Chest wall resection for adult soft tissue sarcomas and chondrosarcomas: analysis of prognostic factors.

BACKGROUND: Wide resection with tumor-free margins is necessary in soft-tissue sarcomas to minimize local recurrence and to contribute to long-term survival. Information about treatment outcome and prognostic factors of adult sarcoma requiring chest wall resection (CWR) is limited. METHODS: Sixty consecutive patients were retrospectively studied for overall survival (OS), local recurrence-free survival (LRFS), and disease-free survival (DFS). Twenty-one prognostic factors regarding survival were analyzed by univariate analysis using the Kaplan-Meier method and the log-rank test. RESULTS: With a median survival of 2.5 years, the OS was 46% (33%) at 5 (10) years. The LRFS was 64% at 5 and 10 years, and the DFS was 30% and 25% at 5 and 10 years. At the end of the study period, 26 patients (43%) were alive, of which 20 patients (33%) had no evidence of disease and 40 patients (67%) had no chest wall recurrence. In the group of 9 patients with a radiation-induced soft-tissue sarcoma, the median survival was 8 months. Favorable outcome in univariate analysis in OS and LRFS applied for the low-grade sarcoma, bone invasion, and sternal resection. For OS only, age below 60 years and no radiotherapy were significant factors contributing to an improved survival. CWR was considered radical (R0) at the pathological examination in 43 patients. There were 52 patients with an uneventful recovery. There was one postoperative death. CONCLUSIONS: CWR for soft-tissue sarcoma is a safe surgical procedure with low morbidity and a mortality rate of less than 1%. With proper patient selection acceptable survival can be reached in a large group of patients. Care must be given to patients with radiation-induced soft-tissue sarcoma who have a significantly worse prognosis.

Prognostic factors in 77 curative chest wall resections for isolated breast cancer recurrence.

BACKGROUND: Full-thickness chest wall resection (CWR) is the preferred treatment for breast cancer (BC) patients with extensive isolated locoregional recurrence. It remains a challenge to select patients that will benefit most from this treatment. The aim of this study was to define prognostic factors in patients who undergo CWR with curative intent. METHODS: BC patients who underwent a CWR with curative intent for recurrence of disease between 1986 and 2006 were included in this retrospective study. Twenty-two factors were studied in a univariate analyses, and multivariate stepwise Cox regression analyses was performed. RESULTS: Seventy-seven patients were included in this study. The 5-year overall survival was 25%. There was one postoperative death. Univariate analyses showed that three prognostic factors were significantly correlated with OS and disease-free survival: (1) interval between primary treatment and CWR (P = .02 and .004, respectively), (2) chemotherapy for recurrence (P = .05 and .05, respectively), and (3) resection specimen smaller than 150 cm2 (P = .03 and .009, respectively). An interval lasting >10 years between primary treatment and CWR remained statistically significantly correlated with better overall survival and disease-free survival after multivariate analyses. CONCLUSIONS: CWR is a safe treatment in patients who have isolated extensive BC recurrence. The best survival outcome was seen in patients after a disease-free interval of >or= 10 years. Existing data show that adjuvant radiotherapy and adjuvant hormone therapy for estrogen-positive tumors improves overall survival. Neoadjuvant chemotherapy may be considered in individual patients.

Quality of life of oropharyngeal cancer patients treated with brachytherapy.

Brachytherapy (BT) is a highly conformal (accurate clinical target volume delineation, no planning target volume margin) radiotherapy technique; the radioactive source, guided by afterloading catheters, is implanted into the heart of the tumor. The localized high dose of radiation enables high tumor control rates and, because of rapid dose fall-off, sparing of the adjacent normal tissues. At the Erasmus Medical Center, excellent results were observed: 5-year local regional control of 84%, 5-year disease-free survival of 59%, and 5-year overall survival of 64%. Therefore, in the case of moderately sized tumors, for well-trained, skillful physicians, BT is the therapy of choice (if technically feasible). However, side effects are not totally negligible, partly because of the cumulative dose of BT and the first series of 46/2 Gy. However, patients treated with BT still have a better swallowing-related quality of life, which might improve further if summation of BT and the first series of 46/2 Gy, as well as autocontouring of the neck levels, are realized. So far, there is no significant relationship between the -quality index of the BT implants and local control/overall survival and/or quality of life.

Correlation between circulating endothelial cell counts and plasma thrombomodulin levels as markers for endothelial damage.

Increased numbers of circulating endothelial cells (CEC) in peripheral blood have been observed in diseases with vascular involvement, and are considered a promising surrogate marker for vascular damage. It was the objective of this study to evaluate the correlation between putative soluble markers of endothelial injury, activation, and endothelial proliferation, and absolute numbers of CEC. CEC were evaluated in 125 healthy donors and 40 patients with metastatic carcinoma by automated CD146 driven immunomagnetic isolation. Plasma concentrations of E-selectin, endoglin, and thrombomodulin were assessed by ELISA in plasma obtained from 40 healthy donors and 40 patients. CEC numbers in blood were positively correlated with plasma thrombomodulin levels, but not with levels of E-selectin and endoglin. Multivariate analysis demonstrated a significant increase in CEC numbers with age. The levels of plasma biomarkers were not influenced by age. Higher levels of thrombomodulin and E-selectin were observed in males when compared to females. In conclusion, CEC numbers correlate positively with plasma levels of thrombomodulin.

Results of fiberoptic endoscopic evaluation of swallowing vs. radiation dose in the swallowing muscles after radiotherapy of cancer in the oropharynx.

BACKGROUND AND PURPOSE: Dysphagia is a serious complaint but frequently underreported. This paper assesses for oropharyngeal cancer (OPC) the relationship between the dose received by the swallowing structures, and the findings of a fiberoptic endoscopic evaluation of the swallowing process (FEES). MATERIALS AND METHODS: Between 2000 and 2005, 60 of 67 OPC patients local-regionally NED for at least one year following treatment responded to three types of QoL questionnaires; i.e. Performance Status Scales, EORTC H&N35, and M.D. Anderson Dysphagia Inventory. Twenty-four patients agreed to the FEES procedure. The main swallowing muscles were delineated, with the mean dose per muscle calculated using the original 3D CT-based treatment plans. Regression analysis was performed between FEES variables and the doses in the different swallowing muscles and the dysphagia related questionnaires. RESULTS: A significant relationship was found between the results of FEES and the mean dose in the superior constrictor muscle (SCM). Some of the subjective dysphagia complaints were significantly correlated with the FEES variables in this retrospectively study. CONCLUSION: A higher dose in the SCM generally results in worsening of the findings obtained by the FEES examination.

Longitudinal changes in quality of life and costs in long-term survivors of tumors of the oropharynx treated with brachytherapy or surgery.

PURPOSE: Based on earlier studies we were interested in finding out if longitudinal assessment of quality of life (QoL) and costs in long-term survivors of oropharyngeal cancers treated with external beam radiation therapy and brachytherapy (BT) or surgery and postoperative radiotherapy showed a change in QoL over the years. Besides, we were curious to know how much the costs per life year and the QALY would be for this patient group. METHODS AND MATERIALS: Performance status scales: eating in public, understandability of speech, normalcy of diet, xerostomia and ability to swallow were determined in 2003 and 2005. In 2005, the responses to EORTC QLQ-C30, EORTC H&N35, and the Euroqol questionnaire were also measured. Costs and quality-adjusted life years (QALYs) were calculated. RESULTS: Eating in public, understandability of speech, and normalcy of diet significantly differed in favor of BT. Surgical patients experienced more speech, teeth, and mouth-opening problems. Mean costs and QALYs for BT were 16,112 euros and 56,060 euros and for surgery 26,590 euros and 93,275 euros, respectively. CONCLUSIONS: QoL scores don't change over time. Due to the number of admission days, surgery is more costly. Difference in costs for QALYs in favor of BT was observed.

Can IMRT or brachytherapy reduce dysphagia associated with chemoradiotherapy of head and neck cancer? The Michigan and Rotterdam experiences.

PURPOSE: Dysphagia is a major late complication of intensive chemoradiotherapy of head and neck cancer. The initial clinical results of intensity-modulated radiotherapy (IMRT), or brachytherapy, planned specifically to reduce dysphagia are presented. PATIENTS AND METHODS: Previous research at Michigan University has suggested that the pharyngeal constrictors and glottic and supraglottic larynx are likely structures whose damage by chemo-RT causes dysphagia and aspiration. In a prospective Michigan trial, 36 patients with oropharyngeal (n = 31) or nasopharyngeal (n = 5) cancer underwent chemo-IMRT. IMRT cost functions included sparing noninvolved pharyngeal constrictors and the glottic and supraglottic larynx. After a review of published studies, the retropharyngeal nodes at risk were defined as the lateral, but not the medial, retropharyngeal nodes, which facilitated sparing of the swallowing structures. In Rotterdam, 77 patients with oropharyngeal cancer were treated with IMRT, three dimensional RT, or conventional RT; also one-half received brachytherapy. The dysphagia endpoints included videofluoroscopy and observer-assessed scores at Michigan and patient-reported quality-of-life instruments in both studies. RESULTS: In both studies, the doses to the upper and middle constrictors correlated highly with the dysphagia endpoints. In addition, doses to the glottic and supraglottic larynx were significant in the Michigan series. In the Rotterdam series, brachytherapy (which reduced the doses to the swallowing structures) was the only significant factor on multivariate analysis. CONCLUSION: The dose-response relationships for the swallowing structures found in these studies suggest that reducing their doses, using either IMRT aimed at their sparing, or brachytherapy, might achieve clinical gains in dysphagia.

Dysphagia disorders in patients with cancer of the oropharynx are significantly affected by the radiation therapy dose to the superior and middle constrictor muscle: a dose-effect relationship.

PURPOSE/OBJECTIVE: To assess the relationship between the radiation therapy (RT) dose received by the muscular components of the swallowing (sw) apparatus and - dysphagia related - quality of life (QoL) in oropharyngeal cancer. MATERIALS/METHODS: Between 2000 and 2005, 81 patients with SCC of the oropharynx were treated by 3DCRT or IMRT, with or without concomitant chemotherapy (CHT); 43 out of these 81 patients were boosted by brachytherapy (BT). Charts of 81 patients were reviewed with regard to late dysphagia complaints; 23% experienced severe dysphagia. Seventeen patients expired. Fifty-six out of 64 (88%) responded to quality of life (QoL) questionnaires; that is, the Performance Status Scales of List, EORTC H&N35, and the M.D. Anderson Dysphagia Inventory. The superior (scm), middle (mcm), and inferior constrictor muscle (icm), the cricopharyngeus muscle and the inlet of the esophagus, are considered of paramount importance for swallowing. The mean dose was calculated in the muscular structures. Univariate analysis and multivariate analysis were performed using the proportional odds model. RESULTS: Mean follow-up was 18 months (range 2-34) for IMRT, and 46 months for 3DCRT (range 2-72). At 3-years, a LRC of 84%, DFS of 78% and OS of 77% were observed. A significant correlation was observed between the mean dose in the scm and mcm, and severe dysphagia complaints (univariate analysis). A steep dose-effect relationship, with an increase of the probability of dysphagia of 19% with every additional 10 Gy, was established. In the multivariate analysis, BT (dose) was the only significant factor. CONCLUSION: A dose-effect relationship between dose and swallowing complaints was observed. One way to improve the QoL is to constrain the dose to be received by the swallowing muscles.

Course and prognosis of childhood epilepsy: 5-year follow-up of the Dutch study of epilepsy in childhood.

Knowing the prognosis of epilepsy will undoubtedly influence the treatment strategy. This study aimed to define the prospects of newly diagnosed childhood epilepsy, assess the dynamics of its course, identify relevant variables and develop models to assess the individual prognosis. Four hundred and fifty-three children with newly diagnosed epilepsy were followed for 5 years. Terminal remission at 5 years (TR5) was compared with terminal remission at 2 years (TR2) and with the longest remission during follow-up. Variables defined at intake and at 6 months of follow-up were analysed for their prognostic relevance. In multivariate analyses, combinations of variables were tested to develop reliable models for the calculation of the individual prognosis. Data on treatment, course during follow-up and epilepsy syndromes were also studied. Three hundred and forty-five children (76%) had a TR5 >1 year, 290 (64%) >2 years and 65 (14%) had not had any seizure during the entire follow-up. Out of 108 children (24%) with TR5 <1 year, 27 were actually intractable at 5 years. Medication was started in 388 children (86%). In 227 of these (59%), anti-epileptic drugs (AEDs) could be withdrawn. A TR5 >1 year was attained by 46% on one AED, on the second AED by 19%, and by 9% on all additional AED regimes. Almost 60% of the children treated with a second or additional AED regime had a TR5 >1 year. Variables predicting the outcome at intake were aetiology, history of febrile seizures and age. For intake and 6-month variables combined, sex, aetiology, postictal signs, history of febrile seizures and TR at 6 months were significant. The model derived from intake variables only predicted TR5 <1 year correctly in 36% and TR5 >1 year in 85% (sensitivity 0.65, specificity 0.64). The corresponding values for the model derived from intake and 6-month variables were 43 and 88% (sensitivity 0.69, specificity 0.71). The course of the epilepsy was constantly favourable in 51%, steadily poor in 17%, improving in 25% and deteriorating in 6%. Intractability was in part only a temporary phenomenon. The outcome at 5 years in this cohort of children with newly diagnosed epilepsy was favourable in 76%; 64% were off medication at that time. Almost a third of the children had a fluctuating course; improvement was clearly more common than deterioration. After failure of the first AED, treatment can still be successful. Models predicting the outcome have fewer misclassifications when predicting a long terminal remission than when predicting continuing seizures.

Role of endocavitary brachytherapy with or without chemotherapy in cancer of the nasopharynx.

PURPOSE: We previously reported our preliminary experience with nasopharyngeal cancer boosted after 60-70 Gy external beam radiotherapy (EBRT) by fractionated endocavitary brachytherapy (ECBT) to cumulative doses of 78-82 Gy. As for Stage III-IVB disease, cisplatin (CDDP)-based neoadjuvant chemotherapy (CHT) was given. The aim of the present study was to define the role of ECBT more accurately. METHODS AND MATERIALS: Ninety-one patients with primary nasopharyngeal cancer, staged according to the 1997 UICC/AJCC classification system, were treated between 1991 and 2000 with 60-70 Gy external beam radiotherapy and 11-18 Gy ECBT. Of the 91 patients, 21 were treated in conjunction with CHT and 70 without CHT. Tumors were subdivided into undifferentiated (UD) and well, moderately, and poorly differentiated (WMP-D) subtypes. Treatment results were analyzed for local control (LC), disease-free survival (DFS), freedom from distant metastasis, and overall survival (OS). RESULTS: A univariate and multivariate Cox regression analysis found stage, treatment period, age, and grade significant for LC, DFS, and OS. At 2 years, for Stage I-IIB (1st period, 1991-1996), the LC, DFS, and OS were 96%, 88%, and 80%, respectively, vs. 65%, 46%, and 52% for Stage III-IVB. For the 2nd treatment period (1996-2000; CHT for Stage III-IVB), the LC, DFS, and OS at 2 years was 100%, 90%, and 61% (Stage I-IIB), respectively, vs. 86%, 74%, and 66% (Stage III-IVB). Three prognostic groups (PGs) were constructed. For the 1991-1996 period, at 2 years, patients in the good PG (UD Stage I-IIB disease) had 100% LC and 92% OS; those in the intermediate PG (UD Stage III-IVB or WMP-D Stage I-IIB), had 94% LC and 71% OS; and those in the poor PG (WMP-D Stage III-IVB) had 47% LC and 40% OS. For the 1996-2000 period, at 2 years, the good PG had 100% LC and 88% OS; the intermediate PG had 100% LC and 64% OS; and the poor PG had 71% LC and 60% OS. CONCLUSION: For Stage I-IIB disease treated between 1991 and 2000, at 3 years, the LC and OS was 97% and 67%, respectively. The results with 77-81 Gy without CHT warrant EBRT combined with ECBT to remain our standard of care for Stage I-IIB disease. For N2-3 and/or T3-4 tumors, in addition to high doses of RT, neoadjuvant CHT was administered as of 1996. For the 1991-2000 period, at 3 years, the LC was 86% and the OS was 72% with CHT, with little extra morbidity; they were 68% and 35% without CHT. Because of better target coverage and sparing, T3-4 tumors are currently boosted by stereotactic RT to 81.2 Gy.

Optimisation of conformal radiation therapy by intensity modulation: cancer of the larynx and salivary gland function.

PURPOSE: Prevention of damage to critical normal tissues is of paramount importance for the quality of life of patients irradiated for cancers in the head and neck. The purpose of this paper was to evaluate the parotid gland sparing 3D conformal radiation therapy technique (3DCRT) in a prospective study in node negative cancer of the larynx. MATERIALS AND METHODS: Twenty-six patients with node negative squamous cell cancer of the larynx were irradiated by a 3DCRT technique (class solution) to both sides of the neck (elective dose 46 Gy to levels II, III and IV) and primary tumour (70 Gy). Dose distributions of the major salivary glands were correlated with objective (stimulated whole saliva flow, WS) and subjective (questionnaire; visual analogue scale, VAS) salivary gland function. Apart from the clinically used 3DCRT technique, in order to optimise 3DCRT dose distributions, intensity modulated (IMRT) treatment plans were generated for the same patient population. Dose-volume histograms of 3DCRT and IMRT treatment plans were analysed and compared. RESULTS: For the 26 patients irradiated with the 3DCRT class solution technique: VAS scores and questionnaires reached their nadir 3 months post-radiotherapy; WS reached its nadir 6 months post-radiotherapy. WS flow rates improved significantly, but never normalised; 2 years post-treatment WS measurements were 48% of the pre-treatment values. VAS scores deteriorated during ERT from 0 pre-treatment to 6.1 immediately post-treatment. Compared to pre-treatment, questionnaires were answered affirmative by increasing numbers of patients. For all patients, IMRT treatment plans resulted in a significant reduction of the dose delivered to the parotid glands compared to the 3DCRT-treatment technique. CONCLUSIONS: The class solution for the 3DCRT salivary gland sparing technique is inadequate for fully preserving salivary gland function, given the dose distributions (DVHs) as well as the subjective- and objective salivary gland function assessments. The results can be optimised in the future, that is a further reduction of xerostomia can be achieved, by using IMRT techniques focused at sparing major and minor salivary glands.

Long-term impact on work and private life after Guillain-Barré syndrome.

OBJECTIVE: To determine the long-term impact of Guillain-Barré syndrome (GBS) on work and private life of patients and their partners. METHODS: Three to six years after the onset of GBS 150 patients who participated in the Dutch Guillain-Barré trial received a questionnaire specifically drafted for this study to survey their present psychosocial status. Furthermore, their present physical status was established. RESULTS: A total of 122 patients participated. Thirty-one percent showed moderate to serious physical residua after a functional assessment. Due to GBS, 38% of the patients who held a job had to change it, 44% altered their leisure activities, 37% of the patients did not function as well at home as before GBS and 39% reported a change in their partners' lives. Almost half of the patients still had negative comments on their present psychosocial situation. CONCLUSION: GBS has a serious long-term impact on the patients' work and private life and that of their partners.

Fractionated stereotactic radiotherapy for uveal melanoma, late clinical results.

PURPOSE: To determine local control, late toxicity and metastatic free survival (MFS) of patients treated with fractionated stereotactic radiation therapy (fSRT) for uveal melanoma (UM). METHODS AND MATERIALS: Between 1999 and 2007, 102 UM patients were included in a prospective study of a single institution (median follow-up (FU) 32 months; median tumor thickness 6 mm); five fractions of 10 Gy were given. Primary endpoints were local tumor control and late toxicity (including visual outcome and eye preservation). Secondary endpoint was MFS. RESULTS: Local tumor control was achieved in 96% of the patients. Fifteen enucleations were performed, 2-85 months after radiation. Four eyes were enucleated because of local tumor progression. Nine patients developed grade 3 or 4 neovascular glaucoma (NVG), 19 developed severe retinopathy, 13 developed opticoneuropathy grade 3 or 4, 10 developed cataract grade 3, and 10 patients suffered from keratitis sicca. Best corrected visual acuity (BCVA) decreased from a mean of 0.26 at diagnosis to 0.16, 3 months after radiation and it gradually declined to 0.03, 4 years after therapy. The 5-year actuarial MFS was 75% (95% CIs: 62-84%). CONCLUSIONS: fSRT is an effective treatment modality for uveal melanoma with a good local control. With that, fSRT is a serious eye sparing treatment modality. However, our FU is relatively short. Also, the number of secondary enucleations is substantial, mainly caused by NVG.

Addition of serum-containing medium to cerebrospinal fluid prevents cellular loss over time.

Immediately after sampling, leukocyte counts in native cerebrospinal fluid (CSF) start to decrease rapidly. As the time lapse between CSF collection to analysis is not routinely registered, the clinical significance of decreasing cell counts in native CSF is not known. Earlier data suggest that addition of serum-containing medium to CSF directly after sampling prevents this rapid decrease in leukocyte counts and, thus, may improve the accuracy of CSF cell counting and cell characterization. Here, we prospectively examined the effect of storage time after lumbar puncture on counts of leukocytes and their major subsets in both native CSF and after immediate addition of serum-containing medium, measured by flow cytometry and microscopy. We collected CSF samples of 69 patients in tubes with and tubes without serum-containing medium and determined counts of leukocytes and subsets at 30 minutes, 1 hour, and 5 hours after sampling. Compared to cell counts at 30 minutes, no significant decrease in cell number was observed in CSF with serum-containing medium 1 and 5 hours after sampling, except for the granulocytes at 1 hour. In native CSF, approximately 50% of leukocytes and all their subsets were lost after 1 hour, both in flow cytometric and microscopic counting. In 6/7 (86%) samples with mild pleocytosis (5-15 × 10(6) leukocytes/l), native CSF at 1 hour was incorrectly diagnosed as normocellular. In conclusion, addition of serum-containing medium to CSF directly after sampling prevents cell loss and allows longer preservation of CSF cells prior to analysis, both for microscopic and flow cytometric enumeration. We suggest that this protocol results in more accurate CSF cell counts and may prevent incorrect conclusions based on underestimated CSF cell counts.

Randomized phase II study comparing efficacy and safety of combination-therapy trastuzumab and docetaxel vs. sequential therapy of trastuzumab followed by docetaxel alone at progression as first-line chemotherapy in patients with HER2+ metastatic breast cancer: HERTAX trial.

BACKGROUND: Because chemotherapy for metastatic breast cancer (MBC) is associated with relevant toxicity, sequential monotherapy trastuzumab followed by cytotoxic therapy at disease progression might be an attractive approach. METHODS: In a multicenter phase II trial, 101 patients with overexpression of human epidermal growth factor receptor 2 (HER2(+)) MBC were randomized between combination-therapy trastuzumab (Herceptin) plus docetaxel (H+D) and sequential therapy of single-agent trastuzumab followed at disease progression by docetaxel alone (H→D) as first-line chemotherapy for metastatic disease. The primary endpoint was progression-free survival (PFS) after completed sequential or combination therapy. RESULTS: For the H+D group the median PFS was 9.4 vs. 9.9 months for the H→D group and 1-year PFS rates were 44% vs. 35%, respectively. However the overall response rates (ORRs) were 79% vs. 53%, respectively (P = .016), and overall survival was 30.5 vs. 19.7 months, respectively (P = .11). In the H→D group, response rates to monotherapy trastuzumab and subsequent docetaxel were 34% and 39%, respectively, with a median PFS during single-agent trastuzumab of 3.9 months. The incidence and severity of neuropathy were significantly higher in the H+D group. Retrospective analysis of trastuzumab treatment beyond progression (applied in 46% of patients in the H+D group and 37% in the H→D group) showed a correlation with longer overall survival in both treatment arms (36.0 vs. 18.0 months and 30.3 vs. 18.6 months, respectively). CONCLUSION: First-line treatment in patients with MBC with H→D resulted in a similar PFS compared with H+D, but the response rate was lower and the overall survival nonsignificantly shorter.

EORTC Melanoma Group sentinel node protocol identifies high rate of submicrometastases according to Rotterdam Criteria.

Sentinel node (SN) status is the most important prognostic factor for disease-free survival (DFS) and overall survival (OS) in stages I-II melanoma. We evaluated the positive sentinel node identification rate of the EORTC Melanoma Group (MG) protocol as well as its capacity to identify minimal tumour burden, according to the Rotterdam Criteria in 421 consecutive patients. Correlations between primary tumour characteristics and SN tumour burden were investigated. The same 2 pathologists worked up all SNs according to the EORTC MG protocol and tumour burden was scored according to the Rotterdam Criteria (<0.1 mm, 0.1-1.0 mm and >1.0 mm for the largest diameter of the largest metastasis in the SN). The positive SN detection rate was 28.7% with a false negative rate of 10.4% at a median Breslow thickness of 2.1 mm. The high positive identification rate of about 30% of the EORTC MG protocol has been confirmed in this study. The protocol is sensitive and identifies submicrometastases (<0.1 mm) in a high percentage (18%). The variables SN tumour load, non-SN (NSN) status and ulceration of the primary were independent prognostic factors for DFS and OS in the multivariate analysis. At a median follow-up time of 4.3 years patients with minimal tumour burden (<0.1 mm) had a 5 year OS rate of 91%, virtually identical to 90% for SN-negative patients. The NSN positivity rate of 0% in these patients indicates that they may be spared a completion lymph node dissection (CLND) and its morbidity.

BRCA1-associated breast cancers present differently from BRCA2-associated and familial cases: long-term follow-up of the Dutch MRISC Screening Study.

PURPOSE: The Dutch MRI Screening Study on early detection of hereditary breast cancer started in 1999. We evaluated the long-term results including separate analyses of BRCA1 and BRCA2 mutation carriers and first results on survival. PATIENTS AND METHODS: Women with higher than 15% cumulative lifetime risk (CLTR) of breast cancer were screened with biannual clinical breast examination and annual mammography and magnetic resonance imaging (MRI). Participants were divided into subgroups: carriers of a gene mutation (50% to 85% CLTR) and two familial groups with high (30% to 50% CLTR) or moderate risk (15% to 30% CLTR). RESULTS: Our update contains 2,157 eligible women including 599 mutation carriers (median follow-up of 4.9 years from entry) with 97 primary breast cancers detected (median follow-up of 5.0 years from diagnosis). MRI sensitivity was superior to that of mammography for invasive cancer (77.4% v 35.5%; P<.00005), but not for ductal carcinoma in situ. Results in the BRCA1 group were worse compared to the BRCA2, the high-, and the moderate-risk groups, respectively, for mammography sensitivity (25.0% v 61.5%, 45.5%, 46.7%), tumor size at diagnosis≤1 cm (21.4% v 61.5%, 40.9%, 63.6%), proportion of DCIS (6.5% v 18.8%, 14.8%, 31.3%) and interval cancers (32.3% v 6.3%, 3.7%, 6.3%), and age at diagnosis younger than 30 years (9.7% v 0%). Cumulative distant metastasis-free and overall survival at 6 years in all 42 BRCA1/2 mutation carriers with invasive breast cancer were 83.9% (95% CI, 64.1% to 93.3%) and 92.7% (95% CI, 79.0% to 97.6%), respectively, and 100% in the familial groups (n=43). CONCLUSION: Screening results were somewhat worse in BRCA1 mutation carriers, but 6-year survival was high in all risk groups.

Chest wall resection for internal mammary lymph node metastases of breast cancer.

Evaluation of morbidity, mortality and oncologic outcome of patients treated with a chest wall resection for isolated breast cancer recurrences in the Internal Mammary Chain. Retrospectively we retrieved data from 29 patients. Multivariate analysis was performed to identify prognostic factors for (disease-free) survival. There were no postoperative deaths. Complications occurred in 11 patients. The median follow-up after CWR for all 16 patients still alive at the end of this study is 18.4 months. Nine patients were free of cancer. The 3-year overall and disease-free survival is 59.2% and 8.6%. The median survival is 40.7 months. After multivariate analysis for each of the four endpoints studied, only one prognostic factor remains significant for survival: systemic therapy before CRW (p=0.004). For local recurrence-free survival a first CRW recurrence (p<0.00001) and for disease-free survival radicality of the resection (p=0.008) are independent prognostic factors. Chest wall resection is a safe and effective treatment for isolated breast cancer recurrences in the IMC. Surgically treated patients have a fair survival and some of them are even cured.

Multimodality treatment for anaplastic thyroid carcinoma--treatment outcome in 75 patients.

PURPOSE: To retrospectively analyze the outcome of patients with anaplastic thyroid carcinoma (ATC) treated in the Erasmus MC. MATERIAL AND METHODS: Seventy-five ATC-patients were treated between 1972 and 2003. Mean age was 68 years. Tumor stage was IVA in 9%, IVB in 51%, and IVC in 40%. Thirty-six patients underwent up-front surgery, with 53% resulting in R0/R1 resection. Before 1988 adjuvant treatment consisted of conventional radiotherapy (RT) and/or chemotherapy (CT). As of 1988, 30 eligible patients were enrolled in a newly designed protocol. This consists of locoregional RT in 46 fractions of 1.1 Gy, given twice daily, followed by prophylactic irradiation of the lungs (PLI) in 5 daily fractions of 1.5 Gy. During radiation, low-dose Doxorubicine (15 mg/m(2)) is administered weekly and is followed by adjuvant Doxorubicine (50 mg/m(2)) 3-weekly up to a cumulative dose of 550 mg/m(2). Twenty-five ineligible patients were treated conventionally. RESULTS: Overall median survival was 3 months, 1-year OS 9%. Locoregional control was significantly higher in patients who had undergone R0/R1 resection or chemoradiation, with best results for patients who underwent both (complete remission in 89%). However, the survival benefit of patients who reached CR remained borderline (median OS 7 months, 1-year OS 32%). Three patients survived for more than 5 years; all had undergone R0/R1 surgical resection and chemoradiation. Acute toxicity in the protocol group was significantly higher than in the nonprotocol group, with 46% versus 11% grade 3 pharyngeal and/or esophageal toxicity. CONCLUSION: Despite the ultimately dismal prognosis of ATC-patients, multimodality treatment significantly improved local control and improved the median survival.

Complications in wound healing after chest wall resection in cancer patients; a multivariate analysis of 220 patients.

BACKGROUND: Extensive chest wall resections can provoke a wide variety of complications, in particular, complicated wound healing. A lower complication rate will be achieved when local factors contributing to wound healing can be identified and improved. The aim of this study is to describe these factors, irrespective of prognosis, survival, or systemic complications. METHODS: Retrospectively, the files of all patients undergoing an extended chest wall resection in a single institute during a 20-year period were retrieved. Patient demographics, use of preoperative therapy, tumor histology, the type of prosthesis (if any), and postoperative wound complications were recorded. Univariate and multivariate analysis were performed to identify factors contributing significantly to wound healing problems. RESULTS: From January 1987 to December 2006, 220 patients underwent a chest wall resection, defined as resection of at least one rib, and/or part of the sternum. In 145 patients (66%) this procedure was uneventful. Multivariate analysis showed that ulceration of tumor and the use of omentum for soft tissue reconstruction comprised independent factors contributing to impaired wound healing. CONCLUSION: Several factors leading to wound healing problems exist preoperatively. In a multidisciplinary setting, these factors should be weighed carefully against the possible benefits of an extended chest wall resection. Especially when ulceration of a tumor exists, or when omentum is considered for soft tissue reconstruction, increased risk on wound healing problems occurs. For the majority of patients chest wall resection will remain a safe and suitable procedure.