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Importance: Neoadjuvant short-course radiotherapy was routinely applied for nonlocally advanced rectal cancer (cT1-3N0-1M0 with >1 mm distance to the mesorectal fascia) in the Netherlands following the Dutch total mesorectal excision trial. This policy has shifted toward selective application after guideline revision in 2014., Objective: To determine the association of decreased use of neoadjuvant radiotherapy with cancer-related outcomes and overall survival at a national level., Design, Setting, and Participants: This multicenter, population-based, nationwide cross-sectional cohort study analyzed Dutch patients with rectal cancer who were treated in 2011 with a 4-year follow-up. A similar study was performed in 2021, analyzing all patients that were surgically treated in 2016. From these cohorts, all patients with cT1-3N0-1M0 rectal cancer and radiologically unthreatened mesorectal fascia were included in the current study. The data of the 2011 cohort were collected between May and October 2015, and the data of the 2016 cohort were collected between October 2020 and November 2021. The data were analyzed between May and October 2022., Main Outcomes and Measures: The main outcomes were 4-year local recurrence and overall survival rates., Results: Among the 2011 and 2016 cohorts, 1199 (mean [SD] age, 68 [11] years; 430 women [36%]) of 2095 patients (57.2%) and 1576 (mean [SD] age, 68 [10] years; 547 women [35%]) of 3057 patients (51.6%) had cT1-3N0-1M0 rectal cancer and were included, with proportions of neoadjuvant radiotherapy of 87% (2011) and 37% (2016). Four-year local recurrence rates were 5.8% and 5.5%, respectively (P = .99). Compared with the 2011 cohort, 4-year overall survival was significantly higher in the 2016 cohort (79.6% vs 86.4%; P < .001), with lower non-cancer-related mortality (13.8% vs 6.3%; P < .001)., Conclusions and Relevance: The results of this cross-sectional study suggest that an absolute 50% reduction in radiotherapy use for nonlocally advanced rectal cancer did not compromise cancer-related outcomes at a national level. Optimizing clinical staging and surgery following the Dutch total mesorectal excision trial has potentially enabled safe deintensification of treatment.

Background and Objectives: To evaluate the representativeness of Dutch patients participating in the European Organization for Research and Treatment of Cancer EORTC boost-no-boost trial to the target breast cancer patient population., Methods: All female breast cancer patients diagnosed between 1989 and 1996, aged ≤70 years, treated with breast-conserving surgery and radiation therapy, were selected from the Netherlands Cancer Registry (NCR) and linked to the EORTC trial database. Baseline characteristics were compared between trial and non-trial participants, for the Dutch population and according to seven participating institutions. Kaplan-Meier curves and multivariable Cox regression were used to explore potential heterogeneity in overall survival between low, medium and high-volume institutes., Results: Overall, 20,880 patients were identified from the NCR: 2,445 of 2,602 (94%) trial participants could be linked, and 18,435 were treated outside the trial. Trial participants had similar age, morphology, topography, laterality and socioeconomic status as non-trial participants, but more often stage I (62.7% vs. 56.4%) tumours and less often adjuvant treatment (22.9% vs. 26.5%). Crude 20-year survival ranged from 52.5% to 57.4%, without significant differences in multivariable analyses., Conclusion: This case study showed that participants in the boost-no-boost trial well represented the Dutch target population. Data linkage comes with challenges, but can close the gap between research and clinical practice., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: In line with the paradigm to minimize surgical morbidity in patients with primary breast cancer, there is increasing evidence for the safety of a repeat breast-conserving treatment (BCT) of an ipsilateral breast tumour recurrence (IBTR) in selected patients. The conditions for the feasibility of a repeat BCT vary widely in literature. In clinical practice, many physicians have ongoing concerns about the oncological safety and possible toxicity of repeat BCT., Aim: To investigate the attitude of Dutch breast surgeons and radiation oncologists towards repeat BCT and to report on their experiences with, objections against and perceived requirements to consider a repeat BCT in case of IBTR., Patients and Methods: An online survey consisting of a maximum of 26 open and multiple-choice questions about repeat BCT for IBTR was distributed amongst Dutch breast surgeons and radiation oncologists., Results: Forty-nine surgeons representing 49% of Dutch hospitals and 20 radiation oncologists representing 70% of Dutch radiation oncology centres responded. A repeat BCT was considered feasible in selected cases by 28.7% of breast surgeons and 55% of radiation oncologists. The most important factors to consider a repeat BCT for both groups were the patient's preference to preserve the breast and surgical feasibility of a second lumpectomy. Arguments against a repeat BCT were based on the perceived unacceptable toxicity and cosmesis of a second course of radiotherapy. The technique of preference for re-irradiation would be partial breast irradiation (PBI) according to all radiation oncologists. Differentiating between new primary tumours (NPT) and true recurrences (TR) was reported to be done by 57.1% of breast surgeons and 60% of radiation oncologists. The most important reason to differentiate between NPT and TR was to establish prognosis and to consider whether a repeat BCT would be feasible., Conclusion: An increasing number of Dutch breast cancer specialists is considering a repeat BCT feasible in selected cases, at the patient's preference and with partial breast re-irradiation.

Background: Extended resections (i.e., major hepatectomy and/or pancreatoduodenectomy) are rarely performed for gallbladder cancer (GBC) because outcomes remain inconclusive. Data regarding extended resections from Western centers are sparse. This Dutch, multicenter cohort study analyzed the outcomes of patients who underwent extended resections for locally advanced GBC., Methods: Patients with GBC who underwent extended resection with curative intent between January 2000 and September 2018 were identified from the Netherlands Cancer Registry. Extended resection was defined as a major hepatectomy (resection of ≥ 3 liver segments), a pancreatoduodenectomy, or both. Treatment and survival data were obtained. Postoperative morbidity, mortality, survival, and characteristics of short- and long-term survivors were assessed., Results: The study included 33 patients. For 16 of the patients, R0 resection margins were achieved. Major postoperative complications (Clavien Dindo ≥ 3A) occurred for 19 patients, and 4 patients experienced postoperative mortality within 90 days. Recurrence occurred for 24 patients. The median overall survival (OS) was 12.8 months (95% confidence interval, 6.5-19.0 months). A 2-year survival period was achieved for 10 patients (30%) and a 5-year survival period for 5 patients (15%). Common bile duct, liver, perineural and perivascular invasion and jaundice were associated with reduced survival. All three recurrence-free patients had R0 resection margins and no liver invasion., Conclusion: The median OS after extended resections for advanced GBC was 12.8 months in this cohort. Although postoperative morbidity and mortality were significant, long-term survival (≥ 2 years) was achieved in a subset of patients. Therefore, GBC requiring major surgery does not preclude long-term survival, and a subgroup of patients benefit from surgery.

Importance: The percentage of tumor-positive surgical resection margin rates in patients treated for locally advanced primary or recurrent rectal cancer is high. Image-guided navigation may improve complete resection rates., Objective: To ascertain whether image-guided navigation during rectal cancer resection improves complete resection rates compared with surgical procedures without navigation., Design, Setting, and Participants: This prospective single-center nonrandomized controlled trial was conducted at the Netherlands Cancer Institute-Antoni van Leeuwenhoek in Amsterdam, the Netherlands. The prospective or navigation cohort included adult patients with locally advanced primary or recurrent rectal cancer who underwent resection with image-guided navigation between February 1, 2016, and September 30, 2019, at the tertiary referral hospital. Clinical results of this cohort were compared with results of the historical cohort, which was composed of adult patients who received rectal cancer resection without image-guided navigation between January 1, 2009, and December 31, 2015., Intervention: Rectal cancer resection with image-guided navigation., Main Outcomes and Measures: The primary end point was the complete resection rate, measured by the amount of tumor-negative resection margin rates. Secondary outcomes were safety and usability of the system. Safety was evaluated by the number of navigation system-associated surgical adverse events. Usability was assessed from responses to a questionnaire completed by the participating surgeons after each procedure., Results: In total, 33 patients with locally advanced or recurrent rectal cancer were included (23 men [69.7%]; median [interquartile range] age at start of treatment, 61 [55.0-69.0] years). With image-guided navigation, a radical resection (R0) was achieved in 13 of 14 patients (92.9%; 95% CI, 66.1%-99.8%) after primary resection of locally advanced tumors and in 15 of 19 patients (78.9%; 95% CI, 54.4%-94.0%) after resection of recurrent rectal cancer. No navigation system-associated complications occurred before or during surgical procedures. In the historical cohort, 142 patients who underwent resection without image-guided navigation were included (95 men [66.9%]; median [interquartile range] age at start of treatment, 64 [55.0-70.0] years). In these patients, an R0 resection was accomplished in 85 of 101 patients (84.2%) with locally advanced rectal cancer and in 20 of 41 patients (48.8%) with recurrent rectal cancer. A significant difference was found between the navigation and historical cohorts after recurrent rectal cancer resection (21.1% vs 51.2%; P = .047). For locally advanced primary tumor resection, the difference was not significant (7.1% vs 15.8%; P = .69). Surgeons stated in completed questionnaires that the navigation system improved decisiveness and helped with tumor localization., Conclusions and Relevance: Findings of this study suggest that image-guided navigation used during rectal cancer resection is safe and intuitive and may improve tumor-free resection margin rates in recurrent rectal cancer., Trial Registration: Netherlands Trial Register Identifier: NTR7184.

Background: Desmoplastic melanoma (DM) is an uncommon type of melanoma. Two histological subtypes of DM can be distinguished: pure and mixed (PDM and MDM). We hypothesized that discrimination between these subtypes is associated with sentinel lymph node biopsy (SLNB) status and survival., Methods: Clinicopathological data from PALGA, the Dutch Pathology Register were retrieved from patients diagnosed with DM in The Netherlands between 2000 and 2014. Clinical and pathological variables were extracted from pathology text files, including pure or mixed desmoplastic morphology. A Cox proportional hazard model was performed for overall and recurrence-free survival (OS and RFS)., Results: A total of 239 patients with DM were included, representing 0.4% of all primary cutaneous melanoma in The Netherlands. A total of 114 PDM and 125 MDM patients were identified. MDM was significantly associated with positive SLNB status (P = .035). In multivariable analysis, age (HR 1.10, 95% CI 1.07-1.14, P < .001) and ulceration (HR 1.98, 95% CI 1.05-3.75, P = .036) were significant predictors for OS. For RFS, mixed subtype (HR 2.72 95% CI 1.07-6.89, P = .035), male gender (HR 2.54, 95% CI 1.03-6.27, P = .043), and Breslow thickness (HR 1.13 per mm, 95% CI 1.05-1.21, P = .001) were significant predictors., Conclusion: MDM is significantly associated with a positive SLNB status. Mixed subtype is significantly correlated with RFS, but not with OS. The distinction between pure and mixed desmoplastic subtype therefore seems to be of clinical importance., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Dermatofibrosarcoma protuberans is a rare soft tissue tumour with a very low (p < 0.5%) rate of metastasis. Rates of re-excision and recurrence were determined using data from the Netherlands Cancer Registry between 1989 and 2016. Of the 1,890 instances of dermatofibrosarcoma protuberans included, 87% were treated with excision, 4% with Mohs micrographic surgery, and 9% otherwise or unknown. Linked pathology data were retrieved for 1,677 patients. Half of all excisions (847/1,644) were incomplete and 29% (192/622) of all re-excisions were incomplete. The cumulative incidence of a recurrence was 7% (95% confidence interval (95% CI) 6-8) during a median follow-up of 11 years (interquartile range (IQR) 6-17). After Mohs micrographic surgery (n = 34), there were no recurrences during a median follow-up of 4 years (IQR 3-6). Due to the high rate of incomplete excisions and recurrences after excision, this study supports the European guideline, which recommends treating dermatofibrosarcoma protuberans with Mohs micrographic surgery in order to decrease the rate of recurrence.

Comparative studies of the overall survival (OS) in elderly patients with nonsmall cell lung cancer (NSCLC) after surgery or stereotactic body radiotherapy (SBRT) have been limited by mixed extents of resection and different surgical approaches.792 patients aged ≥65 years with clinical stage I NSCLC underwent video-assisted thoracic surgery (VATS) lobectomy or SBRT between 2010 and 2015. The propensity score-matched primary analysis included data from the full cohort; the secondary analysis included data from a subgroup of patients with data on pulmonary function.Median OS for unmatched patients was 77 months for patients undergoing VATS lobectomy and 38 months for SBRT. The 1-, 3- and 5-year OS rates after VATS lobectomy were 92%, 76% and 65%, and after SBRT were 90%, 52% and 29% (p<0.001). Median OS for matched patients in the primary analysis was 77 months for patients undergoing VATS lobectomy and 33 months for SBRT. The 1-, 3- and 5-year OS rates after VATS lobectomy were 91%, 68% and 58%, and after SBRT were 87%, 46% and 29% (p<0.001). The survival advantage with VATS lobectomy persisted in the secondary analysis after adjusting for non-matched variables (p=0.034).We suggest that elderly patients with stage I NSCLC undergoing VATS lobectomy have a better rate of OS than patients undergoing SBRT, irrespective of matching. This could be clinically important in decision-making for elderly patients who can tolerate surgery., Competing Interests: Conflict of interest: D.D.E.M.A. Detillon has nothing to disclose. Conflict of interest: M.J. Aarts has nothing to disclose. Conflict of interest: K. De Jaeger has nothing to disclose. Conflict of interest: C.H.J. Van Eijck has nothing to disclose. Conflict of interest: E.J. Veen has nothing to disclose., (Copyright ©ERS 2019.)

Background: The time interval between CRT and surgery in rectal cancer patients is still the subject of debate. The aim of this study was to first evaluate the nationwide use of restaging magnetic resonance imaging (MRI) and its impact on timing of surgery, and, second, to evaluate the impact of timing of surgery after chemoradiotherapy (CRT) on short- and long-term outcomes., Methods: Patients were selected from a collaborative rectal cancer research project including 71 Dutch centres, and were subdivided into two groups according to time interval from the start of preoperative CRT to surgery (< 14 and ≥ 14 weeks)., Results: From 2095 registered patients, 475 patients received preoperative CRT. MRI restaging was performed in 79.4% of patients, with a median CRT-MRI interval of 10 weeks (interquartile range [IQR] 8-11) and a median MRI-surgery interval of 4 weeks (IQR 2-5). The CRT-surgery interval groups consisted of 224 (< 14 weeks) and 251 patients (≥ 14 weeks), and the long-interval group included a higher proportion of cT4 stage and multivisceral resection patients. Pathological complete response rate (n = 34 [15.2%] vs. n = 47 [18.7%], p = 0.305) and CRM involvement (9.7% vs. 15.9%, p = 0.145) did not significantly differ. Thirty-day surgical complications were similar (20.1% vs. 23.1%, p = 0.943), however no significant differences were found for local and distant recurrence rates, disease-free survival, and overall survival., Conclusions: These real-life data, reflecting routine daily practice in The Netherlands, showed substantial variability in the use and timing of restaging MRI after preoperative CRT for rectal cancer, as well as time interval to surgery. Surgery before or after 14 weeks from the start of CRT resulted in similar short- and long-term outcomes.

Background: Laparoscopic surgery for colon cancer is associated with improved recovery and similar cancer outcomes at 3 and 5 years in comparison with open surgery. However, long-term survival rates have rarely been reported. Here, we present survival and recurrence rates of the Dutch patients included in the COlon cancer Laparoscopic or Open Resection (COLOR) trial at 10-year follow-up., Methods: Between March 1997 and March 2003, patients with non-metastatic colon cancer were recruited by 29 hospitals in eight countries and randomised to either laparoscopic or open surgery. Main inclusion criterion for the COLOR trial was solitary adenocarcinoma of the left or right colon. The primary outcome was disease-free survival at 3 years, and secondary outcomes included overall survival and recurrence. The 10-year follow-up data of all Dutch patients were collected. Analysis was by intention-to-treat. The trial was registered at ClinicalTrials.gov (NCT00387842)., Results: In total, 1248 patients were randomised, of which 329 were Dutch. Fifty-eight Dutch patients were excluded and 15 were lost to follow-up, leaving 256 patients for 10-year analysis. Median follow-up was 112 months. Disease-free survival rates were 45.2 % in the laparoscopic group and 43.2 % in the open group (difference 2.0 %; 95 % confidence interval (CI) -10.3 to 14.3; p = 0.96). Overall survival rates were 48.4 and 46.7 %, respectively (difference 1.7 %; 95 % CI -10.6 to 14.0; p = 0.83). Stage-specific analysis revealed similar survival rates for both groups. Sixty-two patients were diagnosed with recurrent disease, accounting for 29.4 % in the laparoscopic group and 28.2 % in the open group (difference 1.2 %; 95 % CI -11.1 to 13.5; p = 0.73). Seven patients had port- or wound-site recurrences (laparoscopic n = 3 vs. open n = 4)., Conclusions: Laparoscopic surgery for non-metastatic colon cancer is associated with similar rates of disease-free survival, overall survival and recurrences as open surgery at 10-year follow-up.

Objective: The value of secondary cytoreductive surgery (SCS) in patients with recurrent epithelial ovarian cancer is controversial. The aim of this population-based study was to investigate the role of SCS in the Netherlands., Methods: Data of 408 patients who underwent SCS between 2000 and 2013 were retrospectively collected from 38 Dutch hospitals. Survival after complete and incomplete SCS was estimated by Kaplan-Meier curves. Factors associated with overall survival (OS) were explored with Cox regression., Results: Median OS after SCS was 51 months (95% confidence interval [95% CI], 44.8-57.2). Complete SCS was achieved in 295 (72.3%) patients, with an OS of 57 months (95% CI, 49.0-65.0) compared with 28 months (95% CI, 20.8-35.2) in patients with incomplete SCS (log-rank test; P < 0.001). Nonserous histology (HR 0.65; 95% CI 0.45-0.95), a long progression free interval (hazard ratio [HR], 0.29; 95% CI, 0.07-1.18), a good performance status (HR, 0.68; 95% CI, 0.49-0.94), SCS without preoperative chemotherapy (HR, 0.72; 95% CI, 0.51-1.01), and complete SCS (HR, 0.46; 95% CI, 0.33-0.64) were prognostic factors for survival., Conclusions: This population-based retrospective study showed that there might be a role for SCS in recurrent epithelial ovarian cancer especially when complete SCS can be accomplished. However, before adopting SCS as a standard treatment modality for recurrent epithelial ovarian cancer, results of 3 ongoing prospectively randomized trials are needed.

Background: The standard of care for operable, stage I, non-small-cell lung cancer (NSCLC) is lobectomy with mediastinal lymph node dissection or sampling. Stereotactic ablative radiotherapy (SABR) for inoperable stage I NSCLC has shown promising results, but two independent, randomised, phase 3 trials of SABR in patients with operable stage I NSCLC (STARS and ROSEL) closed early due to slow accrual. We aimed to assess overall survival for SABR versus surgery by pooling data from these trials., Methods: Eligible patients in the STARS and ROSEL studies were those with clinical T1-2a (<4 cm), N0M0, operable NSCLC. Patients were randomly assigned in a 1:1 ratio to SABR or lobectomy with mediastinal lymph node dissection or sampling. We did a pooled analysis in the intention-to-treat population using overall survival as the primary endpoint. Both trials are registered with ClinicalTrials.gov (STARS: NCT00840749; ROSEL: NCT00687986)., Findings: 58 patients were enrolled and randomly assigned (31 to SABR and 27 to surgery). Median follow-up was 40·2 months (IQR 23·0-47·3) for the SABR group and 35·4 months (18·9-40·7) for the surgery group. Six patients in the surgery group died compared with one patient in the SABR group. Estimated overall survival at 3 years was 95% (95% CI 85-100) in the SABR group compared with 79% (64-97) in the surgery group (hazard ratio [HR] 0·14 [95% CI 0·017-1·190], log-rank p=0·037). Recurrence-free survival at 3 years was 86% (95% CI 74-100) in the SABR group and 80% (65-97) in the surgery group (HR 0·69 [95% CI 0·21-2·29], log-rank p=0·54). In the surgery group, one patient had regional nodal recurrence and two had distant metastases; in the SABR group, one patient had local recurrence, four had regional nodal recurrence, and one had distant metastases. Three (10%) patients in the SABR group had grade 3 treatment-related adverse events (three [10%] chest wall pain, two [6%] dyspnoea or cough, and one [3%] fatigue and rib fracture). No patients given SABR had grade 4 events or treatment-related death. In the surgery group, one (4%) patient died of surgical complications and 12 (44%) patients had grade 3-4 treatment-related adverse events. Grade 3 events occurring in more than one patient in the surgery group were dyspnoea (four [15%] patients), chest pain (four [15%] patients), and lung infections (two [7%])., Interpretation: SABR could be an option for treating operable stage I NSCLC. Because of the small patient sample size and short follow-up, additional randomised studies comparing SABR with surgery in operable patients are warranted., Funding: Accuray Inc, Netherlands Organisation for Health Research and Development, NCI Cancer Center Support, NCI Clinical and Translational Science Award., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The 70-gene signature (MammaPrint) has been developed to predict the risk of distant metastases in breast cancer and select those patients who may benefit from adjuvant treatment. Given the strong association between locoregional and distant recurrence, we hypothesize that the 70-gene signature will also be able to predict the risk of locoregional recurrence (LRR). 1,053 breast cancer patients primarily treated with breast-conserving treatment or mastectomy at the Netherlands Cancer Institute between 1984 and 2006 were included. Adjuvant treatment consisted of radiotherapy, chemotherapy, and/or endocrine therapy as indicated by guidelines used at the time. All patients were included in various 70-gene signature validation studies. After a median follow-up of 8.96 years with 87 LRRs, patients with a high-risk 70-gene signature (n = 492) had an LRR risk of 12.6% (95% CI 9.7-15.8) at 10 years, compared to 6.1% (95% CI 4.1-8.5) for low-risk patients (n = 561; P < 0.001). Adjusting the 70-gene signature in a competing risk model for the clinicopathological factors such as age, tumour size, grade, hormone receptor status, LVI, axillary lymph node involvement, surgical treatment, endocrine treatment, and chemotherapy resulted in a multivariable HR of 1.73 (95% CI 1.02-2.93; P = 0.042). Adding the signature to the model based on clinicopathological factors improved the discrimination, albeit non-significantly [C-index through 10 years changed from 0.731 (95% CI 0.682-0.782) to 0.741 (95% CI 0.693-0.790)]. Calibration of the prognostic models was excellent. The 70-gene signature is an independent prognostic factor for LRR. A significantly lower local recurrence risk was seen in patients with a low-risk 70-gene signature compared to those with high-risk 70-gene signature.

Objective: Evidence of randomized comparative clinical trials on surgery in recurrent platinum-sensitive ovarian cancer is non-existing. Three randomized phase 3 trials are ongoing. The aim of this study is to evaluate the current opinion of Dutch gynecologists and medical oncologists awaiting the results of these three trials., Methods: A 16-item questionnaire was sent to all gynecologists (N=124) and medical oncologists (N=195) with special interest in gynecologic oncology in the Netherlands. The data were collected and analyzed using descriptive statistics., Results: In total, 80 (65.0%) gynecologists and 67 (34.0%) medical oncologists responded. Among the respondents, 11.3% and 26.9% were not convinced of the benefit of secondary cytoreductive surgery, respectively. For most gynecologists and medical oncologists completeness of primary surgery (74.6% and 75.5%, respectively) and performance status (100% and 98%, respectively) were important factors when considering surgery. For only about 17.5% of all respondents diagnostic laparoscopy before surgery is a prerequisite. Most respondents (81.7% and 87.8%, respectively) would use platinum-based chemotherapy with paclitaxel as their agents of choice after surgery. In general medical oncologists settle for a smaller gain in both progression free as well as overall survival than gynecologists., Conclusions: Although most gynecologists and medical oncologists are already convinced of the usefulness of secondary cytoreductive surgery in certain patients, a better understanding of the real advantages and disadvantages and patient's selection criteria for secondary cytoreductive surgery will be achieved after the completion of three ongoing randomized controlled trials (DESKTOP III, GOG 213 and the SOCceR)., (© 2013.)

Studies investigating perioperative chemotherapy and/or radiotherapy changed the treatment of curable gastric cancer in The Netherlands. These changes were evaluated including their influence on survival. Data on patients diagnosed with gastric cancer from 1989 to 2009 were obtained from The Netherlands Cancer Registry. Changes over time in surgery and administration of perioperative chemotherapy, 30-day mortality, 5-year survival and adjusted relative excess risk (RER) of dying were analyzed with multivariable regression for cardia and noncardia cancer. In stages I and II disease, most patients underwent surgery. Since 2005, more patients are treated with (neo)adjuvant chemotherapy. Postoperative mortality ranged from 1% to 7% and 0.4% to 12.2% in cardia and noncardia cancer (<55 to 75+ years). Five-year survival for cardia cancer and noncardia cancer stages I-III and X (unknown stage) was 33% and 50% (2005-2008). The RER of dying was associated with period of diagnosis, age, gender, region, stage, (neo)adjuvant chemotherapy in case of cardia cancer and type of gastric resection in case of noncardia cancer. Administration of (neo)adjuvant chemotherapy has increased. No improvement in long-term survival could yet be seen, though it is still too early to expect an improvement in survival as a result of the use of chemotherapy., (Copyright © 2013 UICC.)

Purpose: To analyze results of multimodality treatment in relation to subsite of locally recurrent rectal cancer (LRRC)., Method and Materials: A total of 170 patients with LRRC who underwent treatment between 1994 and 2008 were studied. The basic principle of multimodality treatment was preoperative (chemo)radiotherapy, intended radical surgery, and intraoperative radiotherapy. The subsites of LRRC were classified as presacral, posterolateral, (antero)lateral, anterior, anastomotic, or perineal. Subsites were related to radicality of the resection, local re-recurrence rate, distant metastasis rate, and cancer-specific survival., Results: R0 resections were achieved in 54% of the patients, and 5-year cancer-specific survival was 40.5%. The worst outcomes were seen in presacral LRRC, with only 28% complete resections and 19% 5-year survival (p = 0.03 vs. other subsites). Anastomotic LRRC resulted in the most favorable outcomes, with 77% R0 resections and 60% 5-year survival (p = 0.04). Generally, if a complete resection was achieved, survival improved, except in posterolateral LRRC. Local re-recurrence and metastasis rate were lowest in anastomotic LRRC., Conclusions: Classification of the subsite of LRRC is a predictor of potentially resectable and consequently curable disease. Treatment of posterior LRRC imposes poor results, whereas anastomotic LRRC location shows superior results.

Purpose: There is an increasing tendency for an aggressive approach to colorectal liver metastases (CLM), even as second stage procedures after initial hepatic resection. This study assesses the efficacy of intensive follow-up after resection of CLM., Patients and Methods: Hundred and three patients, operated on for CLM, were followed for disease recurrence. Outcome measures were time and imaging modality that revealed recurrence, performed treatment for recurrence, and overall survival., Results: After hepatic resection, 1- and 3-year overall survival (OS) rates were 91% and 50%, the disease-free survival rates 63% and 45%. Seventy-four patients developed recurrent disease during follow-up. Resection of recurrence was performed in 25 patients. OS of this group was 51 months. Patients with recurrence treated by chemotherapy had an OS of 34 months. In case of recurrence, 70% was observed within 12 months, 92% within 24 months. CT appeared to be far a very useful surveillance modality, directing surgical treatment in 19 asymptomatic patients., Discussion: Follow-up of patients after surgical treatment of CLM proves worthwhile, resulting in meaningful re-operations in a quarter of all patients that underwent hepatic resection for CLM.

Purpose: Sarcomas of the chest wall are rare, and wide surgical resection is generally the cornerstone of treatment. The objective of our study was to evaluate outcome of full-thickness resections of recurrent and primary chest wall sarcomas., Patients and Methods: To evaluate morbidity, mortality, and overall and disease-free survival after surgical resection of primary and recurrent chest wall sarcomas, we performed a retrospective review of all patients with sarcomas of the chest wall surgically treated at two tertiary oncologic referral centers between January 1980 and December 2006. Patient, tumor, and treatment characteristics, as well as the follow-up of these patients, were retrieved from the patients' original records., Results: One hundred twenty-seven patients were included in this study, 83 patients with a primary sarcoma and 44 patients with a recurrence. Age, sex, tumor size, histologic type, grade and localization on the chest wall were similar for both groups. Fewer neoadjuvant and adjuvant therapies were used in the treatment of recurrences. Chest wall resection was more extensive in the recurrent group, which did not result in more complications (23%) or more reinterventions (5%). Microscopically radical resection was achieved in 80% of the primary sarcomas and 64% of the recurrences. With a median follow-up of 73 months, disease-free survival after surgery for recurrences was 18 months versus 36 months for primary sarcomas, with 5-year survival rates of 50% and 63%, respectively., Conclusion: Although chances for local control are lower after surgical treatment of recurrent chest wall sarcoma, chest wall resection is a safe and effective procedure, with an acceptable survival.

The most important factor for tumour recurrence after breast-saving surgery is the margin status. In the Netherlands a 1-mm free margin has been formulated as sufficient, and totally free margins are not necessary in all cases. The current Dutch Health Inspectorate performance indicator, i.e. 10% reexcisions allowed to achieve free margins, is a performance indicator of questionable validity. As long as there is worldwide discussion about the ideal margin in breast-saving surgery a specific norm cannot not be dictated. The aim of the discussion should be how to prevent local recurrence. This percentage is the real performance indicator.

Objective: Analyse the outcome of pelvic exenteration for gynaecological malignancies in a tertiary referral center. Post-operative in-hospital morbidity, long-term morbidity, disease free and overall survival rates were studied., Study Design: Between 1991 and 2004, 42 patients underwent an anterior, total or posterior exenteration for gynaecological malignancies. Follow-up was obtained from patient files; disease free and overall survival were calculated and prognostic factors were studied., Results: A pelvic exenteration was performed in 14 patients for primary and 28 patients for recurrent gynaecological cancers. In-hospital complications occurred in 19 patients (45%) of whom seven patients needed a reoperation (17%). Late complications occurred in 31 patients (75%); 21 reinterventions were performed (50%). Five-year disease free and overall survival was, respectively, 48 and 52%. Age, type of surgery, histology, localisation of the tumour, lateral wall involvement, completeness of resection and primary versus recurrent cancer were not identified as prognostic factors for recurrence or survival., Conclusion: Long-term survival is possible in about 50% of patients after pelvic exenteration for gynaecological cancers, but is associated with significant post-operative morbidity.

We studied the use of radiotherapy (RT) (especially secondary RT) in a cohort of 6561 patients in southern Netherlands with invasive breast cancer diagnosed between 1996 and 2000 (median follow-up: 66 months, range 0-107 months). Radiation within 6 months of diagnosis was considered primary RT (PRT). RT given 6 months or later after diagnosis or after PRT was considered secondary RT (SRT). Of all patients, 67% received RT, 3554 only PRT, 323 only SRT and 503 both. The cumulative use of SRT at 100 months was 17%. The 826 patients receiving SRT underwent 1846 courses 0-105 months (median 36) after diagnosis; the retreat rate was 35%. Elderly patients received SRT significantly less often (OR(age50-69)=0.7, 95%CI=0.6-0.8, OR(age> or 70)=0.4, 95%CI=0.3-0.5). The following factors increased the chance for SRT: patients from the eastern region (OR=1.3, 95%CI=1.1-1.6); patients who received PRT (OR=1.3, 95%CI=1.0-1.5) and patients who underwent mastectomy including axillary node dissection as well as unresected patients (OR=1.9, 95%CI=1.5-2.4, OR=2.6, 95%CI=1.7-3.9, respectively). Thirteen percent of all patients with breast cancer received SRT, with a large variation in age and between the 2 RT departments in the region.

Sentinel lymph node biopsy (SLNB) has been validated in the treatment of breast carcinoma and is considered to stage the axilla adequately in this disease. However, long-term follow-up data are scarce. We evaluated the results of SLNB with respect to loco-regional failures in the axilla in SN-negative patients with invasive breast carcinoma and analysed their causal factors. Between 1997 and May 2004, 656 patients without clinically palpable lymph nodes were included in our study. Data with regard to demographics, diagnostics, therapy and follow up were gathered prospectively from all patients. Patients treated after May 2004 were excluded from this study to permit at least one year of follow-up. Out of the 656 patients, 344 patients with a negative sentinel lymph node biopsy did not undergo axillary dissection and were followed up clinically. Median follow up was 43 months. In 3 patients (0.9%) axillary recurrences developed. All three patients subsequently underwent a completion axillary dissection, chemotherapy and radiotherapy. The low rate of clinical axillary recurrence after an intermediate follow up period suggests that a negative SN biopsy accurately reflects the nodal stage in patients with breast cancer.

Background: Both cryosurgery, with and without prior curettage, and surgical excision (SE) are common therapeutic strategies for basal cell carcinoma (BCC)., Objective: The objective was to compare the efficacy between curettage plus cryosurgery (C&C) and SE in nonaggressive BCC of the head and neck., Materials and Methods: A randomized controlled trial was carried out, in which tumors were assigned to either C&C (n=51) or SE (n=49). C&C was performed with a double freeze-thaw cycle after prior curettage of the tumor. SE was performed with a margin of 3 mm and with delayed histologic examination., Results: Recurrences occurred 9 times after C&C (17.6%) and 4 times after SE (8.2%). The overall 5-year recurrence probability was 19.6% for C&C and 8.4% for SE (p=.10). A hazard ratio of 2.57 (95% CI, 0.79-8.34) indicated a putative, but not statistically significant, advantage of SE., Conclusion: These data reflect the outcome of the first randomized controlled trial with long-term follow-up in the treatment of BCC, comparing C&C with SE. Although not statistically significantly different, the observed differences could still be of clinical relevance. Owing to the trend toward lower recurrence rates, better cosmetic results, and reduced wound healing time, we believe that SE should be preferred to C&C in the treatment of primary, nonaggressive BCC of the head and neck.

Background: The aim of our study was to analyse data of patients treated by salvage surgery for locally recurrent rectal cancer, with emphasis on the question whether salvage surgery is still worthwhile when adjuvant radiotherapy is no longer a treatment option., Methods: Forty patients (19 males/21 females) treated by surgery with curative intent for locally recurrent rectal carcinoma were analysed. Local recurrence was defined as cancer recurrence within the lower pelvis. Salvage surgery included abdominoperineal resection, abdominosacral resection, exenteration (posterior or total) and local resection. Clinical and pathological factors were analysed to identify prognostic factors for survival., Results: The median overall survival was 25 months (95% CI: 13-37 months) and 5-year survival was 28% (95% CI: 12-45%). The absence of symptoms at the time of recurrence, central localisation and the absence of microscopic involvement of surgical margins, but not additional radiotherapy, were found to be significant independent prognostic factors for better survival after salvage surgery., Conclusion: Salvage surgery, alone or in combination with radiotherapy, can achieve radical resection of locally recurrent rectal cancer and can result in long-term survival.

Purpose: To evaluate the rate of axillary recurrences in sentinel node (SN) negative breast cancer patients without further axillary lymph node dissection (ALND)., Patients and Methods: Between October 1994 and November 1999, all SN negative breast cancer patients who did not underwent complete ALND were enrolled in this prospective study. SN biopsy was performed by using the triple technique which combines preoperative lymphoscintigraphy, intraoperative use of blue dye, and a handheld gamma probe to visualize and localize the SN. SNs were examined by standard hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC). During the first year after surgery all patients underwent clinical examination at 3 monthly intervals. This follow-up interval was prolonged to 6 month after the first year., Results: From the 104 patients, 93 (89%) underwent breast-conserving therapy; all remaining patients were treated by modified radical mastectomy. In 91 cases a ductal carcinoma and in 13 cases a lobular carcinoma was diagnosed. One SN was removed in 80, two SNs in 18, and three SNs in 2 patients. Twenty patients received systemic therapy based on age and primary tumor characteristics. After a median follow-up of 57 month only one axillary recurrence was observed. During follow-up three patients developed distant metastases. One of these patient with metastases to the bone is alive with evidence of disease. The remaining two patients died 9 and 19 month after surgery., Conclusions: Our long term follow-up results indicate that survival is excellent (98%) and local axillary control is adequate (99%) after omitting ALND in a group of 104 SN negative breast cancer patients.

Aims: The aim of this study is to report initial experience with radiofrequency thermoablation (RFA) of malignant hepatic tumours., Methods: From June 1999 to November 2001, a seven centre study of 50 patients who had undergone RFA, included 102 primary or metastatic tumours. Multimodality therapy, complications, disease free survival and location of recurrence were recorded. Histopathologic examination was performed in a number of tumours treated with RFA and subsequently resected to determine the effect of RFA on the tissue level., Results: 11 tumours (seven patients) were resected after prior treatment with RFA; NADH-diaphorase staining in all these tumours demonstrated non-viable tumour. Postoperative morbidity and mortality occurred in 14 patients and one patient, respectively, in three cases related to the RFA procedure. Median follow-up of 41 patients with non-resected RF ablated tumours was 11 months (range 1-24 months). 26 patients developed a recurrence of which three at the RFA site after 6-12 months., Conclusions: RFA provides a simple method for local treatment of liver tumours. The introduction of this technique nevertheless involves morbidity and mortality.

Background: Local control and survival following surgical treatment of rectal cancer have been improved by the introduction of total mesorectal excision (TME). The aim of this study was to determine the nationwide impact of the introduction and training of TME on recurrence and survival in rectal cancer., Methods: Short- and long-term outcomes of a recently published trial of rectal cancer surgery (TME trial) were compared with results from an older trial (cancer recurrence and blood transfusion (CRAB) trial), in which conventional surgery was performed without quality control. Only patients who were operated on with curative intent and who did not receive neoadjuvant radiotherapy were studied. Differences in clinicopathological characteristics were corrected for by multivariate analysis. To ensure valid comparisons, only events that occurred within 2 years of operation were analysed with regard to long-term outcome., Results: In the univariate analysis, a higher clinical anastomotic leak rate was found in patients following low anterior resection in the TME trial (P = 0.046), but this association was not significant in the multivariate analysis. The local recurrence rate decreased from 16 per cent in the CRAB trial to 9 per cent in the TME trial, and type of operation (conventional (CRAB trial) versus TME (TME trial)) was an independent predictor of local recurrence (P = 0.002). Type of operation was also an independent predictor of overall survival (P = 0.019); there was a higher survival rate in the TME trial., Conclusion: The introduction and training of TME has led to improved long-term outcome of patients with rectal cancer in the Netherlands.

Objective: Survey of the results of multimodality treatment for primary irresectable rectum carcinoma and local recurrence of rectal cancer., Design: Retrospective., Methods: During the period 1 February 1994 to 31 August 1999, 43 patients with locally advanced primary rectal cancer (25 men and 18 women; mean age: 64 years (range: 36-86)) and 53 patients with a local recurrence (33 men and 20 women; mean age: 61 years (39-82)) were treated with a multimodality treatment: i.e. preoperative radiotherapy (doses 50.4 Gy, or 30.0 Gy in the case of reirradiation), extensive surgery and intraoperative radiotherapy (doses 10-17.5 Gy). This treatment took place at two hospitals in the Netherlands, the Catharina Hospital in Eindhoven and, since 1997, the Daniel den Hoed Cancer Centre in Rotterdam. In 2000 data were collected for the local control and (disease-free) survival; these were analysed using the Kaplan-Meier method. Patients also completed a questionnaire about the quality of life at a median period of 14 months (range: 4-60) after the operation; the response level was 96% (76/79)., Results: After 3 years, the local control, disease-free survival and survival rates for the locally advanced primary rectal cancer group were 74%, 60% and 55% respectively, and for the locally recurrent rectal cancer group 64%, 34% and 50% respectively. Tumour resection with microscopically negative margins had a statistically significant positive effect on the local control and disease-free survival in both groups as well as on the survival in the locally advanced primary patient group. Seven of the 96 patients (7%) died as a result of complications. Of the patients with a primary irresectable carcinoma or a local recurrent tumour who completed the questionnaire the results were as follows: 56% and 63% respectively had been able to resume employment, 53% and 59% respectively had been able to resume their previous lifestyle, 15% and 27% respectively indicated radicular pain as a new symptom, 26% and 46% respectively stated problems with walking, 42% and 44% respectively stated problems with urinating and 59% and 52% respectively a reduction in sexual activity.

Background: Evaluation of the results of CO2 laser treatment of recurrent glottic carcinoma after radiotherapy., Methods: Records of all patients treated in the University Hospital Rotterdam and the Dr. Daniel den Hoed Cancer Center between 1980 and 1996 by CO2 laser for recurrent glottic carcinoma were studied., Results: Forty patients were treated by laser surgery. Average follow-up was 77 months. Twenty-three patients (58%) had another recurrence develop after laser surgery. Three were cured by a second laser procedure. Therefore, 20 patients (50%) were successfully treated with laser surgery. In 23 patients the recurrence did not extend into the anterior commissure; in 57% a total laryngectomy could be avoided. In 17 patients the recurrence did extend into the anterior commissure; in 41% a total laryngectomy was avoided., Conclusion: Most patients with recurrent carcinoma of the larynx after radiotherapy can be cured by laser surgery if the tumor does not extend into the anterior commissure.

We present our experience with intraoperative radiotherapy (IORT) multimodality treatment for patients with locally recurrent rectal cancer, but without distant metastases. Between 1994 and early 2000, 62 patients were treated according to a set protocol. Three-year survival rate was 49%. The local control rate was 63%. Total dose of irradiation and completeness of resection were significantly correlated to a better prognosis.