Radiofrequency ablation and chemotherapy versus chemotherapy alone for locally advanced pancreatic cancer (PELICAN): study protocol for a randomized controlled trial.

BACKGROUND: Approximately 80% of patients with locally advanced pancreatic cancer (LAPC) are treated with chemotherapy, of whom approximately 10% undergo a resection. Cohort studies investigating local tumor ablation with radiofrequency ablation (RFA) have reported a promising overall survival of 26-34 months when given in a multimodal setting. However, randomized controlled trials (RCTs) investigating the effect of RFA in combination with chemotherapy in patients with LAPC are lacking. METHODS: The "Pancreatic Locally Advanced Unresectable Cancer Ablation" (PELICAN) trial is an international multicenter superiority RCT, initiated by the Dutch Pancreatic Cancer Group (DPCG). All patients with LAPC according to DPCG criteria, who start with FOLFIRINOX or (nab-paclitaxel/)gemcitabine, are screened for eligibility. Restaging is performed after completion of four cycles of FOLFIRINOX or two cycles of (nab-paclitaxel/)gemcitabine (i.e., 2 months of treatment), and the results are assessed within a nationwide online expert panel. Eligible patients with RECIST stable disease or objective response, in whom resection is not feasible, are randomized to RFA followed by chemotherapy or chemotherapy alone. In total, 228 patients will be included in 16 centers in The Netherlands and four other European centers. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, RECIST response, CA 19.9 and CEA response, toxicity, quality of life, pain, costs, and immunomodulatory effects of RFA. DISCUSSION: The PELICAN RCT aims to assess whether the combination of chemotherapy and RFA improves the overall survival when compared to chemotherapy alone, in patients with LAPC with no progression of disease following 2 months of systemic treatment. TRIAL REGISTRATION: Dutch Trial Registry NL4997 . Registered on December 29, 2015. ClinicalTrials.gov NCT03690323 . Retrospectively registered on October 1, 2018.

The treatment and survival of elderly patients with locally advanced pancreatic cancer: A post-hoc analysis of a multicenter registry.

BACKGROUND: The treatment options for patients with locally advanced pancreatic cancer (LAPC) have improved in recent years and consequently survival has increased. It is unknown, however, if elderly patients benefit from these improvements in therapy. With the ongoing aging of the patient population and an increasing incidence of pancreatic cancer, this patient group becomes more relevant. This study aims to clarify the association between increasing age, treatment and overall survival in patients with LAPC. METHODS: Post-hoc analysis of a multicenter registry including consecutive patients with LAPC, who were registered in 14 centers of the Dutch Pancreatic Cancer Group (April 2015-December 2017). Patients were divided in three groups according to age (<65, 65-74 and ≥75 years). Primary outcome was overall survival stratified by primary treatment strategy. Multivariable regression analyses were performed to adjust for possible confounders. RESULTS: Overall, 422 patients with LAPC were included; 162 patients (38%) aged <65 years, 182 patients (43%) aged 65-74 and 78 patients (19%) aged ≥75 years. Chemotherapy was administered in 86%, 81% and 50% of the patients in the different age groups (p<0.01). Median overall survival was 12, 11 and 7 months for the different age groups (p<0.01).Patients treated with chemotherapy showed comparable median overall survival of 13, 14 and 10 months for the different age groups (p=0.11). When adjusted for confounders, age was not associated with overall survival. CONCLUSION: Elderly patients are less likely to be treated with chemotherapy, but when treated with chemotherapy, their survival is comparable to younger patients.

Node negative colorectal cancer patients: assesment of high-risk features on recurrence.

BACKGROUND: The introduction of population-based screening programs for colorectal cancer (CRC) results in less patients with advanced disease. There is an increase in the amount of node negative CRC, which makes adequate risk stratification for this particular group of patients necessary. The addition of more risk factors to the conventional histological high-risk factors is investigated in this retrospective study. PATIENTS AND METHODS: A cohort of 227 node negative (stage I and II) CRC patients who were not treated with adjuvant chemotherapy were selected from two previously conducted cohort studies. Detailed histopathological examination was performed by two independent observers and molecular background (BRAF/RAS mutations, microsatellite status (MSI)) was studied. Univariate analyses were used to analyse differences in histological and mutational characteristics between patients with and without recurrence. P-values below 0.05 were considered statistically significant. RESULTS: Poorly differentiated histology (p:0.002), BRAF mutation (p:0.002) and MSI status (p:0.006) were found significant relevant risk factors that were related to recurrent disease. Poorly differentiated histology was associated with intermediate/high tumor budding (TB) (p:0.001), a BRAF mutation (p:0.001) and MSI status (p:0.001). A combination of all three features (poorly differentiated histology, BRAF and MSI) was more often present in the recurrence group. CONCLUSIONS: Recurrence in node negative CRC patients could be better predicted when molecular features such as, BRAF mutation and MSI status are incorporated into a model with poorly differentiated CRC. Therefore, these features might help in the selection of patients who possibly will benefit from adjuvant treatment.

Low radiographic muscle density is associated with lower overall and disease-free survival in early-stage colorectal cancer patients.

BACKGROUND: In cancer patients with a poor prognosis, low skeletal muscle radiographic density is associated with higher mortality. Whether this association also holds for early-stage cancer is not very clear. We aimed to study the association between skeletal muscle density and overall mortality among early-stage (stage I-III) colorectal cancer (CRC) patients. Furthermore, we investigated the association between skeletal muscle density and both CRC-specific mortality and disease-free survival in a subset of the study population. METHODS: Skeletal muscle density was assessed in 1681 early-stage CRC patients, diagnosed between 2006 and 2015, using pre-operative computed tomography images. Adjusted Cox proportional hazard models were used to evaluate the association between muscle density and overall mortality, CRC-specific mortality and disease-free survival. RESULTS: The median follow-up time was 48 months (range 0-119 months). Low muscle density was detected in 39% of CRC patients. Low muscle density was significantly associated with higher mortality (low vs. normal: adjusted HR 1.91, 95% CI 1.53-2.38). After stratification for comorbidities, the association was highest in patients with ≥ 2 comorbidities (HR 2.11, 95% CI 1.55-2.87). Furthermore, low skeletal muscle density was significantly associated with poorer disease-free survival (HR 1.68, 95% CI 1.14-2.47), but not with CRC-specific mortality (HR 1.68, 95% CI 0.89-3.17) in a subset of the study population. CONCLUSION: In early-stage CRC patients, low muscle density was significantly associated with higher overall mortality, and worse disease-free survival.

Translating the ABC-02 trial into daily practice: outcome of palliative treatment in patients with unresectable biliary tract cancer treated with gemcitabine and cisplatin.

BACKGROUND: Biliary tract cancer (BTC) is an uncommon cancer with an unfavorable prognosis. Since 2010, the standard of care for patients with unresectable BTC is palliative treatment with gemcitabine plus cisplatin, based on the landmark phase III ABC-02 trial. This current study aims to evaluate the efficacy and safety of gemcitabine and cisplatin in patients with unresectable cholangiocarcinoma and gallbladder cancer in daily practice that meet the criteria for the ABC-02 trial in comparison to patients who did not. METHODS: Patients diagnosed with unresectable BTC between 2010 and 2015 with an indication for gemcitabine and cisplatin were included. We divided these patients into three groups: (I) patients who received chemotherapy and met the criteria of the ABC-02 trial, (II) patients who received chemotherapy and did not meet these criteria and (III) patients who had an indication for chemotherapy, but received best supportive care without chemotherapy. Primary outcome was overall survival (OS) and secondary outcome was progression-free survival (PFS). RESULTS: We collected data of 208 patients, of which 138 (66.3%) patients received first line chemotherapy with gemcitabine and cisplatin. Median OS of 69 patients in group I, 63 patients in group II and 65 patients in group III was 9.6 months (95%CI = 6.7-12.5), 9.5 months (95%CI = 7.7-11.3) and 7.6 months (95%CI = 5.0-10.2), respectively. Median PFS was 6.0 months (95%CI = 4.4-7.6) in group I and 5.1 months (95%CI = 3.7-6.5) in group II. Toxicity and number of dose reductions (p = .974) were comparable between the two chemotherapy groups. CONCLUSION: First-line gemcitabine and cisplatin is an effective and safe treatment for patients with unresectable BTC who do not meet the eligibility criteria for the ABC-02 trial. Median OS, PFS and treatment side effects were comparable between the patients who received chemotherapy (group I vs. group II).

Truly selective primary IgM deficiency is probably very rare.

Isolated decreased serum-immunoglobulin (Ig)M has been associated with severe and/or recurrent infections, atopy and autoimmunity. However, the reported high prevalence of clinical problems in IgM-deficient patients may reflect the skewed tertiary centre population studied so far. Also, many papers on IgM deficiency have included patients with more abnormalities than simply IgM-deficiency. We studied truly selective primary IgM deficiency according to the diagnostic criteria of the European Society for Immunodeficiencies (ESID) (true sIgMdef) by reviewing the literature (261 patients with primary decreased serum-IgM in 46 papers) and analysing retrospectively all patients with decreased serum-IgM in a large teaching hospital in 's-Hertogenbosch, the Netherlands [1 July 2005-23 March 2016; n = 8049 IgM < 0·4 g/l; n = 2064 solitary (IgG+IgA normal/IgM < age-matched reference)]. A total of 359 of 2064 (17%) cases from our cohort had primary isolated decreased serum-IgM, proven persistent in 45 of 359 (13%) cases; their medical charts were reviewed. Our main finding is that true sIgMdef is probably very rare. Only six of 261 (2%) literature cases and three of 45 (7%) cases from our cohort fulfilled the ESID criteria completely; 63 of 261 (24%) literature cases also had other immunological abnormalities and fulfilled the criteria for unclassified antibody deficiencies (unPAD) instead. The diagnosis was often uncertain (possible sIgMdef): data on IgG subclasses and/or vaccination responses were lacking in 192 of 261 (74%) literature cases and 42 of 45 (93%) cases from our cohort. Our results also illustrate the clinical challenge of determining the relevance of a serum sample with decreased IgM; a larger cohort of true sIgMdef patients is needed to explore fully its clinical consequences. The ESID online Registry would be a useful tool for this.

Recurrence-free and overall survival among elderly stage III colon cancer patients treated with CAPOX or capecitabine monotherapy.

The aim of this study is to investigate the effects of CAPOX and capecitabine on recurrence-free survival (RFS) and overall survival (OS) among elderly stage III colon cancer patients and to evaluate the effect of (non-)completion. Patients aged ≥70 years who underwent resection only or who were subsequently treated with CAPOX or capecitabine in 10 large non-academic hospitals were included. RFS and OS were analyzed with Kaplan-Meier curves and multivariable Cox regression adjusted for patient and tumor characteristics. 982 patients were included: 630 underwent surgery only, 191 received CAPOX and 161 received capecitabine. Five-year RFS and OS did not differ between capecitabine and CAPOX (RFS: 63% vs. 60% (p = 0.91), adjusted HR = 0.99 (95%CI 0.68-1.44); OS: 66% vs. 66% (p = 0.76), adjusted HR = 0.93 (95%CI 0.64-1.34)). After resection only, RFS was 38% and OS 37%. Completion rates were 48% for CAPOX and 68% for capecitabine. Three-year RFS and OS did not differ between patients who discontinued CAPOX early and patients who completed treatment with CAPOX (RFS: 61% vs. 69% (p = 0.21), adjusted HR = 1.42 (95%CI 0.85-2.37); OS: 68% vs. 78% (p = 0.41), adjusted HR = 1.17 (95%CI 0.70-1.97)). Three-year RFS and OS differed between patients who discontinued capecitabine early and patients who completed treatment with capecitabine (RFS: 54% vs. 72% (p = 0.01), adjusted HR = 2.07 (95%CI 1.11-3.84); OS: 65% vs. 80% (p = 0.01), adjusted HR = 2.00 (95%CI 1.12-3.59)). Receipt of CAPOX or capecitabine is associated with improved RFS and OS. The advantage does not differ by regimen. The addition of oxaliplatin might not be justified in elderly stage III colon cancer patients.

Intensity of adjuvant chemotherapy regimens and grade III-V toxicities among elderly stage III colon cancer patients.

PURPOSE: The aim of this study was to provide insight in the use, intensity and toxicity of therapy with capecitabine and oxaliplatin (CAPOX) and capecitabine monotherapy (CapMono) among elderly stage III colon cancer patients treated in everyday clinical practice. METHODS: Data from the Netherlands Cancer Registry were used. All stage III colon cancer patients aged ≥70 years diagnosed in the southeastern part between 2005 and 2012 and treated with CAPOX or CapMono were included. Differences in completion of all planned cycles, cumulative dosages and toxicity between both regimens were evaluated. RESULTS: One hundred ninety-three patients received CAPOX and 164 patients received CapMono; 33% (n = 63) of the patients receiving CAPOX completed all planned cycles of both agents, whereas 55% (n = 90) of the patients receiving CapMono completed all planned cycles (P < 0.0001). The median cumulative dosage capecitabine was lower for patients treated with CAPOX (163,744 mg/m(2), interquartile range [IQR] 83,397-202,858 mg/m(2)) than for patients treated with CapMono (189,195 mg/m(2), IQR 111,667-228,125 mg/m(2), P = 0.0003); 54% (n = 105) of the patients treated with CAPOX developed grade III-V toxicity, whereas 38% (n = 63) of the patients treated with CapMono developed grade III-V toxicity (P = 0.0026). After adjustment for patient and tumour characteristics, CapMono was associated with a lower odds of developing grade III-V toxicity than CAPOX (odds ratio 0.54, 95% confidence interval 0.33-0.89). For patients treated with CAPOX, the most common toxicities were gastrointestinal (29%), haematological (14%), neurological (11%) and other toxicity (13%). For patients treated with CapMono, dermatological (17%), gastrointestinal (13%) and other toxicity (11%) were the most common. CONCLUSION: CAPOX is associated with significantly more grade III-V toxicities than CapMono, which had a pronounced impact on the cumulative dosage received and completion of all planned cycles. In this light, CapMono seems preferable over CAPOX.

Adjuvant chemotherapy is not associated with improved survival for all high-risk factors in stage II colon cancer.

Adjuvant chemotherapy can be considered in high-risk stage II colon cancer comprising pT4, poor/undifferentiated grade, vascular invasion, emergency surgery and/or <10 evaluated lymph nodes (LNs). Adjuvant chemotherapy administration and its effect on survival was evaluated for each known risk factor. All patients with high-risk stage II colon cancer who underwent resection and were diagnosed in the Netherlands between 2008 and 2012 were included. After stratification by risk factor(s) (vascular invasion could not be included), Cox regression was used to discriminate the independent association of adjuvant chemotherapy with the probability of death. Relative survival was used to estimate disease-specific survival. A total of 4,940 of 10,935 patients with stage II colon cancer were identified as high risk, of whom 790 (16%) patients received adjuvant chemotherapy. Patients with a pT4 received adjuvant chemotherapy more often (37%). Probability of death in pT4 patients receiving chemotherapy was lower compared to non-recipients (3-year overall survival 91% vs. 73%, HR 0.43, 95% CI 0.28-0.66). The relative excess risk (RER) of dying was also lower for pT4 patients receiving chemotherapy compared to non-recipients (3-year relative survival 94% vs. 85%, RER 0.36, 95% CI 0.17-0.74). For patients with only poor/undifferentiated grade, emergency surgery or <10 LNs evaluated, no association between receipt of adjuvant chemotherapy and survival was observed. In high-risk stage II colon cancer, adjuvant chemotherapy was associated with higher survival in pT4 only. To prevent unnecessary chemotherapy-induced toxicity, further refinement of patient subgroups within stage II colon cancer who could benefit from adjuvant chemotherapy seems indicated.

Metachronous peritoneal carcinomatosis after curative treatment of colorectal cancer.

INTRODUCTION: Population-based data on metachronous peritoneal carcinomatosis (PC) after curative resection of colorectal origin are scarce. The aim of this study was to investigate the incidence of and risk factors for developing metachronous PC from colorectal cancer as well as survival since diagnosis of PC. METHODS: Data on metachronous metastases were collected between 2010 and 2011 for all patients diagnosed with M0 colorectal cancer between 2003 and 2008 in the Dutch Eindhoven Cancer Registry. Median follow-up was 5.0 years. Survival was defined as time from metastases diagnosis to death. RESULTS: Of the 5671 colorectal cancer patients, 1042 (18%) were diagnosed with metachronous metastases of whom 197 (19%) developed metachronous PC. The peritoneal surface was the only site of metastasis in 81 (41%) patients while 116 (59%) patients were diagnosed with both PC and metastases elsewhere. Median survival after diagnosis of PC was 6 months compared to 15 months for patients with distant metastases in other organs. Patients with an advanced primary tumour stage, positive lymph nodes at initial diagnosis, primary mucinous adenocarcinoma, positive resection margin and a primary tumour located in the colon were at increased risk of developing metachronous PC. CONCLUSION: Of the colorectal cancer patients who developed metachronous metastases, approximately one fifth is diagnosed with PC. Prognosis of these patients is poor with a median survival of 6 months after diagnosis. Identifying patients at high risk for developing metachronous PC is important as it may contribute to more accurate patient information, tailor-made follow-up schemes, and more adequate treatment.

Quality of life more impaired in younger than in older diffuse large B cell lymphoma survivors compared to a normative population: a study from the population-based PROFILES registry.

The objective of this study was to compare health-related quality of life (HRQOL) between diffuse large B cell lymphoma (DLBCL) survivors of different age categories (18-59/60-75/76-85 years) and to compare their HRQOL with an age- and sex-matched normative population. The population-based Eindhoven Cancer Registry was used to select all patients diagnosed with DLBCL from 1999 to 2010. Patients (n = 363) were invited to complete the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) questionnaire, and 307 survivors responded (85 %). Data from an age- and sex-matched normative population (n = 596) were used for comparison. DLBCL survivors aged 18-59 years scored better on physical functioning, quality of life, appetite loss and constipation than survivors of 76-85 years old (all p < 0.05). Financial problems more often occurred in survivors aged 18-59 years compared to survivors of 76-85 years old (p < 0.01). Compared to the normative population, DLBCL survivors aged 18-59 years showed worse scores on cognitive and social functioning and on dyspnea and financial problems (p < 0.01, large- and medium-size effects). In survivors of the other age categories, only differences with trivial or small-size effects were found. Although younger DLBCL survivors have better HRQOL than older survivors, the differences found between younger survivors and normative population were the largest. This suggests that having DLBCL has a greater impact on younger than older survivors and that the worse HRQOL observed in older DLBCL survivors in comparison with younger survivors is caused mostly by age itself and not by the disease.

No improvement in median survival for patients with metastatic gastric cancer despite increased use of chemotherapy.

BACKGROUND: Gastric cancer often presents in a metastasized stage. We conducted a population-based study to evaluate trends in systemic treatment and survival of metastatic noncardia gastric cancer. PATIENTS AND METHODS: All patients with noncardia adenocarcinoma of the stomach, diagnosed between 1990 and 2011 in the Eindhoven Cancer Registry area in the Netherlands were included (N = 4797). We conducted multivariable logistic regression analysis to evaluate trends in administration of palliative chemotherapy and multivariable proportional hazards regression analyses to evaluate trends in crude overall survival. RESULTS: The proportion of patients presenting with metastatic gastric cancer increased from 24% in 1990 to 44% in 2011 (P < 0.0001). The use of palliative chemotherapy increased, from 5% in 1990 to 36% in 2011, with a strong increase in particular after 2006 (P < 0.0001). Younger patients [<50 years: adjusted odds ratio (ORadj) 3.9, P < 0.001; 50-59 years: ORadj 1.7, P = 0.01] and patients with a high socioeconomic status (ORadj 1.7, P = 0.01) more often received chemotherapy. In contrast, older patients (70-79 years: ORadj 0.3, P < 0.001; 80+ years: ORadj 0.02, P < 0.001), patients with comorbidity (ORadj 0.6, P = 0.03), linitis plastica (ORadj 0.5, P = 0.03) and multiple distant metastases (ORadj 0.5, P = 0.01) were less often treated with chemotherapy. A large hospital variation was observed in the administration of palliative chemotherapy (9%-27%). Median overall survival remained constant between 15 [95% confidence interval (CI) 11.9-17.7] and 17 (95% CI 15.0-20.0) weeks (P = 0.10). CONCLUSIONS: The increased administration of chemotherapy in patients with metastatic gastric cancer did not lead to an increase in population-based overall survival. Identification of the subgroup of patients which benefits from palliative chemotherapy is of utmost importance to avoid unnecessary treatment.

Prognosis and value of adjuvant chemotherapy in stage III mucinous colorectal carcinoma.

BACKGROUND: Colorectal mucinous adenocarcinoma (MC) has been associated with impaired prognosis compared with nonmucinous adenocarcinoma (NMC). Response to palliative chemotherapy is poor in metastatic disease, but the benefit of adjuvant chemotherapeutic treatment has never been assessed in large patient groups. This study analyses overall survival and efficacy of adjuvant chemotherapy in terms of survival in patients following radical resection for MC. PATIENTS AND METHODS: This population-based study involved 27 251 unselected patients diagnosed with colorectal carcinoma between 1990 and 2010 and recorded in a prospective pathology-based registry. Kaplan-Meier analysis and log-rank testing were used to estimate survival. Cox proportional hazard model was used to calculate multivariate hazard ratios for death. RESULTS: MC was found in 12.3% (N = 3052) of colorectal tumors with a different distribution compared with NMC, with 24.4% located in the rectum and 54.3% in the proximal colon (versus 38.0% and 30.6%), P < 0.0001. NMC was more often classified as stage I disease than MC (20.5% versus 10.9%), P < 0.0001. After adjustments for covariates, MC was associated with a higher risk of death only when located in the rectum [hazard ratio 1.22; 95% confidence interval (CI) 1.11-1.34]. Multivariate regression analysis showed a similar survival after adjuvant chemotherapy for stage III MC and NMC patients. CONCLUSIONS: The poor prognosis for MC is only present in rectal cancer. In the adjuvant setting, there is no difference in the efficacy of chemotherapy between MC and NMC; therefore, current adjuvant treatment recommendations should not take histology into account.

Diminishing differences in treatment between patients with colorectal cancer with and without diabetes: a population-based study.

AIMS: An increasing number of oncologists will be confronted with individuals having diabetes and cancer. We assessed changes in patient-, tumour- and treatment-related variables in patients with colorectal cancer with and without diabetes. METHODS: All 17 170 cases of primary colorectal cancer between 1995 and 2010 in the South-Eastern Netherlands were included. The Cochrane-Armitage test and logistic regression analysis were used to analyse trends. RESULTS: In total, 11 893 patients were diagnosed with colon cancer and 5277 with rectal cancer, of whom 1711 (14%) and 609 (12%), respectively, had diabetes at the time of cancer diagnosis. Patients with colorectal cancer with diabetes compared with those without were approximately 5 years older and more often diagnosed with proximal colon tumours (60 vs. 54%; P < 0.0001). Chemotherapy administration significantly increased in patients with stage III colon cancer with and without diabetes (from 17% in 1995-1998 to 50% in 2007-2010, 38% to 63%, respectively; P < 0.0001). However, in the most recent period, and after adjusting for the co-variables age, gender, year of diagnosis and specific co-morbidities, patients with stage III colon cancer with diabetes received adjuvant chemotherapy less frequently than those without [odds ratio 0.7 (95% CI 0.5-0.9); P = 0.002]. The proportion of patients with stage II/III rectal cancer with and without diabetes who underwent radiotherapy has been similar in recent years (91 vs. 87%). CONCLUSIONS: Although the administration of chemotherapy and radiotherapy increased between 1995 and 2010 in patients with colorectal cancer with and without diabetes, patients with colorectal cancer with diabetes continue to receive chemotherapy less frequently than those without diabetes.

A high level of fatigue among long-term survivors of non-Hodgkin's lymphoma: results from the longitudinal population-based PROFILES registry in the south of the Netherlands.

The course of fatigue and quality of life in survivors of non-Hodgkin's lymphoma is unknown. The aims of this study were, therefore, to assess fatigue and quality of life in patients with non-Hodgkin's lymphoma following primary treatment, compare fatigue and quality of life in these patients with those of an age- and sex matched normative population to assess the severity of concerns and identify associations with fatigue of survivors who remained fatigued. The population-based Eindhoven Cancer Registry was used to select all patients diagnosed with non-Hodgkin's lymphoma from 1999-2009. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and the Fatigue Assessment Scale were completed once by 824 survivors of non-Hodgkin's lymphoma (80% response rate); 434 survivors completed these questionnaires again 1 year later. Survivors of non-Hodgkin's lymphoma reported more clinically relevant fatigue up till 10 years post-diagnosis compared to a normative population (P<0.001). Mean fatigue scores remained fairly stable over time (T1: x=28, SD=26; T2: x=30, SD=27, P=0.14): 22-28% of survivors reported deterioration, 19-23% reported improvement and 44-54% reported constant fatigue. Survivors who reported constant fatigue were more often diagnosed with stage IV disease and had more comorbid diseases. They were additionally more often female and divorced. Having comorbidities and being without a partner were also associated with constant fatigue in the normative population. In conclusion, six out of every ten responding non-Hodgkin's lymphoma survivors reported a high level of fatigue up till 10 years after diagnosis. Mean fatigue scores remained stable over time and survivors reporting constant fatigue more often had stage IV disease at diagnosis and comorbidities.

Ultrasound-guided radiofrequency ablation of early breast cancer in a resection specimen: lessons for further research.

PURPOSE: To assess the feasibility and effectiveness of radiofrequency ablation (RFA) in breast cancer, using different histopathologic staining methods to evaluate tissue viability. MATERIALS AND METHODS: In twenty patients with unifocal small (≤1, 5 cm) invasive ductal carcinoma, ultrasound-guided RFA was performed immediately after surgery. Cell viability was assessed using cytokeratin 8 (CK 8) and nicotinamide adenine dinucleotide diaphorase (NADHD) in addition to hematoxylin-eosin (HE). RESULTS: At histopathological examination, ex vivo RFA resulted in complete cell death of the target lesion in 17/20 patients. In two cases viable ductal carcinoma in situ (DCIS) was found just outside the completely ablated lesion. CONCLUSION: RFA of small invasive breast cancer seems to be a feasible treatment option. Both NADHD and CK 8 demonstrate a clear and comparable demarcation between viable and non-viable tissue. A high level of accuracy is required in proper positioning of the needle electrode and a "hot retraction" is mandatory.

The number of high-risk factors is related to outcome in stage II colonic cancer patients.

BACKGROUND: A subgroup of stage II colonic cancer patients are considered to be at high-risk for recurrent/metastatic disease based on 1) tumour obstruction/perforation 2) <10 lymph nodes 3) T4 lesions and 4) lymphangio-invasion. Their prognosis is regarded as comparable to stage III (T1-4N+M0) colonic cancer and it is therefore strongly advised to treat them with adjuvant chemotherapy. The purpose of this study was i) to determine the magnitude of prognostic significance of the conventional high-risk factors and ii) to determine whether the number of high-risk factors influences outcome. METHODS: We retrospectively analyzed 212 stage II colonic cancer patients undergoing surgery between January 2002 and December 2008. No adjuvant chemotherapy was given. Survival analyses were performed. RESULTS: 154/212 (73%) patients were considered to be high-risk patients based on conventional high-risk factors. 58 patients did not meet any high-risk factor, 125 patients met 1 high-risk factor and 29 patients met ≥2 high-risk factors. Median follow up was 40 months. Multivariate analysis identified four independent risk factors for recurrent/metastatic disease: age, obstruction, perforation and lymphangio-invasion. The three-year-DFS-rates for the low-risk group, the high-risk group with 1 high-risk factor and the high-risk group with ≥2 high-risk criteria are 90.4%, 87.6% and 75.9% respectively. Patients meeting ≥2 conventional high-risk criteria had a significantly worse three-year disease free survival (p < 0.002). CONCLUSIONS: Four independent high-risk factors were identified. The number of high-risk factors does influence outcome. More attention should be given to the definition and treatment of high-risk stage II colonic cancer patients.

Large age and hospital-dependent variation in administration of adjuvant chemotherapy for stage III colon cancer in southern Netherlands.

BACKGROUND: The purpose was to assess factors associated with the administration of chemotherapy and their relation to survival at a population-based level. METHODS: All patients diagnosed with primary colon cancer stage III from 2001 to 2007 in the area of the Eindhoven Cancer Registry were included (N = 1637). We examined determinants of the administration of adjuvant chemotherapy and their relation to survival. RESULTS: The proportion of patients receiving adjuvant chemotherapy decreased with increasing age from 85% for patients <65 years to 68% for those 65-74 years and 17% for patients > or =75 years, with large interhospital variation. Elderly patients {odds ratio (OR) 0.1 [95% confidence interval (CI) 0.1-0.1]} and those with comorbidity [OR 0.6 (95% CI 0.5-0.8)] received adjuvant chemotherapy less often. Patients with an intermediate [OR 1.4 (95% CI 1.1-1.9)] or high socioeconomic status [OR 1.5 (95% CI 1.1-2.0)] or stage IIIC [OR 1.5 (95% CI 1.1-2.0)] received adjuvant chemotherapy more often. Adjuvant chemotherapy was the most important predictor of survival. In a multivariable analysis, older age was no longer a significant negative predictor of survival, in contrast to comorbidity, higher tumor stage, poor tumor grade, and male gender. The improvement in survival from 2001 to 2006 did not reach statistical significance. CONCLUSION: Adherence to guidelines for adjuvant chemotherapy was still suboptimal in 2007, especially for elderly patients, and differed widely between hospitals.