Patterns of Care and Outcomes of Rectal Cancer Patients from the Iowa Cancer Registry: Role of Hospital Volume and Tumor Location.

BACKGROUND: Centralization of rectal cancer surgery has been associated with high-quality oncologic care. However, several patient, disease and system-related factors can impact where patients receive care. We hypothesized that patients with low rectal tumors would undergo treatment at high-volume centers and would be more likely to receive guideline-based multidisciplinary treatment. METHODS: Adults who underwent proctectomy for stage II/III rectal cancer were included from the Iowa Cancer Registry and supplemented with tumor location data. Multinomial logistic regression was employed to analyze factors associated with receiving care in high-volume hospital, while logistic regression for those associated with ≥ 12 lymph node yield, pre-operative chemoradiation and sphincter-preserving surgery. RESULTS: Of 414 patients, 38%, 39%, and 22% had low, mid, and high rectal cancers, respectively. Thirty-two percent were > 65 years, 38% female, and 68% had stage III tumors. Older age and rural residence, but not tumor location, were associated with surgical treatment in low-volume hospitals. Higher tumor location, high-volume, and NCI-designated hospitals had higher nodal yield (≥ 12). Hospital-volume was not associated with neoadjuvant chemoradiation rates or circumferential resection margin status. Sphincter-sparing surgery was independently associated with high tumor location, female sex, and stage III cancer, but not hospital volume. CONCLUSIONS: Low tumor location was not associated with care in high-volume hospitals. High-volume and NCI-designated hospitals had higher nodal yields, but not significantly higher neoadjuvant chemoradiation, negative circumferential margin, or sphincter preservation rates. Therefore, providing educational/quality improvement support in lower volume centers may be more pragmatic than attempting to centralize rectal cancer care among high-volume centers.

Validation of 70-gene prognosis signature in node-negative breast cancer.

PURPOSE: The 70-gene prognosis signature (van't Veer et al., Nature 415(6871):530-536, 2002) may improve the selection of lymph node-negative breast cancer patients for adjuvant systemic therapy. Optimal validation of prognostic classifiers is of great importance and we therefore wished to evaluate the prognostic value of the 70-gene prognosis signature in a series of relatively recently diagnosed lymph node negative breast cancer patients. METHODS: We evaluated the 70-gene prognosis signature in an independent representative series of patients with invasive breast cancer (N = 123; <55 years; pT1-2N0; diagnosed between 1996 and 1999; median follow-up 5.8 years) by classifying these patients as having a good or poor prognosis signature. In addition, we updated the follow-up of the node-negative patients of the previously published validation-series (Van de Vijver et al., N Engl J Med 347(25):1999-2009, 2002; N = 151; median follow-up 10.2 years). The prognostic value of the 70-gene prognosis signature was compared with that of four commonly used clinicopathological risk indexes. The endpoints were distant metastasis (as first event) free percentage (DMFP) and overall survival (OS). RESULTS: The 5-year OS was 82 +/- 5% in poor (48%) and 97 +/- 2% in good prognosis signature (52%) patients (HR 3.4; 95% CI 1.2-9.6; P = 0.021). The 5-years DMFP was 78 +/- 6% in poor and 98 +/- 2% in good prognosis signature patients (HR 5.7; 95% CI 1.6-20; P = 0.007). In the updated series (N = 151; 60% poor vs. 40% good), the 10-year OS was 51 +/- 5% and 94 +/- 3% (HR 10.7; 95% CI 3.9-30; P < 0.01), respectively. The DMFP was 50 +/- 6% in poor and 86 +/- 5% in good prognosis signature patients (HR 5.5; 95% CI 2.5-12; P < 0.01). In multivariate analysis, the prognosis signature was a strong independent prognostic factor in both series, outperforming the clinicopathological risk indexes. CONCLUSION: The 70-gene prognosis signature is also an independent prognostic factor in node-negative breast cancer patients for women diagnosed in recent years.

Secondary intention healing after excision of nonmelanoma skin cancer of the head and neck: statistical evaluation of prognostic values of wound characteristics and final cosmetic results.

BACKGROUND: Most data on secondary intention healing of skin cancer defects in the head and neck are empirical and descriptive. This study statistically evaluates the prognostic value of several wound characteristics and location on the final cosmetic result of skin defects left to heal by secondary intention after tumor removal. METHODS: A chart review of all facial reconstructions using secondary intention healing performed in one center between 1992 and 2001 was undertaken. Patient and wound characteristics were analyzed. For analysis of cosmetic outcome, the most recent photographs of the scars were assessed by three independent raters using a categorical judgment scale. RESULTS: There were a total of 89 patients with 95 wounds. Forty-three percent of the wounds (41 of 95) healed with an "excellent" outcome. In the univariate analysis, the rating excellent was given more often to scars derived from wounds that were small and superficial and that were located in concave areas of the face, in particular, near the medial canthus and medial cheek. Multivariable logistic regression revealed independent associations of an excellent cosmetic outcome with wound size and contour of wound surface only. CONCLUSION: This is the first study presenting statistical evidence of what has been known empirically for a long time: wounds in concave areas of the face that are left to heal by secondary intention have a high chance of healing with an excellent cosmetic outcome, especially if these wounds are small, superficial, and located near the medial canthus and medial cheek.

PRAME expression and clinical outcome of breast cancer.

The tumour antigen PReferentially expressed Antigen of MElanoma (PRAME) is expressed in a variety of malignancies, including breast cancer. We have analysed PRAME gene expression in relation to clinical outcome for 295 primary breast cancer patients. Kaplan-Meier survival curves show a correlation of PRAME expression levels with increased rates of distant metastases and decreased overall patient survival. This correlation existed both for the entire patient group (n=295) and for the subgroup of patients (n=185) who did not receive adjuvant chemotherapy. Multivariable analysis indicated that PRAME is an independent marker of shortened metastasis-free interval in patients who did not receive adjuvant chemotherapy. PRAME expression was associated with tumour grade and negative oestrogen receptor status. We conclude that PRAME expression is a prognostic marker for clinical outcome of breast cancer, independent of traditional clinicopathological markers.

How to assess and compare the accuracy of continuous glucose monitors?

Continuous glucose monitors may be valuable tools for improving glycemic control and avoiding hypoglycemia in patients with diabetes. To this goal, sensor readings must adequately reflect the actual blood glucose, emphasizing the need for solid accuracy assessment methods for continuous glucose sensor readings. Analysis of continuous glucose data is challenging, and despite many efforts there still is no all-embracing method to overcome the obstacles in the assessment of continuous data. In this review we disclose the weaknesses of currently available methods and propose a guideline for sensor accuracy assessment and comparison. For accuracy assessment it is best to first plot the sensor readings against the reference values and draw a line of identity, visualizing the degree of agreement. Thereafter data pairs should be given in a Bland-Altman plot to detect a possible relationship between the difference and the mean. The next step is to calculate the absolute relative difference over all paired readings together and per glucose range. A possible lag time between the measurements of both methods can be detected by combined curve fitting. Finally, sensitivity and positive predictive value for detecting hypoglycemia are important indicators of the sensors' performance. For comparing the accuracy between different glucose sensors it is best to use indirect comparison against blood glucose, rather than direct comparison methods, since none of the current glucose sensors is accurate enough to be considered the reference value.

Cisplatin-DNA adduct formation in patients treated with cisplatin-based chemoradiation: lack of correlation between normal tissues and primary tumor.

PURPOSE: In this study, the formation of cisplatin-DNA adducts after concurrent cisplatin-radiation and the relationship between adduct-formation in primary tumor tissue and normal tissue were investigated. METHODS: Three intravenous cisplatin-regimens, given concurrently with radiation, were studied: daily low-dose (6 mg/m(2)) cisplatin, weekly 40 mg/m(2), three-weekly 100 mg/m(2). A (32)P-postlabeling technique was used to quantify adducts in normal tissue [white blood cells (WBC) and buccal cells] and tumor. RESULTS: Normal tissue samples for adduct determination were obtained from 63 patients and tumor biopsies from 23 of these patients. Linear relationships and high correlations were observed between the levels of two guanosine- and adenosine-guanosine-adducts in normal and tumor tissue. Adduct levels in tumors were two to five times higher than those in WBC (P<0.001). No significant correlations were found between adduct levels in normal tissues and primary tumor biopsies, nor between WBC and buccal cells. CONCLUSIONS: In concurrent chemoradiotherapy schedules, cisplatin adduct levels in tumors were significantly higher than in normal tissues (WBC). No evidence of a correlation was found between adduct levels in normal tissues and primary tumor biopsies. This lack of correlation may, to some extent, explain the inconsistencies in the literature regarding whether or not cisplatin-DNA adducts can be used as a predictive test in anticancer platinum therapy.

Stage of breast cancers found during the surveillance of women with a familial or hereditary risk.

AIM: To compare the breast cancer stages found during MG alone surveillance in women at increased risk with those detected in a program where MRI was added. METHODS: Stage results of in a retrospective MG alone study of prospectively followed patients, compared with the pooled stage results of breast cancers MG/MRI surveillance. RESULTS: One hundred and-fifty-one patients were detected with a first or contralateral breast cancer. Interval cancers were diagnosed in 56% of the BRCA1, 42% of the BRCA2 and 28% of the non-BRCA carriers. A considerable proportion of the breast cancers were detected with breast self-examination alone: 41%, 27% and 31% respectively. Nevertheless the established goals for biennial population screening were reached, except for the BRCA2 carriers, but this group was small. Comparison with pooled data from published MG/MRI surveillance studies did not show significant differences in the stages, except for the BRCA2 carriers. CONCLUSION: Breast cancers detected in a MG alone surveillance program for women at increased risk fulfill most goals set for population screening except for the BRCA2 carriers. Breast self-examination appears to be a valuable additional detection method especially for BRCA1 carriers, who are at risk of developing a highly proliferating breast cancer.

Goblet cell carcinoid of the appendix: a specific type of carcinoma.

AIMS: Goblet cell carcinoid is a poorly understood tumour of the appendix. The aim of this study was to determine whether it should be regarded as a separate entity or as a variant of classical carcinoid. METHODS AND RESULTS: The immunohistochemical expression pattern of 21 markers and the mutation status of KRas codon 12 were determined in 16 goblet cell carcinoids and compared with 14 classical carcinoids, 19 colonic adenocarcinomas and 10 appendiceal mucinous cystadeno (carcino)mas. The results were subjected to a stepwise linear discriminant analysis. Goblet cell carcinoids were significantly different from the control groups. The most important markers for discriminating between the groups were CEA (classical carcinoid versus all others), KRas mutation (present in all mucinous cystadeno (carcino)mas), beta-catenin (goblet cell carcinoid versus left sided colonic adenocarcinoma) and chromogranin (goblet cell carcinoid versus right sided colonic adenocarcinoma). Expression of Math1 and HD5 was similar in goblet cell carcinoid and colonic adenocarcinoma but absent in classical carcinoid. CONCLUSION: The results suggest that goblet cell carcinoids should be regarded as a separate entity. The formerly used term 'crypt cell carcinoma' may be more appropriate because it reflects the more aggressive clinical behaviour of these tumours as well as their greater similarity to adenocarcinomas rather than to carcinoids.

The psychological impact of annual chest X-ray follow-up in head and neck cancer.

CONCLUSION: Annual post-treatment screening of head and neck squamous cell carcinoma (HNSCC) patients for second primary lung cancer and metastatic recurrence appeared to form no major burden for head and neck cancer patients. A majority of patients regard the annual chest X-ray as a reassurance. Given these results a more intensive screening program seems psychologically justifiable for this group. OBJECTIVE: To assess the psychological impact of annual post-treatment screening for second primary lung cancer and metastases in HNSCC patients. PATIENTS AND METHODS: In a cohort of 106 patients, 68 men and 38 women, with a mean age of 56, the impact of the yearly chest radiograph was evaluated by means of a nine-item questionnaire. RESULTS: In all, 90% of the patients were in favor of annual post-treatment screening, 2% would not like to receive this screening, and 8% had no preference. A majority (98%) considered the screening as an extra medical check and 76% felt reassured. Although 21% of the patients were very nervous about the outcome of the screening, only 3% wanted to avoid the yearly chest X-ray for this reason.

The correlation of mammographic-and histologic patterns of breast cancers in BRCA1 gene mutation carriers, compared to age-matched sporadic controls.

Breast cancers in BRCA1 gene mutation carriers often have specific histologic features: grade III tumors with pushing margins. Our purpose was to compare the mammographic and histologic features of breast cancers in carriers with those in age-matched sporadic controls. The features of breast cancers in 27 BRCA1 carriers found during annual surveillance were compared to those in 107 age-matched sporadic controls. The carriers had no (classic) spiculated mammographic lesions, a high percentage of well-defined masses and hardly any masses with microcalcifications, whereas the controls had significantly fewer well-defined ones and only in 27% spiculated lesions on the mammogram. The well-defined mammographic tumors correlated in 83% of the carriers and in 70% of the controls with histologic circumscribed tumor margins. Spiculated mammographic lesions in the controls were in 90% grade I or II tumors. DCIS with or without infiltration was seen in 22% of the carriers and in 45% of the controls. In conclusion, breast cancers diagnosed in BRCA1 carriers do not have classic malignant mammographic features. A minority of the young sporadic controls show the classic malignant lesion on the mammogram. Both carriers and controls generally show a good correlation between their mammographic- and histologic tumor pattern.

Prediction of poor outcome within the first 3 days of postanoxic coma.

OBJECTIVE: To determine the optimal timing of somatosensory evoked potential (SSEP) recordings and the additional value of clinical and biochemical variables for the prediction of poor outcome in patients who remain comatose after cardiopulmonary resuscitation (CPR). METHODS: A prospective cohort study was conducted in 32 intensive care units including adult patients still unconscious 24 hours after CPR. Clinical, neurophysiologic, and biochemical variables were recorded 24, 48, and 72 hours after CPR and related to death or persisting unconsciousness after 1 month. RESULTS: Of 407 included patients, 356 (87%) had a poor outcome. In 301 of 305 patients unconscious at 72 hours, at least one SSEP was recorded, and in 136 (45%), at least one recording showed bilateral absence of N20. All these patients had a poor outcome (95% CI of false positive rate 0 to 3%), irrespective of the timing of SSEP. In the same 305 patients, neuron-specific enolase (NSE) was determined at least once in 231, and all 138 (60%) with a value >33 microg/L at any time had a poor outcome (95% CI of false positive rate 0 to 3%). The test results of SSEP and NSE overlapped only partially. The performance of all clinical tests was inferior to SSEP and NSE testing, with lower prevalences of abnormal test results and wider 95% CI of false positive rates. CONCLUSION: Poor outcome in postanoxic coma can be reliably predicted with somatosensory evoked potentials and neuron-specific enolase as early as 24 hours after cardiopulmonary resuscitation in a substantial number of patients.

The impact of the physician on the accrual to randomized clinical trials in patients with primary operable breast cancer.

Randomized clinical trials (RCT) are the best way to define optimal treatment, but the accrual rates for hardly any trials have been reported. We analyzed retrospectively the participation of patients in eight phase III multicenter RTCs. Out of a total of 738 patients treated in a single institution for operable breast cancer over a 3-year period, 455 patients (62%) were eligible for at least one of the ongoing trials. Overall, 81% of the patients were informed and 47% of the eligible patients consented to participate. The accrual was 100% to a study with an aggressive combined modality treatment arm for patients with a poor prognosis. A low accrual rate was seen in two trials: 6% in the "elderly" trial comparing tamoxifen only with mastectomy and 10% to the "axilla" trial comparing surgery with radiotherapy to the axilla. The clinicians failed to inform most of these patients about the two trials. In the literature seven of the eight trials were reported; two of them (29%) failed to accrue enough patients.

Survival after bladder-preservation with brachytherapy versus radical cystectomy; a single institution experience.

OBJECTIVE: To evaluate the long-term survival following brachytherapy and following cystectomy of patients with invasive bladder cancer treated in our institution. PATIENTS AND METHODS: Between 1988 and 2000 108 patients with solitary, organ confined T1-T2 invasive bladder cancer of < or = 5 cm were treated with a transurethral resection, and a course of external beam radiotherapy (30 Gy) followed by 40 Gy brachytherapy. The overall and disease specific survival rates of these patients are compared with those of 77 patients with T1-T2 invasive bladder cancer treated with cystectomy between 1988-2003. RESULTS: The 5/10 year overall survival rates were 62%/50% after brachytherapy and 67%/58% after cystectomy (p = 0.67). The 5/10 year disease specific survival rates were 73%/67% after brachytherapy and 72%/72% after cystectomy (p = 0.28). When adjusted for age, multiplicity, T-stage, N-stage and grade, the 5/10 year overall survival rates were 65%/53% after brachytherapy and 62%/51% after cystectomy, respectively. The adjusted disease specific survival rates were 75%/70% after brachytherapy and 66%/66% after cystectomy. CONCLUSIONS: This study does not provide evidence regarding survival against the use of bladder preservation with brachytherapy for patients with solitary, T1-T2 invasive bladder cancer of < or = 5 cm diameter, seeking bladder-sparing alternatives to radical cystectomy.

Predictive value of neonatal MRI with respect to late MRI findings and clinical outcome. A study in infants with periventricular densities on neonatal ultrasound.

PURPOSE: The aim of this study was to correlate hypoxic-ischemic white matter damage on neonatal MRI with MRI appearance and neurological outcome at the age of 1 1/2 years. PATIENTS AND METHODS: A sequential cohort of infants with periventricular densities on neonatal ultrasound was studied with neonatal MRI. Images of 46 infants with a mean gestational age of 31 weeks were obtained at a mean age of 20 days after birth and at 1 1/2 years. To establish agreement between the neonatal and follow-up MRI (general, motor, and visual scores), the weighted Cohen's kappa test was used. To establish the predictive power of neonatal MRI with respect to the neurologic indices at the age of 1 1/2 years, the sensitivity, specificity, and positive and negative predictive values were calculated. RESULTS: There was a moderately good to good agreement between the general, motor, and visual neonatal and follow-up MRI scores: weighted kappa = 0.59 (95% CI: 0.44 - 0.74), 0.82 (95% CI: 0.72 - 0.93), and 0.70 (95% CI: 0.56 - 0.84), respectively. Neonatal MRI scores provided a good prediction of the three neurological outcome measures (developmental delay, cerebral palsy, and cerebral visual impairment): sensitivity, specificity, and predictive values were high, with little difference between the three MRI scores. The 32 patients with (nearly) normal neonatal MRI scores were neurologically (nearly) normal at 1 1/2 years on all three outcome measures, whereas 8 patients with seriously abnormal neonatal MRI scores were neurologically abnormal at 1 1/2 years on all three outcome measures. CONCLUSION: Neonatal MRI is able to predict the precise localization and size of perinatal leukomalacia on follow-up MRI and provides a good prediction of neurological outcome at 1 1/2 years.

The relevance of intraventricular chemotherapy for leptomeningeal metastasis in breast cancer: a randomised study.

To assess the benefit of intraventricular chemotherapy, patients with leptomeningeal metastasis (LM) from breast cancer were randomised to treatment including intraventricular (IT) chemotherapy (n=17) or to non-intrathecal (non-IT) treatment (n=18). Appropriate systemic therapy and involved field radiation therapy (RT) were given in both arms. Intention-to-treat analysis showed neurological improvement or stabilisation in 59% of the IT and in 67% of the non-IT group, with median time to progression of 23 weeks (IT) and 24 weeks (non-IT). Median survival of IT patients was 18.3 weeks and 30.3 weeks for non-IT patients (difference 12.9 weeks; 95% Confidence Interval (CI) -5.5 to +34.3 weeks; P=0.32). Neurological complications of treatment occurred in 47% (IT) vs 6% (non-IT) (P=0.0072). In conclusion, standard systemic chemotherapy with involved field RT for LM from breast cancer is feasible. Addition of intraventricular chemotherapy does not lead to survival benefit or improved neurological response, and is associated with an increased risk of neurotoxicity.

Pseudomyxoma peritonei: a review of 62 cases.

AIM: Pseudomyxoma peritonei (PMP) is a rare disease characterized by the abundance of mucus in the abdomen without extra-peritoneal growth. METHODS: Our patients with PMP have been treated with cytoreduction and hyperthermic intraperitoneal chemotherapy since 1996. The clinical and histopathological features of PMP and the relation of these features with disease-free interval and survival were assessed. RESULTS: Sixty-two patients with PMP (24 M/38 F) were studied. Adenomatous mucosal changes were present in 31 patients. In females, the ovaries were normal in 5 patients and pseudomyxoma ovarii was present in 20 patients. Patients with minimal atypia and with 1% focal proliferation or less (n=38) had a better survival (p=0.0008) than those with more focal proliferation (n=14). CONCLUSION: In most patients with PMP the appendix is affected; in females the ovaries are usually also involved. Focal proliferation appears to be a prognostic factor.

[The prevalence of use of restraints in a Dutch teaching hospital. An exploration in two wards]. / De prevalentie van vrijheidsbeperkende middelen in een academisch ziekenhuis. Een oriënterende studie op twee afdelingen.

UNLABELLED: The use of restraints in The Netherlands has mainly been studied in psychiatric, geropsychiatric, elderly, and retarded persons. No study is known on this subject in Dutch general hospitals. The objective of our study was to determine the prevalence of the use of physical restraints and side-rails and factors associated with restraint and side-rail use in a Dutch teaching hospital. On two acute care wards (internal medicine and neurology) 208 consecutively admitted patients were personally observed for the use of side-rails in February 2001. The use of restraints was abstracted from the nursing records. RESULTS: Of the patients 34% at least one time had side-rails raised, and 9% was subjected to physical restraints at some point during hospitalisation. In the logistic model, the neurology ward (OR: 4; 95% CI: 2-10), age of 80 or over (OR 12; 95% CI 3-51), stroke (OR 7; 95% CI 2-24), disorientation (OR: 9; 95% CI: 3-29) and restlessness or agitation (OR: 68; 95% CI: 7-596) were found to be independently associated with use of side-rails. For the use of restraints restlessness or agitation (OR: 125; 95% CI: 18-856) was found to be an independent factor. Differences in study design make comparisons between institutions and countries difficult.

Heat penetration in locally applied hyperthermia in the abdomen during intra-operative hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) with mitomycin C has been applied following cytoreductive surgery for various peritoneal surface malignancies. The aim of this study was to evaluate heat penetration in the abdomen during 10 HIPEC procedures. MATERIALS AND METHODS: Temperature measurements were taken at 5 levels through the abdominal wall. Core temperature and room temperature were also measured. The relationships between the temperature gradient and room or core temperature were studied. RESULTS: At the start of perfusion, the temperature was estimated on average to be 40.6 degrees C at the first level, then it decreased by 1.7 degrees C (SD 1.0 degree C, p = 0.0001) in the first mm. In outward direction, it decreases by a further 1.5 degrees C per cm (SD 0.3 degree C/cm, p < 0.0001). The core temperature influenced the temperature gradient; the room temperature was not found to be a significant factor. At the end of perfusion, the temperature is estimated on average to be 40.1 degrees C at the first level, then it decreased by 0.8 degree C (SD 0.7 degree C, p = 0.011) in the first mm. In an outward direction, it decreased by a further 1.7 degrees C per cm (SD 0.4 degree C/cm, p = 0.0001). No evidence of an association between the temperature gradient and the room temperature or the core temperature was observed. CONCLUSION: Hyperthermia used during HIPEC procedures has a limited penetration depth. The slope in temperature seems to be related to the core temperature.

High response rates and lasting remissions after low-dose involved field radiotherapy in indolent lymphomas.

PURPOSE: To study the response rates and duration of response after low-dose (4 Gy) involved field radiotherapy (LD-IF-RT) in patients with recurrent indolent lymphoma. PATIENTS AND METHODS: A total of 109 assessable patients (304 symptomatic sites) were irradiated (53 males and 56 females; median age, 62 years; range, 35 to 93), including 98 patients with follicular lymphoma (43 grade 1 and 55 grade 2), nine extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue-type and two patients with lymphoplasmacytoid lymphoma. Bulky disease (> or =5 cm) was present in 52% of all patients. A median of two prior regimens (range, 0 to 11) preceded LD-IF-RT. The median time since diagnosis was 41 months (range, 2 to 358 months). Time to (local) progression was calculated according to the Kaplan-Meier method. Differences in response rates between treatments within the same patient were compared using the McNemar test. RESULTS: The overall response rate was 92%; complete response was reached in 67 patients (61%), partial response in 34 patients (31%), stable disease in six patients (6%), and progressive disease in two patients (2%). The median time to progression was 14 months. The median time to local progression was 25 months. The 67 patients with complete response showed a median time to progression of 25 months and a median time to local progression of 42 months. None of the factors studied (age, sex, follicular lymphoma grade, radiotherapy regimen, number of previous regimens and previous history, number of positive sites or largest lymphoma diameter) were found to be related to response rate. CONCLUSION: LD-IF-RT is a valuable asset in the management of patients with follicular lymphoma and should be considered in patients with recurrent disease.

Marker genes for circulating tumour cells predict survival in metastasized breast cancer patients.

We investigated the prognostic significance of circulating breast cancer cells in peripheral blood detected by quantitative RT-PCR of marker genes in patients with advanced breast cancer. Blood samples from 94 breast cancer patients with metastatic disease (M1) were examined for circulating tumour cells by studying the mRNA expression of CK19, p1B, PS2 and EGP2 by real-time PCR. Using a score function, developed for predicting circulating tumour cells by quadratic discriminant analysis (QDA), the four expression levels were combined into a single discriminant value. Tumour cells were present in 24 out of 94 (31%) of the patients. In 77% (72 out of 94) of the patients distant metastatic disease was localised in the bone. In 36% (26 out of 72) of the patients with bone metastases at the time of blood sampling, a positive QDA for the four genes was found, in contrast to only 14% (three out of 22) without bone involvement. Overall survival rates by Kaplan-Meier revealed no prognostic effect for the presence of bone metastases (P=0.93). However, patients with a positive QDA value did have a progression-free survival at 1 year of 3% and overall survival at 2 years of 17%, against 22 and 36% for patients with a negative QDA value (P=0.015 and 0.0053, respectively). Breast cancer patients with metastatic disease have a significantly worse progression-free and overall survival when circulating tumour cells can be detected in their peripheral blood.