T) and regional lymph nodes (LN).

Results: The accuracy of TRUS for T stage after chemoradiation was 92.8% (positive predictive value [PPV] 94.4%, negative predictive value [NPV] 90.0%). The accuracy for LN staging after chemoradiation was 60.7% (PPV 100.0%, NPV 54.0%), because LN located outside the scanning range were missed.

Conclusion: Based on our results, we conclude that TRUS of the primary tumor is an accurate staging technique for patients with rectal cancer treated with preoperative chemoradiation.     

直肠癌新辅助治疗后病理降期相关研究进展

术前同步放化疗已成为局部晚期直肠癌的标准治疗模式.新辅助治疗后病理降期与直肠癌预后关系密切,找到能预测直肠癌新辅助治疗病理降期标记,有着重要的临床意义.不同放化疗方案、靶向药物在新辅助治疗中的应用、新辅助治疗后至手术间隔时间与病理降期相关.