Predictors of local recurrence after treatment of ductal carcinoma in situ - A meta-analysis

lBACKGROUND. Management of patients with ductal carcinoma in situ (DCIS) is a dilemma, as mastectomy provides nearly a 100% cure rate but at the expense of physical and psychologic morbidity. It would be helpful if we could predict which patients with DCIS are at sufficiently high risk of local recurrence after conservative surgery (CS) alone to warrant postoperative radiotherapy (RT) and which patients are at sufficient risk of local recurrence after CS + RT to warrant mastectomy. The authors reviewed the published studies and identified the factors that may be predictive of local recurrence after management by mastectomy, CS alone, or CS + RT. METHODS. The authors examined patient, tumor, and treatment factors as potential predictors for local recurrence and estimated the risks of recurrence based on a review of published studies. They examined the effects of patient factors (age at diagnosis and family history), tumor factors (sub-type of DCIS, grade, tumor size, necrosis, and margins), and treatment (mastectomy, CS alone, and CS + RT). The 95% confidence intervals (CI) of the recurrence rates for each of the studies were calculated for subtype, grade, and necrosis, using the exact binomial; the summary recurrence rate and 95% CI for each treatment category were calculated by quantitative meta-analysis using the fixed and random effects models applied to proportions. RESULTS, Meta-analysis yielded a summary recurrence rate of 22.5% (95% CI = 16.9-28.2) for studies employing CS alone, 8.9% (95% CI = 6.8-11.0) for CS + RT, and 1.4% (95% CI = 0.7-2.1) for studies involving mastectomy alone. These summary figures indicate a clear and statistically significant separation, and therefore outcome, between the recurrence rates of each treatment category, despite the likelihood that the patients who underwent CS alone were likely to have had smaller, possibly low grade lesions with clear margins. The patients with risk factors of presence of necrosis, high grade cytologic features, or comedo subtype were found to derive the greatest improvement in local control with the addition of RT to CS. Local recurrence among patients treated by CS alone is approximately 20%, and one-half of the recurrences are invasive cancers. For most patients, RT reduces the risk of recurrence after CS alone by at least 50%. The differences in local recurrence between CS alone and CS + RT are most apparent for those patients with high grade tumors or DCIS with necrosis, or of the comedo subtype, or DCIS with close or positive surgical margins. CONCLUSIONS, The authors recommend that radiation be added to CS if patients with DCIS who also have the risk factors for local recurrence choose breast conservation over mastectomy. The patients who may be suitable for CS alone outside of a clinical trial may be those who have low grade lesions with little or no necrosis, and with clear surgical margins. Use of the summary statistics when discussing outcomes with patients may help the patient make treatment decisions. Cancer 1999;85:616-28. (C) 1999 American Cancer Society.

Treatment implications of a positive sentinel lymph node biopsy for patients with early-stage breast carcinoma

BACKGROUND. Sentinel lymph node (SLN) mapping and biopsy is emerging as an alternative to axillary lymph node dissection (ALND) in determining the lymph node status of patients with early-stage breast carcinoma. The hypothesis of the technique is that the SLN is the first lymph node in the regional lymphatic basin that drains the primary tumor. Non-SLN (NSLN) metastasis in the axilla is unlikely if the axillary SLN shows no tumor involvement, and, thus, further axillary interference may be avoided. However, the optimal treatment of the axilla in which an SLN metastasis is found requires ongoing evaluation. The objectives of this study were to evaluate the predictors for NSLN metastasis in the presence of a tumor-involved axillary SLN and to examine the treatment implications for patients with early-stage breast carcinoma. METHODS. Between June 1998 and May 2000, 167 patients participated in the pilot study of SLN mapping and biopsy at Westmead Hospital. SLNs were identified successfully and biopsied in 140 axillae. All study patients also underwent ALND. The incidence of NSLN metastasis in the 51 patients with a SLN metastasis was correlated with clinical and pathologic characteristics. RESULTS. Of 51 patients with a positive SLN, 24 patients (47%) had NSLN metastases. The primary tumor size was the only significant predictor for NSLN involvement. NSLN metastasis occurred in 25% of patients (95% confidence interval [95%CI], 10-47%) with a primary tumor size less than or equal to 20 mm and in 67% of patients (95%CI, 46-83%) with a primary tumor size > 20 mm (P = 0.005). The size of the SLN metastasis was not associated significantly with NSLN involvement. Three of 7 patients (43%) with an SLN micrometastasis (< 1 mm) had NSLN involvement compared with 38 of 44 patients (48%) with an SLN macrometastasis (greater than or equal to 1 mm). CONCLUSIONS. The current study did not identify a subgroup of SLN positive patients in whom the incidence of NSLN involvement was low enough to warrant no further axillary interference. At present, a full axillary dissection should be performed in patients with a positive SLN. (C) 2001 American Cancer Society.

Surgical caseload and outcomes for women with invasive breast cancer treated in Western Australia

We have assessed the outcomes for all women diagnosed with invasive breast cancer in Western Australia during 1989, 1994 and 1999, and compared the results for surgeons who treat 20 or more cases per year with those of surgeons who treat less. Women treated by high caseload surgeons were more likely to retain their breast (53.3% vs. 36.7%, p < 0.001), have adjuvant radiotherapy (50.0% vs. 30.6%, p < 0.001), and be alive after 4 years (1989, 86% vs. 82%; 1994, 89% vs. 84%; 1999, 90% vs. 79%, HR 0.71, p = 0.03). Adjusting for age and year of diagnosis, women were not more likely to be treated with adjuvant chemotherapy (29.2% vs. 20.9%, p = 0.28). In 1989 35% of women were treated by high caseload surgeons. By 1999 this had risen to 82%. The results confirm that women treated by high caseload surgeons have better outcomes. (C) 2004 Elsevier Ltd. All rights reserved.

Second primary oesophageal cancer following radiation for breast cancer

The management of 12 women who presented with a second primary oesophageal cancer following radiotherapy for breast cancer was reviewed. It was concluded that nine cases fitted the classical description of a radiation-induced malignancy. Most cases were successfully managed with combined modality therapy in spite of their previous radiotherapy. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Total pharyngolaryngectomy for squamous cell carcinoma of the hypopharynx: A review

Objectives. To evaluate our experience with total pharyngolaryngectomy in the treatment of hypopharyngeal squamous cell carcinoma. Study Design: Retrospective analysis of consecutively treated patients in an academic otolaryngology, head and neck department. Methods. One hundred eighty patients who had total pharyngolaryngectomy performed for hypopharyngeal carcinoma were included in this study. Patients with a history of previous head and neck cancer were excluded. Clinicopathologic parameters were recorded and survival calculated using the Kaplan-Meier method. Results. One hundred sixty-two (90%) of the patients were male, and the patients had a mean age of 62 years. The majority (91%) of patients had advanced overall clinical stage disease (stage 3,4). Thirty-one (17.8%) and 43 (24%) patients developed locoregional and metastatic disease recurrence, respectively. The 2- and 5-year disease-specific survival rates were 72% and 52%, respectively. Advanced nodal stage, perineural invasion, lymphovascular invasion, and positive margins were predictors of poor survival on univariate analysis, and lymphovascular invasion was an independent prognostic factor on multivariate analysis. Conclusion: Surgery and postoperative radiotherapy remains the treatment against which other modalities should be compared for advanced stage hypopharyngeal squamous cell carcinoma.

Postoperative vaginal vault brachytherapy for node-negative Stage II (occult) endometrial carcinoma

Objective. The aim of this study is to look at the efficacy of extended surgical staging and postoperative vaginal vault brachytherapy in patients with Stage II (occult) endometrial carcinoma. Methods. Between January 1989 and December 1997, there were 30 patients with Stage II (occult) endometrial carcinoma who received postoperative vaginal vault brachytherapy as the only adjuvant treatment. The study group consisted of 15 of these patients who had extended surgical staging (including lymphadenectomy). Results. At a median follow-up of 36 months (range 17 to 113 months), there has been no recurrence. There were no major complications from surgery. Only 1 patient had mild rectal bleeding following vaginal vault brachytherapy and there were no grade 3 or 4 bowel toxicities. Conclusions. Extended surgical staging and postoperative vaginal vault brachytherapy for Stage II (occult) endometrial carcinoma is associated with minimal morbidity and excellent survival. (C) 2001 Academic Press.

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.

Audit of postoperative chemoradiotherapy as adjuvant therapy for resected gastroesophageal adenocarcinoma: An Australian multicentre experience

Background: Improved disease free and overall survivals were seen in curatively resected patients with gastric and gastroesophageal adenocarcinoma treated with the Intergroup 0116 (INT 0116) protocol of postoperative adjuvant chemoradiotherapy compared to surgery alone. This protocol has not been widely adopted in Australian centres because of perceived risks of toxicity. Methods: We reviewed the case records from 45 consecutive patients treated between May 1998 and August 2003 with the INT 0116 protocol and variations at five Australian institutions. The median age was 61.5 years (range 38-79). Twenty-nine patients had gastric and 12 had gastroesophageal junction primaries. All patients had attempted curative resection, however, seven had involved microscopic margins (R1 resection). Thirty-five had regional node involvement and none had evidence of distant metastasis. Results: The overall National Cancer Institute - Common Toxicity Criteria (NCI-CTC) version 2.0 grade 3 and grade 4 toxicity rates for all patients were 37.8% and 4.4%, respectively. There were no treatment related deaths. Gastrointestinal grade 3 toxicity was observed in 20% of patients, while haematologic grade 3 and 4 toxicity was observed in 17.8%. Toxicities experienced led to chemotherapy dose reductions in 22 patients and dose delay in 11 patients. Seven patients had a delay in radiotherapy and two did not proceed with radiotherapy. At a median follow up of 16 months (range 5-35) from surgery, 28 patients have relapsed (six with local recurrence alone) with 22 deaths occurring, all but one caused by cancer. Conclusion: The INT 0116 protocol is a safe and feasible schedule in a multicentre setting with an acceptable rate of toxicity and is an appropriate adjuvant treatment option for high-risk resected gastroesophageal adenocarcinoma.

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.

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.

Using postoperative cardiac troponin-I (cTi) levels to detect myocardial ischaemia in patients undergoing vascular surgery

Background, Cardiac complications occur commonly in vascular surgery patients. Diagnosis of cardiac complications is difficult because of the inaccuracies associated with traditional cardiac enzyme measurements. CTi, a highly sensitive and specific marker of myocardial injury, may be able to detect cardiac complications with greater ease and accuracy. Methods. The study prospectively examined 100 consecutive patients who underwent major vascular surgery between 6/7/98 and 31/12/98 at the Royal Brisbane Hospital. Daily measurements of cTi, creatine kinase (CK), creatine kinase MB (CKMB), CKMB index, renal function and haemoglobin were taken for three postoperative days. One postoperative electrocardiograph (ECC) was taken. An extensive cardiac history was taken. Intraoperative and postoperative events were recorded. Findings. There were 100 patients, 18 patients (18%) had a cTi elevation. On the basis of classical diagnostic criteria, 15 patients (15%) suffered one or more cardiac complication (either myocardial infarction, congestive cardiac failure, unstable angina or atrial fibrillation), One patient (1%) who had a cTi elevation died. CTI elevation occurred in five patients (5%) who were not diagnosed with cardiac complications based on traditional criteria. Despite not meeting specific diagnostic criteria for cardiac complications, all patients showed signs and symptoms that could be attributed to myocardial ischaemia, Every patient who developed congestive cardiac failure or atrial fibrillation had a cTi elevation. A Chi-square analysis revealed a significant association between cTi elevation and postoperative cardiac complications. Four variables contributed small but significant amounts of unique variance to the prediction of peak cTi on linear regression analysis. These were peak CKMB index, postoperative congestive cardiac failure, postoperative chest pain and postoperative cardiac complications. Conclusions. Routine cTi monitoring of postoperative vascular patients would be an effective and inexpensive way to detect patients with cardiac complications. The relationship between postoperative cTi elevation and significant coronary artery disease remains to be shown, (C) 2001 The international Society for Cardiovascular Surgery. Published by Elsevier Science Ltd. All rights reserved.

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.

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)