Thymoma and thymic carcinoma in children and adolescents: A report from the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT)

BackgroundThymomas and thymic carcinomas belong to a group of thymic epithelial tumours arising from the anterior mediastinum and, are extremely rare in children in which no therapeutic guidelines have been established. The aim is to describe paediatric characteristics of these tumours and give some therapeutic indications.MethodsRetrospective analysis of clinical data and therapeutic characteristics of paediatric patients less than 18 years with thymic tumours treated between 2000 and 2012 registered in the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) database of the cooperating national rare paediatric tumour working groups from France, Italy, Germany and Poland.ResultsSixteen children with thymoma, median age 11 years and 20 patients with thymic carcinoma, median age 14 years were enrolled into study. At diagnosis complete primary resection was possible in 11 patients with thymoma and one with thymic carcinoma; resection with microscopic residue was performed in three cases and incomplete resection with macroscopic residue in four patients. Chemotherapy with various regimens was administered to 22 children; 17 of them as neoadjuvant chemotherapy. Eight patients with thymic carcinoma received additional radiotherapy. Seventeen children died (15 thymic carcinoma, two thymoma). Five-year overall survival for patients with thymic carcinoma is 21.0 ± 10.0%.ConclusionsThis study confirms the possibility to perform European retrospective analysis even in very rare paediatric tumours. Thymic carcinoma is associated with paediatric patients to give a very poor prognosis independently despite multimodal management. Multidisciplinary, multicenter approach and collaboration with adults’ physician are necessary in order to propose homogenous guidelines.     

Tumour vasculogenic mimicry is associated with poor prognosis of human cancer patients: A systemic review and meta-analysis

BackgroundVasculogenic mimicry (VM) has been reported in various malignant tumours and is known to play an important role in cancer progression and metastasis. However, the impact of VM on the overall survival of human cancer patients remains controversial. The goal of this study was to evaluate whether VM is associated with 5-year survival of human cancer patients.MethodsTwenty-two eligible clinical studies with data on both tumour cell-dominant VM and the 5-year survival of 3062 patients involved in 15 types of cancers were pooled in the meta-analysis.ResultsThe 5-year overall survival of VM-positive and -negative cancer patients was 31% and 56%, respectively. The relative risk (RR) of the 5-year survival of VM-positive patients was significantly higher than that of VM-negative cases (RR = 1.531; 95% confidence interval (CI): 1.357–1.726; P < 0.001). Notably, metastatic melanoma patients demonstrated a higher VM rate (45.3%) than patients with primary melanoma (23.1%) and showed worse 5-year survival, suggesting that VM contributes to tumour metastasis and poor prognosis in cancer patients. Subgroup analysis indicated that a poor 5-year survival was significantly associated with eight types of VM-positive malignant tumours, such as lung, colon, liver cancers, sarcomas and melanoma; but was not associated with the seven other types of cancers, such as prostate cancer. Heterogeneity and publication biases were found among the 22 studies, mainly due to the divergent characteristics of cancers and extremely low survival rate in six types of malignant tumours.ConclusionVM-positive cancer patients show a poor 5-year overall survival compared with VM-negative malignant tumour cases, particularly in metastatic cancer.     

Treatment and prognostic factors in pleuropulmonary blastoma: An EXPeRT report

BackgroundPleuropulmonary blastoma (PPB) is an aggressive embryonal malignancy presenting in early childhood, presumably arising from pleuropulmonary mesenchyme. The European Cooperative Study Group for Paediatric Rare Tumours (EXPeRT) analysed its data on this tumour.MethodsThis analysis concerns patients aged 0–17 years with histologically-confirmed PPB registered up to 2008 in national databases in Italy, France and the United Kingdom and Poland. Lesions were classified as type I, II or III according to Dehner’s classification.FindingsSixty-five patients were considered (13 type I, 24 type II and 28 type III). Most tumours were large (91% >5 cm) and invaded the parietal pleura (29), mediastinum (10), major vessels (four) or pericardium (three). Regional nodes were involved in two cases, and three had metastases. The median follow-up was 5 years (0.6–22). For type I patients, 5-year progression free survival (PFS) was 83.3% and overall survival 91.7%; six patients received no further treatment after surgery, but two relapsed. All type II/III PPB had chemotherapy (CT) and their 5-year PFS was 42.9% (27.7–57.2). On univariate analysis, favourable prognostic factors were: complete tumour resection at diagnosis (p = 0.008); and absence of invasiveness (p = 0.02); for type II/III tumours, type of CT was also a significant factor (patients given doxorubicin fared better, with a 5-year PFS of 70% versus 31.3% [p = 0.01]).InterpretationsType I PPB patients’ outcome was satisfactory. Complete resection at diagnosis seems important but rarely feasible for type II/III tumours, who benefited from doxorubicin-containing CT regimens. These results will inform the EXPeRT group’s PPB treatment guidelines.     

443 paediatric cases of malignant melanoma registered with the German Central Malignant Melanoma Registry between 1983 and 2011

BackgroundMalignant melanoma is a very rare paediatric tumour. This study was performed in order to understand clinical features and prognosis of malignant melanoma in children and adolescents.Methods443 patients ⩽18 years of age with malignant melanoma were prospectively registered with the German Central Malignant Melanoma Registry between 1983 and 2011. Cases were collected from 58 participating centres. 276 paediatric cases with a follow-up >3 months were evaluated for survival probabilities and prognostic factors by Kaplan–Meier method.ResultsAge of diagnosis ranged from 3 months to 18 years (median age 16 years). The male to female ratio was 0.8 (202 male, 240 female). Most melanoma were located at the trunk (n = 195) and the lower extremity (n = 114). Patients with >3 months of follow-up (median 55 months) showed an overall survival (OS) of 94.8% in 5 years. Survival according to tumour stage was 98.5% for stage I (n = 190), 91.1% for stage II (n = 39) and 53.0% for stage III/IV tumours (n = 11). Worse outcome was seen in patients with nodular melanoma (OS 77.9%, n = 42) compared to superficial spread histotype (OS 100%, n = 138) or other histotype (OS 96.9%, n = 88) (p < 0.0001), in case of thicker tumours (Clark level IV or V, OS 87.1%, n = 84) compared to thinner tumours (Clark level I, II, III, OS 99.1%, n = 164) (p = 0.0008) and in case of ulceration (OS 65.6%, n = 17) compared to no ulceration (OS 99.2%, n = 182).ConclusionPatient and tumour characteristics in paediatric melanoma patients show no evident differences to adult melanoma cases. The same clinical approach as in adults should be used.     

Urinary tract cancer survival in Europe 1999–2007: Results of the population-based study EUROCARE-5

BackgroundThis work presents relative survival estimates regarding urinary tract tumours among adult patients (age ⩾ 15 years) diagnosed in Europe. It reports on survival estimates of cases diagnosed in 2000–2007, and on survival time trends from 1999–2001 to 2005–2007.MethodsData on 677,340 adult urinary tract tumour patients, (429,154 cases of invasive and non-invasive bladder and 248,186 cases of invasive kidney cancers) diagnosed between 2000 and 2007 were provided by 86 population-based cancer registries from 29 European countries.The complete approach was used to estimate survival in 2000–2007; the period approach was used to estimate survival over time.ResultsThe age-standardised 5-year relative survival for patients with kidney tumours diagnosed in Europe during 2000–2007 was 60%. The best prognosis was observed in Southern and Central Europe and prognosis improved in all regions along the time period. For invasive and non-invasive patients with bladder tumours combined the age-standardised 5-year relative survival in Europe was 68%. The best prognosis was observed in Southern and Northern Europe. However, in Scotland and The Netherlands the relative survival was significantly lower, although the survival estimates for these two countries were based on invasive tumours only.ConclusionsDifferences in registration practices affect comparisons of survival values between European countries, especially in patients with urinary bladder cancers. The between-country variation in survival is influenced by the varying use of diagnostic investigation in urinary tract tumours. Further data on stage at diagnosis can help to elucidate the influence of diagnostic intensity or early diagnosis on the survival patterns.     

Ovarian Sertoli Leydig cell tumours in children and adolescents: An analysis of the European Cooperative Study Group on Pediatric Rare Tumors (EXPeRT)

ObjectiveTo analyse ovarian Sertoli-Leydig cell tumours (SLCTs) for potential prognostic markers and their use for treatment stratification.PatientsForty-four patients were included. Patients were prospectively reported to the German MAKEI (Maligne Keimzelltumoren) studies (n = 23), French TGM protocols (n = 10), Italian Rare Tumour Project (TREP) registry (n = 6), and the Polish Pediatric Rare Tumour Study group (n = 5). Tumours were classified according to World Health Organisation (WHO) and staged according to International Federation of Gynecological Oncology (FIGO).ResultsMedian age was 13.9 (0.5–17.4) years. All patients underwent resection by tumour enucleation (n = 8), ovariectomy (n = 17), adenectomy isolated (n = 18) or with hysterectomy (n = 1). FIGO-stage: Ia 24 pts., Ic 17 pts., II/III 3 pts. One patient had bilateral tumours. Four patients (stage Ia: 3, stage Ic: 1) developed a metachronous contralateral tumour. Otherwise, all stage Ia patients remained in complete remission. Among 20 patients with incomplete resection or tumour spread (stage Ic–III), eight relapsed, and five patients died. Eleven patients were initially treated with two to six cycles of cisplatin-based chemotherapy. Of these, seven patients are in continuous remission. Poor histological differentiation was associated with higher relapse rate (5/13) compared to intermediate (3/18) and high differentiation (0/4). Tumours with retiform pattern or heterologous elements showed a high relapse rate, too (5/11). After a median follow-up of 62 months, event-free survival is 0.70 ± 0.07, relapse-free survival 0.81 ± 0.06 and overall survival 0.87 ± 0.05.ConclusionsPrognosis of SLCTs is determined by stage and histopathologic differentiation. Complete resection with careful avoidance of spillage is a prerequisite of cure. The impact of chemotherapy in incompletely resected and advanced stage tumours remains to be evaluated.     

Multifocal breast cancer and survival: Each focus does matter particularly for larger tumours

PurposeThe objective of this study is to determine whether the aggregate tumour size of every focus in multifocal breast cancer more accurately predicts 10-year survival than current staging systems which use the largest or dominant tumour size.Patients and methodsThis study examined the original histological reports of 848 consecutive patients with invasive breast cancer treated in New South Wales (NSW), Australia between 1 April 1995 and 30 September 1995. Multifocal tumours were assessed using two estimates of pathologic tumour size: largest tumour focus diameter and the aggregate diameter of every tumour focus. The 10-year survival of patients with multifocal tumours measured in both ways was compared to that with unifocal tumours.ResultsAt a median follow-up of 10.4 years, 27 of 94 patients (28.7%) with multifocal breast cancer have died of breast cancer compared to 141 of 754 (18.7%) with unifocal breast cancer (P = .022). Ten-year survival was not affected by size for tumours measuring 20 mm or less, whether or not dominant tumour size (87.9%) or aggregate tumour size (87.0%) was used for multifocal tumours, compared to unifocal tumours (88.1%). For tumours larger than 20 mm, 10-year survival was 72.1% for unifocal tumours compared to 54.7% (P = .008) for multifocal tumours using dominant tumour size, but this was 69.5% and not significant when multifocal tumours were classified using aggregate tumour size (P = .49). Multivariate analysis also confirmed the above-mentioned results after adjustment for important prognostic factors.ConclusionAggregate size of every focus should be considered along with other prognostic factors for metastasis when treatment is planned. The current convention of using the largest (dominant) lesion as a measure of stage and associated breast cancer survival needs further validation.     

Résultats thérapeutiques du cancer du cavum : y a-t-il une différence entre enfants et adultes ?

PurposeTo compare therapeutic results of nasopharyngeal carcinoma between adults and children.Patients and methodsThree hundred and seventy seven patients with nasopharyngeal carcinoma received a radiotherapy between 1993 and 2007. Sixty-nine of them were 20 years old or less. Two hundred and sixty eight patients received a chemotherapy (neoadjuvant or concomitant).ResultsOverall survival and disease-free survival at 5 years were 67 % and 59.4 % in all patients, respectively. Overall survival rates at 5 years in children and adults were 66 % and 64 %, respectively (P = 0.17), disease-free survival rates at 5 years were 66 % and 57 %, respectively (P = 0.17). Local failures occurred more frequently in adults than in children (1.4 % versus 14 %). However, metastatic events were frequently seen in children. Late toxicities were important in children, xerostomia was the most common one.ConclusionDespite locally advanced disease in children, therapeutic results were better than in adults but not statistically significant. The use of treatment combination (chemotherapy and radiotherapy) in juvenile nasopharyngeal carcinoma may explain our findings.     

Prognostic factors in malignant ovarian germ cell tumours (The Surveillance,Epidemiology and End Results experience 1978–2010)

PurposeTo evaluate the prognostic significance of age at diagnosis, extent of the disease (EOD) and socioeconomic (SES) and sociodemographic status (civil status, residency) on cause specific survival (CSS) in patients with malignant ovarian germ cell tumours (MOGCTs). To explore the cumulative incidence of a second cancer in 10-year MOGCT survivors.Patients and methods2541 patients with MOGCT, reported to the Surveillance, Epidemiology and End Results programme (1978–2010), were identified. The above mentioned prognostic factors were assessed separately for dysgerminoma and non-dysgerminoma, using Kaplan–Meier estimates and Cox Hazards Models, providing 95% confidence intervals (95% CI).ResultsFive-year CSS was 97% (95% CI, 96–98%), and 92% (95% CI, 91–93%), respectively for dysgerminoma, and non-dysgerminoma. Age >40 years at diagnosis and presence of metastases were significantly associated with cause specific mortality. Among non-dysgerminoma patients, decreasing SES (hazard ratio (HR), 1.59; 95% CI, 1.11–2.28) and treatment before 1990 (HR, 2.65; 95% CI, 1.83–3.85) increased mortality. In the adjusted analysis, patients from Michigan were almost 2.5 times more likely to die from MOGCT than patients from other states (HR, 2.48; 95% CI, 1.17–5.25). Second cancer was diagnosed in 10% of 10-year survivals who underwent radiotherapy and in 2% of survivals in non-radiotherapy group (p = .002).ConclusionsIncreased attention should be directed towards the management of elderly MOGCT patients and those with non-dysgerminoma histology with low SES. Radiotherapy should be avoided as much as possible. Survival differences related to residency may occur when new cancer treatments are introduced.     

Survival and selected outcomes of older adults with locally advanced head/neck cancer treated with chemoradiation therapy

ObjectivesChemoradiation therapy (CRT) remains a potentially curative treatment in patients with locally advanced head/neck cancer (LA-HNC). However, survival and other outcomes in older patients with head/neck cancer receiving chemoradiotherapy are not well established. This study was performed to elucidate selected outcomes in this patient population.Materials and MethodsRetrospective study of LA-HNC patients ≥ 70 years of age who had received 5-fluorouracil-hydoxyurea-based CRT with a minimum of 3 years of follow up after therapy initiation was performed. Pre-treatment patient- and cancer-related characteristics were recorded. Survival data in addition to gastrostomy tube utilization, swallowing function, and hematologic toxicity were captured.ResultsEighty-nine patients treated between 1997 and 2009 were eligible for analysis (median age, 76 years; range, 70–94; male, 61%; ECOG PS, 0–1 43%; stage IVA/B, 71%). 86 were evaluable for survival analysis. 5-year overall and event-free survival were both at 32% with a median follow-up time of 39.2 months. The majority (86.5%) were able to complete all planned treatment cycles. A significant proportion of patients, however, required gastrostomy tube during CRT (62%) and developed aspiration during swallowing evaluation post-treatment (44%). Several patients required hospice (9%) or skilled nursing facility (13%) referrals during treatment.ConclusionSelect older adults with LA-HNC can still experience long-term benefits despite 5-year survival rates lower than those historically reported in younger patients undergoing identical CRT regimens although potentially at higher risk for acute toxicities. Assessment and selection of those who can tolerate more intense combined-modality strategies and their long-term outcomes merit further larger, prospective studies.     

Postoperative adjuvant chemotherapy followed by adjuvant tamoxifen versus nil for patients with operable breast cancer: a randomised phase III trial of the European Organisation for Research and Treatment of Cancer Breast Group

BackgroundThe contribution of adjuvant tamoxifen in breast cancer patients after receiving adjuvant chemotherapy is not fully established. We investigated the impact of tamoxifen, given sequentially after completion of adjuvant chemotherapy in patients with operable breast cancer.Patients and methodsBetween March 1991 and June 1999, 1863 women with stages I–IIIA operable breast cancer who had undergone surgery and completed six cycles of adjuvant combination chemotherapy with either CMF, CAF, CEF, FAC or FEC were randomised to receive either tamoxifen 20 mg daily for 3 years or no further treatment. Irrespective of menstrual status and hormone receptor content of the primary tumour, patients were stratified by institute, chemotherapy scheme and age (above 50 years or younger). The main end-point was to detect a 5% increase in the 5 year survival (from 80% to 85%) in favour of antioestrogen therapy. Secondary end-points were relapse free survival (RFS), local control, incidence of second primary breast cancer and correlation of results with hormone receptor content.ResultsAfter exclusion of all patients from three sites because of inadequate documentation, a total of 1724 patients (93%) were analysed (Tam 861 and Control 863). At a median follow-up of 6.5 years, 5-year RFS on tamoxifen was 73% versus 67% in controls (p = 0.035). No difference was seen in overall survival. The benefit of tamoxifen therapy was mainly seen in the subgroup of patients with histologically documented positive axillary nodes (5-year RFS on tamoxifen 71% versus 64% in the control group, p = 0.044) and in patients with tumours expressing the ER and PR positive phenotype (5-year RFS on tamoxifen 77% versus 70% in the control group, p = 0.014).ConclusionsTamoxifen administered for 3 years after completion of adjuvant chemotherapy in this otherwise unselected group of patients for endocrine sensitivity had a limited impact on relapse and had no detectable effect on overall survival. The beneficial effect of tamoxifen is mainly confined to the subgroup of patients with node-positive disease and to patients with tumours expressing the ER and PR positive phenotype.     

Second cancers in patients with the Ewing sarcoma family of tumours

BackgroundPatients are at risk of second malignancies (SM) after treatment for Ewing sarcoma family of tumours (ESFT).MethodsWe performed a retrospective review of 237 patients with ESFT treated at our institution from September 1979 through to February 2004. Cumulative incidence (CI) of SM by the type of malignancy and treatment was estimated.ResultsTwelve patients with SM were identified. Secondary leukaemia (SL) developed in 8 patients (2 ALL, 6 MDS/AML), a median 2.6 years (range 1.4–19.6 years) after diagnosis of ESFT. Four patients had secondary solid tumours, a median 8.0 years (range 7.4–9.4 years) after the ESFT diagnosis. Five- and 10-year estimates of the CI of SM were 3.0 ± 1.1% and 4.7 ± 1.5%, respectively. Patients treated on recent protocols with higher cumulative doses or an increased dose intensity of alkylators and epipodophyllotoxins and the use of G-CSF had a higher estimated CI of SL than those in earlier studies (5-year CI 6.4 ± 2.4% versus 0.0 ± 0.0%, respectively, P = 0.004).ConclusionsPatients with ESFT are at risk for SM after treatment. The cumulative incidence of SM is higher with the current treatment protocols and may be related to the intensification of chemotherapeutic agents.     

The efficacy of adjuvant chemotherapy with 5-fluorouracil in colorectal cancer depends on the mismatch repair status

AimsThe aim of this study is to evaluate if mismatch repair (MMR) defective colorectal cancer has a different response to adjuvant 5-fluorouracil (5-FU) chemotherapy in a cohort of patients prospectively followed during 5 years.MethodsThe cohort included 754 surgically treated patients with colorectal cancer. MMR status was diagnosed by MLH1 and MSH2 immunohistochemistry and microsatellite instability analysis. Median follow-up was 49.2 months (range 1–73). At inclusion, 505 patients were diagnosed as TNM II or III stage, analysis of the efficacy of adjuvant chemotherapy was made on this population. Adjuvant chemotherapy was applied to 248 patients (98.2% 5-FU based).ResultsMMR deficiency was found in 76 patients (10.1%). No differences were found in overall survival (log-rank p = 0.3) or disease-free survival (log-rank p = 0.3) regarding MMR status. Adjuvant chemotherapy improves survival in patients in the II or III stage, but this improvement is only evident in patients with MMR-competent tumours (log-rank p = 0.00001). Survival of patients with MMR-defective tumours does not improve with adjuvant chemotherapy (log-rank p = 0.7). A multivariate analysis showed an independent effect of the interaction between MMR status and adjuvant chemotherapy (Hazard ratio 2.04; 95% confidence interval: 1.42–2.93).ConclusionIn a cohort of colorectal cancer patients, those with MMR-deficient tumours seem not to benefit from 5-FU-based chemotherapy.     

Matched-case comparison of neoadjuvant chemotherapy in patients with FIGO stage IB1-IIB cervical cancer to establish selection criteria

ObjectiveNeoadjuvant chemotherapy (NACT) for cervical cancer still remains controversial. NACT was evaluated to establish selection criteria.MethodsA matched-case comparison was designed for the NACT group (n = 707) and primary surgery treatment (PST; n = 707) group to investigate short-term responses and high/intermediate risk factors (HRFs/IRFs). The 5-year disease-free survival (DFS) and overall survival (OS) rates were stratified by NACT response, HRFs/IRFs, International Federation of Gynecology and Obstetrics (FIGO) stage and tumour size, respectively.ResultsThe clinical and pathological response rates were 79.3% and 14.9% in the NACT group. In comparison to the PST group, IRFs but not HRFs were significantly decreased (P < 0.05), and the 5-year DFS rate was significantly improved in the NACT group (88.4% versus 83.1%, P = 0.021). Moreover, the 5-year DFS and OS rates were favourably increased in the clinical responders in comparison to the PST group and the clinical non-responders (P < 0.05). Compared to those of clinical non-responders, the 5-year DFS and OS rates of clinical responders, with or without HRFs, were also significantly increased (P < 0.01). In stage IB2, the 5-year DFS and OS rates were significantly increased, whereas operation duration declined in the NACT group (P < 0.05). For patients with stage IB tumours of 2–5 cm, the 5-year DFS and OS rates of clinical responders were significantly improved (P < 0.05).ConclusionsNACT is a suitable option for patients with cervical cancer, especially for NACT responders and patients with stage IB, which provides a new concept of fertility preservation for young patients.     

Target-driven exploratory study of imatinib mesylate in children with solid malignancies by the Innovative Therapies for Children with Cancer (ITCC) European Consortium

AimTo explore imatinib efficacy and pharmacokinetics in children and adolescents with refractory/relapsing solid tumours, expressing imatinib-sensitive receptor tyrosine kinases.MethodsExploratory study on imatinib in tumours expressing, at least, one of the receptors KIT or platelet-derived growth factor receptor (PDGFR). Standard radiological response evaluation, pharmacokinetics, gene mutations and positron emission tomography imaging were assessed.ResultsThirty-six patients (median age: 13.7 years) with brain (12), mesenchymal/bone (14) or other solid tumours, received imatinib 340 mg/m²/d over a total of 255 months. Fifteen tumours expressed KIT in ?30% cells, 19 expressed PDGFRA and 25 expressed PDGFRB. Twenty patients experienced grades 1–2 treatment-related toxicities. Ten patients achieved stable disease; one chordoma had metabolic response. Pharmacokinetic data showed high inter-patient variability (variation coefficient: 44% and 53% for plasma imatinib and CGP 74588 AUCs, respectively).ConclusionsImatinib was tolerated well, but failed to show efficacy according to standard criteria in paediatric malignancies expressing KIT or PDGFR.     

Long-term survival outcomes after definitive chemoradiation versus surgery in patients with resectable squamous carcinoma of the esophagus: results from a randomized controlled trial

BackgroundThe aim of this study was to report on the 5-year survival outcomes of patients with resectable esophageal carcinoma who were treated by definitive chemoradiotherapy (CRT) or standard esophagectomy.Patients and methodsBetween July 2000 and December 2004, 81 patients with resectable squamous cell carcinoma of the mid- or lower thoracic esophagus were randomized to receive esophagectomy or definitive CRT. The primary outcome was the overall survival and secondary outcomes included disease-free survival, morbidities and mortalities.ResultsForty-five patients received esophagectomy and 36 patients were treated by definitive CRT. The overall 5-year survival favors CRT but the difference did not reach statistical significance (surgery 29.4% and CRT 50%, P = 0.147). A trend to improved 5-year survival was observed for patients suffering from node-positive disease (P = 0.061). The 5-year disease-free survival also showed a trend to significance favoring CRT (P = 0.068), particularly for patients suffering from node-positive disease (P = 0.017). Both the stage of the disease and albumin level were significant predictors to mortality and disease-free survival.ConclusionsDefinitive CRT for squamous esophageal carcinoma resulted in comparable long-term survival to surgery. Further large-scale studies would be required to further investigate the role of CRT in node-positive patients. Clinicaltrials.gov identifier: NCT01032967.     

The influence of menopausal hormone therapy on tumour characteristics and survival in endometrial cancer patients

IntroductionMenopausal hormone therapy (MHT) is a well-established factor in endometrial carcinogenesis, and therefore, could have prognostic implications. We investigated the effects of ever use of MHT on tumour grade and depth of myometrial invasion and 5-year relative survival in postmenopausal endometrial cancer patients.Materials and methodsWe used a nationwide, population-based case–case design, of 683 Swedish women aged 50–74 years diagnosed with endometrial cancer during 1994 to 1995, followed up to 5 years after diagnosis. We applied polytomous multiple logistic regression to investigate the associations between the use of MHT and tumour grade, and myometrial invasion and Poisson regression for modelling 5-year excess mortality.ResultsCompared to never use, ever use of any MHT entailed lower risks of having moderately and poorly differentiated tumours. The lowest odds ratios for poorly differentiated tumours were seen for ever users of cyclically combined oestrogen–progestin [OR = 0.23 (95% CI = 0.07 – 0.73)]. Ever users of any form of MHT; particularly, medium potency MHT users, had significantly lower risks for tumours with deep myometrial invasion. Adjusted estimated relative excess hazard ratios revealed significantly improved survival for ever users of any form of MHT [RER = 0.40 (95% CI = 0.16 – 0.97)]; in particular ever users of any form of oestrogens [RER = 0.38 (95% CI = 0.15 – 0.99)].ConclusionEndometrial cancer patients who were ever users of MHT had more favourable tumour characteristics and better survival compared to never users of MHT. These findings support the notion that MHT induces endometrial cancer with less aggressive characteristics.     

Overall survival in patients with a re-excision following breast conserving surgery compared to those without in a large population-based cohort

AimTo investigate the overall survival of invasive breast cancer patients with primary breast conserving surgery (BCS) followed by re-excision compared to those with primary BCS only. The Dutch re-excision indications are less stringent compared to other European and Northern American countries (Society of Surgical Oncology-American Society for Radiation Oncology (SSO/ASTRO) guideline).MethodsRetrospective analyses in women <75 years with breast cancer stage pT1–T3 treated by BCS and radiotherapy between 1999 and 2012 from a population-based database. The national guideline recommends to reserve re-excision for invasive tumours showing ‘more than focally positive’ margin since 2002. Patients were divided into ‘primary BCS only’, ‘re-excision by BCS’, and ‘re-excision by mastectomy’. Multivariable Cox regression analysis was adjusted for patient and systemic treatment characteristics.ResultsA total of 11,695 patients were included of which 2156 (18.4%) underwent re-excision. Median time of follow-up was 61 months (interquartile range (IQR) 26–101). The 5-year overall survival rates in the ‘primary BCS only’, ‘re-excision by BCS’ and ‘re-excision by mastectomy’ group were 92%, 95% and 91%, respectively. The 10-year overall survival rates were 81%, 82% and 79%, respectively (P = 0.20). After multivariable analyses no significant association was observed between use of and type of re-excision and overall survival.ConclusionsThe overall survival of breast cancer patients with a re-excision did not significantly differ from the survival of women who underwent primary BCS only. Advising re-excision only for those tumours showing ‘more than focally positive’ resection margin appears safe, supposing the long-term safety of the recent SSO/ASTRO guideline that more cautiously recommended re-excision for tumours showing ‘ink on tumour’.     

Age and bromodeoxyuridine labelling index as prognostic factors in high-grade gliomas treated with surgery and radiotherapy

AimsTo determine the prognostic value of proliferative potential and DNA ploidy in 72 brain tumours (36 grade III and 36 grade IV astrocytomas) using bromodeoxyuridine (BrdUrd) incorporation and flow cytometry.Material and methodsAll 72 patients underwent excision, mostly incomplete of the tumour. After surgery, eight patients received conventionally fractionated radiotherapy, 11 patients received accelerated radiotherapy, and 53 patients received hypofractionated radiotherapy. Tumour samples taken during surgery from each patient were incubated in vitro for 1 h at 37°C with BrdUrd using the high pressure oxygen method. The percentage of BrdUrd-labelled cells (BrdUrd labelling index [BrdUrd LI]), and the total DNA content were evaluated.ResultsThe tumours showed variability in the BrdUrd LI values, which ranged from 0.3 to 19.1%. No difference was observed in mean BrdUrd LI between grade III and grade IV sub-groups. A significantly higher percentage of DNA aneuploidy was observed in grade III gliomas (69.4%) than in grade IV gliomas (52.8%). Univariate analysis showed that younger patients (≤51 years) (P = 0.021) with grade III gliomas (P = 0.030) and low tumour proliferation rate (BrdUrd LI ≤ 2.7%, P = 0.028) had significantly higher 5-year survival rates. Tumour ploidy had no influence on patients' survival (P = 0.591). However, Cox multi-variate analysis showed that only age over 51 years, and high tumour proliferation rate (BrdUrd LI > 2.7%), were significant unfavourable prognostic factors in patient survival.ConclusionIn this study, independent prognostic factors for patients with high-grade gliomas treated with surgery and post-operative radiotherapy are age and tumour proliferation rate assessed according to the BrdUrd LI.