Personalized Prehabilitation Improves Tolerance to Chemotherapy in Patients with Oesophageal Cancer.

BACKGROUND: Prehabilitation programmes aim to optimise patients before and after cancer treatment including surgery. Previous studies in surgical patients demonstrate that prehabilitation improves pre-operative fitness and overcomes the negative impact of neoadjuvant chemotherapy on fitness. The aim of this study was to assess the impact of prehabilitation on the tolerance of neoadjuvant chemotherapy in patients with oesophageal cancer. METHODS: Patients with oesophageal or gastroesophageal junction (GOJ) cancer from two oncology centres were retrospectively included in the present comparative cohort study; one provided a multimodal prehabilitation programme and one did not offer any prehabilitation. Tolerance of chemotherapy, defined as completion of the full chemotherapy regime as per protocol, was compared between the two groups. RESULTS: In terms of participants, 92 patients were included in this study, 47 patients in the prehabilitation cohort and 45 in the control cohort. Compared with the control group, the prehabilitation group demonstrated an improved rate of chemotherapy completion (p = 0.029). In multivariate analysis, participation in prehabilitation was significantly associated with an improved rate of chemotherapy completion. CONCLUSION: The findings of this exploratory study suggest that prehabilitation is associated with better tolerance for chemotherapy. Further research is needed to establish the long-term impact of prehabilitation on oncological outcomes.

Compliance to chemoradiation in squamous cell carcinoma of the anus.

The randomized controlled trial (RCT) remains the preferred design to determine effectiveness of a novel intervention in patients with cancer. The accepted method of primary analysis of phase III trials of radical chemoradiotherapy is by intention to treat (ITT). Yet, investigators often resort to 'post hoc' analyses comparing only patients who received the treatment per protocol (PP). Analysis of treatment PP aims to maintain the comparable groups achieved by randomisation, whilst identifying a true or more accurate treatment effect if the planned chemoradiotherapy is optimally applied with full compliance. Poor compliance is recognised to be associated with inferior outcomes. Reasons for poor compliance if identified and understood, might influence the design of future trials. Yet this entire methodology risks substantial bias and is often disparaged. In localised squamous cell carcinoma of the anus (SCCA) chemoradiotherapy with concurrent 5-flurouracil (or capecitabine) and mitomycin C achieves high rates of local control, but results in substantial acute toxicities. Some novel radiotherapy techniques (intensity modulated radiotherapy (IMRT), meticulous organs-at-risk (OAR) contouring, and techniques such as sparing of PET-active bone marrow) appear to reduce acute toxicity. Good quality assurance in the design of trials, patient education, optimizing nutrition, proactive surveillance during treatment, and early interventions might also improve compliance. This review examines the recently published findings on compliance in the ACT II trial and data from other studies using chemoradiotherapy in SCCA to explore compliance.

A prospective audit evaluating use of urokinase in oncology patients with occluded central venous access devices.

This article reports the results of a single-site prospective audit evaluating the safety and effectiveness of urokinase (Syner-Kinase®) to restore patency in central venous access devices (CVADs) for cancer patients. CVADs are routinely inserted to allow the safe and timely administration of systemic anti-cancer therapies; therefore, catheter dysfunction can interrupt the treatment schedule and adversely affect patient outcome. The aim was to contribute to the development of evidence-based, standardised, best practice guidelines. Prospective data were collected from all patients (n=22) identified with an occluded CVAD, requiring use of Syner-Kinase to manage a persistent withdrawal occlusion or total occlusion, over a 6-month period. Findings revealed a single administration of Syner-Kinase for catheter occlusion clearance to be effective in 92% of cases. Results suggest that use of the thrombolytic agent is well-tolerated and an effective means of restoring patency for long-term CVADs in cancer patients.

Management of toxicities following pelvic irradiation for gynaecological cancers.

PURPOSE OF REVIEW: With increasing numbers of cancer survivors, management of the consequences of treatment is a major clinical problem. This article discusses recent advances in preventing and managing radiotherapy-related toxicity. RECENT FINDINGS: Often underreported in clinical studies, radiation toxicity should be assessed with validated assessment tools to assess impact on quality of life. Prevention strategies targeting reactive oxygen species and proinflammatory cytokines show promise. Bowel toxicity is the most common late effect, and algorithm-led investigation and management can significantly improve outcomes. Oral and intravesical therapies are options for bladder toxicity if conservative measures fail. SUMMARY: With better understanding of the mechanisms of acute and chronic radiation-induced changes, more effective treatments are now possible. Following pelvic radiotherapy, patients should be proactively assessed for early intervention by a specialist multidisciplinary team.

Use of raltitrexed as an alternative to 5-fluorouracil and capecitabine in cancer patients with cardiac history.

AIM: Fluoropyrimidines are the backbone of the majority of approved chemotherapy regimens for colorectal cancer (CRC). However, there are reports of fluoropyrimidine treatments being associated with cardiotoxicity which have led to permanent cardiovascular damage and even death. Raltitrexed is indicated for palliative treatment of advanced CRC where 5-fluorouracil (5-FU) is not tolerated or inappropriate. A systematic review was undertaken to determine the incidence of cardiotoxicity associated with 5-FU, capecitabine and raltitrexed. METHODS: An electronic search of PubMed was undertaken to identify articles relating to cardiotoxicity associated with 5-FU, capecitabine or raltitrexed, published between January 1991 and August 2011. Additionally, a retrospective review of cardiotoxicity associated with raltitrexed at our treatment centres was conducted. RESULTS: Twenty studies were examined. The overall incidence of cardiotoxicity associated with 5-FU/capecitabine varied between 0.55% and 19% (mean: 5.0%, median: 3.85%). No published data were identified reporting cardiotoxicity associated with raltitrexed. A retrospective review at our treatment centres revealed that the incidence was 4.5% amongst high-risk patients treated with raltitrexed (n=111) for advanced gastrointestinal cancer with a significant cardiac history and/or previous cardiotoxicity with 5-FU or capecitabine. CONCLUSION: The incidence of cardiotoxicity associated with raltitrexed in patients with advanced CRC treated is favourable in a highly skewed, at-risk patient population, all of whom had documented cardiotoxicity with other fluoropyrimidines or were unable to tolerate capecitabine due to cardiac history. Raltitrexed is therefore a suitable option for patients with fluoropyrimidine-induced cardiotoxicity or significant cardiovascular risk factors.

Intraductal tubulopapillary neoplasm of the pancreas as a radiation induced malignancy.

Pancreatic malignancies account for 3% of all cancer diagnoses in the UK and prognosis is poor with overall 1-year survival rates at 20% and 5-year survival rates at 5%. The majority of these cancers (75%-95%) arise from the exocrine part of the gland and are almost all invasive ductal adenocarcinomas. One per cent of all pancreatic tumours are endocrine tumours. There is limited data regarding the management of such rare neoplasms of the pancreas and some evidence suggests that prognoses and risk factors may be different. Therefore, it is important to report experience of this type of malignancy in order to build a knowledge base to guide the practice of future clinicians. The authors report a case of an intraductal tubulopapillary neoplasm of the pancreas. This is very unusual form of intraductal pancreatic tumour, which is now thought to occupy a distinct histological subcategory and has arisen within a previously irradiated field.

The management of metastatic hepatic germ cell tumour in a young woman: case report and literature review.

Germ cell tumours (GCTs) have an excellent prognosis but rarely arise from the liver. Our case describes a young woman referred for urgent radiotherapy for a bone metastasis. There was also a large lesion in the liver and marked elevation of the serum α-fetoprotein (AFP) level. Liver biopsy indicated a germ cell tumour. Reduced intensity chemotherapy was commenced using the combination of etoposide, cisplatin and paclitaxel. After four cycles the AFP values had fallen, the liver function tests had normalised and the previous bone lesions had healed. The predominant lesion in the liver had also regressed. Hepatocellular carcinoma (HCC) is the main differential diagnosis. Hepatic germ cell tumours predominantly occur in young, healthy women whereas hepatocellular carcinoma occurs in cirrhotic male livers. These two malignancies are very different and accurate diagnosis is essential. Diagnosing this rare condition early allows the delivery of effective therapy and a better outcome.

Therapy of testicular cancer: a surgeon's view.

Treatment for metastatic testicular cancer has generally met greatest success when it has involved platinum-based chemotherapy and this is widely used for metastatic disease in most centers. However, surgical techniques should not be excluded. Retroperitoneal lymph node dissection has enabled a high cure rate to be achieved when used in conjunction with chemotherapy in patients with more advanced stage cancers.