Stop routine screening for associated malignancies in cutaneous noninvasive vulvar Paget disease?

BACKGROUND: Vulvar Paget disease (VPD) is extremely rare and thought to be associated with other malignancies. OBJECTIVES: To evaluate the risk of developing breast, intestinal and urological malignancies in patients with VPD compared with the general population, and in particular to focus on the risk of malignancy in patients with cutaneous noninvasive VPD. METHODS: Data on the oncological history of patients with any type of VPD between 2000 and 2015 were obtained from PALGA, a nationwide archive containing all pathology reports in the Netherlands. Follow-up data and a control group from the general population were obtained from the Netherlands Cancer Registry. After correction for age and calendar year at time of diagnosis, standardized incidence ratios (SIRs) for the first 3 years after VPD diagnosis were estimated with 95% confidence intervals (CIs). RESULTS: We identified 199 patients with a first diagnosis of VPD [164 noninvasive, 35 (micro)invasive] between 2000 and 2015. The SIR of developing an associated malignancy in the first 3 years after diagnosis was 4·67 (95% CI 2·66-7·64). This was due mainly to the high incidence of intestinal malignancies among patients with secondary VPD. Subgroup analysis for cutaneous noninvasive VPD did not reveal a significantly increased risk for associated malignancies: SIR 2·08 (95% CI 0·76-4·62). CONCLUSIONS: Of our patients with VPD, 76·9% were diagnosed with cutaneous noninvasive VPD, and this group has no increased risk for developing malignancies of the breast, intestine or urological tract. Our study suggests that routine screening for these malignancies in patients diagnosed with cutaneous noninvasive VPD may not be necessary.

Treatment and outcome of elderly patients with advanced stage ovarian cancer: A nationwide analysis.

OBJECTIVE: To provide an overview of treatment strategies for elderly patients with advanced stage epithelial ovarian cancer (EOC) in daily practice, evaluate changes over time and relate this to surgical mortality and survival. METHODS: All women diagnosed with advanced stage (FIGO IIB and higher) EOC between 2002 and 2013 were selected from the Netherlands Cancer Registry (n=10,440) and stratified by age, stage and period of diagnosis. Elderly patients were defined as aged ≥70years. Time trends in treatment patterns and postoperative mortality were described by age category and tested using multivariable logistic regression. Relative survival was calculated. RESULTS: With advancing age, less patients received ((neo-)adjuvant) treatment. Over time, elderly patients were less often treated (OR 2002-2004 versus 2011-2013: 0.73; 95%CI:0.58-0.92). But if treated, more often standard treatment was provided and 30-day postoperative mortality decreased from 4.5% to 1.9% between 2005 and 2007 and 2011-2013. In all age categories treatment shifted from primary surgery towards primary chemotherapy, in patients aged 70-79years combination therapy increased (+5%) between 2002 and 2004 and 2011-2013. Five-year relative survival for patients diagnosed in 2008-2010 aged <70years was 34% compared to 18% for elderly patients. CONCLUSION: Large treatment differences exist between younger and elderly patients. Over time, selection of elderly patients eligible for curative surgical treatment may have improved. More elderly patients were treated with neoadjuvant chemotherapy while less patients underwent surgery and simultaneously postoperative mortality decreased. However, the large and increasing number of elderly patients without treatment and the large survival gap suggests opportunities for further improvements in the care for elderly EOC patients.

Ultrafast Dissociation of Metastable CO

We triply ionize the van der Waals bound carbon monoxide dimer with intense ultrashort pulses and study the breakup channel (CO)_{2}^{3+}→C^{+}+O^{+}+CO^{+}. The fragments are recorded in a cold target recoil ion momentum spectrometer. We observe a fast CO^{2+} dissociation channel in the dimer, which does not exist for the monomer. We found that a nearby charge breaks the symmetry of a X^{3}Π state of CO^{2+} and induces an avoided crossing that allows a fast dissociation. Calculation on the full dimer complex shows the coupling of different charge states, as predicted from excimer theory, gives rise to electronic state components not present in the monomer, thereby enabling fast dissociation with higher kinetic energy release. These results demonstrate that the electronic structure of molecular cluster complexes can give rise to dynamics that is qualitatively different from that observed in the component monomers.

Risk factors for second primary melanoma among Dutch patients with melanoma.

BACKGROUND: Patients with melanoma are at increased risk of developing subsequent primary melanomas. Knowledge about risk factors for these subsequent primaries is scarce. More evidence may help clinicians in tailoring surveillance schedules by selecting patients who could benefit from intensified surveillance. OBJECTIVES: To identify risk factors for a second primary cutaneous melanoma. METHODS: Possible risk factors for a second primary melanoma were assessed in 1127 patients with cutaneous melanoma who were diagnosed between 2003 and 2011 and completed a baseline questionnaire. Additional data were extracted from the Netherlands Cancer Registry and medical files. RESULTS: Fifty-three patients were diagnosed with a second melanoma during a median follow-up time of 6·3 years. The 5-year cumulative risk was 3·7% and the conditional cumulative risk was 4·6% in years 5-10 after diagnosis. In multivariable analyses, the risk of a second melanoma increased with older age at diagnosis [hazard ratio (HR) 1·03 per year; 95% confidence interval (CI) 1·00-1·06], a high naevus density (HR 7·16, 95% CI 2·89-17·75) and working outside for > 10 years (HR 2·88, 95% CI 1·38-6·03). Patients with invasive melanoma (> 1 mm) had a decreased risk compared with patients with melanoma in situ (HR 0·35, 95% CI 0·13-0·93). CONCLUSIONS: Besides phenotypic characteristics, cumulative sun exposure seemed to increase the risk of a second melanoma. Patients with melanoma in situ may need to be offered follow-up, which is currently not advised. As the risk of a second melanoma did not decline in years 5-10 after diagnosis, a subgroup of patients may need a longer follow-up than is currently advised.

Rare vulvar malignancies; incidence, treatment and survival in the Netherlands.

OBJECTIVE: To describe trends in incidence, treatment and survival of patients with basal cell carcinomas and melanomas of the vulva. Also to compare survival of vulvar and cutaneous melanoma patients. METHODS: All women with a vulvar malignancy between 1989 and 2012 were selected from the Dutch Cancer Registry (n=6436). Standardized incidence rates, estimated annual percentage change (EAPC) and 5-year relative survival rates were calculated for basal cell carcinomas (BCCs) and melanomas. Patients with vulvar melanomas were matched to women with cutaneous melanomas on period of diagnosis, age, Breslow thickness, tumour ulceration, lymph node status and distant metastases. Differences in survival were evaluated using Kaplan-Meier curves and the log rank test. RESULTS: 489 women were diagnosed with a BCC and 350 with a melanoma of the vulva. The EAPC in incidence for melanomas was 0.2% and 1.1% for BCCs. Eighty-six percent of patients with BCC underwent surgical treatment in 1989-2006 and 95% in 2005-2012. Forty-five percent with BCC and 79% with melanoma were treated in a referral centre. Five-year relative survival for BCCs was 100% and for melanomas survival increased from 37% (95%CI 28-47%) in 1989-1999 to 45% (95%CI: 37-54%) in 2000-2012. Five years after diagnosis survival of women with vulvar melanoma was 15% lower compared to matched cutaneous melanoma patients (p=0.002). CONCLUSION: No trends in age-adjusted incidence have been observed but more patients with BCC received surgical treatment over time. Having had vulvar BCC did not affect life expectancy. Well-known prognostic factors explained most of the differences in survival between cutaneous and vulvar melanoma patients, however a difference of 15% remained unexplained.

Variation in the management of cT1 renal cancer by surgical hospital volume: A nationwide study.

Objectives: To analyse variation in clinical management of cT1 renal cell carcinoma (RCC) in the Netherlands related to surgical hospital volume (HV). Materials and methods: Patients diagnosed with cT1 RCC during 2014-2020 were identified in the Netherlands Cancer Registry. Patient and tumour characteristics were retrieved. Hospitals performing kidney cancer surgery were categorised by annual HV as low (HV < 25), medium (HV = 25-49) and high (HV > 50). Trends over time in nephron-sparing strategies for cT1a and cT1b were evaluated. Patient, tumour and treatment characteristics of (partial) nephrectomies were compared by HV. Variation in applied treatment was studied by HV. Results: Between 2014 and 2020, 10 964 patients were diagnosed with cT1 RCC. Over time, a clear increase in nephron-sparing management was observed. The majority of cT1a underwent a partial nephrectomy (PN), although less PNs were applied over time (from 48% in 2014 to 41% in 2020). Active surveillance (AS) was increasingly applied (from 18% to 32%). For cT1a, 85% received nephron-sparing management in all HV categories, either with AS, PN or focal therapy (FT). For T1b, radical nephrectomy (RN) remained the most common treatment (from 57% to 50%). Patients in high-volume hospitals underwent more often PN (35%) for T1b compared with medium HV (28%) and low HV (19%). Conclusion: HV is related to variation in the management of cT1 RCC in the Netherlands. The EAU guidelines have recommended PN as preferred treatment for cT1 RCC. In most patients with cT1a, nephron-sparing management was applied in all HV categories, although differences in applied strategy were found and PN was more frequently used in high HV. For T1b, high HV was associated with less appliance of RN, whereas PN was increasingly used. Therefore, closer guideline adherence was found in high-volume hospitals.

Peritoneal metastases in elderly patients with colorectal cancer.

BACKGROUND: With the introduction of cytoreductive surgery with intraperitoneal chemotherapy and the development of new systemic anti-cancer agents, the treatment of colorectal cancer (CRC) patients with peritoneal metastases has changed. Real-world data on the treatment of elderly patients and their clinical outcomes is lacking. METHODS: All CRC patients diagnosed with synchronous peritoneal metastases (SPM) during 2008-2019 (n = 7,748) were identified from the Netherlands Cancer Registry. Trends in treatment and postoperative mortality were described by age category (<70, 70-74, 75-79, ≥80 years) and period of diagnosis (2008-2013, 2014-2019). Kaplan-Meier curves were constructed, and log-rank tests were performed to evaluate differences in overall survival (OS). RESULTS: With increasing age, less patients received multimodality treatment and systemic treatment. Of the patients aged <70 years, 38% underwent multimodality treatment and 35% palliative systemic therapy, declining to 4% and 12% in patients ≥80 years. A large and increasing proportion of elderly patients did not receive cancer-directed treatment, this increased from 32% in 2008-2013 to 41% in 2014-2019 in 75-79 years old patients and from 52% to 65% in ≥80 years old. Postoperative mortality decreased in all age categories over time, OS remained stable. The median OS of elderly patients ranged from 8 months in 70-74 years old to 3 months in patients aged ≥80 years. DISCUSSION: Age strongly affects treatment of patients with SPM, with a large and increasing proportion of elderly patients not receiving cancer-directed treatment. Their prognosis remains very poor. There is a need for therapeutic options that are well tolerable for elderly patients.

Survival of sentinel node biopsy versus observation in intermediate-thickness melanoma: A Dutch population-based study.

BACKGROUND: The Multicenter Selective Lymphadenectomy Trial (MSLT-1) comparing survival after a sentinel lymph node biopsy (SLNB) versus nodal observation in melanoma patients did not show a significant benefit favoring SLNB. However, in subgroup analyses melanoma-specific survival among patients with nodal metastases seemed better. AIM: To evaluate the association of performing a SLNB with overall survival in intermediate thickness melanoma patients in a Dutch population-based daily clinical setting. METHODS: Survival, excess mortality adjusted for age, gender, Breslow-thickness, ulceration, histological subtype, location, co-morbidity and socioeconomic status were calculated in a population of 1,989 patients diagnosed with malignant cutaneous melanoma (1.2-3.5 mm) on the trunk or limb between 2000-2016 in ten hospitals in the South East area, The Netherlands. RESULTS: A SLNB was performed in 51% of the patients (n = 1008). Ten-year overall survival after SLNB was 75% (95%CI, 71%-78%) compared to 61% (95%CI 57%-64%) following observation. After adjustment for risk factors, a lower risk on death (HR = 0.80, 95%CI 0.66-0.96) was found after SLNB compared to observation only. CONCLUSIONS: SLNB in patients with intermediate-thickness melanoma on trunk or limb resulted in a 14% absolute and significant 10-year survival difference compared to those without SLNB.

Time-resolved nuclear dynamics in bound and dissociating acetylene.

We have investigated nuclear dynamics in bound and dissociating acetylene molecular ions in a time-resolved reaction microscopy experiment with a pair of few-cycle pulses. Vibrating bound acetylene cations or dissociating dications are produced by the first pulse. The second pulse probes the nuclear dynamics by ionization to higher charge states and Coulomb explosion of the molecule. For the bound cations, we observed vibrations in acetylene (HCCH) and its isomer vinylidene (CCHH) along the CC-bond with a periodicity of around 26 fs. For dissociating dication molecules, a clear indication of enhanced ionization is found to occur along the CH- and CC-bonds after 10 fs to 40 fs. The time-dependent ionization processes are simulated using semi-classical on-the-fly dynamics revealing the underling mechanisms.

Trends in incidence and survival of Dutch women with vulvar squamous cell carcinoma.

AIM: Previous studies showed an increase in incidence of vulvar intraepithelial neoplasia (VIN), the premalignant lesion of Vulvar Squamous Cell Carcinoma (VSCC). Furthermore, during the last decades treatment of VSCC became less radical. Considering these changes the aim of this study was to describe trends of incidence and survival of patients with VSCC in the Netherlands. METHODS: All patients with VSCC diagnosed between 1989 and 2010 (n=4614) were selected from the Netherlands Cancer Registry. Trends in age-adjusted incidence rates were evaluated by calculating the estimated annual percentage change (EAPC). Joinpoint regression analysis was used to detect changes in trends. Five-year relative survival rates were calculated for four time periods. RESULTS: The incidence of VSCC has increased since 2002 (EAPC 5.0; 95% confidence interval (CI): 2.7-7.7%). In women aged <60years incidence rates increased significantly during the whole study period (EAPC 3.5%; 95% CI: 2.0-4.9), while in women aged ≥ 60 years only an increase has observed from 2004 onwards (EAPC 5.0; 95% CI: 1.5-8.6). Survival rates did not change over time. CONCLUSION: The incidence rate of VSCC has increased from 2002 onwards in all women. Over the whole study period the increase was strongest in women aged <60 years. The introduction of less radical surgery did not affect survival.