Cognitive-existential group psychotherapy for women with primary breast cancer: a randomised controlled trial

BACKGROUND: We conducted a randomised, controlled trial of cognitive-existential group therapy (CEGT) for women with early stage breast cancer receiving adjuvant chemotherapy with the aim of improving mood and mental attitude to cancer. METHODS: Women were randomised to 20 sessions of weekly group therapy plus 3 relaxation classes or to a control arm receiving 3 relaxation classes. Assessments, independently done at baseline, 6 and 12 months, included a structured psychiatric interview and validated questionnaires covering mood, attitudes to cancer, family relationships, and satisfaction with therapy. RESULTS: Three hundred and three of 491 (62%) eligible patients participated over 3 years. Distress was high pre-intervention: 10% were diagnosed as suffering from major depression, 27% from minor depression and 9% from anxiety disorders. On an intention-to-treat analysis, there was a trend for those receiving group therapy (n=154) to have reduced anxiety (p=0.05, 2-sided) compared to controls (n=149). Women in group therapy also showed a trend towards improved family functioning compared to controls (p=0.07, 2-sided). The women in the groups reported greater satisfaction with their therapy (p<0.001, 2-sided), appreciating the support and citing better coping, self-growth and increased knowledge about cancer and its treatment. They valued the CEGT therapy. Overall effect size for the group intervention was small (d=0.25), with cancer recurrence having a deleterious effect in three of the 19 therapy groups. Psychologists as a discipline achieved a moderate mean effect size (d=0.52). CONCLUSION: CEGT is a useful adjuvant psychological therapy for women with early stage breast cancer. Interaction effects between group members and therapists are relevant to outcome. Group-as-a-whole effects are powerful, but the training and experience of the therapist is especially critical to an efficacious outcome.     

A prospective randomised controlled trial of tamoxifen and cyproterone acetate in pancreatic carcinoma

In a prospective controlled clinical trial, 108 patients with pancreatic adenocarcinoma were randomly allocated to receive tamoxifen 20 mg b.d., cyproteron acetate 100 mg t.d.s. or no active treatment. The median survival of those receiving tamoxifen was longer than either of the other two groups (5.25 compared to 4.25 and 3 months, respectively) but this difference did not achieve statistical significance. Cox regression analysis of 12 clinical and biochemical features showed that, for the entire group of patients, survival was significantly longer in younger patients, those undergoing surgical bypass and those with better initial performance status. However, even when adjustment was made to allow for the distribution of these prognostic variables within the three groups, the difference in survival still did not achieve statistical significance. No side-effects attributable to treatment was observed.     

Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial

BACKGROUND: 5-Aminolevulinic acid is a non-fluorescent prodrug that leads to intracellular accumulation of fluorescent porphyrins in malignant gliomas-a finding that is under investigation for intraoperative identification and resection of these tumours. We aimed to assess the effect of fluorescence-guided resection with 5-aminolevulinic acid on surgical radicality, progression-free survival, overall survival, and morbidity. METHODS: 322 patients aged 23-73 years with suspected malignant glioma amenable to complete resection of contrast-enhancing tumour were randomly assigned to 20 mg/kg bodyweight 5-aminolevulinic acid for fluorescence-guided resection (n=161) or to conventional microsurgery with white light (n=161). The primary endpoints were the number of patients without contrast-enhancing tumour on early MRI (ie, that obtained within 72 h after surgery) and 6-month progression-free survival as assessed by MRI. Secondary endpoints were volume of residual tumour on postoperative MRI, overall survival, neurological deficit, and toxic effects. We report the results of an interim analysis with 270 patients in the full-analysis population (139 assigned 5-aminolevulinic acid, 131 assigned white light), which excluded patients with ineligible histological and radiological findings as assessed by central reviewers who were masked as to treatment allocation; the interim analysis resulted in termination of the study as defined by the protocol. Primary and secondary endpoints were analysed by intention to treat in the full-analysis population. The study is registered at http://www.clinicaltrials.gov as NCT00241670. FINDINGS: Median follow-up was 35.4 months (95% CI 1.0-56.7). Contrast-enhancing tumour was resected completely in 90 (65%) of 139 patients assigned 5-aminolevulinic acid compared with 47 (36%) of 131 assigned white light (difference between groups 29% [95% CI 17-40], p<0.0001). Patients allocated 5-aminolevulinic acid had higher 6-month progression free survival than did those allocated white light (41.0% [32.8-49.2] vs 21.1% [14.0-28.2]; difference between groups 19.9% [9.1-30.7], p=0.0003, Z test). Groups did not differ in the frequency of severe adverse events or adverse events in any organ system class reported within 7 days after surgery. INTERPRETATION: Tumour fluorescence derived from 5-aminolevulinic acid enables more complete resections of contrast-enhancing tumour, leading to improved progression-free survival in patients with malignant glioma.     

Radiosurgery versus surgery, both with adjuvant whole brain radiotherapy, for solitary brain metastases: a randomised controlled trial

Aims

This randomised non-inferiority trial was designed to assess whether radiosurgery plus adjuvant whole brain radiotherapy (RS + WBRT) is as effective as surgery plus whole brain radiotherapy (S + WBRT) for cancer patients with a solitary brain metastasis, with respect to overall survival and quality of life.

Materials and methods

Major inclusion criteria were a history of systemic cancer within 5 years and enhanced magnetic resonance imaging-confirmed solitary brain metastasis suitable for both radiosurgery and surgery. All patients were to receive WBRT (30 Gy in 10 fractions). Between February 2003 and April 2009, 40 patients were considered eligible, 22 consented to randomisation and 21 were analysed (11 RS + WBRT, 10 S + WBRT). The trial was closed early due to slow accrual.

Results

The estimated median overall survival times for RS + WBRT and S + WBRT patients were 6.2 and 2.8 months, respectively (hazard ratio 0.53, 95% confidence interval 0.20–1.43, P = 0.20). Corresponding median failure-free survival times were 3.1 and 1.7 months (P = 0.20). For 19 ‘per protocol’ patients, 2/10 in the RS + WBRT arm had distant intracranial failure (one also had local failure) and 3/9 S + WBRT patients had distant intracranial failure (no local failures). There were no grade 3–4 late radiation toxicities. Two months after starting treatment there were no significant differences in quality of life between the arms.

Conclusion

This randomised trial encountered the accrual difficulties and consequent low statistical power commonly associated with interdisciplinary studies drawing from a small eligible population, but can contribute to future overviews on the management of solitary brain metastases.     

New primary basal cell carcinomas arising in skin flaps following Mohs micrographic surgery for primary and recurrent basal cell carcinoma

Two patients developed new primary basal cell carcinomas (BCCs) in skin flaps used to reconstruct wounds that followed an earlier primary BCC and a recurrent BCC treated by Mohs micrographic surgery. Criteria for distinguishing a new primary BCC arising in a skin flap or full-thickness skin graft at a previous treatment site for BCC from a truly recurrent BCC are presented. The distinction between a new primary BCC and true tumor recurrence is important for accurate clinical assessment and may have a dramatic impact on the type of subsequent treatment. In addition, there may be less medicolegal liability in the case of a new primary BCC arising at the site of a previously treated BCC than for a BCC that is determined to be recurrent.     

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 0.61-1.10] 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 squamous-cell tumours.     

Laparoscopic surgery versus open surgery for colon cancer: short-term outcomes of a randomised trial

BACKGROUND: The safety and short-term benefits of laparoscopic colectomy for cancer remain debatable. The multicentre COLOR (COlon cancer Laparoscopic or Open Resection) trial was done to assess the safety and benefit of laparoscopic resection compared with open resection for curative treatment of patients with cancer of the right or left colon. METHODS: 627 patients were randomly assigned to laparoscopic surgery and 621 patients to open surgery. The primary endpoint was cancer-free survival 3 years after surgery. Secondary outcomes were short-term morbidity and mortality, number of positive resection margins, local recurrence, port-site or wound-site recurrence, metastasis, overall survival, and blood loss during surgery. Analysis was by intention to treat. Here, clinical characteristics, operative findings, and postoperative outcome are reported. FINDINGS: Patients assigned laparoscopic resection had less blood loss compared with those assigned open resection (median 100 mL [range 0-2700] vs 175 mL [0-2000], p<0.0001), although laparoscopic surgery lasted 30 min longer than did open surgery (p<0.0001). Conversion to open surgery was needed for 91 (17%) patients undergoing the laparoscopic procedure. Radicality of resection as assessed by number of removed lymph nodes and length of resected oral and aboral bowel did not differ between groups. Laparoscopic colectomy was associated with earlier recovery of bowel function (p<0.0001), need for fewer analgesics, and with a shorter hospital stay (p<0.0001) compared with open colectomy. Morbidity and mortality 28 days after colectomy did not differ between groups. INTERPRETATION: Laparoscopic surgery can be used for safe and radical resection of cancer in the right, left, and sigmoid colon.     

General practice vs surgical-based follow-up for patients with colon cancer: randomised controlled trial

This trial examined the optimal setting for follow-up of patients after treatment for colon cancer by either general practitioners or surgeons. In all, 203 consenting patients who had undergone potentially curative treatment for colon cancer were randomised to follow-up by general practitioners or surgeons. Follow-up guidance recommended three monthly clinical review and annual faecal occult blood tests (FOBT) and were identical in both study arms. Primary outcome measures (measured at baseline, 12 and 24 months were (1) quality of life, SF-12; physical and mental component scores, (2) anxiety and depression: Hospital Anxiety and Depression Scale and (3) patient satisfaction: Patient Visit-Specific Questionnaire. Secondary outcomes (at 24 months) were: investigations, number and timing of recurrences and deaths. In all, 170 patients were available for follow-up at 12 months and 157 at 24 months. At 12 and 24 months there were no differences in scores for quality of life (physical component score, P=0.88 at 12 months; P=0.28 at 24 months: mental component score, P=0.51, P=0.47; adjusted), anxiety (P=0.72; P=0.11) depression (P=0.28; P=0.80) or patient satisfaction (P=0.06, 24 months). General practitioners ordered more FOBTs than surgeons (rate ratio 2.4, 95% CI 1.4-4.4), whereas more colonoscopies (rate ratio 0.7, 95% CI 0.5-1.0), and ultrasounds (rate ratio 0.5, 95% CI 0.3-1.0) were undertaken in the surgeon-led group. Results suggest similar recurrence, time to detection and death rates in each group. Colon cancer patients with follow-up led by surgeons or general practitioners experience similar outcomes, although patterns of investigation vary.     

Surgical outcomes of colonic stents as a bridge to surgery versus emergency surgery for malignant colorectal obstruction: A systematic review and meta-analysis of high quality prospective and randomised controlled trials

Self-expanding metallic stent placement as a bridge to surgery has been reported as an alternative to emergency surgery for acute malignant colorectal obstruction. However, results from clinical trials and previous meta-analyses are conflicting. We carried out a meta-analysis to compare the surgical and oncological outcomes between emergency surgery and self-expanding metallic stents for malignant large bowel obstruction. Pubmed, Embase, CINAHL, Web of Science and Cochrane were searched for prospective and randomised controlled trials. The outcomes of focus included 3- and 5-year overall and disease-free survival, overall tumour recurrence, overall complication and 30-day mortality rate, length of hospital and ICU stay, overall blood loss, number of patients requiring transfusion, total number of lymph nodes harvested, stoma and primary anastomosis rate. Twenty-seven studies were included with a total of 3894 patients. There was no significant difference in terms of 3-year and 5-year disease-free and overall survival. Stenting resulted in less blood loss (mean difference −234.72, P < 0.00001) and higher primary anastomosis rate (RR 1.25, P < 0.00001). For curative cases, bridge to surgery groups had lower 30-day mortality rate (RR 0.65, P = 0.01), lower overall complication rate (RR 0.65, P < 0.0001), more lymph nodes harvested (mean difference 2.51, P = 0.005), shorter ICU stay (mean difference −2.27, P = 0.02) and hospital stay (mean difference −7.24, 95% P < 0.0001). Compared to emergency surgery, self-expanding metallic stent interventions improve short-term surgical outcomes, especially in the curative setting, but have similar long-term oncological and survival outcomes.     

Cisplatinum and Bleomycin for advanced or recurrent squamous cell carcinoma of the head and neck: a randomised factorial phase III controlled trial

Summary A phase III 2x2 factorial trial of cisplatinum and bleomycin in 116 patients with recurrent or advanced squamous cell carcinoma of the head and neck is reported.Thirty percent of patients proved to be unfit for chemotherapy, and of those treated progression of tumour was the commonest response. However, 25% of patients achieved a partial or complete response, with no significant difference in response rates between the treated arms.The median number of courses received was 1 (range 0–6) and the commonest causes for discontinuation of treatment were renal toxicity and death.Bleomycin reduced survival, but not significantly so, whereas cisplatinum prolonged median survival significantly by 10 weeks.Significant predictors of survival, in addition to treatment by cisplatinum, were age, performance status, N status, number of courses and response of the tumor.The work described in this paper was supported by the North West Cancer Research Fund     

5-Hydroxytryptamine-receptor antagonists versus prochlorperazine for control of delayed nausea caused by doxorubicin: a URCC CCOP randomised controlled trial

BACKGROUND: Despite widespread use of short-acting antagonists for the 5-hydroxytryptamine (5-HT) receptor, about 50% of patients given moderately emetogenic chemotherapy have delayed nausea. We aimed to assess whether a 5-HT-receptor antagonist was more effective than was prochlorperazine for control of delayed nausea and delayed vomiting caused by doxorubicin. METHODS: 691 patients who previously had not had chemotherapy and who were scheduled to receive doxorubicin were given a short-acting 5-HT-receptor antagonist and dexamethasone before doxorubicin (day 1), and were randomly assigned to one of three regimens for days 2 and 3: 10 mg prochlorperazine taken orally every 8 h; any first-generation 5-HT-receptor antagonist (except palonosetron) taken as standard dose intravenously or orally; or 10 mg prochlorperazine taken as needed. Nausea and vomiting were assessed by use of a home record. The primary endpoint was mean severity of delayed nausea. The secondary endpoint was quality of life. Analyses were done by intention to treat. FINDINGS: 519 (77%) of the 671 evaluable patients had delayed nausea, with a mean severity of 3.33 (95% CI 3.22-3.44). 161 (71%) of 226 patients assigned prochlorperazine every 8 h reported delayed nausea (mean severity 3.37 [3.16-3.58]), as did 179 (79%) of 226 patients assigned 5-HT-receptor antagonists (3.29 [3.09-3.48]) and 179 (82%) of 219 patients assigned prochlorperazine as needed (3.33 [3.15-3.50]); groups did not differ in mean severity (p=0.853, one-way ANOVA). Patients allocated prochlorperazine every 8 h had less delayed nausea than did those allocated 5-HT-receptor antagonists (p=0.05, t test) and those allocated prochlorperazine as needed (p=0.009, t test). INTERPRETATION: Short-acting 5-HT-receptor antagonists are no better than is prochlorperazine in control of delayed nausea caused by doxorubicin. Although fewer patients taking prochlorperazine report delayed nausea, the proportion was unacceptably high.