Neoadjuvant radiotherapy for rectal cancer management

Thirty per cent of all colorectal tumours develop in the rectum.The location of the rectum within the bony pelvis and its proximity to vital structures presents significant therapeutic challenges when considering neoadjuvant options and surgical interventions.Most patients with early rectal cancer can be adequately managed by surgery alone.However,a significant proportion of patients with rectal cancer present with locally advanced disease and will potentially benefit from down staging prior to surgery.Neoadjuvant therapy involves a variety of options including radiotherapy,chemotherapy used alone or in combination.Neoadjuvant radiotherapy in rectal cancer has been shown to be effective in reducing tumour burden in advance of curative surgery.The gold standard surgical rectal cancer management aims to achieve surgical removal of the tumour and all draining lymph nodes,within an intact mesorectal package,in order to minimise local recurrence.It is critically important that all rectal cancer cases are discussed at a multidisciplinary meeting represented by all relevant specialties.Pre-operative staging including CT thorax,abdomen,pelvis to assess for distal disease and magnetic resonance imaging to assess local involvement is essential.Staging radiology and MDT discussion are integral in identifying patients who require neoadjuvant radiotherapy.While Neoadjuvant radiotherapy is potentially beneficial it may also result in morbidity and thus should be reserved for those patients who are at a high risk of local failure,which includes patients with nodal involvement,extramural venous invasion and threatened circumferential margin.The aim of this review is to discuss the role of neoadjuvant radiotherapy in the management of rectal cancer.     

Multimodal therapy of esophageal cancer

Surgery is still the treatment of choice in patients with resectable oesophageal cancer. However, recent randomised controlled trials suggest beneficial effects of adjuvant or neoadjuvant treatment modalities on progression-free and overall survival compared to surgery alone. Neoadjuvant chemoradiotherapy in combination with surgery is most effective in squamous cell carcinomas. Increased perioperative morbidity and mortality should be minimised by surgery in a high-volume centre. In adenocarcinomas of the gastro-oesophageal junction neoadjuvant chemotherapy shows beneficial effects compared to surgery alone. A transhiatal resection should be preferred in distal oesophageal cancer compared to a transthoracic oesophageal resection if the patient is in poor condition. In all other cases a transthoracic resection remains the procedure of choice. Chemoradiotherapy alone is an alternative to surgery in high-risk patients with squamous cell carcinomas of the oesophagus. Therefore the treatment of patients with oesophageal cancer should always include an individualised, multimodal approach including surgery, chemotherapy, and radiotherapy.     

Role of radical prostatectomy in high-risk prostate cancer

Many methods exist to define high-risk prostate cancer. These include clinical stage, serum PSA, and pathological features such as Gleason score and the number of positive biopsies. Partin tables are widely used to stratify patients according to risk of adverse pathological features at surgery, and to identify those more likely to remain free of recurrent disease following surgery. The priority in most patients with localized prostate cancer remains the selection of a treatment that will provide them with the best chance for cure. While treatment-related morbidity is an important issue, we believe that side effects of surgery or radiation therapy are not increased in patients with high-risk cancer. Results from a small number of population studies indicate a highly significant improvement in disease-specific survival for radical prostatectomy compared to radiotherapy, and it appears that this difference may become more pronounced as the grade of the cancer increases. While acknowledging the need for adjuvant radiotherapy and/or hormonal therapy, we suggest that radical prostatectomy may offer a better primary treatment option for patients with high-grade cancer. However, urologists must be prepared for higher failure rates when performing this surgery in patients with high-risk disease compared to those with low-risk disease.     

Surgery in the era of neoadjuvant therapy for cancer of the esophagus

Multimodality treatment strategies have become commonplace and stand-of-care in the management of esophageal cancer. In Japan, preoperative chemotherapy is routine, while in many centers around the globe chemoradiotherapy is widely practiced. How surgery should be integrated and the manner in which esophagectomy should be carried out remain controversial. From the literature, it seems that esophagectomy for salvage after definitive chemoradiotherapy is associated with increased morbidity rates. In the neoadjuvant setting, however, where less chemotherapy and lower dose of radiotherapy is usually given, results are comparable with upfront surgery. Video-assisted thoracoscopic esophagectomy is also safe after neoadjuvant therapy; special adjunct like recurrent laryngeal nerve monitoring may be helpful for extended mediastinal lymphadenectomy. There is not enough evidence to suggest that lesser degree of lymphadenectomy is required after neoadjuvant therapy. As such the same degree of nodal dissection is recommended. Further work is required to delineate the role of surgery in multimodality treatment programs.     

Preoperative Radiotherapy Improves Outcome in Recurrent Rectal Cancer

PURPOSE When local recurrent rectal cancer is diagnosed without signs of metastases, a potentially curative resection can be performed. This study was designed to compare the results of preoperative radiotherapy followed by surgery with surgery only.METHODS Between 1985 and 2003, 117 patients with recurrent rectal cancer were prospectively entered in our database. Ninety-two patients were suitable for resection with curative intent. Preoperative radiation with a median dosage of 50 Gy was performed in 59 patients; 33 patients did not receive preoperative radiotherapy. The median age of the patients was respectively 66 and 62 years.RESULTS The median follow-up of patients alive for the total group was 16 (range, 4–156) months. Tumor characteristics were comparable between the two groups. Complete resections were performed in 64 percent of the patients who received preoperative radiation and 45 percent of the nonirradiated patients. A complete response after radiotherapy was found in 10 percent of the preoperative irradiated patients (n = 6). There were no differences in morbidity and reintervention rate between the two groups. Local control after preoperative radiotherapy was statistically significantly higher after three and five years (P = 0.036). Overall survival and metastases-free survival were not different in both groups. Complete response to preoperative radiotherapy was predictive for an improved survival.CONCLUSIONS Preoperative radiotherapy for recurrent rectal cancer results in a higher number of complete resections and an improved local control compared with patients treated without radiotherapy. Preoperative radiotherapy should be standard treatment for patients with recurrent rectal cancer.     

Critical review of the management of early-stage breast cancer in elderly women

The treatment of elderly women (> or =70 years) with early-stage breast cancer is an emerging clinical problem in the setting of an ageing population. There is a lack of clinical trial evidence to formulate clinical guidelines for management because of the small number of elderly women included in previous clinical trials of adjuvant therapy. This often results in elderly patients being denied standard management based on age alone. The often-complex interaction between age, comorbid conditions and function complicate the planning and outcomes of surgery and can have an effect on the delivery of postoperative adjuvant therapy. A comprehensive assessment of the elderly patient is essential to determine overall prognosis and morbidity risk from treatments; however, a simple comorbidity scale for use in routine clinical practice remains elusive. Thus, treatment decisions should be tailored to the individual to ensure that therapies are not unduly withheld and are appropriate for the patient's overall condition. The assessment of the elderly patient with breast cancer requires the involvement of a multidisciplinary team. The evidence for efficacy, safety and potential risks of surgery and adjuvant therapies (including radiotherapy, hormone therapy and chemotherapy) in the elderly population is discussed in this review and the role of comprehensive geriatric assessment is outlined.     

Neo-adjuvant radiotherapy in rectal cancer

In rectal cancer treatment,attention has focused on the local primary tumour and the regional tumour cell deposits to diminish the risk of a loco-regional recurrence.Several large randomized trials have also shown that combinations of surgery,radiotherapy and chemotherapy have markedly reduced the risk of a locoregional recurrence,but this has not yet had any major influence on overall survival.The best results have been achieved when the radiotherapy has been given preoperatively.Preoperative radiotherapy improves loco-regional control even when surgery has been optimized to improve lateral clearance,i.e.,when a total mesorectal excision has been performed.The relative reduction is then 50%-70%.The value of radiotherapy has not been tested in combination with more extensive surgery including lateral lymph node clearance,as practised in some Asian countries.Many details about how the radiotherapy is performed are still open for discussion,and practice varies between countries.A highly fractionated radiation schedule(5 Gy×5),proven efficacious in many trials,has gained much popularity in some countries,whereas a conventionally fractionated regimen(1.8-2.0 Gy×25-28),often combined with chemotherapy,is used in other countries.The additional therapy adds morbidity to the morbidity that surgery causes,and should therefore be administered only when the risk of loco-regional recurrence is sufficiently high.The best integration of the weakest modality,to date the drugs(conventional cytotoxics and biologicals)is not known.A new generation of trials exploring the best sequence of treatments is required.Furthermore,there is a great need to develop predictors of response,so that treatment can be further individualized and not solely based upon clinical factors and anatomic imaging.     

Penile cancer: current challenges

Penile cancer remains a formidable challenge in many developing countries because of its high incidence and the advanced disease stage at diagnosis. For early penile cancer, surgery alone offers a high cure rate. Penile sparing therapies are proposed as alternative treatment options for select patients with the added advantages of preservation of body image and improved quality of life. The optimal management of lymph node disease remains controversial. The role of the sentinel lymph node biopsy, lymphatic mapping, prophylactic lymphadenectomy and the template for lymph node dissection are discussed. For advanced, metastatic penile cancer, more effective and less toxic chemotherapy is needed. This may be coupled with palliative surgery or radiotherapy for the primary tumor and inguinal disease.     

Cancer of the anal region

Cancer of the anal region represents 3-3.5% of all anorectal tumours. The peak incidence is between 58 and 64 years. Since 1960 an increased incidence among men younger than 45 years, and among women has been observed. The number of women diagnosed with anal canal cancer (7 per 1,000,000 person per years) is twice as much as that of men, while anal margins cancers are more frequent in men (4 per 1,000,000 person per years). Tumour extension determines the different treatment strategies, aiming at definite cure, with a conservative approach. Small tumours can be resected without mutilating surgery, while for larger tumours combination of chemotherapy and radiotherapy is the standard treatment, even though a combination of chemotherapy and radiotherapy has been recently introduced. Long-term quality of life (QOL) scores are acceptable, with the exception of patients who experience severe anal dysfunction.     

乙醛脱氢酶1在胶质瘤中的研究进展

胶质瘤是中枢神经系统最常见的原发性恶性肿瘤。目前,治疗的方法主要是依靠手术切除,结合术后放疗、化疗等综合治疗,但该肿瘤具有高复发率、高致死率的特点,临床疗效尚不理想,推测是因为经治疗后杀灭了大多数的肿瘤细胞,仍残留有少数肿瘤干细胞,成为复发,抵抗放、化疗的根源。乙醛脱氢酶1已被证实为多种恶性肿瘤干细胞的表面标记物,本文就乙醛脱氢酶1在胶质瘤中的研究进展作一综述。     

Quality assurance of surgery in gastric and rectal cancer

Multimodality and quality controlled treatment result in improved treatment outcome in patients with solid tumours. Quality assurance focuses on identifying and reducing variations in treatment strategy. Treatment outcome is subsequently improved through the introduction of programs that reduce treatment variations to an acceptable level and implement standardised treatment. In chemotherapy and radiotherapy, such programmes have been introduced successfully. In surgery however, there has been little attention for quality assurance so far. Surgery is the mainstay in the treatment of patients with gastric and rectal cancer. In gastric cancer, the extent of surgery is continuously being debated. In Japan, extended lymph node dissection is favoured whereas in the West this type of surgery is not routinely performed with two large European trials concluding that there is no survival benefit from regional lymph node clearance. Post-operative chemoradiation is part of the standard treatment in the United States, although its role in combination with adequate surgery has not been established yet. These global differences in treatment policy clearly relate to the extent and quality of surgical treatment. As for gastric cancer, surgical treatment of rectal cancer patients determines patient's prognosis to a large extent. With the introduction of total mesorectal excision, local control and survival have improved substantially. Most rectal cancer patients receive adjuvant treatment, either pre- or post-operatively. The efficacy of many adjuvant treatment regimens has been investigated in combination with conventional suboptimal surgery. Traditional indications of adjuvant treatment might have to be re-examined, considering the substantial changes in surgical practise. Quality assurance programs enable the introduction of standardised and quality controlled surgery. Promising adjuvant regimens should be investigated in combination with optimal surgery.     

Modern techniques for pituitary radiotherapy

Radiotherapy (RT) remains an effective treatment for residual or recurrent pituitary adenomas with excellent rates of tumour control and normalisation of excess hormone secretion. The main late toxicity is hypopituitarism: other side effects are rare. We discuss technical developments in the delivery of radiotherapy (stereotactic conformal radiotherapy (SCRT) and stereotactic radiosurgery (SRS)), all aiming to reduce the amount of normal brain receiving significant doses of radiation. We provide a comprehensive review of published data on outcome of conventional fractionated radiotherapy and modern RT techniques. SCRT is a suitable treatment technique for all sizes of pituitary adenoma and efficacy is comparable to conventional RT; the lack of long term follow up means that currently there is no information on potential reduction in the incidence of late radiation induced toxicity. Single fraction SRS can only be safely delivered to small tumours away from critical structures. There is no evidence that it produces faster decline of elevated hormone levels than fractionated treatment and is not associated with lesser morbidity.     

Radiotherapy for craniopharyngioma

Radiotherapy remains the mainstay of multidisciplinary management of patients with incompletely resected and recurrent craniopharyngioma. Advances in imaging and radiotherapy technology offer new alternatives with the principal aim of improving the accuracy of treatment and reducing the volume of normal brain receiving significant radiation doses. We review the available technologies, their technical advantages and disadvantages and the published clinical results. Fractionated high precision conformal radiotherapy with image guidance remains the gold standard; the results of single fraction treatment are disappointing and hypofractionation should be used with caution as long term results are not available. There is insufficient data on the use of protons to assess the comparative efficacy and toxicity. The precision of treatment delivery needs to be coupled with experienced infrastructure and more intensive quality assurance to ensure best treatment outcome and this should be carried out within multidisciplinary teams experienced in the management of craniopharyngioma. The advantages of the combined skills and expertise of the team members may outweigh the largely undefined clinical gain from novel radiotherapy technologies.     

Watch and wait approach in rectal cancer: Current controversies and future directions

According to the main international clinical guidelines, the recommended treatment for locally-advanced rectal cancer is neoadjuvant chemoradiotherapy followed by surgery. However, doubts have been raised about the appropriate definition of clinical complete response(cCR) after neoadjuvant therapy and the role of surgery in patients who achieve a cCR. Surgical resection is associated with significant morbidity and decreased quality of life(QoL), which is especially relevant given the favourable prognosis in this patient subset. Accordingly, there has been a growing interest in alternative approaches with less morbidity, including the organ-preserving watch and wait strategy, in which surgery is omitted in patients who have achieved a cCR. These patients are managed with a specific follow-up protocol to ensure adequate cancer control, including the early identification of recurrent disease. However, there are several open questions about this strategy, including patient selection, the clinical and radiological criteria to accurately determine cCR, the duration of neoadjuvant treatment, the role of dose intensification(chemotherapy and/or radiotherapy), optimal followup protocols, and the future perspectives of this approach. In the present review, we summarize the available evidence on the watch and wait strategy in this clinical scenario, including ongoing clinical trials, Qo L in these patients, and the controversies surrounding this treatment approach.     

Reconstruction of the perineum following anorectal cancer excision

Purpose  Most patients with anal cancer receive chemoradiotherapy as first-line treatment. Persistent/recurrent tumours will subsequently require an abdomino-perineal resection (APR). A proportion of the 20,000 new cases of rectal carcinoma diagnosed in the UK each year receive neo-adjuvant chemoradiation and then an APR. Healing of the irradiated perineal bed is compromised, resulting in high morbidity. Reconstruction of the perineam with well-vasularised tissue is thought to enhance healing. This study investigates a series of 18 patients who underwent APR for anorectal cancer with flap reconstruction of their perineum. Materials and methods  A retrospective analysis of all anorectal cancers requiring an APR and flap reconstruction was performed. Casenotes were reviewed and documentation made of risk factors putting them at increased risk of wound complications. Length of stay, morbidity and outcome variables including primary flap healing were recorded. Results  Between November 2000 and October 2007, 18 cases were performed (M/F = 7:11), six for anal cancer and 12 for low rectal tumours. Pre-operative treatment was chemoradiotherapy in 14 (78%), radiotherapy alone in two (11%) and none in two (11%). Perineal reconstruction consisted of 14 vertical rectus abdominis myocutaneous flaps, three free latissimus dorsi flap and one transverse rectus abdominis myocutaneous flap. Mean hospital stay was 21.8 days (10–54 days). Complete healing was noted in 16 cases with the remaining two continuing to improve under current follow-up. There were no flap losses. Conclusions  Despite most patients being treated with pre-operative radiotherapy, we have had significant success in obtaining primary healing of the perineal defect after APR.     

Diagnosing and treating breast cancer in elderly women: a call for improved understanding

Breast cancer is the most common nondermatological malignancy in women, and the incidence increases with age until the eighth decade. Breast cancer pathology and biology appear to be different in elderly patients than in younger ones, and therefore treatment recommendations cannot be generalized from one group to the other. Most elderly women can tolerate breast cancer surgery without significant complications and should be offered a definitive surgical procedure. Improved mechanisms to predict which patients will tolerate and benefit from various therapies are under development. Because most breast cancers in the elderly are hormone responsive, hormonal therapy remains the mainstay of systemic treatment in the adjuvant and metastatic settings. Chemotherapy can be used in elderly women, but treatment decisions must be individualized based upon risk-benefit analyses. Elder-specific studies are underway to identify the most-efficacious and best-tolerated therapies for breast cancer in this population. Primary care physicians must be aware of these issues to provide adequate counseling and care to these patients.     

Androgen-deprivation therapy in prostate cancer: clinical evidence and future perspectives

Androgens are involved in the development and progression of prostate cancer even if the mechanism is not well-recognized. For this reason androgen-deprivation therapy remains a milestone for the treatment of patients with advanced and metastatic disease and, in the last years, in conjunction with radiotherapy and surgery in locally advanced tumors. Alternative options, such as intermittent deprivation suppression, seem to be promising in terms of clinical benefits and toxicity profile. However, current therapies present side effects, such as testosterone surge with consequent clinical flare-up, metabolic syndrome and hormone-resistance, which develops after a variable number of years. Novel therapies such as LH-RH antagonists and prolonged depot LH-RH analogues have been developed in order to avoid clinical flare-up and testosterone microsurges. Novel androgen synthesis inhibitors, such as abiraterone acetate and MDV3100, have been recently discovered and tested as promising hormonal second-line agents in patients with castration-resistant prostate cancer. Finally, long-term side effects from androgen deprivation, such as osteoporosis, sarcopenic obesity and cardiovascular morbidity should be carefully monitored and properly treated.     

Cancer of the oropharynx.

Oropharyngeal cancer is a rare tumour. Tobacco use and alcohol consumption are recognised as major risk factors. Several carcinogens, occupational exposures and vitamin deficiencies represent the most significant predisposing factors. A varying host susceptibility to carcinogens can be inferred. Carcinoma of the oropharynx has to be suspected whenever sore throat, odynophagia, and ear-ache are described by the patient. Biopsy is mandatory for the definitive diagnosis. TNM classification is crucial for treatment decision-making, while stage grouping is less important. Prognostic factors are treatment-related. Standard treatment of T1-T2 tumours is radiation therapy, for T3 and T4 tumour treatment options are controversial. More advanced tumours can be treated either with surgery followed by conventional radiotherapy or by combined chemo-radiation. Non-conventional fractionation radiotherapy in combination with chemotherapy may represent a third option. Acute toxicity needs to be managed promptly. Late sequelae are less known. Treatment of such tumours requires a multidisciplinary approach within experienced centres.     

Cholangiocarcinoma

Cholangiocarcinoma is an uncommon adenocarcinoma with poor prognosis. Although the 1-year survival has increased over time, the 5-year survival has not shown any significant change (less than 5%). Cure can only be expected from surgical resection of early stage tumours but most patients initially present with advanced disease. Cancer cachexia, liver failure, and recurrent sepsis due to biliary obstruction are among the main causes of mortality.Patients’ prognosis is strongly related to radical surgery and complete resection is the most effective therapy; the location within the biliary tree (proximal versus distal) has no impact on survival when a complete resection is achieved despite the fact the rate of resectability is up to 70% in case of distal cancer and 15–20% for high bile ducts tumours. Prognosis of cholangiocarcinoma remains poor even with aggressive surgical therapy because of the high incidence of local or regional recurrence and distant metastasis.Based on these data many questions need an answer: is there a role for adjuvant chemotherapy or radiotherapy? Neoadjuvant treatments provide best results? There is a standard therapy in unresectable or metastatic cholangiocarcinoma?This report tries to answer to frequently asked questions that the readers are faced with their patients every day (from diagnostic procedures to palliative treatment) and tries to suggest useful information for their professional practice.     

Prognostic impact of increasing age and co-morbidity in cancer patients: a population-based approach

This large population-based study focuses on the prognostic role of increasing age and co-morbidity in cancer patients diagnosed in the southern Netherlands. Data of patients diagnosed between 1995 and 2002 and recorded in the population-based Eindhoven Cancer Registry were used. Older patients (with serious co-morbidity) with non-small cell lung cancer or prostate cancer underwent surgery less often than younger patients. Elderly with stage III colon cancer, small cell lung cancer, FIGO II or III ovarian cancer or non-Hodgkin's lymphoma (NHL) received (adjuvant) chemotherapy less often, probably because of the higher rate of haematological complications. Administration of adjuvant radiotherapy decreased with age and co-morbidity in patients with rectal cancer, limited small cell lung cancer or breast cancer. In general, elderly did not suffer from more complications than younger patients, except for cardiac complications (colorectal cancer and NHL) and postoperative death (non-small cell lung cancer). For most tumours relative survival was lower for the elderly, except for patients with colon cancer, prostate cancer or indolent NHL. Co-morbidity had an independent prognostic effect, except for tumours with a very poor prognosis. Future prospective studies should investigate whether the guidelines for cancer treatment should be adjusted for elderly with serious co-morbidity.