Trends and Variation in the Use of Radiotherapy in Non-metastatic Rectal Cancer: a 14-year Nationwide Overview from the Netherlands.

AIMS: This study describes nationwide primary radiotherapy utilisation trends for non-metastasised rectal cancer in the Netherlands between 2008 and 2021. In 2014, both colorectal cancer screening and a new guideline specifying prognostic risk groups for neoadjuvant treatment were implemented. MATERIALS AND METHODS: Patients with non-metastasised rectal cancer in 2008-2021 (n = 37 510) were selected from the Netherlands Cancer Registry and classified into prognostic risk groups. Treatment was studied over time and age. Multilevel logistic regression analyses were carried out to identify factors associated with (i) radiotherapy versus chemoradiotherapy use for intermediate rectal cancer and (ii) chemoradiotherapy without versus with surgery for locally advanced rectal cancer. RESULTS: For early rectal cancer, the use of neoadjuvant radiotherapy decreased (15% to 5% between 2008 and 2021), whereas the use of endoscopic resections increased (8% in 2015, 17% in 2021). In intermediate-risk rectal cancer, neoadjuvant chemoradiotherapy (43% until 2011, 25% in 2015) shifted to radiotherapy (42% in 2008, 50% in 2015), the latter being most often applied in older patients. In locally advanced rectal cancer, the use of chemoradiotherapy without surgery increased (2-4% in 2008-2013, 17% in 2019-2021). Both neoadjuvant treatment in intermediate disease and omission of surgery following chemoradiotherapy in locally advanced disease varied with increasing age (odds ratio>75vs<50: 2.17, 95% confidence interval 1.54-3.06) and treatment region (Southwest and Northwest odds ratio 0.63, 95% confidence interval 0.42-0.93 and odds ratio 0.65, 95% confidence interval 0.44-0.95, respectively, compared with the North). CONCLUSION: Treatment patterns in non-metastasised rectal cancer significantly changed over time. Effects of both the national screening programme and the new treatment guideline were apparent, as well as a paradigm shift towards organ preservation (watch-and-wait). Observed regional variations may indicate adoption differences regarding new treatment strategies.

Impact of Age and Comorbidity on Choice and Outcome of Two Different Treatment Options for Patients with Potentially Curable Esophageal Cancer.

PURPOSE: This study was designed to assess the impact of age and comorbidity on choice and outcome of definitive chemoradiotherapy (dCRT) or neoadjuvant chemoradiotherapy plus surgery. METHODS: In this population-based study, all patients with potentially curable EC (cT1N+/cT2-3, TX, any cN, cM0) diagnosed in the South East of the Netherlands between 2004 and 2014 were included. Kaplan-Meier method with log-rank tests and multivariable Cox regression analysis were used to compare overall survival (OS). RESULTS: A total of 702 patients was included. Age ≥ 75 years and multiple comorbidities were associated with a higher probability for dCRT (odds ratio [OR] 8.58; 95% confidence interval [CI] 4.72-15.58; and OR 3.09; 95% CI 1.93-4.93). The strongest associations were found for the combination of hypertension plus diabetes (OR 3.80; 95% CI 1.97-7.32) and the combination of cardiovascular with pulmonary comorbidity (OR 3.18; 95% CI 1.57-6.46). Patients with EC who underwent dCRT had a poorer prognosis than those who underwent nCRT plus surgery, irrespective of age, number, and type of comorbidities. In contrast, for patients with squamous cell carcinoma with ≥ 2 comorbidities or age ≥ 75 years, OS was comparable between both groups (hazard ratio [HR] 1.52; 95% CI 0.78-2.97; and HR 0.73; 95% CI 0.13-4.14). CONCLUSIONS: Histological tumor type should be acknowledged in treatment choices for patients with esophageal cancer. Neoadjuvant chemoradiotherapy plus surgery should basically be advised as treatment of choice for operable esophageal adenocarcinoma patients. For patients with esophageal squamous cell carcinoma with ≥ 2 comorbidities or age ≥ 75 years, dCRT may be the preferred strategy.

The cognitive and socio-emotional development of 5-year-old children born after PGD.

STUDY QUESTION: Does PGD increase the risk on adverse cognitive and socio-emotional development? SUMMARY ANSWER: The cognitive and socio-emotional development in children born after PGD seems to be normal when compared to control groups. WHAT IS KNOWN ALREADY: A limited number of studies with small sample sizes indicate that the cognitive and socio-emotional development of (pre)school-aged children born after either PGD or PGS seem to be comparable to those of children born after IVF/ICSI and to naturally conceived (NC) children from the general population. STUDY DESIGN, SIZE, DURATION: For this study we invited 72 5-year-old PGD children, 128 5-year-old IVF/ICSI children and 108 5-year-old NC children from families with a genetic disorder. All children were invited between January 2014 and July 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 51 PGD children, 52 IVF/ICSI children and 35 NC children underwent neuropsychological testing (WPPSI-III-NL and AWMA). The children's parent(s) and teachers filled in questionnaires evaluating children's executive functioning (Behaviour Rating Inventory of Executive Functions; BRIEF) and socio-emotional development (Child Behaviour Checklist; CBCL and Caregiver-Teacher Report Form; C-TRF). MAIN RESULTS AND THE ROLE OF CHANCE: The mean full-scale intelligence quotient scores (P = 0.426) and performance on the AWMA Listening Span task (P = 0.873) and Spatial Span task (P = 0.458) were comparable between the three groups. Regarding socio-emotional development, the teachers' scores revealed more externalizing (P = 0.011) and total problem (P = 0.019) behaviour in PGD children than for IVF/ICSI children; both groups did not differ significantly from the NC children (P = 0.11). More children (13%) with an affected first-degree family member (mostly parent) were included in the PGD group than in the NC group. Scores in all groups fell within the normal population range and should be considered normal. LIMITATIONS, REASONS FOR CAUTION: The number of NC children from families with a genetic disorder was relatively small. Furthermore, the fathers' CBCL results were based on small samples. WIDER IMPLICATIONS OF THE FINDINGS: PGD children show levels of cognitive and socio-emotional development at 5 years that are within the normal range, despite the biopsy involved in PGD and the potential extra psychological burden associated with the presence of a genetic disorder in the family. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by ZonMw (70-71300-98-106). None of the authors have any competing interests to declare. TRIAL REGISTRATION NUMBER: NCT02149485.

Long-term survival improvement in oesophageal cancer in the Netherlands.

BACKGROUND: Treatment for oesophageal cancer has evolved due to developments including the centralisation of surgery and introduction of neoadjuvant treatment. Therefore, this study evaluated trends in stage distribution, treatment and survival of oesophageal cancer patients in the last 26 years in the Netherlands. PATIENTS AND METHODS: Patients with oesophageal cancer diagnosed in the period 1989-2014 were selected from the Netherlands Cancer Registry. Patients were divided into two groups: non-metastatic (M0) and metastatic (M1). Trends in stage distribution, treatment and relative survival rates were evaluated according to histology. RESULTS: Among all 35,760 patients, the percentage of an unknown tumour stage decreased from 34% to 10% during the study period, whereas the percentage of patients with metastatic disease increased from 21% to 34%. Among surgically treated patients 32% underwent a resection in a high-volume hospital in 2005 which increased to 92% in 2014. Use of neoadjuvant chemoradiotherapy increased in non-metastatic oesophageal adenocarcinoma (OAC) and squamous cell carcinoma (OSCC) patients from respectively 4% and 2% in 2000-2004 to 43% and 26% in 2010-2014. Five-year relative survival increased from 8% to 22% for all patients; from 12% to 36% for non-metastatic OAC and from 9% to 27% for non-metastatic OSCC over 26 years. Median overall survival of metastatic patients improved from 18 to 22 weeks. CONCLUSION: In the Netherlands, survival for oesophageal cancer patients improved significantly, especially in the period 2005-2014 which might be the result of better treatment related to the centralisation of surgery and introduction of neoadjuvant chemoradiotherapy.

Influence of the Extent and Dose of Radiation on Complications After Neoadjuvant Chemoradiation and Subsequent Esophagectomy With Gastric Tube Reconstruction With a Cervical Anastomosis.

PURPOSE: To determine, in a large series, the influence of the extent and dose of radiation to the fundus of the stomach and mediastinum on the development and severity of anastomotic complications in patients with esophageal cancer treated with neoadjuvant chemoradiation followed by esophagectomy with cervical anastomosis. METHODS AND MATERIALS: Between 2005 and 2012, 364 consecutive patients with esophageal cancer treated with neoadjuvant chemoradiation (41.4 Gy combined with chemotherapy) followed by esophagectomy were included. The future anastomotic region in the fundus was determined, and the mean dose, V20-V40, and upper planning target volume border in relation to mediastinal length, expressed as the mediastinal ratio, were calculated. RESULTS: Anastomotic leakage occurred in 22% and anastomotic stenosis in 41%. Logistic regression analysis revealed no influence of age, comorbidity, mean fundus dose, V20-V40, or the mediastinal ratio on the incidence of anastomotic leakage or anastomotic stenosis. In 28% of the patients severe complications (Clavien-Dindo score of ≥IIIB) occurred. The presence of multiple comorbidities (hazard ratio 2.4 [95% confidence interval 1.3-4.5], P=.006) and a mediastinal ratio of 0.5 to 1.0 (hazard ratio 1.9 [95% confidence interval 1.0-3.5], P=.036) were both independent predictors of severe complications. CONCLUSION: With a mean radiation dose of 24.2 Gy to the future anastomotic region of the gastric fundus, the radiation dose was not associated with the incidence of anastomotic leakage or anastomotic stenosis. The incidence of severe complications was associated with a high superior mediastinal planning target volume border.

Cone-Beam CT-based position verification for oesophageal cancer: Evaluation of registration methods and anatomical changes during radiotherapy.

PURPOSE: To evaluate different registration methods, setup margins and number of corrections for CBCT-based position verification for oesophageal cancer and to evaluate anatomical changes during the course of radiotherapy treatment. METHODS: From 50 patients, 440 CBCT-scans were registered automatically using a soft tissue or bone registration algorithm and compared to the clinical match. Moreover, relevant anatomical changes were monitored. A sub-analysis was performed to evaluate if tumour location influenced setup variations. Margin calculation was performed and the number of setup corrections was estimated. Results were compared to a patient group previously treated with MV-EPID based position verification. RESULTS: CBCT-based setup variations were smaller than EPID-based setup variations, resulting in smaller setup margins of 5.9 mm (RL), 7.5 mm (CC) and 4.7 mm (AP) versus 6.0 mm, 7.8 mm and 5.5 mm, respectively. A reduction in average number of setup corrections per patient was found from 0.75 to 0.36. From all automatically registered CBCT-scans, a clipbox around PTV and vertebras combined with soft tissue registration resulted in the smallest setup margins of 5.9 mm (RL), 7.7 mm (CC), 4.8 mm (AP) and smallest average number of corrections of 0.38. For distally located tumours, a setup margin of 7.7 mm (CC) was required compared to 5.6 mm for proximal tumours. Reduction of GTV volume, heart volume and change in diaphragm position were observed in 16, 10 and 15 patients, respectively. CONCLUSIONS: CBCT-based set-up variations are smaller than EPID-based variations and vary according to tumour location. When using kV-CBCT a large variety of anatomical changes is revealed, which cannot be observed with MV-EPID.

Delaying surgery after neoadjuvant chemoradiotherapy does not significantly influence postoperative morbidity or oncological outcome in patients with oesophageal adenocarcinoma.

BACKGROUND: Patients with resectable oesophageal cancer are treated with neoadjuvant chemoradiotherapy (nCRT) followed by surgery within 3-8 weeks. In practice, surgery is often delayed for various reasons. The aim of this study was to evaluate whether delaying surgery beyond 8 weeks has an effect on postoperative morbidity, long-term survival, and pathologic response in patients treated for oesophageal ADC. METHODS: Patients who underwent nCRT followed by surgery, for cT1-3, N0-3, M0 ADC between 2001 and 2014 were retrospectively included from a prospectively obtained database. Patients with a time from the end of nCRT to surgery (TTS) ≤8 weeks were compared with patients with a TTS >8 weeks. RESULTS: Of 190 patients, 65 had a TTS ≤8 weeks, and 125 had a TTS >8 weeks. Patient characteristics were comparable for both groups, but patients with TTS >8 weeks exhibited higher ASA scores (p = 0.013) and more comorbidities (p = 0.007). Multivariate analysis revealed that TTS did not significantly influence postoperative morbidity, pathologic complete response rates, and five-year survival rates (42% in patients with TTS ≤8 weeks and 37% in patients with TTS >8 weeks). CONCLUSIONS: Delaying surgery beyond 8 weeks after nCRT did not significantly influence postoperative morbidity, pathologic response, and survival in patients with non-metastatic ADC. Therefore, it appears reasonable to postpone surgery beyond 8 weeks in patients who have not yet recovered from nCRT. However, if the patient is fit for surgery, postponing surgery does not have any additional advantages.

Improvement in survival for patients with synchronous metastatic esophageal cancer in the south of the Netherlands from 1994 to 2013.

BACKGROUND: We assessed the use of external beam radiotherapy, brachytherapy chemoradiotherapy and chemotherapy in patients with metastatic esophageal cancer and evaluated the effect on overall survival. METHODS: We included all patients diagnosed with synchronous metastatic esophageal cancer in the south of the Netherlands between 1 January 1994 and 31 December 2013. Proportions of patients treated with external beam radiotherapy, brachytherapy, chemoradiotherapy and chemotherapy were described with respect to the period of diagnosis, patient and tumor characteristics. Independent risk factors for death were discriminated. RESULTS: A total of 1020 patients were included, 61.5% of these patients received palliative treatment with external beam radiotherapy, chemoradiotherapy, brachytherapy and/or chemotherapy. The use of external beam radiotherapy decreased from 44.5% in 1994 to 22.2% in 2013 (p = 0.0001), whereas the use of chemoradiotherapy increased from 2.9% in 1994 to 19.1% in 2013 (p < 0.0001). The prescription of systemic chemotherapy as single modality increased from 13.9% to 30.5% (p < 0.0001). The use of brachytherapy decreased from 20.9% in 1994 to 7.4% in 2013 (p = 0.0013). The odds of receiving external beam radiotherapy, brachytherapy, chemoradiotherapy and chemotherapy were influenced by different tumor and patient characteristics, such as age, gender, histologic subtype and number of metastatic sites. The median overall survival in patients with metastatic esophageal cancer significantly improved over time from 18 weeks (one-year survival rate 14.4%) in 1994-1998 to 25 weeks (one-year survival rate 22.4%) in 2009-2013. Patients treated with chemoradiotherapy had the most favorable prognosis, followed by patients treated with chemotherapy as a single modality. CONCLUSION: The median overall survival of patients diagnosed with metastatic esophageal cancer improved from 18 weeks in 1994-1998 to 25 weeks in 2009-2013. Although this increase could be attributed to stage migration, our population-based study suggests that major changes in treatment strategies and appropriate patient selection might have played a role as well.

Effectiveness of routine follow-up in the detection of contralateral breast cancer in young women with early breast cancer.

BACKGROUND: The purpose of the study was to determine the effectiveness of routine follow-up to detect contralateral breast cancer (CBC) in young women. METHODS: We used the data of the population-based Eindhoven Cancer Registry, which covers the southern part of the Netherlands. Between 1988 and 2005, 1451 women aged ≤ 40 years were treated for early-stage breast cancer with breast-conserving treatment or mastectomy. RESULTS: Of the 94 patients who developed CBC 17 had an in situ carcinoma. Fifty-seven CBCs (61%) were diagnosed more than 5 years after the primary tumour. Forty-two CBCs (45%) were detected during routine follow-up visits, while 52 (55%) presented between two visits. Of the CBC diagnosed between two visits, only 27 (60%) were visible on mammography. Of the invasive CBCs more than 25% was larger than 2 cm in diameter and in 34% positive axillary lymph nodes were found. CONCLUSIONS: These figures indicate that routine follow-up does not guarantee early detection of CBC in young women with breast cancer.

Prognosis following local recurrence after breast conserving treatment in young women with early breast cancer.

BACKGROUND: Few studies have focussed on the prognosis of young women with local recurrence (LR) after breast-conserving therapy and the factors that can be used to predict their prognosis. METHODS: We studied the outcome and related prognostic factors in 124 patients with an isolated local recurrence in the breast following breast-conserving surgery and radiotherapy for early stage breast cancer diagnosed at the age of 40 years or younger. RESULTS: The median follow-up of the patients after diagnosis of LR was 7.0 years. At 10 years from the date of salvage treatment, the overall survival rate was 73% (95% CI, 63-83), the distant recurrence-free survival rate was 61% (95% CI, 53-73), and the local control rate (i.e. survival without subsequent LR or local progression) was 95% (95% CI, 91-99). In the multivariate analysis, the risk of distant metastases also tended to be higher for patients with LR occurring within 5 years after BCT, as compared to patients with LR more than 5 years after BCT (Hazard ratio [HR], 1.89; p = 0.09). A worse distant recurrence-free survival was also observed for patients with a LR measuring more than 2 cm in diameter, compared to those with a LR of 2 cm or smaller (HR, 2.88; p = 0.007), and for patients with a LR causing symptoms or suspicious findings at clinical breast examination, compared to those with a LR detected by breast imaging only (HR 3.70; p = 0.03). CONCLUSIONS: These results suggest that early detection of LR after BCT in young women can improve treatment outcome.

Local recurrence following breast-conserving treatment in women aged 40 years or younger: trends in risk and the impact on prognosis in a population-based cohort of 1143 patients.

AIM: To evaluate trends in the risk of local recurrences after breast-conserving treatment (BCT) and to examine the impact of local recurrence (LR) on distant relapse-free survival in a large, population-based cohort of women aged ≤40 years with early-stage breast cancer. METHODS: All women (n=1143) aged ≤40 years with early-stage (pT1-2/cT1-2, N0-2, M0) breast cancer who underwent BCT in the south of the Netherlands between 1988 and 2010 were included. BCT consisted of local excision of the tumour followed by irradiation of the breast. RESULTS: After a median follow-up of 8.5 (0.1-24.6)years, 176 patients had developed an isolated LR. The 5-year LR-rate for the subgroups treated in the periods 1988-1998, 1999-2005 and 2006-2010 were 9.8% (95% confidence interval (CI) 7.1-12.5), 5.9% (95% CI 3.2-8.6) and 3.3% (95% CI 0.6-6.0), respectively (p=0.006). In a multivariate analysis, adjuvant systemic treatment was associated with a reduced risk of LR of almost 60% (hazard ratio (HR) 0.42; 95%CI 0.28-0.60; p<0.0001). Patients who experienced an early isolated LR (≤5 years after BCT) had a worse distant relapse-free survival compared to patients without an early LR (HR 1.83; 95% CI 1.27-2.64; p=0.001). Late local recurrences did not negatively affect distant relapse-free survival (HR 1.24; 95% CI 0.74-2.08; p=0.407). CONCLUSION: Local control after BCT improved significantly over time and appeared to be closely related to the increased use and effectiveness of systemic therapy. These recent results underline the safety of BCT for young women with early-stage breast cancer.

Preoperative chemoradiotherapy for esophageal or junctional cancer.

BACKGROUND: The role of neoadjuvant chemoradiotherapy in the treatment of patients with esophageal or esophagogastric-junction cancer is not well established. We compared chemoradiotherapy followed by surgery with surgery alone in this patient population. METHODS: We randomly assigned patients with resectable tumors to receive surgery alone or weekly administration of carboplatin (doses titrated to achieve an area under the curve of 2 mg per milliliter per minute) and paclitaxel (50 mg per square meter of body-surface area) for 5 weeks and concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week), followed by surgery. RESULTS: From March 2004 through December 2008, we enrolled 368 patients, 366 of whom were included in the analysis: 275 (75%) had adenocarcinoma, 84 (23%) had squamous-cell carcinoma, and 7 (2%) had large-cell undifferentiated carcinoma. Of the 366 patients, 178 were randomly assigned to chemoradiotherapy followed by surgery, and 188 to surgery alone. The most common major hematologic toxic effects in the chemoradiotherapy-surgery group were leukopenia (6%) and neutropenia (2%); the most common major nonhematologic toxic effects were anorexia (5%) and fatigue (3%). Complete resection with no tumor within 1 mm of the resection margins (R0) was achieved in 92% of patients in the chemoradiotherapy-surgery group versus 69% in the surgery group (P<0.001). A pathological complete response was achieved in 47 of 161 patients (29%) who underwent resection after chemoradiotherapy. Postoperative complications were similar in the two treatment groups, and in-hospital mortality was 4% in both. Median overall survival was 49.4 months in the chemoradiotherapy-surgery group versus 24.0 months in the surgery group. Overall survival was significantly better in the chemoradiotherapy-surgery group (hazard ratio, 0.657; 95% confidence interval, 0.495 to 0.871; P=0.003). CONCLUSIONS: Preoperative chemoradiotherapy improved survival among patients with potentially curable esophageal or esophagogastric-junction cancer. The regimen was associated with acceptable adverse-event rates. (Funded by the Dutch Cancer Foundation [KWF Kankerbestrijding]; Netherlands Trial Register number, NTR487.).

Small but significant socioeconomic inequalities in axillary staging and treatment of breast cancer in the Netherlands.

BACKGROUND: The use of sentinel node biopsy (SNB), lymph node dissection, breast-conserving surgery, radiotherapy, chemotherapy and hormonal treatment for breast cancer was evaluated in relation to socioeconomic status (SES) in the Netherlands, where access to care was assumed to be equal. METHODS: Female breast cancer patients diagnosed between 1994 and 2008 were selected from the nationwide population-based Netherlands Cancer Registry (N=176 505). Socioeconomic status was assessed based on income, employment and education at postal code level. Multivariable models included age, year of diagnosis and stage. RESULTS: Sentinal node biopsy was less often applied in high-SES patients (multivariable analyses, ≤ 49 years: odds ratio (OR) 0.70 (95% CI: 0.56-0.89); 50-75 years: 0.85 (0.73-0.99)). Additionally, lymph node dissection was less common in low-SES patients aged ≥ 76 years (OR 1.34 (0.95-1.89)). Socioeconomic status-related differences in treatment were only significant in the age group 50-75 years. High-SES women with stage T1-2 were more likely to undergo breast-conserving surgery (+radiotherapy) (OR 1.15 (1.09-1.22) and OR 1.16 (1.09-1.22), respectively). Chemotherapy use among node-positive patients was higher in the high-SES group, but was not significant in multivariable analysis. Hormonal therapy was not related to SES. CONCLUSION: Small but significant differences were observed in the use of SNB, lymph node dissection and breast-conserving surgery according to SES in Dutch breast cancer patients despite assumed equal access to health care.

Hormone treatment without surgery for patients aged 75 years or older with operable breast cancer.

PURPOSE: To evaluate the trend in the use of primary endocrine treatment (PET) for elderly patients with operable breast cancer and to study mean time to response (TTR), local control, time to progression (TTP), and overall survival. METHODS: Data of 184 patients aged≥75 years, diagnosed with breast cancer in the south of the Netherlands between 2001 and 2008 and receiving PET, were analyzed. RESULTS: The percentage of women≥75 years with breast cancer receiving PET in the south of the Netherlands decreased from 23% in the period 1988-1992 to 12% in 1997-2000, and increased to 29% in 2005-2008. Mean age at diagnosis of 184 patients treated with PET in the period 2001-2008 was 84 years (range 75-89 years). Mean length of follow-up was 2.6 years. In 107 patients (58%), an initial response was achieved (mean TTR 7 months), 21 patients (12%) showed stable disease. A total of 64 patients (35%), with or without prior response, eventually displayed progression (mean TTP 20 months). No differences in TTR and TTP were observed between the patients starting with tamoxifen or an aromatase inhibitor. One hundred nineteen (65%) of 184 patients had died by January 1, 2010. In 17 patients (14%), breast cancer was the cause of death. CONCLUSIONS: Tumor progression was observed in a substantial proportion of the cohort, but only a small number of patients died of breast cancer. Further research is needed on the safety and effectiveness of PET for elderly women with breast cancer to justify the current widespread use.

Staging and management of axillary lymph nodes in patients with local recurrence in the breast or chest wall after a previous negative sentinel node procedure.

OBJECTIVE: To evaluate axillary staging and management in patients with local recurrence (LR) after a previous negative sentinel lymph node biopsy (SNB). METHODS: Between 1999 and 2008, 130 patients with previous negative SNB developed a LR of breast or chest wall. After examination of clinical records, 70 patients met the inclusion criteria and remained available for analysis. RESULTS: Thirty-seven patients were treated with axillary lymph node dissection (ALND), followed by axillary radiotherapy in 9 cases. In 26 of these 37 patients no positive axillary lymph nodes were found. Nineteen patients received no treatment of the axilla at all. Of those, 9 were older than 70 years of age at diagnosis of LR. In 13 patients a second SNB was attempted, but was successful in only 5 cases. Eight patients underwent a complementary ALND. Overall, positive lymph nodes were detected in 13 of the 50 patients who underwent axillary staging, either by SNB or ALND. The median length of follow-up of the 70 patients following their diagnosis of LR was 24 months (range 2-81 months). During this follow-up period one patient developed an axillary recurrence. This was a patient who refused to undergo ALND but was given locoregional radiotherapy instead. CONCLUSIONS: In the absence of guidelines for staging and management of the axilla at time of LR of breast or chest wall, many different strategies are being used. Considering the high rate of positive axillary lymph nodes in these patients, repeat surgical staging is appropriate.

[Breast cancer in young women: epidemiology and treatment dilemmas]. / Mammacarcinoom bij jonge vrouwen: epidemiologie en dilemma's in de behandeling.

The incidence of breast cancer in the Netherlands in women under 40 years has been more or less stable for the last 2 decades, while the mortality rate has decreased in the same period. Breast cancer in young women generally has a worse prognosis than in older women. Systemic therapy reduces the risk oflocoregional relapse after breast-conserving therapy from approximately 2% to less than 1% on an annual basis. Breast-conserving therapy therefore seems to be a safe option in young women who have consented beforehand to receive adjuvant systemic therapy. According to current treatment guidelines, adjuvant systemic therapy will be offered to approximately 80% of young breast cancer patients. The risk of premature postmenopausal symptoms, osteoporosis and unwanted infertility are, however, disadvantages of adjuvant chemotherapy and hormonal therapy. This specific treatment-related toxicity in young breast cancer patients requires support by experts with endowments for these specific issues.

A highly active and tolerable neoadjuvant regimen combining paclitaxel, carboplatin, 5-FU, and radiation therapy in patients with stage II and III esophageal cancer.

BACKGROUND: The present phase II study aimed to assess the feasibility and efficacy of a new paclitaxel-based neoadjuvant chemoradiation regimen followed by surgery in patients with stage II-III esophageal cancer. METHODS: From January 2002 to November 2004, 50 patients with a potentially resectable stage II-III esophageal cancer received chemotherapy with paclitaxel, carboplatin, and 5-FU in combination with radiotherapy 45 Gy in 25 fractions. Surgery followed 6-8 weeks after completion of neoadjuvant treatment. PATIENT CHARACTERISTICS: male/female: 44/6, median age 60 years (34-75), median WHO 1 (0-2), adenocarcinoma (n = 42), squamous cell carcinoma (n = 8). Toxicity was mild, and 84 % of the patients completed the whole regimen. Forty-seven patients underwent surgery with a curative intention (transhiatal n = 44, transthoracic n = 3). Pathologic complete tumor regression was achieved in 18 of 47 operated patients (38%). R0 resection was achieved in 45 of 47 operated patients (96%). There were four postoperative deaths (8.5). Postoperative complications were comparable with other studies. After a median follow-up of 41.5 months (21-59) estimated 3- and 5-year survival on an intention-to-treat basis was 56 and 48%. Estimated 3-year survival in responders was 61%, in nonresponders 33%. CONCLUSION: This novel neoadjuvant chemoradiation regimen for treatment of patients with stage II-III esophageal cancer is feasible. Results are encouraging with a high pathologic complete tumor regression and R0 resection rate and an acceptable morbidity and mortality. Preliminary survival data are very promising.

Margin status and the risk of local recurrence after breast-conserving treatment of lobular breast cancer.

BACKGROUND: Invasive lobular breast carcinoma is known for its multicentricity and is associated with a higher incidence of incomplete excision after breast-conserving therapy. The aim of the study was to examine the influence of positive surgical margins on the local recurrence rate in patients diagnosed with invasive lobular cancer and treated with breast-conserving therapy. METHODS: All 416 women diagnosed with invasive lobular breast cancer and undergoing breast-conserving treatment between 1995 and 2002 were selected from the population-based Eindhoven Cancer Registry. Their medical charts were reviewed and detailed information was collected. RESULTS: The risk of margin involvement was 29% after the first operation and 17% when taking into account the final margin status of the patients undergoing re-excision. During follow-up, 18 patients developed a local recurrence. The 5 year actuarial risk of developing a local recurrence was 3.5% (95% confidence interval 2.5-4.5) and the 8 year risk was 6.4% (95% confidence interval 4.7-8.0). There was no influence of positive surgical margins on the risk of local recurrence, neither in the univariate analysis nor after adjustment for age, tumour size, nodal status and adjuvant systemic treatment. CONCLUSION: Patients with invasive lobular cancer, treated with breast-conservation, have a low risk of local recurrence, despite their high risk of having a microscopically incomplete excision of the tumour.

Increased risk of second malignancies after in situ breast carcinoma in a population-based registry.

Among 1276 primary breast carcinoma in situ (BCIS) patients diagnosed in 1972-2002 in the Southern Netherlands, 11% developed a second cancer. Breast carcinoma in situ patients exhibited a two-fold increased risk of second cancer (standardised incidence ratios (SIR): 2.1, 95% confidence interval (CI): 1.7-2.5). The risk was highest for a second breast cancer (SIR: 3.4, 95% CI: 2.6-4.3; AER: 66 patients per 10,000 per year) followed by skin cancer (SIR: 1.7, 95% CI: 1.1-2.6; AER: 17 patients per 10,000 per year). The increased risk of second breast cancer was similar for the ipsilateral (SIR: 1.9, 95% CI: 1.3-2.7) and contralateral (SIR: 2.0, 95% CI: 1.4-2.8) breast. Risk of second cancer was independent of age at diagnosis, type of initial therapy, histologic type of BCIS and period of diagnosis. Standardised incidence ratios of second cancer after BCIS (SIR: 2.3, 95% CI: 1.8-2.8) resembled that after invasive breast cancer (SIR: 2.2, 95% CI: 2.1-2.4). Surveillance should be directed towards second (ipsi- and contra-lateral) breast cancer.

The prognosis of patients with local recurrence more than five years after breast conservation therapy for invasive breast carcinoma.

AIMS: The increasing use of breast-conserving therapy (BCT) and the rising incidence and improved prognosis of early breast are causing a substantial increase in the absolute number of patients with a late local recurrence following BCT. This study examined the characteristics and the prognosis of patients with a local recurrence occurring more than 5 years after BCT. METHODS: In the period 1982-1997, 3280 patients with invasive breast cancer underwent breast-conserving therapy in one of the eight community hospitals in the South-eastern part of The Netherlands. Of these patients, 98 developed a local recurrence in the breast more than 5 years after BCT. RESULTS: Eighty-five of the 98 recurrences were invasive, 12 were purely in situ and for one patient this information was not available. The 5 years distant recurrence-free survival rate of 85 patients with a late invasive local recurrence was 68% (95% confidence interval [CI], 56-80) and significantly better than the rate of 41% (95% CI, 33-48) in an existing cohort of 173 patients with invasive recurrence within 5 years after BCT (p=0.007). Local excision of the recurrence was followed by a significantly lower local control rate than salvage mastectomy (50 vs 89%; p=0.004). CONCLUSION: The prognosis of patients with a local recurrence more than 5 years after BCT is significantly better than of patients with local recurrence within 5 years after BCT.