Neoadjuvant chemotherapy (NACT) is a term originally used to describe the administration of chemotherapy preoperatively before surgery. The original rationale for administering NACT or so-called induction chemotherapy to shrink or downstage a locally advanced tumour, and thereby facilitate more effective local treatment with surgery or radiotherapy, has been extended with the introduction of more effective combinations of chemotherapy to include reducing the risks of metastatic disease. It seems logical that survival could be lengthened, or organ preservation rates increased in resectable tumours by NACT. In rectal cancer NACT is being increasingly used in locally advanced and nonmetastatic unresectable tumours. Randomised studies in advanced colorectal cancer show high response rates to combination cytotoxic therapy. This evidence of efficacy coupled with the introduction of novel molecular targeted therapies (such as Bevacizumab and Cetuximab), and long waiting times for radiotherapy have rekindled an interest in delivering NACT in locally advanced rectal cancer. In contrast, this enthusiasm is currently waning in other sites such as head and neck and nasopharynx cancer where traditionally NACT has been used. So, is NACT in rectal cancer a real advance or just history repeating itself? In this review, we aimed to explore the advantages and disadvantages of the separate approaches of neoadjuvant, concurrent and consolidation chemotherapy in locally advanced rectal cancer, drawing on theoretical principles, preclinical studies and clinical experience both in rectal cancer and other disease sites. Neoadjuvant chemotherapy may improve outcome in terms of disease-free or overall survival in selected groups in some disease sites, but this strategy has not been shown to be associated with better outcomes than postoperative adjuvant chemotherapy. In particular, there is insufficient data in rectal cancer. The evidence for benefit is strongest when NACT is administered before surgical resection. In contrast, the data in favour of NACT before radiation or chemoradiation (CRT) is inconclusive, despite the suggestion that response to induction chemotherapy can predict response to subsequent radiotherapy. The observation that spectacular responses to chemotherapy before radical radiotherapy did not result in improved survival, was noted 25 years ago. However, multiple trials in head and neck cancer, nasopharyngeal cancer, non-small-cell lung cancer, small-cell lung cancer and cervical cancer do not support the routine use of NACT either as an alternative, or as additional benefit to CRT. The addition of NACT does not appear to enhance local control over concurrent CRT or radiotherapy alone. Neoadjuvant chemotherapy before CRT or radiation should be used with caution, and only in the context of clinical trials. The evidence base suggests that concurrent CRT with early positioning of radiotherapy appears the best option for patients with locally advanced rectal cancer and in all disease sites where radiation is the primary l...
Background: Bone is the most common site of metastatic disease in advanced prostate cancer. Radium-223 (223 Ra) is a calcium-mimetic alpha-particle emitter, which has been shown to have activity in prostate cancer with clinical benefit in patients with symptomatic bone metastasis. The recommended schedule is six cycles of 223 Ra, 5 kBq/kg, at 4-weekly intervals. Although previous studies have assessed clinical outcomes in patients who received six cycles of Ra 223 , there is very little information about outcomes of patients receiving fewer courses of treatment. Patients and Methods: Patients with hormone-refractory metastatic prostate cancer treated from May 2014 to August 2016 were included in this retrospective study. A total of 113 patients were identified with a median age of 76 (range=52-92) years. The median number of cycles administered was 5 (range=1-6) with 54 (48%) completing six cycles of treatment. Eighty-five patients (75%) received 223 Ra prior to docetaxel chemotherapy and 28 (25%) received it after receiving docetaxel. Results: Eleven patients developed grade 2/3 thrombocytopenia, and none of these received further 223 Ra. Only 25% of patients who had a haemoglobin level of 10 g/dl or below at the start of the treatment were able to complete six courses of 223 Ra. Of the patients who completed fewer than six cycles of 223 Ra (1-5 cycles), the survival was 121 days, compared to 398 days in men who received six cycles (odds ratio(OR)=4.767, 95% confidence internal(CI)=1.07-21.25; p=0.0005). Conclusion: Careful selection of patients is essential to obtain good clinical outcomes from 223 Ra therapy. When fewer than six cycles were delivered then a beneficial survival effect was not seen. Prostate cancer is the second most common cancer in men, with a worldwide incidence of 1.1 million new cases/year (1, 2). The treatment of metastatic prostate cancer has evolved with the use of docetaxel chemotherapy and third-generation endocrine agents such as abiraterone and enzalutamide (3-7). Since the first trials with mitoxantrone plus prednisolone, numerous agents have been found to improve outcomes for patients with this disease. Bone is the most common site of metastasis in prostate cancer and leads to an increased risk of skeletal-related events which include pathological fractures, spinal cord/nerve root compression, limited mobility, increased morbidity, hypercalcaemia, increased pain and dependence on opioids. These can have a serious impact on quality of life and in turn affect survival in patients with advanced disease (8, 9). Newer bone-targeted therapies with different mechanisms of action, such as zolendronate and denosumab, are significant additions to the management of prostate cancer (10). Radium-223 (223 Ra) is a first in its class calcium-mimetic alpha-particle emitter which has been shown to have activity in prostate cancer, with clinical benefit in patients with symptomatic bone metastasis. It has a half-life of 11.43 days and is taken up preferentially in areas of high bone turnover, partic...
Objective: A review of stereotactic body radiotherapy (SBRT) for oligometastases defined as three or fewer sites of isolated metastatic disease. The aim was to identify local control, overall survival (OS) and progression-free survival (PFS) of patients receiving SBRT for oligometastatic (OM) disease. Methods: Data were analysed for SBRT delivered between 01 September 2010 and 31 March 2014. End points included local control, PFS, OS and toxicity. Results: 76 patients received SBRT. The median age was 60 years (31-89 years). 44 were male. Median follow-up was 12.3 months (0.2-36.9 months). Major primary tumour sites included colorectal (38%), the breast (18%) and the prostate (12%). The treatment sites included lymph nodes (42%), the bone and spine (29%) and soft tissue (29%). 42% were previously treated with conventional radiotherapy. 45% were disease free after SBRT. 4% had local relapse, 45% had distant relapse, and 6% had local and distant relapse. Local control was 89%. The OS was 84.4% at 1 year and 63.2% at 2 years. PFS was 49.1% at 1 year and 26.2% at 2 years. Toxicities included duodenal ulcer and biliary stricture formation. Conclusion: SBRT can achieve durable control of OM lesions and results in minimal radiation-induced morbidity. Advances in knowledge: This cohort is one of the largest reported to date and contributes to the field of SBRT in oligometastases that is emerging as an important research area. It is the only study reported from the UK and uses a uniform technique throughout. The efficacy and low toxicity with durable control of local disease with this approach is shown, setting the foundations for future randomized studies.
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