Early toxicity from preoperative radiotherapy with continuous infusion 5-fluorouracil for resectable adenocarcinoma of the rectum: A phase II trial for the Trans-Tasman Radiation Oncology Group

Purpose: To assess the toxicity and the efficacy of preoperative radiotherapy with continuous infusion 5-fluorouracil (5-FU) for locally advanced adenocarcinoma of the rectum. Methods and Materials: Eligible patients had newly diagnosed localized adenocarcinoma of the rectum within 12 cm of the anal verge, Stage T3-4, and were suitable for curative resection. Eighty-two patients were treated with radiotherapy-50.4 Gy in 28 fractions in 5.6 weeks, given concurrently with continuous infusion 5-FU, using either 96-h/week infusion at 300 mg/m(2)/day or 7-days/week infusion at 225 mg/m(2)/day. Results: The median age was 59 years (range, 27-87), and 67% of patients were male. Pretreatment stages of the rectal cancer were T3, 89% and resectable T4, 11%, with endorectal ultrasound confirmation in 67% of patients. Grade 3 acute toxicity occurred in 5 of 82 patients (6%; 95% confidence interval [CI], 2-14%). Types of surgical resection were anterior resection, 61%; abdominoperineal resection, 35%; and other procedures, 4%. There was no operative mortality. Anastomotic leakage after low anterior resection occurred in 3 of 50 patients (6%; 95% CI, 1-17%). The pathologic complete response rate was 16% (95% CI, 9-26%). Pathologic Stages T2 or less occurred in 51%. Conclusion: Preoperative radiotherapy with continuous infusion 5-FU for locally advanced rectal cancer is a safe regimen, with a significant downstaging effect. It does not seem to lead to a significant increase in serious surgical complications. (C) 2001 Elsevier Science Inc.

Promising results of a cooperative group phase II trial of preoperative chemoradiation for locally advanced rectal cancer (TROG 9801)

PURPOSE: This article reports the overall survival, failure-free survival, local failure, and late radiation toxicity of a phase II trial of preoperative radiotherapy with continuous infusion 5-fluorouracil for rectal cancer after a minimum 3.5 years of follow-up. METHODS: Eligible patients were those with newly diagnosed localized adenocarcinoma of the rectum, within 12 cm of the anal verge, staged T3-T4 and deemed suitable for curative resection. Radiotherapy (50.4 Gy in 28 fractions in five weeks and three days) was given with continuous infusion 5-fluorouracil throughout the course of radiotherapy. RESULTS: A total of 82 patients were accrued in 13 months. The median follow-up time was 4.1 (range, 2.3-4.5) years. There were 55 males (67 percent) and the median age was 59 (range, 27-87) years. Patients were staged pretreatment as T3 (89 percent) and resectable T4 (11 percent). Endorectal ultrasound was performed in 70 percent and magnetic resonance imaging in another 5 percent. The four-year overall and failure-free survival rates were 82 percent (95 percent Cl: 72-89) and 69 percent (95 percent Cl: 58-78), respectively. The cumulative incidence of local failure at four years was 3.9 percent (95 percent CI: 1.3-11). Risk of failures, local and distant, has not reached a plateau phase. CONCLUSION: This regimen can be delivered safely and without leading to a significant increase in late toxicity. It provides excellent local control and favorable overall survival. There is a need for longer follow-up than has commonly been used for the proper evaluation of failures after an effective regimen of preoperative chemoradiation.

Surgery alone versus chemoradiotherapy followed by surgery for resectable cancer of the oesophagus: a randomised controlled phase III trial

Background Resection remains the best treatment for carcinoma of the oesophagus in terms of local control, but local recurrence and distant metastasis remain an issue after surgery. We aimed to assess whether a short preoperative chemoradiotherapy regimen improves outcomes for patients with resectable oesophageal cancer. Methods 128 patients were randomly assigned to surgery alone and 128 patients to surgery after 80 mg/m(2) cisplatin on day 1, 800 mg/m(2) fluorouracil on days 1-4, with concurrent radiotherapy of 35 Gy given in 15 fractions. The primary endpoint was progression-free survival. Secondary endpoints were overall survival, tumour response, toxic effects, patterns of failure, and quality of life. Analysis was done by intention to treat. Findings Neither progression-free survival nor overall survival differed between groups (hazard ratio [HR] 0.82 [95% CI 0.61-1.101 and 0.89 [0.67-1.19], respectively). The chemoradiotherapy-and-surgery group had more complete resections with clear margins than did the surgery-alone group (103 of 128 [80%] vs 76 of 128 [59%], p=0.0002), and had fewer positive lymph nodes (44 of 103 [43%] vs 69 of 103 [67%], p=0.003). Subgroup analysis showed that patients with squamous-cell tumours had better progression-free survival with chemoradiotherapy than did those with non-squamous tumours (HR 0.47 [0.25-0.86] vs 1.02 [0.72-1.44]). However, the trial was underpowered to determine the real magnitude of benefit in this subgroup. Interpretation Preoperative chemoradiotherapy with cisplatin and fluorouracil does not significantly improve progression-free or overall survival for patients with resectable oesophageal cancer compared with surgery alone. However, further assessment is warranted of the role of chemoradiotherapy in patients with squamouscell tumours.

Factors influencing wound healing after surgery for metastatic disease of the spine

Study Design, The study group consisted of 53 patients who underwent 75 operations for spine metastases. Patient and tumor demographic factors, preoperative nutritional status, and perioperative adjunctive therapy were retrospectively reviewed. Objective, To determine the risk factors for wound breakdown and infection in patients undergoing surgery for spinal metastases. Summary of Background Data. Spinal Fusion using spine implants may be associated with an infection rate of 5% or more. Surgery for spine metastases is associated with an infection rate of more than 10%. Factors other than the type of surgery performed may account for the greater infection rate. Methods. Data were obtained by reviewing patient records. Age, sex, and neurologic status of the patient; tumor type and site; and surgical details were noted. Adjunctive treatment with corticosteroids and radiotherapy was recorded, Nutritional status was evaluated by determining serum protein and serum albumin concentrations and by total lymphocyte count. Results. Wound breakdown and Infection occurred in 75 of 75 wounds. No patient or tumor demographic factors other than intraoperative blood loss (P < 0.1) were statistically associated with infection; The correlation between preoperative protein deficiency (P < 0.01) or perioperative corticosteroid administration (P < 0.10) and wound infection was significant. There was no statistical correlation between lymphocyte count or perioperative radiotherapy and wound infection. Conclusions, The results indicate that preoperative protein depletion and perioperative administration of corticosteroids are risk factors for wound infection in patients undergoing surgery for spine metastases, Perioperative correction of nutritional depletion and cessation of steroid therapy may reduce wound complications.

Breast cancer in Western Australia: clinical practice and clinical guidelines

Objectives: To review changes in patterns of care for women with early invasive breast cancer in Western Australia from 1989 to 1999, and compare management with recommendations in the 1995 National Health and Medical Research Council guidelines. Design and setting: Population-based surveys of all cases listed in the Western Australian Cancer Registry and Western Australian Hospital Morbidity Data System. Main outcome measures: Congruence of care with guidelines. Results: Data were available for 1649 women with early invasive breast cancer (categories pT1 or pT2; pN0 or pN1; and M0). In 1999, 96% had a preoperative diagnosis by fine-needle aspiration or core biopsy (compared with 66% in 1989), with a synoptic pathology report on 95%. Breast-conserving surgery was used for 66% of women with mammographically detected tumours (v 35% in 1989) and 46% of those with clinically detected tumours (v 28% in 1989), with radiotherapy to the conserved breast in 90% of these cases (83% in 1989). Adjuvant chemotherapy was given to 92% of premenopausal women with node-positive disease and 63% with poor-prognosis node-negative tumours (v 78% and 14%, respectively, in 1989). Among postmenopausal women with receptor-positive tumours, tamoxifen was prescribed for 91% of those with positive nodes (85% in 1989) and 79% of those with negative nodes (30% in 1989). Among postmenopausal women with receptor-negative tumours, chemotherapy was prescribed for 70% with positive nodes (v 33%) and 58% with negative nodes (v none). Conclusions: Patterns of management of women with early invasive breast cancer in Western Australia during the 1990s changed significantly in all respects toward those recommended in the 1995 guidelines.

The impact of nutrition support on body composition in cancer outpatients receiving radiotherapy

This study investigated the change in body composition in 36 cancer outpatients receiving radiotherapy to the head and neck area (mean age: 63 ± 15 years) randomised to receive either nutrition intervention (NI; n=15) or usual care (UC; n=21). Body weight and composition were measured at the commencement of radiotherapy and 3 months later. The UC group lost significantly more weight; mean decrease = 4.3 kg, than the NI group: mean decrease = 1.1 kg (t(30)=-2.5, p=0.019). Fat-free mass loss was significantly higher in the UC group with a mean loss of 2.2 kg versus 0.3 kg in the NI group (t(30)=- 2.3, p=0.029). Body composition as measured by foot-to-foot bioelectrical impedance analysis provides more information than weight alone and can allow for tailoring of NI.

Shoulder movement after breast cancer surgery: results of a randomised controlled study of postoperative physiotherapy

Breast screening programmes have facilitated more conservative approaches to the surgical and radiotherapy management of women diagnosed with breast cancer. This study investigated changes in shoulder movement after surgery for primary, operable breast cancer to determine the effect of elective physiotherapy intervention. Sixty-five women were randomly assigned to either the treatment (TG) or control group (CG) and assessments were completed preoperatively, at day 5 and at 1 month, 3, 6, 12 and 24 months postoperatively. The CG only received an exercise instruction booklet in comparison to the TG who received the Physiotherapy Management Care Plan (PMCP). Analyses of variance revealed that abduction returned to preoperative levels more quickly in the TG than in the CG. The TG women had 14degrees more abduction at 3 months and 7degrees at 24 months. Functional recovery at 1 month was greater in those randomised to the TG, with a dominant operated arm (OA) or receiving breast-conserving surgery. However, it was not possible to predict recovery over the 2 years postoperatively on the basis of an individual woman's recovery at 1 month postoperatively. The eventual recovery of abduction or flexion range of movement was not related to the dominance of the OA nor to the surgical procedure performed. The PMCP provided in the early postoperative period is effective in facilitating and maintaining the recovery of shoulder movement over the first 2 years after breast cancer surgery.

Chemotherapy and radiotherapy: When to call it quits

Abstract: Background: Patients diagnosed with cancer are often treated with chemotherapy and radiotherapy with curative intent. The transition from curative to palliative intent involves re-evaluation of treatment, and has to take into account the attitudes, beliefs and life aims of the patient. Objective: To discuss the difficulties in determining when to cease chemotherapy and radiotherapy in patients with advanced cancer. Discussion: The concept of treatment evaluation using a ‘burden versus benefit’ paradigm is discussed. Treatment aims must be in concordance with those of the patient, which are often couched in functional terms or linked to future significant life events. Chemotherapy and radiotherapy can offer patients in the palliative phase of cancer illness, benefits in terms of relief of symptoms and meaningful prolongation of life, and should be considered in appropriate circumstances. (author abstract)

A prospective trial of short-fractionation radiotherapy for the palliation of liver metastases

The purpose of this study was to prospectively examine the effectiveness and tolerability of a simple radiotherapy technique for the palliation of symptomatic liver metastases. Twenty-eight patients with symptomatic liver metastases were enrolled from seven centres, and received targeted (partial or whole) liver irradiation consisting of 10 Gy in two fractions over 2 days. Symptoms at baseline were hepatic pain (27 patients), abdominal distension (19), night sweats (12), nausea (18) and vomiting (eight). Twenty-two patients (76%) had failed previous treatment with chemotherapy, hormonal therapy and/or high-dose steroids. Symptoms and potential toxicities were prospectively assessed at the time of treatment, then 2, 6 and 10 weeks later. Individual symptom response rates were 53−66% at 2 weeks. Partial or complete global symptomatic responses were noted in 15 patients (54%) overall. The treatment was well tolerated with two patients (7%) experiencing grade 3 toxicity (one vomiting and one diarrhoea); however, four patients reported temporary worsening of pain shortly after treatment. This simple and well-tolerated treatment achieves useful palliation.

Use of oesophagogastroscopy to assess the response of oesophageal carcinoma to neoadjuvant therapy

Background: Approximately 25 per cent of patients with oesophageal cancer who undergo neoadjuvant chemoradiotherapy have no evidence of tumour in the resected specimen (complete pathological response). Those who do not respond have a poor 5-year survival compared with complete responders, regardless of whether or not they undergo surgery. Selecting for surgery only those who have a response to neoadjuvant therapy has the potential to improve overall survival as well as to rationalize the management of non-responders. This study assessed the accuracy of oesophagogastroscopy in this setting. Methods: A prospective database of 804 patients undergoing oesophageal resection for carcinoma was reviewed. Endoscopic assessment of the response to neoadjuvant therapy in 100 consecutive patients was compared with the pathological assessment of response. The survival for each level of response was compared. Results: At endoscopy 30 patients were considered to have had a complete response. This was confirmed pathologically in 15 patients. Survival was improved in those with a pathologically confirmed complete response (3-year survival rate 62.4 (s.e. 12.9) per cent) compared with non-responders (16.3 (s.e. 6.6) per cent). Those with microscopic residual disease also had an improved 3-year survival rate (46.3 (s.e. 12.2) per cent); however, oesophagogastroscopy failed to identify this subset. Conclusion: Oesophagogastroscopy may be useful in the assessment of tumour response to neoadjuvant therapy. However, owing to its poor accuracy patients should not be excluded from further therapeutic intervention on the basis of this assessment alone.

Parotidectomy: review of treatment and outcomes

Background: Parotidectomy is a common surgical procedure performed for a wide array of benign and malignant tumours. The aim of the present study was to review a single-institution experience with parotidectomy over a 10 year period. Methods: We retrospectively reviewed 170 patients who had parotidectomy performed. The preoperative investigations, clinicopathological parameters, perioperative morbidity and mortality were assessed. Results: One hundred and six (62%) of the patients were men. The mean age was 54 years (range 21-80). Indications for parotidectomy included benign tumour (44%), malignant tumour (42%), inflammatory parotid disease (7%) and miscellaneous (5%). The most common benign tumour was pleomorphic adenoma (25%). The most common malignant tumour was metastatic cutaneous squamous cell carcinoma (SCC) (19%). Fine needle aspiration cytology was performed in 83% patients with a sensitivity and specificity for benign tumours of 76% and 97%, respectively. The sensitivity and specificity for malignant tumours was 90% and 99%, respectively. One (0.6%) patient died in the postoperative period. Postoperative complications included wound infection (2.3%), wound haematoma (3.5%) and seroma (6.6%). Six patients (3.5%) developed temporary complete facial paresis, while 33 patients (20%) developed temporary partial facial palsy in the immediate postoperative period. The 2-year disease-free and disease-specific survival for those patients with metastatic cutaneous SCC were 75% and 76%, respectively. Conclusions: The most common indications for parotidectomy were pleomorphic adenoma and metastatic cutaneous SCC. Our perioperative morbidity and survival for patients with malignant parotid disease compare favourably with other institutional series.

Randomized trial of 8 Gy in 1 versus 20 Gy in 5 fractions of radiotherapy for neuropathic pain due to bone metastases (Trans-Tasman Radiation Oncology Group, TROG 96.05)

Background and purpose: Despite numerous randomized trials investigating radiotherapy (RT) fractionation schedules for painful bone metastases, there are very few data on RT for bone metastases causing pain with a neuropathic component. The Trans-Tasman Radiation Oncology Group undertook a randomized trial comparing the efficacy of a single 8 Gy (8/1) with 20 Gy in 5 fractions (20/5) for this type of pain. Materials and methods: Eligible patients had radiological evidence of bone metastases from a known malignancy with no change in systemic therapy within 6 weeks before or anticipated within 4 weeks after RT, no other metastases along the distribution of the neuropathic pain and no clinical or radiological evidence of cord/cauda equina compression. All patients gave written informed consent. Primary endpoints were pain response within 2 months of commencement of RT and time to treatment failure (TTF). The hypothesis was that 8/1 is at least as effective as 20/5 and the planned sample size was 270 patients. Results: Between February 1996 and December 2002, 272 patients were randomized (8/1:20/5 = 137:135) from 15 centres (Australia 11, New Zealand 3, UK 1). The commonest primary cancers were lung (31%), prostate (29%) and breast (8%); index sites were spine (89%), rib (9%), other (2%); 72% of patients were males and the median age was 67 (range 2989). The median overall survival (95% CI) for all randomized patients was 4.8 mo (4.2-5.7 mo). The intention-to-treat overall response rates (95% Cl) for 8/1 vs 20/5 were 53% (45-62%) vs 61% (53-70%), P = 0.18. Corresponding figures for complete response were 26% (18-34%) vs 27% (19-35%), P = 0.89. The estimated median TTFs (95% CI) were 2.4 mo (2.0-3.3 mo) vs 3.7 mo (3.1-5.9 mo) respectively. The hazard ratio (95% Cl) for the comparison of TTF curves was 1.35 (0.99-1.85), log-rank P = 0.056. There were no statistically significant differences in the rates of re-treatment, cord compression or pathological fracture by arm. Conclusions: 8/1 was not shown to be as effective as 20/5, nor was it statistically significantly worse. Outcomes were generally poorer for 8/1, although the quantitative differences were relatively small. (c) 2004 Elsevier Ireland Ltd. All rights reserved.