Patients requiring surgery for locally advanced rectal cancer often additionally undergo neoadjuvant chemoradiotherapy (NACRT), of which the effects on physical fitness are unknown. The aim of this ...feasibility and pilot study was to investigate the effects of NACRT and a 6 week structured responsive exercise training programme (SRETP) on oxygen uptake (V˙O2) at lactate threshold ( θˆL) in such patients.
We prospectively studied 39 consecutive subjects (27 males) with T3–4/N+ resection margin threatened rectal cancer who completed standardized NACRT. Subjects underwent cardiopulmonary exercise testing at baseline (pre-NACRT), at week 0 (post-NACRT), and week 6 (post-SRETP). Twenty-two subjects undertook a 6 week SRETP on a training bike (three sessions per week) between week 0 and week 6 (exercise group). These were compared with 17 contemporaneous non-randomized subjects (control group). Changes in V˙O2 at θˆL over time and between the groups were compared using a compound symmetry covariance linear mixed model.
Of 39 recruited subjects, 22 out of 22 (exercise) and 13 out of 17 (control) completed the study. There were differences between the exercise and control groups at baseline age, ASA score physical status, World Health Organisation performance status, and Colorectal Physiologic and Operative Severity Score for the Enumeration of Mortality and Morbidity (CR-POSSUM) predicted mortality. In all subjects, V˙O2 at θˆL significantly reduced between baseline and week 0 −1.9 ml kg−1 min−1; 95% confidence interval (CI) −1.3, −2.6; P<0.0001. In the exercise group, V˙O2 at θˆL significantly improved between week 0 and week 6 (+2.1 ml kg−1 min−1; 95% CI +1.3, +2.9; P<0.0001), whereas the control group values were unchanged (−0.7 ml kg−1 min−1; 95% CI −1.66, +0.37; P=0.204).
NACRT before rectal cancer surgery reduces physical fitness. A structured exercise intervention is feasible post-NACRT and returns fitness to baseline levels within 6 weeks.
NCT: 01325909.
Radiation plays an important role in organ preservation for gastrointestinal malignancies, with a watch and wait strategy enabling surgery to be avoided in patients who are not suitable or who are ...refusing surgery. Brachytherapy boost allows the radiation dose to be escalated, which plays a pivotal role in the successful outcome of achieving organ preservation. Here we describe the role of brachytherapy in two common gastrointestinal malignancies (oesophagus and rectum). Their indications and how the brachytherapy procedures are carried out, together with the dose and fractionation commonly used are discussed. The use of brachytherapy needs to be included in the training curriculum at all academic centres so that its use is developed by the newer generation of radiation oncologists. Its current non-use due to bias, lack of training and availability is no longer justified, given the overwhelming published evidence for the role of brachytherapy to improve organ preservation for both radical treatment and palliation in gastrointestinal malignancies.
Postmastectomy radiotherapy in patients with four or more positive axillary nodes reduces breast cancer mortality, but its role in patients with one to three involved nodes is controversial. We ...assessed the effects of postmastectomy radiotherapy on quality of life (QOL) in women with intermediate-risk breast cancer.
SUPREMO is an open-label, international, parallel-group, randomised, controlled trial. Women aged 18 years or older with intermediate-risk breast cancer (defined as pT1–2N1; pT3N0; or pT2N0 if also grade III or with lymphovascular invasion) who had undergone mastectomy and, if node positive, axillary surgery, were randomly assigned (1:1) to receive chest wall radiotherapy (50 Gy in 25 fractions or a radiobiologically equivalent dose of 45 Gy in 20 fractions or 40 Gy in 15 fractions) or no radiotherapy. Randomisation was done with permuted blocks of varying block length, and stratified by centre, without masking of patients or investigators. The primary endpoint is 10-year overall survival. Here, we present 2-year results of QOL (a prespecified secondary endpoint). The QOL substudy, open to all UK patients, consists of questionnaires (European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BR23, Body Image Scale, Hospital Anxiety and Depression Scale HADS, and EQ-5D-3L) completed before randomisation, and at 1, 2, 5, and 10 years. The prespecified primary outcomes within this QOL substudy were global QOL, fatigue, physical function, chest wall symptoms, shoulder and arm symptoms, body image, and anxiety and depression. Data were analysed by intention to treat, using repeated mixed-effects methods. This trial is registered with the ISRCTN registry, number ISRCTN61145589.
Between Aug 4, 2006, and April 29, 2013, 1688 patients were enrolled internationally and randomly assigned to receive chest wall radiotherapy (n=853) or not (n=835). 989 (79%) of 1258 patients from 111 UK centres consented to participate in the QOL substudy (487 in the radiotherapy group and 502 in the no radiotherapy group), of whom 947 (96%) returned the baseline questionnaires and were included in the analysis (radiotherapy, n=471; no radiotherapy, n=476). At up to 2 years, chest wall symptoms were worse in the radiotherapy group than in the no radiotherapy group (mean score 14·1 SD 15·8 in the radiotherapy group vs 11·6 14·6 in the no radiotherapy group; effect estimate 2·17, 95% CI 0·40–3·94; p=0·016); however, there was an improvement in both groups between years 1 and 2 (visit effect −1·34, 95% CI −2·36 to −0·31; p=0·010). No differences were seen between treatment groups in arm and shoulder symptoms, body image, fatigue, overall QOL, physical function, or anxiety or depression scores.
Postmastectomy radiotherapy led to more local (chest wall) symptoms up to 2 years postrandomisation compared with no radiotherapy, but the difference between groups was small. These data will inform shared decision making while we await survival (trial primary endpoint) results.
Medical Research Council, European Organisation for Research and Treatment of Cancer, Cancer Australia, Dutch Cancer Society, Trustees of Hong Kong and Shanghai Banking Corporation.
Chronic Radiation Enteritis Theis, V.S; Sripadam, R; Ramani, V ...
Clinical oncology (Royal College of Radiologists (Great Britain)),
02/2010, Letnik:
22, Številka:
1
Journal Article
Recenzirano
Abstract Chronic radiation enteritis is an increasing problem, as more patients receive radiotherapy as part of their cancer therapy and as the long-term survival of these patients improves. This ...review addresses the causes, investigation, treatment and prevention of this disease. A review of published studies was carried out using a variety of search terms, including radiation enteritis, investigation, treatment and prevention. Chronic radiation enteritis has been reported in up to 20% of patients receiving pelvic radiotherapy, although this may underestimate its true prevalence, as not all patients with gastrointestinal symptoms after radiotherapy will seek medical attention. Predisposing factors to chronic radiation enteritis include a low body mass index, previous abdominal surgery and the presence of co-morbid conditions; the radiation dose, fractionation and technique, as well as the concomitant use of chemotherapy, may also play a role. Clinical features of chronic radiation enteritis are multiple as the disease can affect any part of the gastrointestinal tract. Moreover, symptom aetiology within any one patient may be multifactorial and therefore it is important to adopt a structured approach when planning investigations. The evidence base for current therapies is limited, but nutrition, anti-diarrhoeals, anti-inflammatories, antibiotics, probiotics, pentoxifylline, tocopherol, cholestyramine, hyperbaric oxygen, endoscopic and surgical therapies have all received attention. Given the significant morbidity and mortality associated with chronic radiation enteritis, current available preventative strategies are reviewed, including tissue-sparing radiotherapy techniques. In conclusion, the evidence base for therapeutic and preventative strategies in treating chronic radiation enteritis is limited, but adopting a structured approach to investigating gastrointestinal symptoms after radiotherapy should allow better targeting of current therapies. Closer collaboration between oncologists and gastroenterologists will facilitate a more structured approach, not only in managing individual patients, but also in establishing clinical and research networks for this expanding disease, in order to improve the evidence base for its management.
Abstract Background Neoadjuvant chemoradiotherapy (NACRT) followed by surgery for resectable locally advanced rectal cancer improves outcome compared with surgery alone. Our primary hypothesis was ...that NACRT impairs objectively-measured physical fitness. We also wished to explore the relationship between fitness and postoperative outcome. Method In an observational study, we prospectively studied 27 consecutive patients, of whom 25 undertook cardiopulmonary exercise testing (CPET) 2 weeks before and 7 weeks after standardized NACRT, then underwent surgery. In-hospital post-operative morbidity and mortality were recorded. Patients were followed up to 1 year for mortality. Data was analysed blind to clinical details. Receiver-operating characteristic (ROC) analysis defined the predictive value of CPET for in-hospital morbidity at day 5. Results Oxygen uptake ( V ˙ O 2 in ml kg−1 min−1 ) at estimated lactate threshold ( θ ˆ L ) and at peak exercise ( V ˙ O 2 at peak in ml kg−1 min−1 ) both significantly decreased post-NACRT: V ˙ O 2 at θ ˆ L 12.1 (pre-NACRT) vs. 10.6 (post-NACRT), p < 0.001 (95%CI −1.7, −1.2); V ˙ O 2 at peak 18.1 vs. 16.7, p < 0.001 (95%CI −3.1, −1.0). Optimal V ˙ O 2 at θ ˆ L and peak pre-NACRT for predicting postoperative morbidity were 12.0 and 18.1 ( V ˙ O 2 at θ ˆ L – AUC = 0.71, 77% sensitive and 75% specific; V ˙ O 2 at peak – AUC = 0.75, 78% sensitive and 76% specific). Optimal V ˙ O 2 at θ ˆ L and peak post-NACRT for predicting postoperative morbidity were 10.7 and 16.7 ( V ˙ O 2 at θ ˆ L – AUC = 0.72, 77% sensitive and 83% specific; V ˙ O 2 at peak – AUC = 0.80, 85% sensitive and 83% specific). Conclusion NACRT before major rectal cancer surgery significantly decreased physical fitness as assessed by CPET. Trials Registry Number NCT01334593.
Trastuzumab deruxtecan (T-DXd) has demonstrated efficacy in patients with brain metastasis (BM), a group historically with poor outcomes. The prevalence of BMs in patients commencing T-DXd is ...currently unknown. No direct comparisons have been made of the activity of T-DXd in patients with active BM versus those with extracranial progression alone. This real-world study explored the prevalence of BMs in patients commencing T-DXd, the efficacy of T-DXd in active BM versus extracranial progression alone and the safety of T-DXd.
Patients with human epidermal growth factor receptor 2-positive advanced breast cancer treated with T-DXd between June 2021 and February 2023 at our specialist cancer hospital were identified and notes reviewed. Clinicopathological information, prior treatment, the presence or absence of central nervous system (CNS) disease, outcomes and treatment-emergent adverse events (TEAEs) were recorded.
Twenty-nine female patients, with a median age of 52 years (interquartile range 44-62 years), were identified; the prevalence of BM was 41%. Median number of lines of prior therapy was 2 (range 2-6). At a median follow-up of 13.8 months, median progression-free survival (PFS) for the overall population was 13.9 months 95% confidence interval (CI) 12.4 months-not estimable (NE), 16.1 months (95% CI 15.1 months-NE) for active BMs and 12.4 months (95% CI 8.3 months-NE) for progressive extracranial disease alone. The 12-month overall survival (OS) rate was 74% (95% CI 59% to 95%) in the overall population, and 83% (95% CI 58% to 100%) and 66% (95% CI 45% to 96%) for active BMs and extracranial disease only, respectively. Most common TEAEs were fatigue, alopecia, and constipation. In nine patients (31%, including two deaths), pneumonitis occurred.
In this real-world population, we demonstrate T-DXd to be effective in patients with active BMs and those with progressive extracranial disease alone. PFS and OS were numerically longer in those with active BMs. These data demonstrate that patients with active BM treated with T-DXd have at least comparable outcomes to those with extracranial disease alone. The high rate of pneumonitis warrants further consideration.
•The prevalence of BM in a contemporaneous real-world population commencing T-DXd was found to be 41%.•Median PFS: 16.1 months (95% CI 15.1-NE) active BM vs 12.4 (95% CI 8.3-NE) progressive extracranial disease.•Median OS: 15.3 months (95% CI 15.1-NE) active BM vs 13.4 (95% CI 8.3-NE) for progressive extracranial disease.•The rate of pneumonitis was 31%.
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