Effectiveness and toxicity of lenvatinib in refractory thyroid cancer:Dutch real-life data

Objective: The SELECT trial showed progression-free survival (PFS) benefit for lenvatinib for advanced radioiodine-refractory differentiated thyroid cancer (RAI-refractory or RR-DTC) patients, on which current clinical practice is based. We assessed whether the effectiveness and toxicity of lenvatinib in real-life clinical practice in the Netherlands were comparable to the pivotal SELECT trial. Methods: From three Dutch centres Electronic Health Records (EHRs) of patients treated in the lenvatinib compassionate use program or as standard of care were reviewed and checked for SELECT eligibility criteria. Baseline characteristics, safety, and efficacy measures were compared and PFS and overall survival (OS) were calculated. Furthermore, PFS was compared to estimates of PFS reported in other studies. Results: A total of 39 DTC patients with a median age of 62 years were analysed. Of these, 27 patients (69%) did not fulfil the SELECT eligibility criteria. The most common grade >= 3 toxicities were hypertension (n = 11, 28%), diarrhoea (n = 7, 18%), vomiting (n = 4, 10%), and gallbladder disease (n = 3, 8%). Median PFS and median OS were 9.7 (95% confidence interval (CI): 4.0-15.5) and 18.3 (95% CI: 4.9-31.7) months, respectively, response rate was 38% (95% CI: 23-54%). PFS in the Dutch real-life situation was comparable to previous real-life studies, but inferior to PFS as shown in the SELECT trial (P = 0.04). Conclusions: PFS in our non-trial population was significantly shorter than in the SELECT trial population. In the interpretation of results, differences in the real-life population and the SELECT study population regarding patient characteristics should be taken into account

Can the FIGO 2000 scoring system for gestational trophoblastic neoplasia (GTN) be simplified? A new retrospective analysis from a nationwide data-set

Background: Worldwide introduction of the FIGO 2000 scoring system has provided an effective means to stratify patients with gestational trophoblastic neoplasia (GTN) to single- or multi-agent chemotherapy. However, the system is quite elaborate with an extensive set of risk factors. In this study, we re-evaluate all prognostic risk factors involved in the FIGO 2000 scoring system and examine if simplification is feasible. Patients and methods: Between January 2003 and December 2012, 813 patients diagnosed with GTN were identified at the Trophoblastic Disease Centre in London and scored using the FIGO 2000. Multivariable analysis and stepwise logistic regression were carried out to evaluate if the FIGO 2000 scoring system could be simplified. Results: Of the eight FIGO risk factors only pre-treatment serum human chorionic gonadotropin (hCG) levels exceeding 10,000 IU/l (OR = 5.0; CI 2.5-10.4) and 100,000 IU/l (OR = 14.3; CI 4.7-44.1), interval exceeding 7 months since antecedent pregnancy (OR = 4.1; CI 1.0-16.2) and tumor size of over 5 cm (OR = 2.2; CI 1.3-3.6) were identified as independently predictive for single-agent resistance. In addition, increased risk was apparent for antecedent term pregnancy (OR = 3.4; CI 0.9-12.7) and the presence of 5 or more metastases (OR = 3.5; CI 0.4-30.4), but patient numbers in these categories were relatively small. Stepwise logistic regression identified a simplified risk scoring model comprising age, pre-treatment serum hCG, number of metastases, antecedent pregnancy and interval but omitting tumor size, previous failed chemotherapy and site of metastases. With this model only 1 of 725 patients was classified differently from the FIGO 2000 system. Conclusion: Our simplified alternative using only five of the FIGO prognostic factors appears to be an accurate system for discriminating patients requiring single as opposed to multi-agent chemotherapy. Further work is urgently needed to validate these findings

The impact of adjuvant therapy on contralateral breast cancer risk and the prognostic significance of contralateral breast cancer: a population based study in the Netherlands

Background The impact of age and adjuvant therapy on contralateral breast cancer (CBC) risk and prognostic significance of CBC were evaluated. Patients and Methods In 45,229 surgically treated stage I–IIIA patients diagnosed in the Netherlands between 1989 and 2002 CBC risk was quantified using standardised incidence ratios (SIRs), cumulative incidence and Cox regression analysis, adjusted for competing risks. Results Median follow-up was 5.8 years, in which 624 CBC occurred <6 months after the index cancer (synchronous) and 1,477 thereafter (metachronous). Older age and lobular histology were associated with increased synchronous CBC risk. Standardised incidence ratio (SIR) of CBC was 2.5 (95% confidence interval (95% CI) 2.4–2.7). The SIR of metachronous CBC decreased with index cancer age, from 11.4 (95% CI 8.6–14.8) when <35 to 1.5 (95% CI 1.4–1.7) for ≥60 years. The absolute excess risk of metachronous CBC was 26.8/10,000 person-years. The cumulative incidence increased with 0.4% per year, reaching 5.9% after 15 years. Adjuvant hormonal (Hazard rate ratio (HR) 0.58; 95% CI 0.48–0.69) and chemotherapy (HR 0.73; 95% CI 0.60–0.90) were associated with a markedly decreased CBC risk. A metachronous CBC worsened survival (HR 1.44; 95% CI 1.33–1.56). Conclusion Young breast cancer patients experience high synchronous and metachronous CBC risk. Adjuvant hormonal or chemotherapy considerably reduced the risk of CBC. CBC occurrence adversely affects prognosis, emphasizing the necessity of long-term surveillance directed at early CBC-detection

Aandacht voor veiligheid

De komende decennia worden er tussen de 500.000 en 1.500.000 woningen gebouwd waarvan een groot deel in laag Nederland. Deze studie laat zien dat door deze woningen overstromingsbestendig te bouwen schadereductie mogelijk is. Het schaderisico wordt dan nog eens een factor 2 minder als naast een Business as Usual variant nieuwbouwwoningen worden opgehoogd tot +5 m NAP. De kosten van opgehoogde nieuwbouwhuizen zijn hoger en variëren tussen de 0,4 en 1.7 miljard euro/jaar, hetgeen overeenkomt met 0,1-0,5% van het BNP. Dijkversterking levert de hoogste reductie op in het schaderisico bij de gehanteerde scenario’s. Gevolgbeperkende maatregelen in de ruimtelijk ordening als additionele oplossingsrichting zijn echter goed mogelijk als er ook een economische perspectief is bijvoorbeeld door middel van multifunctioneel ruimtegebruik

Does chemotherapy-induced neutropaenia result in a postponement of adjuvant or neoadjuvant regimens in breast cancer patients? Results of a retrospective analysis

In 2005, 224 patients received adjuvant/neoadjuvant chemotherapy for breast cancer in a single institution according to daily practices. Regimens consisted of epirubicin-based chemotherapy (FEC100, four or six cycles), or three cycles of FEC100 followed by three cycles of docetaxel. An absolute blood count was carried out every 3 weeks, 1–3 days before planned chemotherapy cycle. Overall, 1238 cycles were delivered. An absolute neutrophil count (ANC) <1.5 × 109 l−1 before planned chemotherapy was found in 171 cycles. Of these, 130 cycles (76%) were delivered as planned regardless of whether ANC levels recovered, and 41 (24%) were delayed. None of these patients developed a febrile neutropaenia. Haematopoietic support (granulocyte colony-stimulating factor (G-CSF)) was required in 12 cycles. We found that the majority of patients with an ANC <1.5 × 109 l−1 before planned chemotherapy received planned doses, without complications and need for G-CSF

Clinical research in ovarian cancer: consensus recommendations from the Gynecologic Cancer InterGroup

The Gynecologic Cancer InterGroup (GCIG) sixth Ovarian Cancer Conference on Clinical Research was held virtually in October, 2021, following published consensus guidelines. The goal of the consensus meeting was to achieve harmonisation on the design elements of upcoming trials in ovarian cancer, to select important questions for future study, and to identify unmet needs. All 33 GCIG member groups participated in the development, refinement, and adoption of 20 statements within four topic groups on clinical research in ovarian cancer including first line treatment, recurrent disease, disease subgroups, and future trials. Unanimous consensus was obtained for 14 of 20 statements, with greater than 90% concordance in the remaining six statements. The high acceptance rate following active deliberation among the GCIG groups confirmed that a consensus process could be applied in a virtual setting. Together with detailed categorisation of unmet needs, these consensus statements will promote the harmonisation of international clinical research in ovarian cancer

INOVATYON/ ENGOT-ov5 study : Randomized phase III international study comparing trabectedin/pegylated liposomal doxorubicin (PLD) followed by platinum at progression vs carboplatin/PLD in patients with recurrent ovarian cancer progressing within 6-12 months after last platinum line

BACKGROUND: This trial investigated the hypothesis that the treatment with trabectedin/PLD (TP) to extend the platinum-free interval (TFIp) can improve overall survival (OS) in patients with recurrent ovarian cancer (OC). METHODS: Patients with OC (up to two previous platinum-based lines), with a TFIp of 6-12 months, were randomised to receive carboplatin/PLD (CP) or TP followed by platinum therapy at relapse. The primary endpoint was OS (HR: 0.75). RESULTS: The study enrolled 617 patients. The median TFIp was 8.3 months and 30.3% of patients had received two previous platinum lines. 74% and 73.9% of patients, respectively, received a subsequent therapy (ST) in the CP and TP arm; in the latter TP arm 87.2% of ST was platinum-based, as per protocol. The median OS was 21.4 for CP and 21.9 months for TP (HR 1.13; 95% CI: 0.94-1.35; p = 0.197). Grade 3-5 adverse reactions occurred in 37.1% of patients in the CP arm and 69.7% of patients in the TP arm, and the most frequent were neutropenia (22.8% CP, 39.5% TP), gastrointestinal (7.1% CP, 17.4% TP), hepatic (0.7% CP, 19.1% TP). CONCLUSIONS: This study did not meet the primary endpoint. CP combination remains the standard for patients with recurrent OC and a 6-12 months TFIp; TP is an effective treatment in patients suffering from persistent platinum toxicities. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, number NCT01379989.publishedVersionPeer reviewe