Role of Combined-Modality Therapy in the Management of Locally Advanced Rectal Cancer

The majority of patients with nonmetastatic rectal cancer are candidates for an aggressive multimodality approach with curative intent. Preoperative staging is critical in determining which patients should be offered neoadjuvant therapy. Available staging tools include digital rectal examination, transrectal ultrasound, computed tomography, positron-emission tomography, and magnetic resonance imaging scans. Magnetic resonance imaging has emerged as the most accurate staging modality in experienced centers. Multidisciplinary preoperative patient evaluation, better staging techniques, neoadjuvant chemoradiation, acceptance of shorter distal rectal margins, and transanal excision of T1 N0 rectal tumors in close proximity to the anal sphincter have resulted in decreased rates of abdominoperineal resections. Total mesorectal excision has been adopted as the standard surgical approach because of a reduction in rates of pelvic relapse. Preoperative and postoperative radiation therapy was shown to decrease the local recurrence rate, but not overall survival, in patients with resectable rectal cancer. The addition of chemotherapy to radiation was consistently shown to improve local control, and in some trials, improved overall survival. Neoadjuvant combined chemotherapy and radiation therapy are superior to adjuvant combined-modality therapy because of higher rates of sphincter preservation, less toxicity, and lower local recurrence rates. For patients with stage II or III disease, neoadjuvant continuous-infusion 5-fluorouracil (5-FU), concurrently with pelvic radiation, followed by postoperative 5-FU–based chemotherapy, remains the standard multimodality approach. Ongoing trials are testing the integration of newer cytotoxic agents such as capecitabine, oxaliplatin, irinotecan, and biologic agents such as cetuximab and bevacizumab to chemoradiation.     

Impact of pre- and postoperative multimodality therapy on rectal cancer

Surgery is the primary treatment of rectal cancer. However, variability in surgical outcomes led to development of combined therapies including pelvic radiation and systemic chemotherapy. The evolution of these therapies both individually and combined, their successes and limitations is discussed in the context of an evolving understanding of rectal cancer biology. The impact of standardized optimal surgery on the need for additional therapy and trends in treating complete responders to neoadjuvant therapy is also reviewed.     

Breast conservation therapy (BCT): Surgery as the cornerstone of multi-specialty care

Surgical care has been the mainstay of breast cancer diagnosis and treatment. As care has evolved, increased collaborative approaches among surgeons, radiologists, radiation oncologists and medical oncologists have improved the quality of breast cancer treatment for the patient. Breast conservation therapy (BCT) exemplifies how multi-specialty care can increase cancer cure rates at the same time that the disfiguring aspects of breast cancer treatment can be minimized. New questions are being raised within clinical forums about how to do better both for the patient and for her oncologic treatment. The following questions represent three current issues in BCT:

1. What general operative approaches in BCT can minimize morbidity and optimize the cosmetic outcome from surgery?
2. What role does radiation therapy play in BCT for invasive and non-invasive breast cancer to supplement surgical intervention?
3. What role can neoadjuvant chemotherapy play in improving BCT rates?

     

Treatment of High Rectal Cancers: Do We Need Radiation?

Before total mesorectal excision (TME) and radiation therapy/chemoradiation therapy (RT/CRT) were widely adopted in the treatment of rectal cancer, surgery alone was the standard. Therapies have since evolved to neoadjuvant RT or CRT followed by TME as the established paradigm for locally advanced disease. More recently, issues of toxicity and systemic metastasis have risen to the forefront, prompting the exploration of individualized strategies in an attempt to maximize potential cure and local control yet minimize late toxicities. In this article, we will focus on the treatment of high rectal cancers, exploring the specific role of pelvic radiotherapy in this setting.     

Colorectal cancer

Recent advances in chemotherapy and chemoradiation therapy for colorectal cancer have made neoadjuvant treatment an eligible therapeutic option for selected cases of marginally resectable colorectal cancer. However, marginally resectable colorectal cancer is not well defined. The authors suggest that a primary lesion is marginally resectable if extended resection such as pelvic exenteration and pancreaticoduedenectomy are not completely curative. Even if the lesion itself is resectable, it is marginally resectable if it has unfavorable prognostic factors such as numerous metastases to the regional lymph nodes. Rectal cancer invading beyond mesorectal fascia, or having bilateral or multiple lateral lymph node metastasis, may also be marginally resectable. All locally recurrent lesions may be marginally resectable because the prognosis after surgical resection is poor. Multiple liver metastases, liver metastasis for which resection requires vascular reconstruction, and technically resectable liver metastasis with unfavorable prognostic factors, are also thought to be marginally resectable. Neoadjuvant chemotherapy regimens including oxaliplatin and irinotecan combined with bevacizumab, cetuximab and panitumumab may be effective for hastening the curability of such marginally resectable tumors. For primary advanced rectal cancer and locally recurrent rectal cancer, neoadjuvant radiation combined with chemotherapy using oxaliplatin and irinotecan are being explored. A number of clinical trials are currently ongoing, and are expected to clarify the effectiveness of neoajuvant treatment for marginally resectable colorectal cancer.     

Combined-modality therapy for rectal cancer: future prospects

The management of rectal cancer has undergone significant evolution with advances in surgery, radiation therapy, and chemotherapy. These advances have translated into improved rates of local control, survival, and quality of life. More recently, the integration of newer chemotherapeutic and targeted agents in patients with advanced colorectal cancer have led to further improvements in disease-free survival and overall survival. These agents are now being studied with radiation therapy in the neoadjuvant therapy of rectal cancer.     

Potential Novel Drugs to Combine with Radiation in Rectal Cancer

The management of rectal cancer has seen significant advances in surgery, radiation therapy, and chemotherapy in recent years. These advances have translated into improved rates of local and distant disease control, survival, and quality of life for these patients. The recent implementation of novel chemotherapeutic and targeted agents in patients with advanced colorectal cancer has led to further improvements in disease-free and overall survival. These radiosensitizing agents are now being studied in combination with radiation therapy in the neoadjuvant therapy of rectal cancer.     

Innovative interdisziplin?re Konzepte der Radioonkologie

The classification of the Fédération Internationale de Gynécologie et d??Obstétrique (FIGO) still adheres to the clinical staging of cervical cancer. To avoid undertreatment and overtreatment the following parameters for establishing a treatment concept should be known: infiltration of pelvic and para-aortic lymph nodes, intra-abdominal metastases and histological confirmation of infiltration in adjacent organs. The primary treatment of cervical cancer consists of radical surgery and combined radiochemotherapy. Results from several prospective randomized studies towards the end of the 1990s defined the standard of radiochemotherapy which replaced radiation alone in primary therapy as well as in adjuvant therapy. No data currently exist that neoadjuvant radiochemotherapy can improve total survival of patients in comparison to surgery or primary radiochemotherapy. A standardized secondary hysterectomy following radiochemotherapy according to the current state of the art is not indicated and potentially endangers the patient. Possible radiogenic side effects are manifested as acute reactions, delayed side effects and an increased risk for secondary malignancies.     

直肠癌治疗新模式——全程新辅助治疗

全程新辅助治疗（total neoadjuvant therapy, TNT）即将直肠癌术后辅助化疗提至术前。术前进行新辅助化疗和同步放化疗,旨在提高患者化疗依从性及远期生存。国内有关该治疗模式的报道较少,本文就该模式治疗直肠癌的相关研究作一综述,以提高对直肠癌围手术期辅助治疗的认识,促进对直肠癌综合治疗模式的探索。     

直肠癌的新辅助治疗

局部晚期直肠癌单纯手术后局部复发率高,近年的随机对照Ⅲ期临床研究提示,局部晚期直肠癌的新辅助治疗可明显提高局部控制率,对于治疗后病理完全缓解者还可提高生存率,在欧美国家已成为局部晚期直肠癌的标准治疗.但化疗药物的选择、热疗等的应用等尚需进一步临床研究.     

Role of radiation therapy in patients with resectable pancreatic cancer

The 5-year overall survival of patients with pancreatic cancer is approximately 5%, with potentially resectable disease representing the curable minority. Although surgical resection remains the cornerstone of treatment, local and distant failure rates are high after complete resection, and debate continues as to the appropriate adjuvant therapy. Many oncologists advocate for adjuvant chemotherapy alone, given that high rates of systemic metastases are the primary cause of patient mortality. Others, however, view locoregional failure as a significant contributor to morbidity and mortality, thereby justifying the use of adjuvant chemoradiation. As in other gastrointestinal malignancies, neoadjuvant chemoradiotherapy offers potential advantages in resectable patients, and clinical investigation of this approach has shown promising results; however, phase III data are lacking. Further therapeutic advances and prospective trials are needed to better define the optimal role of adjuvant and neoadjuvant treatment in patients with resectable pancreatic cancer.     

Beyond 5-fluorouracil: the emerging role of newer chemotherapeutics and targeted agents with radiation therapy

The management of rectal cancer has undergone significant evolution with advances in surgery, radiation therapy, and chemotherapy. These advances have translated into improved rates of local control, survival, and quality of life. More recently, the integration of newer chemotherapeutic and targeted agents in patients with advanced colorectal cancer have led to further improvements in disease-free and overall survival. These agents are now being studied with radiation therapy in the neoadjuvant therapy of rectal cancer.     

Neoadjuvant chemoradiation followed by interstitial prostate brachytherapy for synchronous prostate and rectal cancer

PurposeTo describe outcomes with the use of neoadjuvant pelvic chemoradiation followed by prostate interstitial brachytherapy for the treatment of synchronous prostate and rectal cancers.Methods and MaterialsAn Internal Review Board approved retrospective review was undertaken of 4 patients with synchronous prostate and rectal cancer treated between 2006 and 2008. Patients underwent pelvic chemoradiation followed by prostate brachytherapy, then low anterior resection of the rectum with diverting loop ileostomy and adjuvant chemotherapy. Follow-up evaluation included imaging and laboratory analysis of cancer markers in addition to routine interval history and physical examination.ResultsAt 38-62 months postdiagnosis (24-53 months post-treatment), 6 of 8 cancers remained without evidence of relapse. One patient had rising carcinoembryonic antigen levels but no clinically evident rectal cancer relapse; another developed bony metastasis of his high-risk prostate cancer. Three patients experienced grade 1-2 treatment-related toxicity; one patient had grade 3 gastrointestinal toxicity from radiation and surgery, which precluded his receiving adjuvant chemotherapy and ileostomy reversal.ConclusionsChemoradiation followed by prostate brachytherapy, surgery, and adjuvant chemotherapy may be utilized to manage patients with synchronous prostate and rectal cancers.     

Management of stage II/III rectal cancer

Pelvic and distant recurrences in rectal cancer can be associated with substantial morbidity, and patients with stage II and III disease are at increased risk for both local and distant failure when compared to patients with earlier stage disease. Refinement of surgical techniques have helped to reduce the risk of recurrence, and adjuvant therapies such as radiation to the tumor and regional lymph nodes and 5-fluorouracil-based systemic therapies have helped to further provide local control and may have an impact on overall survival. Numerous studies have been completed internationally in an effort to determine the optimal treatment regimen for this patient population. The importance of pre-therapy staging is of key importance as sequencing of therapy appears to significantly impact outcome. In the United States, patients with stage II/III rectal cancer are recommended to undergo preoperative concurrent pelvic radiation and chemotherapy followed by surgery several weeks later in order to maximize treatment response, which is then followed by approximately 4 months of adjuvant 5-fluorouracil-based systemic therapy. In Europe, there is substantial evidence supporting the use of neoadjuvant radiation therapy, however the role of concurrent chemotherapy remains a question of debate. Regardless of definitive management strategy, close follow-up in the post-treatment setting is important for early tumor detection and for managing treatment-related side-effects.     

Intraoperative Radiation After Pelvic Short Course Radiation-Based Total Neoadjuvant Therapy for Patients With Rectal Adenocarcinoma at High Risk for Local Recurrence

BackgroundShort course radiation-based total neoadjuvant therapy can improve disease-free survival for patients with high-risk locally advanced rectal cancer. Tumors that involve or threaten the circumferential resection margin have a particularly high risk of local recurrence. Intraoperative radiation therapy enables treatment escalation at the threatened or involved margin at the time of surgery.Patients and MethodsPatients with rectal adenocarcinoma treated with preoperative short course radiotherapy-based total neoadjuvant therapy and intraoperative radiation at the time of surgery were identified. All patients had a threatened or involved circumferential resection margin on magnetic resonance imaging at the time of diagnosis. Treatment details, radiation toxicities, postoperative complications and oncologic outcomes were recorded.ResultsTen patients received intraoperative radiation after short course radiation-based total neoadjuvant therapy. All patients had an involved or threatened circumferential resection margin, 60% had extramural venous invasion, and 60% had positive lateral pelvic lymph nodes. Seven patients had negative surgical margins (≥ 2 mm), and 3 patients had an R1 resection with radial margins < 2 mm. The median [IQR] length of hospitalization after surgery was 11 [7-14] days. Three patients required readmission and 2 patients required reoperation due to complications including anastamotic leak and abscess. With a median follow up of 19.5 months postoperatively, no patient developed a pelvic recurrence, and 6 patients developed distant recurrences.ConclusionsThe use of intraoperative radiation after a short course radiotherapy-based neoadjuvant therapy is safe and feasible. Further data are needed to determine whether the addition of intraoperative radiation improves local recurrence rates over preoperative radiation alone.     

Have the changes in treatment of rectal cancer made a significant difference to our patients?

The treatment for patients with locally advanced, resectable rectal cancer has evolved over the years. Various combinations and sequences of chemotherapy, radiation therapy, and total mesorectal excision (TME)-based surgery are the mainstay of current therapy. Preoperative combined chemoradiation, followed by surgery, is now the preferred treatment strategy, with the majority of patients receiving either infusion fluorouracil (5-FU) or capecitabine (Xeloda) with radiation. Clinical trials with oxaliplatin (Eloxatin)-based neoadjuvant chemoradiation have not shown improvement in the pathologic complete response rate (pCR) compared with 5-FU; however, final data addressing local recurrence rates and disease-free survival are pending.The use of adjuvant chemotherapy following preoperative chemoradiation and surgery has not been optimally defined. Some studies have shown that patients who obtained significant pathologic downstaging after chemoradiation and surgery have improved survival with the use of adjuvant chemotherapy. Since FOLFOX (folinic acid, 5-FU, and oxaliplatin) is the preferred adjuvant chemotherapy regimen for stage III colon cancer based on randomized clinical trial results, FOLFOX is also recommended for rectal cancer patients as an adjuvant therapy approach.     

Combined modality treatment for rectal cancer

Significant gains have been achieved in the integration of radiation therapy (RT) and chemotherapy with surgery in the management of patients with localized rectal cancer. Treatment combinations of RT and chemotherapy with surgery have evolved to neoadjuvant approaches of these modalities to enhance sphincter preservation, tumor control, and reduction of acute and late treatment-related morbidity. Although 5-fluorouracil (5-FU)-based chemotherapy in combination with RT remains the standard adjuvant therapy for rectal cancer, the integration of novel chemotherapeutic agents and biologic modulators is being actively investigated.     

非小细胞肺癌脑转移的研究进展

非小细胞肺癌脑转移的治疗对肿瘤学家是一种挑战。虽然近年脑转移研究有所进展,但生存率并不乐观。本文阐述非小细胞肺癌脑转移的临床特点、诊断方法、预后因素以及治疗进展。脑转移最常见的症状为因颅内压力增高所致的头痛。评价脑转移时,头颅MRI较CT优越。最常用的预后标准是肿瘤放射治疗组(RTOG)的RPA分级。关于全脑放疗、立体定向放射外科、手术以及化疗治疗脑转移的作用仍存在争议。全脑放疗常作为脑转移的标准治疗方案。SRS对单一或多个脑转移灶的治疗可代替外科切除。许多数据证明化疗有较好的颅内作用,这引起全身化疗治疗脑转移的研究热点。确立预后因素和其他临床特点后,才能制定最适合个体患者的治疗。     

局部进展期食管鳞癌全新辅助治疗可行方案的探索

新辅助放化疗联合手术为局部进展期食管癌患者的标准治疗方案, 这一治疗方案已得到广泛应用, 其疗效也已得到临床医师的认可。然而, 即使是完成了新辅助放疗和随后的手术治疗, 仍有部分患者在短期内出现局部区域复发和/或远处转移, 其中远处转移成为新辅助放化疗后接受手术患者的主要失败模式, 这从另一方面说明该模式还有进一步改善的必要。借助于直肠癌患者从全新辅助治疗模式中获益的经验, 本文探讨了局部进展期食管癌患者进行全新辅助治疗的可能性及其实施方案。     

根治术后盆腔复发直肠癌疗效及预后因素分析

目的 分析直肠癌根治术后盆腔复发规律以及放疗疗效和影响预后的因素.方法 回顾分析2000-2006年直肠癌根治术后盆腔复发接受放疗患者93例,分别为单纯放疗21例、放化疗56例、放疗结合手术和(或)化疗16例.放疗采用60Co或加速器X线,中位剂量59.4Gy,其中90例采用常规分割技术.68例患者放疗后接受了1～8个(中位数3个)疗程化疗,42例行同步放化疗,多为氟尿嘧啶为主的化疗方案.16例患者在放疗后接受了复发灶切除术,其中RO切除7例,姑息性肿块切除9例.结果 全组共132处复发,常见复发部位为直肠周围(31.8%)和骶前区(30.3%),髂外淋巴结和腹股沟淋巴结少见(1.5%和3.0%).总随访率为92%,随访满2、5年者分别为39、4例.有局部症状的84例患者中83%(70例)放疗后症状缓解.全组2、5年局部无进展率分别为49%、22%,2、5年生存率分别为46%、14%.多因素分析结果显示复发后治疗方法是影响直肠癌根治术后复发的局部无进展率的独立预后因素,复发灶最大径、无病间期、放疗后有无远处转移是影响直肠癌根治术后复发患者生存率的独立顶后因素.结论 直肠周围区、骶前区、髂内淋巴结区是直肠癌主要复发部位;放疗可明显改善直肠癌根治术后盆腔复发患者的症状和提高生存质量,放疗联合手术和(或)化疗可提高直肠癌根治术后复发的局部无进展率,复发灶直径＞5 cm、无病间期＜2年、放疗后有远处转移是影响预后的因素.