Management of lobular carcinoma in-situ and atypical lobular hyperplasia of the breast-A review

Objectives

To determine the incidence of malignancy (invasive carcinoma or DCIS) in patients diagnosed with lobular neoplasia (B3) on core needle biopsy (CNB) of breast lesions by reviewing the published literature.

Methods

Medline, Embase, OVID-database and reference lists were searched to identify and review all English-language articles addressing the management of LN diagnosed on CNB. Studies on mixed breast pathologies were excluded.

Results

Of 1229 LN diagnosed on CNB, 789 (64%) underwent surgical excision. 211 (27%) of excisions contained either DCIS or invasive disease. 280 of the excision specimens were classified as ALH, 241 as LCIS, 22 as pleomorphic LCIS and 246 unspecified LN on the original CNB. After surgical excision, 19% of the ALH cases, 32% of the LCIS cases and 41% of the PLCIS cases, contained malignancy. 29% of the unspecified LNs were upgraded to malignancy. The higher incidence of malignancy within excision specimens for LCIS and PLCIS compared to ALH was significant (P < 0.04, <0.003 respectively).

Conclusion

There is a significant underestimation of malignancy in patients diagnosed with breast LN on CNB. 27% cases of CNB-diagnosed LN were found to contain malignancy following surgical excision. All patients diagnosed with LN on CNB should be considered for surgical excision biopsy.     

The impact of short-term psycho-oncological interventions on the psychological outcome of cancer patients of a surgical-oncology department - a randomised controlled study

Background

Anxiety and depression are the two most frequent comorbidities of tumour patients. At present, it is unclear to which degree a patient’s psychological condition can be altered during the treatment period and if psycho-oncological support positively affects a patient’s psychological condition.

Methods

In a random sample analyses, 131 patients beginning inpatient treatment at a hospital specialising in surgical oncology were either classified as ‘low-risk’ or ‘high-risk’, according to the HADS. Patients from both categories were then randomly placed in either a low-threshold ‘intervention’ group or an ‘observation’ group. Anxiety and depression levels were measured again with the HADS scale prior to the patients discharge from the department of surgical oncology, and at a follow up 12 months after.

Results

Our findings showed a significant reduction of anxiety and depression in the high-risk patients who had undergone psycho-oncological intervention at the end of inpatient care and even a year after discharge from the hospital. The effects of psychological intervention could be observed in terms of anxiety and depression in the group of high-risk patients during the hospital stay. In the other three groups, no statistically significant changes could be measured.

Conclusion

Cancer patients on a surgical ward benefit from psycho-oncological support especially at an early stage of therapy but also over a long time after discharge from the hospital. The aim of all interventions should be to decrease psychological distress and disorders and thereby improve the quality of life for cancer patients.     

Assessment of the effect of surgery on the kinetics of circulating tumour cells in patients with operable breast cancer based on cytokeratin-19 mRNA detection

Aims

The aim of this study was to evaluate the effect of surgery on the kinetics of CTCs in breast cancer patients.

Methods

The detection of CK-19 mRNA-positive CTCs in the blood by RT-PCR was analysed in 104 stage 0-IIIA patients at 4 time-points: prior to surgery, upon completion, 24 h after surgery and 15 days after surgery. Furthermore, a late sample was assessed prior to initiation of adjuvant chemotherapy in a subgroup of 53 patients. As negative controls, peripheral blood was obtained from 50 female patients undergoing excision of benign breast lesions and from 11 female patients receiving surgery for early-stage colorectal cancer.

Results

A significant percentage of blood samples from breast cancer patients (14.4%) were negative for CK-19 preoperatively but turned transiently positive early postoperatively. However, no significant difference in CK-19 mRNA detection was noted among the first 4 examined time-points. There was no significant correlation between CK-19 mRNA-positive cells and classic prognostic factors. A significant increase in CK-19 mRNA-positivity (32.1%) was observed in a late sample of the subgroup of 53 patients before adjuvant chemotherapy after a median of 54 days, postoperatively.

Conclusions

Surgery may result in CTC detection in a small proportion of early breast cancer patients. There is no clear correlation to indicate which patients are expected to have detectable CTCs. Although CTCs are detected in a small proportion of patients during the perioperative period, the detection rate may increase over time and with longer follow-up.     

Melanoma cells show a heterogeneous range of sensitivity to ionizing radiation and are radiosensitized by inhibition of B-RAF with PLX-4032

Purpose

To assess the relative radiosensitivities of a large collection of melanoma cell lines and to determine whether pharmacologic inhibition of mutant B-RAF with PLX-4032 can radiosensitize B-Raf+ melanoma cells.

Materials and methods

A large collection of melanoma cell lines (n = 37) were treated with 0-8 Gy IR and clonogenic survival assays used to generate survival curves to rank relative radiosensitivities among the cell lines. The ability of a B-RAF inhibitor, PLX-4032, to radiosensitize highly radioresistant B-Raf+ cells was also assessed by clonogenic cell survival and spheroid invasion assays and the effects of treatment on the cell cycle assessed by FACS.

Results

Melanoma cell lines displayed a very large, heterogeneous range of SF2 values (1.002-0.053) with a mean of 0.51. Cell lines with surviving fractions of 0.29 or less at SF2 and SF4 were observed at a high frequency of 18.9% and 70.2%, respectively. Treatment of B-Raf+ cells with the B-RAF inhibitor PLX-4032 in combination with radiation provided enhanced inhibition of both colony formation and invasion, and radiosensitized cells through an increase in G₁ arrest.

Conclusions

Our data suggest that melanomas are not uniformly radioresistant with a significant subset displaying inherent radiosensitivity. Pharmacologic inhibition of B-RAF with PLX-4032 effectively radiosensitized B-Raf+ melanoma cells suggesting that this combination approach could provide improved radiotherapeutic response in B-Raf+ melanoma patients.     

General practitioners and referral for palliative radiotherapy: A population-based survey

Background and purpose

The suspicion exists that the referral rate for palliative radiotherapy (RT) is too low. RT, especially in a short series, is an essential and established modality within palliative cancer care for localised symptoms.

Material and methods

Questionnaires to evaluate the knowledge of palliative RT were sent to the 1100 general practitioners (GP’s) in the area of the Comprehensive Cancer Centre South in the Netherlands, covering about 2.6 million inhabitants. Four hundred and ninety-eight questionnaires were evaluated.

Results

Forty-six percent of the respondents had cared for patients referred for palliative RT in the last two years. Knowledge about the effects of palliative RT on bone metastases and spinal cord compression was good but about other palliative indications it was moderate to poor. Determinants of the actual referral for palliative RT were mainly patient related. GPs considered their own knowledge to be poor with only 10% reporting previous RT education.

Conclusions

It is absolutely necessary to inform GPs about the possibility of short series of palliative irradiation in order to improve their information for symptomatic cancer patients about all possibilities for palliative treatment.     

Is early stage endometrial cancer safely treated by laparoscopy? Complications of a multicenter study and review of recent literature

Background

To compare the complications after total laparoscopic hysterectomy (LPS) and abdominal hysterectomy with lymphadenectomy (LPT) for early stage endometrial cancer in a series of 226 women and to assess the disease-free survival and the recurrence rate.

Patients and methods

Two hundred and twenty six patients with clinical stage I endometrial cancer were enrolled in a multicenter study and underwent surgical staging consisting of inspecting the intraperitoneal cavity, peritoneal washing, total hysterectomy, bilateral salpingo-oophorectomy, and in all cases we performed systematic bilateral pelvic lymphadenectomy by LPS or LPT approach.

Results

One patient of the LPS group had an uretero-vaginal fistula and another patient had an ureteral stricture temporarily treated with a stent. One patient of the LPS group had a bowel perforation due to dense adhesions with the peritoneum under the umbilicus, resolved with a bowel resection and an end-to-end anastomosis. In three patients of the LPS group we observed a vaginal cuff dehiscence and in one case a pelvic lymphocyst was reported.

Conclusions

The low intraoperative and postoperative complications rate, observed in the LPS group, highlights the feasibility, safety and efficacy of this surgical approach. The operating time was longer in the LPS group but the recurrence rate and the complication rate appear similar and not more than what is traditionally expected with the LPT approach, although further studies and cost-benefit analyses are required to determine whether the use of LPS improves the outcome over standard LPT and whether the advantages of this technique could be extended to a larger proportion of patients.     

Surgical complications of skin sparing mastectomy and immediate prosthetic reconstruction after neoadjuvant chemotherapy for invasive breast cancer

Background

Neoadjuvant chemotherapy is gaining acceptance as an option for breast cancer treatment, particularly in young women. These women may seek immediate breast reconstruction after mastectomy even though it is not known whether such preoperative chemotherapy may be detrimental to post-reconstruction wound healing. Therefore, we set out to assess the influence of neoadjuvant chemotherapy for invasive breast cancer on the short-term complications after skin sparing mastectomy and immediate prosthetic reconstruction.

Methodology

The short-term surgical outcome of 48 immediate breast reconstructions in 37 women treated with neoadjuvant chemotherapy from 2006 through 2009 was prospectively compared to that of 215 immediate reconstructions in 176 women who were operated in the same period without neoadjuvant chemotherapy.

Results

The overall rate of short-term postoperative complications was significantly less among neoadjuvantly treated women (15% vs. 29%; p = 0.042) but this did not result in a reduction of loss of prostheses (8% vs. 11%; p = 0.566).

Conclusion

Because neoadjuvant chemotherapy is not associated with an increase in short-term complications after skin sparing mastectomy and immediate prosthetic reconstruction in patients with invasive breast cancer, such combined surgical therapy may be offered as treatment option for this particular group of patients also.     

Prognostic heterogeneity after the excision of lymph node metastases in patients with cutaneous melanoma

Background

The aim of this study was to compare the overall survival (OS) of different groups of AJCC 2002 stage III cutaneous melanoma patients and to prove that patients with positive sentinel lymph node (SN) are heterogenic group with very different survival rates.

Methods

A total of 325 patients with stage III melanoma were identified from the prospective melanoma database at the Institute of Oncology Ljubljana, Slovenia; 164 had delayed therapeutic lymph node dissection (DLND), 111 had a positive sentinel lymph node biopsy followed by completion lymph node dissection (CLND) and 50 had synchronous primary melanoma and regional lymph node metastases that were treated with radical excision of the primary tumor and therapeutic lymph node dissection (TLND). Univariate and multivariate analyses were used for the assessment of the factors associated with OS and for comparison of OS between different subgroups of patients.

Results

The worst 5-year OS had the patients with synchronous primary melanoma and regional lymph node metastases. The patients with SN metastases with a diameter of 5.0 mm or less had significantly better OS than those with DLND, while the patients with SN metastases with a diameter of more than 5.0 mm had similar survival to those patients with synchronous primary melanoma and regional lymph node metastases.

Conclusion

Melanoma patients within AJCC 2002 stage III group have very different survival rates. The group of patients with positive SN is also prognostically heterogenic because it contains patients that have better survival than those after DLND as well as patients with more aggressive disease, that have similar survival as those with synchronous primary melanoma and regional lymph node metastases.     

Quality of life as predictor of survival: A prospective study on patients treated with combined surgery and radiotherapy for advanced oral and oropharyngeal cancer

Background and purpose

The relation between health-related quality of life (HRQOL) and survival was investigated at baseline and 6 months in 80 patients with advanced oral or oropharyngeal cancer after microvascular reconstructive surgery and (almost all) adjuvant radiotherapy.

Materials and methods

Multivariate Cox regression analyses of overall and disease-specific survival were performed including sociodemographic (age, gender, marital status, comorbidity), and clinical (tumor stage and site, radical surgical, metastasis, radiotherapy) parameters, and HRQOL (EORTC QLQ-C30 global quality of life scale).

Results

Before treatment, younger age and having a partner were predictors of disease-specific survival; younger age predicted overall survival. At 6 months post-treatment, disease-specific and overall survival was predicted by (deterioration of) global quality of life solely. Global health-related quality of life after treatment was mainly influenced by emotional functioning.

Conclusion

Deterioration of global quality of life after treatment is an independent predictor of survival in patients with advanced oral or oropharyngeal cancer.     

Non-invasive modalities for predicting lymph node spread in early stage endometrial cancer?

Background

Lymph node status in EC determines the staging and has important prognostic and therapeutic implications.

Objectives

We have examined the diagnostic value of preoperative and intraoperative non-invasive methods to determine the lymph node status in endometrial cancer, or, indirectly, for identification of patients at increased risk of lymph node involvement.

Search strategy

We conducted a literature search to identify all relevant reports that evaluated lymph node spread in EC.

Selection criteria

Articles were only considered when data of investigational modalities were compared with histopathological findings of the surgical specimens, considered as the gold standard.

Data collection and analysis

When numerous relevant articles were identified for one investigational modality, only series including more than 50 patients were considered.

Main results

Sensitivity of CT and MRI for diagnosis metastatic lymph node is limited. TVS performs as well as MRI in predicting deep myometrial invasion. It is unclear whether intraoperative gross visual examination and frozen section perform better than preoperative methods to predict deep myometrial invasion. There is a limited sensitivity of intraoperative frozen section for predicting poorly differentiated EC.

Conclusion

Accurate non-invasive assessment of lymph node status in patients with EC remains challenging.

Synopsis

Despite imaging advances in the past 20 years, accurate non-invasive assessment of lymph node status in patients with EC remains challenging.     

Preoperative radiotherapy and local excision of rectal cancer with immediate radical re-operation for poor responders

Background and purpose

To report an early analysis of prospective study exploring preoperative radiotherapy and local excision in rectal cancer.

Materials and methods

Mucosa at tumour edges was tattooed. Patients with cT1-3N0 tumour <3-4 cm were treated with either 5 × 5 Gy + 4 Gy boost (N = 31) or chemoradiation (50.4 Gy + 5.4 Gy boost, 1.8 Gy per fraction + 5-fluorouracyl and leucovorin; N = 13). Thirteen patients from the short-course group were unfit for chemotherapy. The interval from radiation to full-thickness local excision was 6 weeks. The protocol called for conversion to a transabdominal surgery in case of ypT2-3 disease or positive margin.

Results

The postoperative complications requiring hospitalization were recorded in 9% of patients. The rate of pathological complete response was 41%. The rate of patients requiring conversion was 34%; however, 18% actually underwent conversion and the remaining 16% refused or were unfit. During the 14 months of median follow-up, local recurrence was detected in 7% of patients and all underwent salvage surgery. Of 19 patients in whom initially anterior resection was likely, 16% had abdominoperineal resection performed for a conversion or as a rescue procedure.

Conclusion

Our study suggests that the short-course radiation prior to local excision is a treatment option for high-risk patients.     

HDR endobronchial brachytherapy (HDRBT) in the management of advanced lung cancer - Comparison of two different dose schedules

Purpose

The aim of this work is to compare the results of various treatment protocols used in palliative HDRBT with the view of analyzing differences in survival and diminishing breathing difficulties.

Material and methods

A total of 648 patients with advanced lung cancer were divided into two groups according to their clinical stage and the Zubrod-ECOG-WHO score. 303 (46.8%) patients received a total dose of 22.5 Gy in 3 fractions once a week, and 345 (53.2%) patients received a single fraction of 10 Gy. They were under clinical and endobronchial observation taking into consideration survival rates, local remission and duration of symptom relief such as dyspnoea, breathing, cough and haemoptysis.

Results

There was no difference in the length of survival time between the two groups of patients (log-rank test, p = 0.055). Patients showing improvement (objective response) survived longer than those who showed no change or progression (F Cox, p = 0.000001). In multivariate analysis the other statistically important prognostic factors were: clinical stage of primary tumor (F Cox, p = 0.000002), Zubrod-ECOG-WHO score (F Cox, p = 0.002) and age of patients (F Cox, p = 0.004).

Conclusions

The two treatment protocols showed similar efficiency in overcoming difficulties in breathing. Prognostic factors that significantly correlated with survival length were: grade of remission after treatment, clinical stage and performance status.     

Direct reconstruction of the Vienna applicator on MR images

Purpose

To introduce and test a direct reconstruction concept for intracavitary tandem ring applicators in MR image-based brachytherapy treatment planning.

Materials and methods

Optical measurements of transparent ring-phantoms provided the geometric relation between source path and the Vienna ring applicator as visible on MRI. For the manual direct reconstruction method (PLATO), the geometry plotted on a transparency was placed on the screen and rotated to fit with visible ring holes. With the software-integrated reconstruction method (OncentraGYN), the applicator geometry was directly used when placing the visible parts of the applicator in the 3D dataset. Clinical feasibility was tested in 10 clinical insertions. Reconstruction and dose calculation were performed independently on two treatment planning systems (PLATO and OncentraGYN) using MRI alone. DVH parameters for targets and organs at risk were analysed and compared to the clinically used radiograph/MRI registration-based method.

Results

The direct reconstruction concept for both methods was feasible and reduced treatment planning time. Evaluated DVH parameters for plans using direct reconstruction methods differed from clinically used plans (traditional reconstruction) in mean differences ?0.2 Gy for plans with 7 Gy prescribed dose.

Conclusion

If the relation between applicator shape visible on MRI and the source path is defined once, the reconstruction process can be performed by directly placing the applicator in the MRI dataset.     

Development, external validation and clinical usefulness of a practical prediction model for radiation-induced dysphagia in lung cancer patients

Introduction

Acute dysphagia is a distressing dose-limiting toxicity occurring frequently during concurrent chemo-radiation or high-dose radiotherapy for lung cancer. It can lead to treatment interruptions and thus jeopardize survival. Although a number of predictive factors have been identified, it is still not clear how these could offer assistance for treatment decision making in daily clinical practice. Therefore, we have developed and validated a nomogram to predict this side-effect. In addition, clinical usefulness was assessed by comparing model predictions to physicians’ predictions.

Materials and methods

Clinical data from 469 inoperable lung cancer patients, treated with curative intent, were collected prospectively. A prediction model for acute radiation-induced dysphagia was developed. Model performance was evaluated by the c-statistic and assessed using bootstrapping as well as two external datasets. In addition, a prospective study was conducted comparing model to physicians’ predictions in 138 patients.

Results

The final multivariate model consisted of age, gender, WHO performance status, mean esophageal dose (MED), maximum esophageal dose (MAXED) and overall treatment time (OTT). The c-statistic, assessed by bootstrapping, was 0.77. External validation yielded an AUC of 0.94 on the Ghent data and 0.77 on the Washington University St. Louis data for dysphagia ? grade 3. Comparing model predictions to the physicians’ predictions resulted in an AUC of 0.75 versus 0.53, respectively.

Conclusions

The proposed model performed well was successfully validated and demonstrated the ability to predict acute severe dysphagia remarkably better than the physicians. Therefore, this model could be used in clinical practice to identify patients at high or low risk.     

The value of pre operative S-100B and SUV in clinically stage III melanoma patients undergoing therapeutic lymph node dissection

Introduction

High preoperative serum S-100B values and Standardized Uptake Values (SUV) of Fluorodeoxyglucose (FDG) in PET for clinically stage III melanoma patients could be indicators of recurrence after surgical treatment. Aim was to assess the correlation and the prognostic value of these markers.

Methods

All melanoma patients with palpable nodal metastases, without distant metastases, were included from February 2004 to December 2007. Preoperative SUV and S-100B was determined. The correlation between SUV and S-100B and their relations with DFS and DSS were calculated by Cox Proportional Hazard Analysis.

Results

62 Patients, median age 56.9 years, were included in the study. An elevated S-100B was found in 31 patients (50%) and elevated SUV in 24 patients (38.7%). No relation was found between S-100B and SUV. DFS was reduced (31.1%) for patients with an elevated S-100B (HR = 3.1; p = 0.02) in comparison to a normal S-100B (44.6%). The DFS was 42.0% for patients with a SUV below the cut-off point and 29.0% for patients with an elevated SUV (HR = 1.1; p = 0.8). DSS was 60.7% in a normal S-100B and 44.7% for patients with an elevated S-100B (HR = 2.2; p = 0.07). DSS was 59.1% for patients with a normal SUV and 43.5% for patients with elevated SUV (HR = 1.1; p = 0.8).

Conclusion

S-100B and SUV in stage III melanoma are not correlated and each have different associations with various histopathological factors. S-100B, in contrast with SUV, is associated with nodal tumor load, and when elevated, predicts a shorter DFS.

Synopsis

Preoperative serum S-100B and Fluorodeoxyglucose (FDG) Standardized Uptake Value (SUV) in clinically stage III melanoma are not correlated. S-100B is a strong predictor for Disease Free Survival (DFS) in stage III melanoma.     

Clear margins for invasive lobular carcinoma: A surgical challenge

Background

The main goal of breast conservative surgery (BCS) is the complete removal of cancer with clear margins and no deformity of the breast. However, in invasive lobular carcinoma (ILC) this goal is hard to achieve because of the underestimation of tumor size. Our study was the first to show the role of surgical techniques in the achievement of clear margins for ILC.

Methods

We reviewed 73 patients with ILC who underwent BCS at Paris Breast Center between January 2005 and June 2008. Full thickness excision (FTE) was performed in a routine basis and oncoplastic surgery (OPS) upon tumor location, volume ratio and overall density of the breast. Margin status was evaluated as positive, close or clear.

Results

Positive/close margins were found in 39% of cases and were lower than what was described in the literature (49-63%). FTE was performed in 47 (64%) patients and OPS in 26 (36%) patients. No positive/close margins were observed in patients with lesions located in the lower/central quadrants. Multivariate analysis showed multifocality, larger tumor size and FTE to be independent risk factors for positive margins at final surgery.

Conclusions

Our rate of positive/close margins for ILC was lower than what was described in the literature. The determinant key difference was in our surgical procedures with FTE or OPS differing from the standard BCS described in the literature and we suggest that OPS is to be considered for ILC. It allows larger breast conservative surgery with good cosmetic results and lower rate of compromised margins.     

Sociodemographic factors and incidence of melanoma in the Netherlands, 1994-2005

Background

Time-space incidence maps of the Netherlands indicated differences in incidence of cutaneous melanoma (melanoma) over the country, which might be related to sociodemographic characteristics of living environment and socioeconomic status (SES) of the patients. The goal of this study was to refine the current approaches to prevention and early detection of melanoma by revealing relationships between sociodemographic factors and incidence of melanoma in the Netherlands.

Methods

Age-adjusted incidence rates were calculated from the Netherlands Cancer Registry. Data on sociodemographic factors were obtained from Statistics Netherlands. Logistic regression analysis was performed to investigate determinants of variation in incidence at the ecological level. At the individual level tumour characteristics were linked to SES based on postal code at the time of diagnosis.

Results

The lowest SES-group had a significantly lower incidence than the highest SES-group; 10.2 (95% confidence intervals (CI): 9.1-11.3) and 14.3 (95% CI: 12.9-15.8), respectively. Increased risk of melanoma was seen in municipalities with high population density, few people living on social security and many people with high income. Patients living in low SES neighbourhoods were diagnosed more often with higher stage disease (13% (95% CI: 12.3-13.8) diagnosed with pT4) than those living in high SES neighbourhoods (9% (95% CI: 8.5-9.8) diagnosed with pT4) (p < 0.001) and with higher Breslow thickness (p < 0.001).

Conclusions

Awareness of the risks of UV radiation (UVR) is important and in the higher SES-groups primary prevention should remain the focus. However, if the incidence rates for the higher SES-groups are illustrative for the lower SES-groups, then the focus should be on both primary and secondary prevention in the low SES-groups.     

Enhancing the quality of care for patients with breast cancer: Seven years of experience with a Dutch auditing system

Background

Hospitals in the Midwestern part of the Netherlands carried out a clinical audit to monitor the quality of breast cancer care during the years 2002-2008. Compliance with the National Guideline was investigated together with improvement in quality over time.

Methods

Patients with a malignancy of the breast (including ductal carcinoma in situ) participated in this study. Nine quality indicators were evaluated over the years. In 2004 and 2005 the hospitals also carried out an intervention project aimed at improvement of the efficiency of both the diagnostic process and the surgical treatment.

Results

At the end of the project all nine indicators showed significant improvement compared to the start of the project. Discussion of treatment strategy in a multidisciplinary breast cancer team took place more often before surgery (83% versus 56%) as well as after surgery (98% versus 70%). The National Guideline for maximum waiting times was met more often for the outpatient clinic (74% versus 61%), time to diagnosis (92% versus 82%), and surgical treatment (52% versus 34%). More sentinel node procedures were performed successfully (92% versus 69%), and for more patients more than 10 lymph nodes were evaluated in case of axillary lymph node dissection (85% versus 58%). More patients had definitive surgical treatment consisting of one surgical intervention (87% versus 75%), and left the hospital within 7 days after hospital admission (98% versus 66%).

Conclusion

The clinical audit contributed to improvement of the quality of breast cancer care in the Midwestern part of the Netherlands between 2002 and 2008.