Search

Background: Uncertainty about the benefit-risk ratio of regional lymph node irradiation led to varying clinical protocols. We investigated long-term late side effects after internal mammary and medial supraclavicular (IM-MS) lymph node irradiation to improve shared decision making., Methods: The multicenter European Organization for Research and Treatment of Cancer trial (ClinicalTrials.gov, NCT00002851) randomly assigned stage I-III breast cancer patients with involved axillary nodes and/or a medially located primary tumor. We analyzed late side effects both longitudinally at every follow-up and cross-sectionally at 5-year intervals. All statistical tests were 2-sided., Results: Between 1996 and 2004, 46 departments from 13 countries accrued 4004 patients. Median follow-up was 15.7 years. Longitudinal follow-up data showed cumulative incidence rates at 15 years of 2.9% (95% confidence interval [CI] = 2.2% to 3.8%) vs 5.7% (95% CI = 4.7% to 6.9%) (P < .001) for lung fibrosis, 1.1% (95% CI = 0.7% to 1.7%) vs 1.9% (95% CI = 1.3% to 2.6%) (P = .07) for cardiac fibrosis, and 9.4% (95% CI = 8.0% to 10.8%) vs 11.1% (95% CI = 9.6% to 12.7%) (P = .04) for any cardiac disease when treated without or with IM-MS lymph node irradiation. There was no evidence for differences between left- and right-sided breast cancer (Wald χ2 test of treatment by breast side interaction, P = .33 and P = .35, for cardiac fibrosis and for any cardiac disease, respectively). The cumulative incidence probabilities of cross-sectionally reported side effects with a score of 2 or greater at 15 years were 0.1% (95% CI = 0.0% to 0.5%) vs 0.8% (95% CI = 0.4% to 1.4%) for pulmonary (P = .02), 1.8% (95% CI = 1.1% to 2.8%) vs 2.6% (95% CI = 1.8% to 3.7%) for cardiac (P = .15), and 0.0% (95% CI not evaluated) vs 0.1% (95% CI = 0.0% to 0.4%) for esophageal (P = .16), respectively. No difference was observed in the incidence of second malignancies, contralateral breast cancer, or cardiovascular deaths., Conclusions: The incidence of late pulmonary side effects was statistically significantly higher after IM-MS lymph node irradiation, as were some of the cardiac events, without a difference between left- and right-sided treatments. Absolute rates and differences were very low, without increased non-breast cancer-related mortality, even before introducing heart-sparing techniques., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: After 5 years of annual follow-up following breast cancer, Dutch guidelines are age based: annual follow-up for women <60 years, 60-75 years biennial, and none for >75 years. We determined how the risk of recurrence corresponds to these consensus-based recommendations and to the risk of primary breast cancer in the general screening population., Subjects, Materials, and Methods: Women with early-stage breast cancer in 2003/2005 were selected from the Netherlands Cancer Registry (n = 18,568). Cumulative incidence functions were estimated for follow-up years 5-10 for locoregional recurrences (LRRs) and second primary tumors (SPs). Risks were compared with the screening population without history of breast cancer. Alternative cutoffs for age were determined by log-rank tests., Results: The cumulative risk for LRR/SP was lower in women <60 years (5.9%, 95% confidence interval [CI] 5.3-6.6) who are under annual follow-up than for women 60-75 (6.3%, 95% CI 5.6-7.1) receiving biennial visits. All risks were higher than the 5-year risk of a primary tumor in the screening population (ranging from 1.4% to 1.9%). Age cutoffs <50, 50-69, and > 69 revealed better risk differentiation and would provide more risk-based schedules. Still, other factors, including systemic treatments, had an even greater impact on recurrence risks., Conclusion: The current consensus-based recommendations use suboptimal age cutoffs. The proposed alternative cutoffs will lead to a more balanced risk-based follow-up and thereby more efficient allocation of resources. However, more factors should be taken into account for truly individualizing follow-up based on risk for recurrence., Implications for Practice: The current age-based recommendations for breast cancer follow-up after 5 years are suboptimal and do not reflect the actual risk of recurrent disease. This results in situations in which women with higher risks actually receive less follow-up than those with a lower risk of recurrence. Alternative cutoffs could be a start toward risk-based follow-up and thereby more efficient allocation of resources. However, age, or any single risk factor, is not able to capture the risk differences and therefore is not sufficient for determining follow-up. More risk factors should be taken into account for truly individualizing follow-up based on the risk for recurrence., (© 2020 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

Background and Purpose: The aim of this study was to assess the effect of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on tumor response to preoperative chemoradiation for rectal cancer., Materials and Methods: Data on patients who received chemoradiation prior to surgery for rectal cancer between 2010 and 2015 were retrieved from linkage between the PHARMO Database Network, Dutch Pathology Registry and Netherlands Cancer Registry. Pathological complete response rates (pCR) were compared between patients who did or did not use ACEIs/ARBs during treatment. Multivariable analysis was performed using logistic regression., Results: Out of 345 patients, 92 patients (26.7%) used ACEIs/ARBs during treatment. Median age was 65 years (range 30-85). Older and male patients were more likely to use ACEIs/ARBs. pCR (ypT0N0) was observed in 17.4% of patients using ACEIs/ARBs compared to 14.6% of patients who did not use ACEIs/ARBs (p = 0.595). A good response (ypT0-1N0) was observed in 21.7% of ACEIs/ARBs patients vs. 19.4% of patients who did not use ACEIs/ARBs (p = 0.724). Multivariable analysis, taking into account background variables and co-medication, showed increased pCR in patients using beta-blockers (odds ratio 2.3, 95% confidence interval 1.0-5.4)., Conclusion: In this retrospective cohort, the use of ACEIs/ARBs was not associated with tumor response to preoperative chemoradiation in rectal cancer patients. Thereby, the suggested potentiating effect of ACEIS/ARBs could not be confirmed in our study. Further research could be directed to investigate a possible benefit of beta-blockers or other anti-hypertensive drugs., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The Dutch guidelines advise to start radiation therapy (RT) within 5 weeks following breast-conserving surgery (BCS). However, much controversy exists regarding timing of RT. This study investigated its effect on 10-year disease-free survival (DFS) in a Dutch population-based cohort., Methods: All women diagnosed with primary invasive stage I-IIIA breast cancer in 2003 treated with BCS+RT were included. Two populations were studied. Population 1 excluded patients receiving chemotherapy before RT. Analyses were stratified for use of adjuvant systemic therapy (AST). Population 2 included patients treated with chemotherapy, and compared chemotherapy before (BCS-chemotherapy-RT) and after RT (BCS-RT-chemotherapy). DFS was estimated using multivariable Cox regression. Locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS) and overall survival (OS) were secondary outcomes., Results: Population 1 (n=2759) showed better DFS and DMFS for a time interval of >55 than a time interval of <42 days. Patients treated with AST showed higher DFS for >55 days (hazards ratio (HR) 0.60 (95% confidence interval (CI): 0.38-0.94)) and 42-55 days (HR 0.64 (95% CI: 0.45-0.91)) than <42 days. Results were similar for DMFS, while timing did not affect LRRFS and OS. For patients without AST, timing was not associated with DFS, DMFS and LLRFS, but 10-year OS was significantly lower for 42-55 and >55 days compared to <42 days. In population 2 (n=1120), timing did not affect survival in BCS-chemotherapy-RT. In BCS-RT-chemotherapy, DMFS was higher for >55 than <42 days., Conclusions: Starting RT shortly after BCS seems not to be associated with a better long-term outcome. The common position that RT should start as soon as possible following surgery in order to increase treatment efficacy can be questioned.

Background: Trials failed to demonstrate additional value of completion axillary lymph node dissection in case of limited sentinel lymph node metastases in breast cancer patients undergoing breast conserving therapy. It has been suggested that the low regional recurrence rates in these trials might partially be ascribed to accidental irradiation of part of the axilla by whole breast radiation therapy, which precludes extrapolation of results to mastectomy patients. The aim of the randomized controlled BOOG 2013-07 trial is therefore to investigate whether completion axillary treatment can be safely omitted in sentinel lymph node positive breast cancer patients treated with mastectomy., Design: This study is designed as a non-inferiority randomized controlled multicentre trial. Women aged 18 years or older diagnosed with unilateral invasive clinically T1-2 N0 breast cancer who are treated with mastectomy, and who have a maximum of three axillary sentinel lymph nodes containing micro- and/or macrometastases, will be randomized for completion axillary treatment versus no completion axillary treatment. Completion axillary treatment can consist of completion axillary lymph node dissection or axillary radiation therapy. Primary endpoint is regional recurrence rate at 5 years. Based on a 5-year regional recurrence free survival rate of 98 % among controls and 96 % for study subjects, the sample size amounts 439 per arm (including 10 % lost to follow-up), to be able to reject the null hypothesis that the rate for study and control subjects is inferior by at least 5 % with a probability of 0.8. Results will be reported after 5 and 10 years of follow-up., Discussion: We hypothesize that completion axillary treatment can be safely omitted in sentinel node positive breast cancer patients undergoing mastectomy. If confirmed, this study will significantly decrease the number of breast cancer patients receiving extensive treatment of the axilla, thereby diminishing the risk of morbidity and improving quality of life, while maintaining excellent regional control and without affecting survival., Trial Registration: The BOOG 2013-07 study is registered in the register of ClinicalTrials.gov since April 10, 2014, Identifier: NCT02112682 .

Background: Coinciding with the relatively good and improving prognosis for patients with stage I-III breast cancer, late recurrences, new primary tumours and late side-effects of treatment may occur. We gained insight into prognosis for long-term breast cancer survivors., Patients and Methods: Data on all 205 827 females aged 15-89 diagnosed with stage I-III breast cancer during 1989-2008 were derived from the Netherlands Cancer Registry. Conditional 5-year relative survival was calculated for every subsequent year from diagnosis up to 15 years., Results: For stage I, conditional 5-year relative survival remained ~95% up to 15 years after diagnosis (a stable 5-year excess mortality rate of 5%). For stage II, excess mortality remained 10% for those aged 15-44 or 45-59 and 15% for those aged 60-74. For stage III, excess mortality decreased from 35% at diagnosis to 10% at 15 years for those aged 15-44 or 45-59, and from ~40% to 30% for those aged ≥60., Conclusions: Patients with stage I or II breast cancer had a (very) good long-term prognosis, albeit exhibiting a small but significant excess mortality at least up to 15 years after diagnosis. Improvements albeit from a lower level were mainly seen for patients who had been diagnosed with stage III disease. Caregivers can use this information to better inform (especially disease-free) cancer survivors about their actual prognosis.

Background: To determine the activity of radiotherapy in patients with inoperable desmoid-type fibromatosis (DF) a multicenter prospective phase II trial was carried out., Materials and Methods: Patients with inoperable progressive disease of primary, recurrent or incompletely resected lesions received a dose of 56 Gy in 28 fractions. Follow-up MRI studies were carried out every 3 months for 2 years and thereafter every 6 months. The primary end point was local control rate at 3 years, estimated by a nonparametric method for interval-censored survival data. Secondary end points were objective tumor response, acute and late toxic effect., Results: Forty-four patients (27 F/17 M) were enrolled from 2001 to 2008. Median age was 39.5 years. Main tumor sites included trunk 15 (34.1%) and extremities 27 (61.3%). Median follow-up was 4.8 years. The 3-year local control rate was 81.5% (90% one-sided confidence interval 74% to 100%). Best overall response during the first 3 years was complete response (CR) 6 (13.6%), partial response (PR) 16 (36.4%), stable disease 18 (40.9%), progressive disease 3 (6.8%) and nonassessable 1 (2.3%). Five patients developed new lesions. After 3 years, the response further improved in three patients: (CR 2, PR 1). Acute grade 3 side-effects were limited to skin, mucosal membranes and pain. Late toxic effect consisted of mild edema in 10 patients., Conclusions: Moderate dose radiotherapy is an effective treatment of patients with DF. Response after radiation therapy is slow with continuing regression seen even after 3 years.

The detection of a local recurrence (LR) in young women with breast cancer after breast-conserving treatment (BCT) was investigated to compare the impact of different long-term follow-up strategies. Between 1988 and 2005, 937 women aged ≤40 years were treated with BCT for early-stage breast cancer in the southern part of the Netherlands. Up to October 2009, 152 had developed an isolated LR. Information on follow-up visits was available for 124 of them. Fifty-four LRs (44%) were diagnosed within 5 years and 70 (56%) more than 5 years after BCT. Fifty-six LRs (45%) were detected during routine follow-up visits and 68 (55%) presented between two visits. Sixty-six LRs (53%) were diagnosed in patients reporting symptoms. In 31 patients (25%) the LR was found by mammography alone. About a quarter of the LRs was larger than 2 cm in diameter. These results imply that current follow-up strategies for young women with BCT do not guarantee a timely detection of LR., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Neoadjuvant chemotherapy (NAC) is increasingly used in the framework of breast-conserving therapy (BCT). Localization of the initial tumor is essential to guide surgical resection after NAC. This study describes the results obtained with I-125 seed localization in BCT including NAC., Patients and Methods: Between January 2009 and December 2010, 85 patients treated with NAC and BCT after I-125 seed localization were included. Radiological and pathological response and resection margins were retrospectively evaluated., Results: BCT was carried out in 85 patients without secondary local excisions. Nineteen patients with unifocal tumors and seven patients with multifocal tumors showed a complete pathological response (P = 0.18). Tumor-free resection margins were obtained in 78 patients (50 patients with unifocal and 28 patients with multifocal tumors, P = 0.27). Focally involved margins were found in four patients (two patients with a unifocal and two patients with a multifocal tumor, P = 0.27). A subsequent mastectomy was carried out in three patients (two patients with multifocal tumors, P = 0.29)., Conclusions: BCT after NAC can be carried out successfully after initial localization with I-125 seeds in both unifocal and multifocal breast tumors with complete resection rates of >90%.

Background: In breast cancer treated with breast-conserving radiotherapy, the influence of the boost dose on cosmetic outcome after long-term follow-up is unknown., Patients and Methods: We included 348 patients participating in the EORTC 'boost versus no boost' mega trial with a minimum follow-up of 6 years. Digitalised pictures were analysed using specific software, enabling quantification of seven relative asymmetry features associated with different aspects of fibrosis., Results: After 3 years, we noted a statistically significantly poorer outcome for the boost patients for six features compared with those of the no boost patients. Up to 9 years of follow-up, results continued to worsen in the same magnitude for the both patient groups. We noted the following determinants for poorer outcome: (i) boost treatment, (ii) larger excision volumes, (iii) younger age, (iv) tumours located in the central lower quadrants of the breast and (v) a boost dose administered with photons., Conclusions: A boost dose worsens the change in breast appearance in the first 3 years. Moreover, the development of fibrosis associated with whole-breast irradiation, as estimated with the relative asymmetry features, is an ongoing process until (at least) 9 years after irradiation.

Long-term local control rates were studied in a series of 659 patients with invasive breast cancer aged 40 years or younger, who underwent mastectomy in general hospitals in the southern part of the Netherlands between 1988 and 2005. During a median follow-up time of 6.0 years, 34 patients developed a local recurrence in the chest wall without previous or simultaneous evidence of distant disease. The 5- and 10-year actuarial local recurrence rates for the total group were 5.6% (95% confidence interval [95% CI], 3.5-7.7%) and 7.3% (95% CI, 4.7-9.9%), respectively. A multivariate analysis showed that patients receiving radiotherapy (hazards ratio [HR], 0.29; 95% CI, 0.10-0.96) or adjuvant systemic treatment (HR 0.23; 95% CI, 0.08-0.65) had a significantly lower risk of local recurrence. It is concluded that excellent local control rates can be obtained with mastectomy in young women with breast cancer, especially in those who receive adjuvant systemic treatment and/or radiotherapy., (Copyright (c) 2009 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the impact of the quality of involved-field radiotherapy (IFRT) on clinical outcome in patients with advanced Hodgkin's lymphoma (HL) in complete remission (CR) after six to eight cycles of mechlorethamine, vincristine, procarbazine, prednisone-doxorubicin, bleomycin, and vinblastine (MOPP-ABV) chemotherapy., Methods and Materials: A retrospective review of clinical and radiologic data, radiation charts, simulator films, and megavoltage (MV) photographs was performed. IFRT consisted of 24 Gy to all initially involved nodal areas and 16-24 Gy to all initially involved extranodal sites. Major violations were defined as no or only partial irradiation of an originally involved area, or a total dose <90% of the prescribed dose., Results: Of the 739 patients who were enrolled in the trial between 1989 and 2000, 57% achieved a CR; 152 of 172 patients randomized to IFRT actually received radiotherapy; and in 135 patients, quality control was performed. The overall major violation rate was 47%, predominantly concerning target volumes. The total dose was correct in 81% of the patients. After a median follow-up of 6.5 years, there was no difference in cumulative failure rate between patients with or without major violations. There was no relationship between incidence or site of relapse and major protocol violations., Conclusion: In advanced-stage HL patients in complete remission after six to eight cycles of MOPP-ABV, the outcome was not influenced by violation of the radiotherapy protocol.

Purpose: To present the results of the dummy run of the European Organization for Research and Treatment of Cancer (EORTC) trial investigating the role of adjuvant internal mammary and medial supraclavicular (IM-MS) irradiation in Stage I--III breast cancer., Methods and Materials: All participating institutions were asked to produce a treatment plan without (Arm 1) and with (Arm 2) simultaneous IM-MS irradiation of 1 patient after mastectomy and of 1 patient after lumpectomy. Thirty-two dummy runs have been evaluated for compliance to protocol guidelines, with respect to treatment technique and dose prescription., Results: A number of more or less important deviations in treatment setup and prescription have been found. The dose in the IM-MS region deviated significantly from the prescribed dose in 10% of the cases for Arm 1, and in 21% for Arm 2. Assuming a true 5% 10-year survival benefit from optimal IM-MS irradiation, an increase of only 3.8% will be found due to this suboptimal dose distribution., Conclusion: In the dummy run, a number of potential systematic protocol deviations that might lead to false-negative results were detected. By providing recommendations to the participating institutions, we expect to improve the interinstitutional consistency and to promote a high quality irradiation in all institutions participating in the trial.