Concurrent palliative chemoradiation leads to survival and quality of life benefits in poor prognosis stage III non-small-cell lung cancer: a randomised trial by the Norwegian Lung Cancer Study Group

Background:

The palliative role of chemoradiation in the treatment of patients with locally advanced, inoperable non-small-cell lung cancer stage III and negative prognostic factors remains unresolved.

Methods:

Patients not eligible for curative radiotherapy were randomised to receive either chemoradiation or chemotherapy alone. Four courses of intravenous carboplatin on day 1 and oral vinorelbin on days 1 and 8 were given with 3-week intervals. Patients in the chemoradiation arm also received radiotherapy with fractionation 42 Gy/15, starting at the second chemotherapy course. The primary end point was overall survival; secondary end points were health-related quality of life (HRQOL) and toxicity.

Results:

Enrolment was terminated due to slow accrual after 191 patients from 25 Norwegian hospitals were randomised. Median age was 67 years and 21% had PS 2. In the chemotherapy versus the chemoradiation arm, the median overall survival was 9.7 and 12.6 months, respectively (P<0.01). One-year survival was 34.0% and 53.2% (P<0.01). Following a minor decline during treatment, HRQOL remained unchanged in the chemoradiation arm. The patients in the chemotherapy arm reported gradual deterioration during the subsequent months. In the chemoradiation arm, there were more hospital admissions related to side effects (P<0.05).

Conclusion:

Chemoradiation was superior to chemotherapy alone with respect to survival and HRQoL at the expense of more hospital admissions due to toxicity.     

RANK/OPG ratio of expression in primary clear-cell renal cell carcinoma is associated with bone metastasis and prognosis in patients treated with anti-VEGFR-TKIs

Background:

Bone metastases (BMs) are associated with poor outcome in metastatic clear-cell renal carcinoma (m-ccRCC) treated with anti-vascular endothelial growth factor tyrosine kinase inhibitors (anti-VEGFR-TKIs). We aimed to investigate whether expression in the primary tumour of genes involved in the development of BM is associated with outcome in m-ccRCC patients treated with anti-VEGFR-TKIs.

Methods:

Metastatic clear-cell renal cell carcinoma patients with available fresh-frozen tumour and treated with anti-VEGFR-TKIs. Quantitative real-time PCR (qRT–PCR) for receptor activator of NF-kB (RANK), RANK-ligand (RANKL), osteoprotegerin (OPG), the proto-oncogene SRC and DKK1 (Dickkopf WNT signalling pathway inhibitor-1). Time-to-event analysis by Kaplan–Meier estimates and Cox regression.

Results:

We included 129 m-ccRCC patients treated between 2005 and 2013. An elevated RANK/OPG ratio was associated with shorter median time to metastasis (HR 0.50 (95% CI 0.29–0.87); P=0.014), shorter time to BM (HR 0.54 (95% CI 0.31–0.97); P=0.037), shorter median overall survival (mOS) since initial diagnosis (HR 2.27 (95% CI 1.44–3.60); P=0.0001), shorter median progression-free survival (HR 0.44 (95% CI 0.28–0.71); P=0.001) and mOS (HR 0.31 (95% CI 0.19–0.52); P<0.0001) on first-line anti-VEGFR-TKIs in the metastatic setting. Higher RANK expression was associated with shorter mOS on first-line anti-VEGFR-TKIs (HR 0.46 (95% CI 0.29–0.73); P=0.001).

Conclusions:

RANK/OPG ratio of expression in primary ccRCC is associated with BM and prognosis in patients treated with anti-VEGFR-TKIs. Prospective validation is warranted.     

Efficacy and safety of sunitinib in elderly patients with metastatic renal cell carcinoma

Background:

We retrospectively analyzed sunitinib outcome as a function of age in metastatic renal cell carcinoma (mRCC) patients.

Methods:

Data were pooled from 1059 patients in six trials. Kaplan–Meier estimates of progression-free survival (PFS) and overall survival (OS) were compared by log-rank test between patients aged <70 (n=857; 81%) and ⩾70 (n=202; 19%) years.

Results:

In first-line patients, median PFS was comparable in younger and older patients, 9.9 vs 11.0 months, respectively (HR, 0.89; 95% CI: 0.73–1.09; P=0.2629), as was median OS, 23.6 vs 25.6 months (HR, 0.93; 95% CI: 0.74–1.18; P=0.5442). Similarly, in cytokine-refractory patients, median PFS was 8.1 vs 8.4 months (HR, 0.79; 95% CI: 0.49–1.28; P=0.3350), while median OS was 20.2 vs 15.8 months (HR, 1.14; 95% CI: 0.73–1.79; P=0.5657). Some treatment-emergent adverse events were significantly less common in younger vs older patients, including fatigue (60% vs 69%), cough (20% vs 29%), peripheral edema (17% vs 27%), anemia (18% vs 25%), decreased appetite (13% vs 29%), and thrombocytopenia (16% vs 25% all P<0.05). Hand–foot syndrome was more common in younger patients (32% vs 24%).

Conclusions:

Advanced age should not be a deterrent to sunitinib therapy and elderly patients may achieve additional clinical benefit.     

Concomitant oral tyrosine kinase inhibitors and bisphosphonates in advanced renal cell carcinoma with bone metastases

Background:

The presence of bone metastases in patients with metastatic renal cell carcinoma treated with oral tyrosine kinase inhibitors (TKIs) is associated with poorer outcome as compared with patients without bone involvement. Concomitant bisphosphonates could probably improve outcomes but also induce osteonecrosis of the jaw (ONJ).

Methods:

Retrospective study on all the renal cell carcinoma patients with bone metastases treated with sunitinib or sorafenib between November 2005 and June 2012 at the University Hospitals Leuven and AZ Groeninge in Kortrijk.

Results:

Seventy-six patients were included in the outcome analysis: 49 treated with concomitant bisphosphonates, 27 with TKI alone. Both groups were well balanced in terms of prognostic and predictive markers. Response rate (38% vs 16% partial responses, P=0.028), median progression-free survival (7.0 vs 4.0 months, P=0.0011) and median overall survival (17.0 vs 7.0 months, P=0.022) were significantly better in patients receiving bisphosphonates. The incidence of ONJ was 10% in patients treated with TKI and bisphosphonates.

Conclusion:

Concomitant use of bisphosphonates and TKI in renal cell carcinoma patients with bone involvement probably improves treatment efficacy, to be confirmed by prospective studies, but is associated with a high incidence of ONJ.     

Aspirin as a neoadjuvant agent during preoperative chemoradiation for rectal cancer

Background:

Recently, many studies have suggested a possible adjuvant role of aspirin in colorectal cancer, reporting a positive prognostic effect with its use in patients with established disease. The aim of this study was to investigate the anticancer effect of aspirin use during preoperative chemoradiation for rectal cancer.

Methods:

Two hundred and forty-one patients with stage II–III rectal cancer and candidates for chemoradiation (CRT) were selected and assigned to two groups: group 1, patients taking aspirin at the time of diagnosis, and group 2, all others. Treatment and oncological outcomes were explored.

Results:

Aspirin use was associated with a higher rate of tumour downstaging (67.6% vs 43.6%, P=0.01), good pathological response (46% vs 19% P<0.001), and a slightly, although not significant, higher rate of complete pathological response (22% vs 13% P=0.196). Aspirin use was also associated with a better 5-year progression-free survival (86.6% vs 67.1% hazard rate (HR)=0.20; 95% CI=0.07–0.60) and overall survival (90.6% vs 73.2% HR=0.21; 95% CI=0.05–0.89). Although chance of local relapse was similar (HR=0.6; 95% CI=0.06–4.5), aspirin use was associated with a lower risk of developing metastasis (HR=0.30; 95% CI=0.10–0.86).

Conclusions:

Aspirin might have anticancer activity against rectal cancer during preoperative CRT. This finding could be clinically relevant and should be further investigated with randomised trials.     

Phase I trial outcomes in older patients with advanced solid tumours

Background:

This study had two aims: (a) to test the hypothesis that advanced age is associated with lower levels of tolerability and clinical benefit to experimental Phase I trial agents; (b) to assess the validity of the Royal Marsden Hospital (RMH) prognostic score as a patient selection tool in older patients.

Methods:

Clinico-pathological characteristics and treatment outcomes of all patients treated consecutively from 2005 to 2009 in phase I trials at the RMH were recorded. All toxicity and clinical outcome data were compared between patients aged below and above 65 years of age.

Results:

One thousand and four patients were treated in 30 Phase I trials, with 315 (31%) patients aged 65 years and older. Grade 3–5 toxicities (22.8% vs 24.8% (P=0.52)), trial discontinuation (6% vs 4% P=0.33), and dose interruptions (8.0% vs 8.0% (P=0.96)) were observed at similar rates in patients below and above 65 years of age, respectively. The overall response rate 5.2% vs 4.1%, progression-free survival (PFS) 1.9 vs 3.5 months and clinical benefit rate (CBR) at 6 months 15.2% vs 14.3% were comparable in both groups. To avoid bias due to the potential therapeutic benefit of abiraterone, comparisons were repeated excluding prostate cancer patients with similar results (ORR 4.6% vs 4%, PFS 1.8 vs 3.0 months, CBR at 6 months 13.5% vs 9.5%). Multivariate analysis indicated that the previously identified RMH score (including albumin and lactate dehydrogenase levels) was an accurate predictor of outcome.

Conclusions:

Phase I clinical trials should be considered in patients with advanced cancers regardless of age, as older patients who enter these have similar safety and efficacy outcomes as their younger counterparts. The RMH prognostic score can assist in the selection of suitable older patients.     

Factors associated with survival in a large series of patients with malignant pleural mesothelioma in New South Wales

Background:

Although the prognosis of most patients presenting with malignant pleural mesothelioma (MPM) is poor, a small proportion survives long term. We investigated factors associated with survival in a large patient series.

Methods:

All patients registered with the NSW Dust Diseases Board (2002–2009) were included in an analysis of prognostic factors using Kaplan–Meier and Cox regression analysis. On the basis of these analyses, we developed a risk score (Prognostic Index (PI)).

Results:

We identified 910 patients: 90% male; histology (epithelioid 60% biphasic 13% sarcomatoid 17%); stage (Tx-I-II 48% III-IV 52%); and calretinin expression (91%). Treatment: chemotherapy(CT) 44%, and extrapleural-pneumonectomy (EPP) 6%. Median overall survival (OS) was 10.0 months. Longer OS was associated with: age <70 (13.5 vs 8.5 months; P<0.001); female gender (12.0 vs 9.9 months; P<0.001); epithelioid subtype (13.3 vs 6.2 months; P<0.001); ECOG status 0 (27.4 vs 9.7 months; P=0.015), calretinin expression (10.9 vs 5.5 months; P<0.001); neutrophil–lymphocyte ratio (NLR) <5 (11.9 vs 7.5 months; P<0.001); platelet count <400 (11.5 vs 7.2 months; P<0.001); and normal haemoglobin (16.4 vs 8.8 months; P<0.001). On time-dependent analysis, patients receiving pemetrexed-based chemotherapy (HR=0.83; P=0.048) or EPP (HR=0.41; P<0.001) had improved survival. Age, gender, histology, calretinin and haematological factors remained significant on multivariate analysis. In all, 24% of patients survived >20 months: 16% of these receiving EPP, and 66% CT. The PI offered improved prognostic discrimination over one of the existing prognostic models (EORTC).

Conclusions:

We identified calretinin expression, age, gender, histological subtype, platelet count and haemoglobin level as independent prognostic factors. Patients undergoing EPP or pemetrexed-based chemotherapy demonstrated better survival, but 84% and 34% of long survivors, respectively, did not receive radical surgery or chemotherapy.     

KRAS and BRAF mutations are prognostic biomarkers in patients undergoing lung metastasectomy of colorectal cancer

Background:

We evaluated KRAS (mKRAS (mutant KRAS)) and BRAF (mBRAF (mutant BRAF)) mutations to determine their prognostic potential in assessing patients with colorectal cancer (CRC) for lung metastasectomy.

Methods:

Data were reviewed from 180 patients with a diagnosis of CRC who underwent a lung metastasectomy between January 1998 and December 2011.

Results:

Molecular analysis revealed mKRAS in 93 patients (51.7%), mBRAF in 19 patients (10.6%). In univariate analyses, overall survival (OS) was influenced by thoracic nodal status (median OS: 98 months for pN−, 27 months for pN+, P<0.0001), multiple thoracic metastases (75 months vs 101 months, P=0.008) or a history of liver metastases (94 months vs 101 months, P=0.04). mBRAF had a significantly worse OS than mKRAS and wild type (WT) (P<0.0001). The 5-year OS was 0% for mBRAF, 44% for mKRAS and 100% for WT, with corresponding median OS of 15, 55 and 98 months, respectively (P<0.0001). In multivariate analysis, WT BRAF (HR: 0.005 (95% CI: 0.001–0.02), P<0.0001) and WT KRAS (HR: 0.04 (95% CI: 0.02–0.1), P<0.0001) had a significant impact on OS.

Conclusions:

mKRAS and mBRAF seem to be prognostic factors in patients with CRC who undergo lung metastasectomy. Further studies are necessary.     

Prognostic factors for survival in patients with metastatic renal cell carcinoma treated with targeted therapies

Background:

The most important prognostic factors for survival in patients with metastatic renal cell carcinoma (mRCC) were evaluated in the era of cytokine therapy, and only recently were revalidating in patients receiving targeted therapies (TTs).

Methods:

Clinical data for consecutive patients with mRCC who received TTs were retrieved from the database of Istituto Nazionale dei Tumori of Milan. Variables with a significant association with overall survival (OS) were estimated by proportional hazard regression, and a backward stepwise multivariate analysis identified the independent prognostic factors.

Results:

Data for 336 consecutive patients treated with TTs for RCC during the period 2004–2011 were evaluated. According to the Motzer classification, 32% patients were low risk, 48% were intermediate risk and 20% were poor risk. One hundred and sixty-seven (49.7%) patients received one TT, 116 (34.5%) received a second-line TT, 42 (12.5%) a third-line TT and 11 (3.3%) patients received a fourth-line TT. The median OS was 24 months (95% CI 20.0, 27.0) and the 5-year OS rate was 24.6% (95% CI 18.7, 30.8%). In the uni- and multivariate analysis Motzer risk classification, Fuhrman grade and previous cytokine therapy were identified as independent prognostic factors (P<0.01).

Conclusion:

The Motzer classification was confirmed as an independent prognostic factor for OS in patients with mRCC receiving TTs. Additionally, Fuhrman grade and previous cytokine therapy were independent prognostic factors for clinical outcome.     

Buccodental side effects of sunitinib in patients with metastatic renal cell carcinoma

Background:

Sunitinib is a tyrosine kinase inhibitor approved for the treatment of renal cell carcinoma (RCC). Few data evaluated severe buccodental adverse events. The aim of this study was to evaluate sunitinib buccodental toxicity in patients with metastatic RCC and to compare it with that of standard chemotherapy in patients with other solid cancers.

Methods:

Patients with RCC treated with sunitinib and patients with other solid tumours treated with chemotherapy were followed for 3 months. Data on dental appliances, oral hygiene/care practices before and during treatment were collected.

Results:

A total of 116 patients were included (58 RCC treated by sunitinib: group S, and 58 treated by chemotherapy: group C). No differences in dental care habits were noted before treatment. In group S, patients reported significantly more frequent pain (P<0.01), teeth instability (P=0.01), gingival bleeding (P=0.01) and change in teeth colour (P=0.02). In all, 58% of patients in this group had to modify their diet (P<0.01). Frequency of dentist'' visits for teeth removal was increased (25% vs 8%, P=0.01).

Conclusion:

Sunitinib seems to increase buccodental toxicity as compared with chemotherapy. This finding emphasises the need for optimal dental care and standardised dental follow-up in patients treated with sunitinib.     

Thrombosis in ovarian cancer: a case control study

Background:

Thrombotic events are common in cancer patients and have been associated with an adverse prognosis in large registry-based studies.

Methods:

A retrospective cohort of 417 patients with ovarian cancer treated at a tertiary cancer centre between 2006 and 2009 was studied to identify the incidence and risk factors for thrombotic events and the prognostic impact of thrombosis. Patient outcomes were evaluated against a matched control group without thrombosis.

Results:

Ninety-nine thrombotic events occurred in 90 patients (21.6%) from 8 months before diagnosis to 56 months following diagnosis, peaking in the 4 months following diagnosis. Patients with thrombosis were older (mean 65 vs 61 years, P=0.007), had a worse performance status (PS ⩾2: 29.9% vs 9.5%, P<0.0001) and had a more advanced FIGO stage (FIGO III/IV 75.6% vs 56.9%, P<0.0001) than patients without thrombosis. Shorter overall survival was seen in patients with pulmonary embolism and pelvic/lower limb deep vein thrombosis than without thrombosis (P=0.001). When the control group was matched for stage and PS, no survival difference was seen (P=0.91).

Conclusion:

Ovarian cancer patients with thrombotic events had a shorter survival. However, when matched for prognostic factors (PS and FIGO stage), thrombosis did not impact upon prognosis.     

Randomised phase II study comparing dose-escalated weekly paclitaxel vs standard-dose weekly paclitaxel for patients with previously treated advanced gastric cancer

Background:

This randomised phase II trial compared dose-escalated weekly paclitaxel (wPTX) vs standard-dose wPTX for patients with previously treated advanced gastric cancer (AGC).

Methods:

Ninety patients were randomised to a standard dose of wPTX (80 mg m⁻²) or an escalated dose of wPTX (80–120 mg m⁻²) to assess the superiority of overall survival (OS) with a one-sided alpha error of 0.3 and a power of 0.8.

Results:

The median OS showed a trend towards longer survival in the dose-escalated arm (11.8 vs 9.6 months; hazard ratio (HR), 0.75; one-sided P=0.12), although it was statistically not significant. The median progression-free survival (PFS) was significantly longer in the dose-escalated arm (4.3 vs 2.5 months, HR, 0.55; P=0.017). Objective response rate was 30.3% with dose escalation and 17.1% with standard dose (P=0.2). The frequency of all grades of neutropenia was significantly higher with dose escalation (88.7% vs 60.0%, P=0.002); however, no significant difference was observed in the proportion of patients experiencing grade 3 or more (40.9% vs 31.1%, P=0.34).

Conclusion:

Dose-escalated wPTX in patients with pretreated AGC met our predefined threshold of primary end point, OS (P<0.3); however, it did not show a significantly longer OS. Progression-free survival was significantly better with dose escalation.     

Physical function as a prognostic biomarker among cancer survivors

Background:

We tested the hypothesis that objectively measured physical function predicts mortality among cancer survivors.

Methods:

We assessed objectively measured physical function including the short physical performance battery (SPPB) and fast walk speed in older adult cancer survivors.

Results:

Among 413 cancer survivors, 315 (76%) died during a median follow-up of 11.0 years. In multivariable-adjusted analyses, each 1-unit increase in the SPPB score and 0.1 m s⁻¹ increase in fast walk speed predicted a 12% reduction in mortality (hazard ratio (HR): 0.88 (95% confidence interval (CI): 0.82–0.94); P<0.001, and HR: 0.88 (95% CI: 0.82–0.96); P=0.003, respectively).

Conclusions:

Objectively measured physical function may predict mortality among cancer survivors.     

Quaternary cytoreductive surgery in ovarian cancer: does surgical effort still matter?

Background:

To evaluate surgical outcome and survival benefit after quaternary cytoreduction (QC) in epithelial ovarian cancer (EOC) relapse.

Methods:

We systematically evaluated all consecutive patients undergoing QC in our institution over a 12-year period (October 2000–January 2012). All relevant surgical and clinical outcome parameters were systematically assessed.

Results:

Forty-nine EOC patients (median age: 57; range: 28–76) underwent QC; in a median of 16 months (range:2–142) after previous chemotherapy. The majority of the patients had an initial FIGO stage III (67.3%), peritoneal carcinomatosis (77.6%) and no ascites (67.3%). At QC, patients presented following tumour pattern: lower abdomen 85.7% middle abdomen 79.6% and upper abdomen 42.9%. Median duration of surgery was 292 min (range: a total macroscopic tumour clearance could be achieved. Rates of major operative morbidity and 30-day mortality were 28.6% and 2%, respectively.Mean follow-up from QC was 18.41 months (95% confidence interval (CI):12.64–24.18) and mean overall survival (OS) 23.05 months (95% CI: 15.5–30.6). Mean OS for patients without vs any tumour residuals was 43 months (95% CI: 26.4–59.5) vs 13.4 months (95% CI: 7.42–19.4); P=0.001. Mean OS for patients who received postoperative chemotherapy (n=18; 36.7%) vs those who did not was 40.5 months (95% CI: 27.4–53.6) vs 12.03 months (95% CI: 5.9–18.18); P<0.001.Multivariate analysis indentified multifocal tumour dissemination to be of predictive significance for incomplete tumour resection, higher operative morbidity and lower survival, while systemic chemotherapy subsequent to QC had a protective significant impact on OS. No prognostic impact had ascites, platinum resistance, high grading and advanced age.

Conclusion:

Even in this highly advanced setting of the third EOC relapse, maximal therapeutic effort combining optimal surgery and chemotherapy appear to significantly prolong survival in a selected patients ‘group''.     

Tumour shrinkage measured with first treatment evaluation under VEGF-targeted therapy as prognostic marker in metastatic renal cell carcinoma (mRCC)

Background:

The aim of our analysis is to further characterise the prognostic relevance of early tumour shrinkage (TS) during VEGF-targeted therapy in mRCC, in order to explore whether this could define a group of patients with long-term survivorship.

Methods:

A hundred patients were stratified into five subgroups according to their change of tumour size with first treatment evaluation: −100% to −60% −59% to −30% and −29% to 0% TS or gain of tumour size from 1% to 19% and ⩾20% or occurrence of new lesions (i.e., progressive disease).

Results:

The median PFS and OS were 10.4 months and 28.2 months, respectively. The median OS stratified according to the subgroups as described above was 77.4, 33.5, 26.9, 30.0 and 14.3 months, respectively. Multivariate analysis revealed early TS as a prognostic marker (P=0.021; HR 1.624).

Conclusion:

The extent of TS defines a small proportion of patients with an excellent prognosis. Larger studies are warranted to define the relationship of long-term survivorship and extent of TS with targeted therapies.     

Randomised phase II trial of S-1 plus oxaliplatin vs S-1 in patients with gemcitabine-refractory pancreatic cancer

Background:

This randomised, open-label, multicenter phase II study compared progression-free survival (PFS) of S-1 plus oxaliplatin (SOX) with that of S-1 alone in patients with gemcitabine-refractory pancreatic cancer.

Methods:

Patients with confirmed progressive disease following the first-line treatment with a gemcitabine-based regimen were randomised to receive either S-1 (80/100/120 mg day⁻¹ based on body surface area (BSA), orally, days 1–28, every 6 weeks) or SOX (S-1 80/100/120 mg day⁻¹ based on BSA, orally, days 1–14, plus oxaliplatin 100 mg m⁻², intravenously, day 1, every 3 weeks). The primary end point was PFS.

Results:

Between January 2009 and July 2010, 271 patients were randomly allocated to either S-1 (n=135) or SOX (n=136). Median PFS for S-1 and SOX were 2.8 and 3.0 months, respectively (hazard ratio (HR)=0.84; 95% confidence interval (CI), 0.65–1.08; stratified log-rank test P=0.18). Median overall survival (OS) was 6.9 vs 7.4 months (HR=1.03; 95% CI, 0.79–1.34; stratified log-rank test P=0.82). The response rate (RR) was 11.5% vs 20.9% (P=0.04). The major grade 3/4 toxicities (S-1 and SOX) were neutropenia (11.4% and 8.1%), thrombocytopenia (4.5% and 10.3%) and anorexia (12.9% and 14.7%).

Conclusions:

Although SOX showed an advantage in RR, it provided no significant improvement in PFS or OS compared with S-1 alone.     

ALDH1 is an independent prognostic factor for patients with stages II–III rectal cancer after receiving radiochemotherapy

Background:

About one in five patients with locally advanced rectal cancer (RC) suffers recurrence or distant metastasis after neoadjuvant therapy. We investigated how cancer stem cell markers change after neoadjuvant therapy and how these markers relate to recurrence.

Methods:

Pretreatment biopsies and postoperative specimens were taken from 64 patients with locally advanced rectal adenocarcinoma who received preoperative radiochemotherapy (RCT) between sampling. Samples were tested immunohistochemically for CD44, LGR5, ALDH1 and CD166; scores were dichotomised as high or low. The median follow-up period was 36 months.

Results:

High expression of CD44, LGR5, ALDH and CD166 was found in 38%, 5%, 48% and 10%, respectively, before RCT and 86%, 33%, 71% and 52%, respectively, after RCT. CD44 (P=0.001), LGR5 (P=0.049) and CD166 (P=0.003) were significantly upregulated after RCT. Whereas no recurrence was seen during the follow-up in the low ALDH group, 40% of the high ALDH group suffered recurrence. In multivariate COX analysis, postoperative ALDH1 independently predicted poor prognosis in patients with RC who received RCT (P=0.0095).

Conclusion:

Preoperative RCT upregulates expression of stem cell markers in patients with RC. High post-treatment ALDH1 expression predicts poor prognosis for these patients after neoadjuvant therapy.     

The risk of cancer in primary care patients with hypercalcaemia: a cohort study using electronic records

Background:

The risk of cancer with hypercalcaemia in primary care is unknown.

Methods:

This was a cohort study using calcium results in patients aged ⩾40 years in a primary care electronic data set. Diagnoses of cancer in the following year were identified.

Results:

Participants (54 267) had calcium results: 1674 (3%) were ⩾2.6 mmol l⁻¹. Hypercalcaemia was strongly associated with cancer, especially in males: OR 2.92, 95% CI 2.17–3.93, P=<0.001; positive predictive value (PPV) 11.5% females: OR 1.86, 95% CI 1.39–2.50, P<0.001: PPV 4.1%.

Conclusions:

Hypercalcaemia is strongly associated with cancer in primary care, with men at most risk, despite hypercalcaemia being more common in women.     

Trends in breast biopsies for abnormalities detected at screening mammography: a population-based study in the Netherlands

Background:

Diagnostic surgical breast biopsies have several disadvantages, therefore, they should be used with hesitation. We determined time trends in types of breast biopsies for the workup of abnormalities detected at screening mammography. We also examined diagnostic delays.

Methods:

In a Dutch breast cancer screening region 6230 women were referred for an abnormal screening mammogram between 1 January 1997 and 1 January 2011. During two year follow-up clinical data, breast imaging-, biopsy-, surgery- and pathology-reports were collected of these women. Furthermore, breast cancers diagnosed >3 months after referral (delays) were examined, this included review of mammograms and pathology specimens to determine the cause of the delays.

Results:

In 41.1% (1997–1998) and in 44.8% (2009–2010) of referred women imaging was sufficient for making the diagnosis (P<0.0001). Fine-needle aspiration cytology decreased from 12.7% (1997–1998) to 4.7% (2009–2010) (P<0.0001), percutaneous core-needle biopsies (CBs) increased from 8.0 to 49.1% (P<0.0001) and surgical biopsies decreased from 37.8 to 1.4% (P<0.0001). Delays in breast cancer diagnosis decreased from 6.7 to 1.8% (P=0.003).

Conclusion:

The use of diagnostic surgical breast biopsies has decreased substantially. They have mostly been replaced by percutaneous CBs and this replacement did not result in an increase of diagnostic delays.