Endothelin B receptor expression correlates with tumour angiogenesis and prognosis in oesophageal squamous cell carcinoma

Background:

The endothelin axis has been shown to have a pivotal role in several human malignancies. The aim of this study was to clarify the clinical importance of endothelin receptor type B (ETBR) in human oesophageal squamous cell carcinoma (OSCC).

Methods:

We evaluated ETBR expression in 107 patients with OSCC by immunohistochemistry. Microvessel density (MVD) and lymphatic vessel density were assessed by CD31 and D2-40 immunostaining, respectively. Furthermore, CD4, CD8, and CD45RO+ tumour-infiltrating lymphocytes (TILs) were immunohistochemically analysed.

Results:

Sixty-one (57%) cases showed high expression of ETBR. Endothelin receptor type B expression was correlated with several clinicopathological factors including tumour differentiation, tumour depth, and lymph node metastasis. The overall and disease-specific survival rates were significantly lower in patients with high ETBR expression than patients with low expression. Furthermore, multivariate analysis revealed that ETBR status was an independent prognostic factor for patient survival. Mechanistic analysis indicated that MVD was significantly higher in tumour tissues with high ETBR expression compared with those with low expression, suggesting that angiogenesis may be a key mechanism in tumour progression and metastasis of OSCC mediated by ETBR expression. By contrast, there were no significant correlations between TILs and ETBR expression.

Conclusion:

Endothelin receptor type B has a pivotal role in oesophageal cancer and may be therapeutic target for this intractable malignancy.     

High-temperature-required protein A2 as a predictive marker for response to chemotherapy and prognosis in patients with high-grade serous ovarian cancers

Background:

High-temperature-required protein A2 (HtrA2), a protein relating with apoptosis in a caspases-dependent and non-dependent manner, has been reported to be associated with chemosensitivity in several human cancers.

Methods:

Tissue microarrays made from 142 patients with high-grade serous ovarian adenocarcinoma were evaluated to assess whether HtrA2 expression was related with several clinical parameters.

Results:

Negative HtrA2 expression was observed in 36 cases (25%) of the patients, and related with significantly lower response rates of primary chemotherapy than those with positive HtrA2 expression (56% vs 83%, P<0.01). In addition, negative HtrA2 expression was identified as an independent worse prognostic factor for progression-free survival and overall survival by multivariate analyses. Furthermore, HtrA2 downregulation modulated sensitivity to platinum in serous ovarian cancer cells in vitro.

Conclusions:

HtrA2 expression was a predictor for sensitivity to chemotherapy, and could be a candidate of molecular target in the treatment of high-grade serous ovarian cancers.     

Different miRNA signatures of oral and pharyngeal squamous cell carcinomas: a prospective translational study

Background:

MicroRNAs (miRNAs) are small non-coding RNAs, which regulate mRNA translation/decay, and may serve as biomarkers. We characterised the expression of miRNAs in clinically sampled oral and pharyngeal squamous cell carcinoma (OSCC and PSCC) and described the influence of human papilloma virus (HPV).

Methods:

Biopsies obtained from 51 patients with OSCC/PSCC and 40 control patients were used for microarray analysis. The results were correlated to clinical data and HPV status. Supervised learning by support vector machines was employed to generate a diagnostic miRNA signature.

Results:

One hundred and fourteen miRNAs were differentially expressed between OSCC and normal oral epithelium, with the downregulation of miR-375 and upregulation of miR-31 as the most significant aberrations. Pharyngeal squamous cell carcinoma exhibited 38 differentially expressed miRNAs compared with normal pharyngeal epithelium. Differences in the miRNA expression pattern of both normal epithelium and SCC were observed between the oral cavity compared with the pharynx. Human papilloma virus infection revealed perturbations of 21 miRNAs, most significantly in miR-127-3p and miR363. A molecular classifier including 61 miRNAs was generated for OSCC with an accuracy of 93%.

Conclusion:

MicroRNAs may serve as useful biomarkers in OSCC and PSCC. The influence of HPV on miRNA may provide a mechanism for the distinct clinical behaviour of HPV-infected tumours.     

Detection of HPV-associated oropharyngeal tumours in a 16-year cohort: more than meets the eye

Background:

Accurate assessment of the prevalence of the human papilloma virus (HPV) in oropharyngeal tumours (OpSCC) is important because HPV-positive OpSCC are consistently associated with an improved overall survival. Recently, an algorithm has become available that reliably detects clinically relevant HPV in tumour tissue, however, no complete cohorts have been tested. The aim was to determine the prevalence of active high-risk HPV infection in a complete cohort of OpSCC collected over a 16-year period.

Methods:

Using a triple algorithm of p16 immunohistochemistry, HPV-BRISH and HPV-PCR, we assessed the prevalence of active HPV infection in all OpSCC diagnosed in our hospital from 1997 to 2012 (n=193) and a random selection of 200 oral tumours (OSCC).

Results:

Forty-seven OpSCC (24%) were HPVGP PCR-positive; 42 cases were HPV16+, 1 HPV18+, 3 HPV33+ and 1 HPV35+. Brightfield in situ hybridisation did not identify additional HPV-positive cases. Human papilloma virus-associated tumour proportion increased from 13% (1997–2004) to 30% (2005–2012). Human papilloma virus-positivity was an independent predictor for longer disease-specific survival (HR=0.22; 95%CI:0.10–0.47). Only one OSCC was HPV+.

Conclusions:

In our cohort, the incidence of HPV-associated OpSCC is low but increasing rapidly. The strict detection algorithm, analysis of disease-specific survival and the complete cohort, including palliatively treated patients, may influence the reported prevalence and prognostic value of HPV in OpSCC.     

Montreal prognostic score: estimating survival of patients with non-small cell lung cancer using clinical biomarkers

Background:

For evidence-based medical practice, well-defined risk scoring systems are essential to identify patients with a poor prognosis. The objective of this study was to develop a prognostic score, the Montreal prognostic score (MPS), to improve prognostication of patients with incurable non-small cell lung cancer (NSCLC) in everyday practice.

Methods:

A training cohort (TC) and a confirmatory cohort (CC) of newly diagnosed patients with NSCLC planning to receive chemotherapy were used to develop the MPS. Stage and clinically available biomarkers were entered into a Cox model and risk weights were estimated. C-statistics were used to test the accuracy.

Results:

The TC consisted of 258 patients and the CC consisted of 433 patients. Montreal prognostic score classified patients into three distinct groups with median survivals of 2.5 months (95% confidence interval (CI): 1.8, 4.2), 8.2 months (95% CI: 7.0, 9.4) and 18.2 months (95% CI: 14.0, 27.5), respectively (log-rank, P<0.001). Overall, the C-statistics were 0.691 (95% CI: 0.685, 0.697) for the TC and 0.665 (95% CI: 0.661, 0.670) for the CC.

Conclusion:

The MPS, by classifying patients into three well-defined prognostic groups, provides valuable information, which physicians could use to better inform their patients about treatment options, especially the best timing to involve palliative care teams.     

Cytokeratins 18 and 8 are poor prognostic markers in patients with squamous cell carcinoma of the oesophagus

Background:

Cytokeratins (CKs) are structural marker proteins specific for epithelial cells. However, recent studies indicate their involvement in cancer progression.

Methods:

We evaluated CK18 and its filament partner, CK8 expression, by immunohistochemistry in 210 resected specimens from patients with oesophageal squamous cell carcinoma (OSCC). We also analysed the relationship between their expression and various clinicopathological parameters including prognosis.

Results:

Neither CK18 nor CK8 was expressed in non-cancerous squamous epithelium whereas proper oesophageal glands expressed both CKs. Ninety (42.9%) tumours were CK18 positive and 85 (40.5%) CK8 positive, and the concordance rate for immunohistochemical classification for CK18 and CK8 was 82.4%. CK18 expression correlated with poorly differentiated tumours, use of neo-adjuvant chemotherapy, and advanced stage. Prognosis of patients with CK18-positive tumours was poorer than that of patients with negative OSCC (P<0.001). A similar trend was noted for CK8 expression. Multivariate analysis identified pT (P=0.020), pN number (P=0.001), and CK18 expression (P=0.004) as independent prognostic factors. CK18 expression in 83 pretreatment biopsy specimens was detected in 47 cases (56.6%) and also correlated with prognosis (P=0.045).

Conclusion:

CK18/CK8 expression correlated with progression of OSCC. The significant correlation with prognosis and stable expression in biopsy specimen suggest usefulness of CK18 in selection of treatment strategies for OSCC.     

Concurrent analysis of human equilibrative nucleoside transporter 1 and ribonucleotide reductase subunit 1 expression increases predictive value for prognosis in cholangiocarcinoma patients treated with adjuvant gemcitabine-based chemotherapy

Background:

The aim of this study was to investigate the predictive and prognostic values of intratumoural human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotide reductase subunit 1 (RRM1) expression in advanced cholangiocarcinoma patients treated with adjuvant gemcitabine-based chemotherapy (AGC).

Methods:

Intratumoural hENT1 and RRM1 expression levels were investigated immunohistochemically in 127 patients with advanced cholangiocarcinoma who underwent surgical resection (68 with AGC and 59 without AGC). The impacts of hENT1 and RRM1 expression on survival were evaluated.

Results:

High intratumoural hENT1 and RRM1 expression levels were observed in 86 (68%) and 67 (53%) patients, respectively. In a multivariate analysis of 68 patients who received AGC, high hENT1 (P=0.044) and low RRM1 expression (P=0.009) were independently associated with prolonged disease-free survival (DFS), whereas low RRM1 expression (P=0.024) was independently associated with prolonged overall survival (OS). Moreover, concurrent high hENT1 and low RRM1 expression was a powerful independent predictor of prolonged DFS (P<0.001) and OS (P=0.001) when the combined classification of hENT1 and RRM1 was introduced.

Conclusions:

Concurrent analysis of hENT1 and RRM1 expression may increase the predictive value of these biomarkers for survival of advanced cholangiocarcinoma patients treated with AGC.     

Lymph node density in oral cavity cancer: results of the International Consortium for Outcomes Research

Background:

Lymph node density (LND) has previously been reported to reliably predict recurrence risk and survival in oral cavity squamous cell carcinoma (OSCC). This multicenter international study was designed to validate the concept of LND in OSCC.

Methods:

The study included 4254 patients diagnosed as having OSCC. The median follow-up was 41 months. Five-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), locoregional control and distant metastasis rates were calculated using the Kaplan–Meier method. Lymph node density (number of positive lymph nodes/total number of excised lymph nodes) was subjected to multivariate analysis.

Results:

The OS was 49% for patients with LND⩽0.07 compared with 35% for patients with LND>0.07 (P<0.001). Similarly, the DSS was 60% for patients with LND⩽0.07 compared with 41% for those with LND>0.07 (P<0.001). Lymph node density reliably stratified patients according to their risk of failure within the individual N subgroups (P=0.03). A modified TNM staging system based on LND ratio was consistently superior to the traditional system in estimating survival measures.

Conclusion:

This multi-institutional study validates the reliability and applicability of LND as a predictor of outcomes in OSCC. Lymph node density can potentially assist in identifying patients with poor outcomes and therefore for whom more aggressive adjuvant treatment is needed.     

Prognostic role of EGFR gene copy number and KRAS mutation in patients with locally advanced rectal cancer treated with preoperative chemoradiotherapy

Background:

Epidermal growth factor receptor (EGFR), evaluated by immunohistochemistry, has been shown to have prognostic significance in patients with colorectal cancer. Gene copy number (GCN) of EGFR and KRAS status predict response and outcome in patients treated with anti-EGFR therapy, but their prognostic significance in colorectal cancer patients is still unclear.

Methods:

We have retrospectively reviewed the baseline EGFR GCN, KRAS status and clinical outcome of 146 locally advanced rectal cancer (LARC) patients treated with preoperative chemoradiotherapy. Pathological response evaluated by Dworak''s tumour regression grade (TRG), disease-free survival (DFS) and overall survival (OS) were analysed.

Results:

Tumour regression grade 4 and TRG3–4 were achieved in 14.4 and 30.8% of the patients respectively. Twenty-nine (19.9%) and 33 patients (19.2%) had an EGFR/nuclei ratio >2.9 and CEP7 polisomy >50% respectively; 28 patients (19.2%) had a KRAS mutation. Neither EGFR GCN nor KRAS status was statistically correlated to TRG. 5-year DFS and OS were 63.3 and 71.5%, respectively, and no significant relation with EGFR GCN or KRAS status was found.

Conclusion:

Our data show that EGFR GCN and KRAS status are not prognostic factors in LARC treated with preoperative chemoradiation.     

The phosphatase and tensin homologue deleted on chromosome 10 mediates radiosensitivity in head and neck cancer

Background:

For locally advanced squamous cell carcinoma of the head and neck (HNSCC), the recurrence rate after surgery and postoperative radiotherapy is between 20 and 40%, and the 5-year overall survival rate is ∼50%. Presently, no markers exist to accurately predict treatment outcome. Expression of proteins in the human epidermal growth factor receptor (EGFR) pathway has been reported as a prognostic marker in several types of cancer.

Methods:

The aim of this study was to investigate the prognostic value of proteins in the EGFR pathway in HNSCC. For this purpose, we collected surgically resected tissue of 140 locally advanced head and neck cancer patients, all treated with surgery and postoperative radiotherapy.

Results:

In a multivariate analysis, expression of the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) was significantly related to worse locoregional control (LRC; HR: 2.2, 95% CI: 1.1–4.6; P=0.03), independent of lymph node metastases (HR: 5.6, 95% CI: 1.2–27.4; P=0.03) and extranodal spread (HR: 2.7; 95% CI: 1.2–6.5; P=0.02). In vitro clonogenic radiosensitivity assays confirmed that overexpression of PTEN resulted in increased radioresistance.

Conclusion:

Our study is the first report showing that expression of PTEN mediates radiosensitivity in vitro and that increased expression in advanced HNSCC predicts worse LRC.     

High MET expression is an adverse prognostic factor in patients with triple-negative breast cancer

Background:

The mesenchymal–epithelial transition (MET) pathway is frequently altered in tumours. The purpose of our study was to determine the prognostic value of tumour MET expression levels in patients with triple-negative breast cancer (TNBC), in order to strengthen the rationale for targeted therapy of TNBC using MET inhibitors.

Methods:

We determined expression of MET in formalin-fixed paraffin-embedded surgical specimens of TNBC by immunohistochemistry. Recurrence-free and overall survival was analysed with Cox models adjusted for clinical and pathological factors.

Results:

Immunostaining for MET was classified as high in 89 of 170 (52%) tumours. MET expression was more frequently observed in G3 carcinomas (P=0.02) but was not significantly associated to any of the other clinical or pathological parameters. High MET expression predicted shorter survival of the patients. Multivariate Cox proportional hazards regression analyses identified MET to be an independent prognostic factor for recurrence (adjusted hazard ratio (HR) for recurrence 3.43; 95% confidence interval (CI) 1.65–7.12; P=0.001) and death (adjusted HR for death 3.74; 95% CI 1.65–8.46; P=0.002).

Conclusion:

These results provide further evidence that the MET pathway could be exploited as a target for TNBC.     

Redefining high-risk patients with stage II colon cancer by risk index and microRNA-21: results from a population-based cohort

Background:

The aim of the present study was to analyse the prognostic value of microRNA-21 (miRNA-21) in patients with stage II colon cancer aiming at a risk index for this group of patients.

Methods:

A population-based cohort of 554 patients was included. MicroRNA-21 was analysed by qPCR based on tumour tissue. An index was created using the coefficients obtained from a collective multiple Cox regression. The entire procedure was cross-validated (10-fold). The performance of the index was quantified by time-dependent receiver operating characteristics curves.

Results:

High miRNA-21 expression was associated with an unfavourable recurrence-free cancer-specific survival (RF-CSS), hazard ratio 1.35 (95% confidence interval, 1.03–1.76) (P=0.028). The generated RF-CSS index divided the traditional high-risk patients into subgroups with 5-year RF-CSS rates of 87% and 73%, respectively (P<0.001). The overall survival (OS) index identified three different subgroups (P<0.001). Cross-validated 5-year OS rates were 88%, 68%, and 50%, respectively.

Conclusions:

This population-based study supports miRNA-21 as an additional prognostic biomarker in patients with stage II colon cancer. Furthermore, the introduction of a risk index may guide the use of postoperative adjuvant treatment in a more appropriate way compared with current practice.     

Long-term outcome after local recurrence of soft tissue sarcoma: a retrospective analysis of factors predictive of survival in 135 patients with locally recurrent soft tissue sarcoma

Background:

The aim of this study was to identify prognostic indicators of survival in patients with locally recurrent soft tissue sarcoma (STS) through a long-term follow-up.

Methods:

We retrospectively assessed the relationship between post-recurrence survival (PRS) and potential prognostic factors in 135 patients who had experienced local recurrence, which was suitable for further surgical treatment. The median follow-up time after initial recurrence was 12.3 years (95% confidence interval (CI): 10.4–14.2 years).

Results:

The 5-year estimate of the PRS rate was 53.1% (95% CI: 44.3–61.2%) for the entire series. Patients with negative margins after the final surgery experienced improved survival compared with patients with positive margins (5-year survival: 46.7% (35.2–57.5%) vs 35.5% (23.4–47.8%); P=0.01). In a multivariate analysis, the significant prognostic indicators for PRS were histologic grade, tumour site, time to initial recurrence, the number of recurrences and the surgical margin status attained at the last resection.

Conclusions:

Complete surgical resection with microscopically clear margins is desirable in patients with locally recurrent STS. However, when achieving clear surgical margins will require major functional impairment of the extremity, a radical surgical approach should be weighed for the patient in each case.     

Protein shedding in urothelial bladder cancer: prognostic implications of soluble urinary EGFR and EpCAM

Background:

Better biomarkers must be found to develop clinically useful urine tests for bladder cancer. Proteomics can be used to identify the proteins released by cancer cell lines and generate candidate markers for developing such tests.

Methods:

We used shotgun proteomics to identify proteins released into culture media by eight bladder cancer cell lines. These data were compared with protein expression data from the Human Protein Atlas. Epidermal growth factor receptor (EGFR) was identified as a candidate biomarker and measured by ELISA in urine from 60 noncancer control subjects and from 436 patients with bladder cancer and long-term clinical follow-up.

Results:

Bladder cancer cell lines shed soluble EGFR ectodomain. Soluble EGFR is also detectable in urine and is highly elevated in some patients with high-grade bladder cancer. Urinary EGFR is an independent indicator of poor bladder cancer-specific survival with a hazard ratio of 2.89 (95% CI 1.81–4.62, P<0.001). In multivariable models including both urinary EGFR and EpCAM, both biomarkers are predictive of bladder cancer-specific survival and have prognostic value over and above that provided by standard clinical observations.

Conclusions:

Measuring urinary EGFR and EpCAM may represent a simple and useful approach for fast-tracking the investigation and treatment of patients with the most aggressive bladder cancers.     

Melanoma sentinel node biopsy and prediction models for relapse and overall survival

Background:

To optimise predictive models for sentinal node biopsy (SNB) positivity, relapse and survival, using clinico-pathological characteristics and osteopontin gene expression in primary melanomas.

Methods:

A comparison of the clinico-pathological characteristics of SNB positive and negative cases was carried out in 561 melanoma patients. In 199 patients, gene expression in formalin-fixed primary tumours was studied using Illumina''s DASL assay. A cross validation approach was used to test prognostic predictive models and receiver operating characteristic curves were produced.

Results:

Independent predictors of SNB positivity were Breslow thickness, mitotic count and tumour site. Osteopontin expression best predicted SNB positivity (P=2.4 × 10⁻⁷), remaining significant in multivariable analysis. Osteopontin expression, combined with thickness, mitotic count and site, gave the best area under the curve (AUC) to predict SNB positivity (72.6%). Independent predictors of relapse-free survival were SNB status, thickness, site, ulceration and vessel invasion, whereas only SNB status and thickness predicted overall survival. Using clinico-pathological features (thickness, mitotic count, ulceration, vessel invasion, site, age and sex) gave a better AUC to predict relapse (71.0%) and survival (70.0%) than SNB status alone (57.0, 55.0%). In patients with gene expression data, the SNB status combined with the clinico-pathological features produced the best prediction of relapse (72.7%) and survival (69.0%), which was not increased further with osteopontin expression (72.7, 68.0%).

Conclusion:

Use of these models should be tested in other data sets in order to improve predictive and prognostic data for patients.     

Extramural venous invasion is a potential imaging predictive biomarker of neoadjuvant treatment in rectal cancer

Background:

Extramural venous invasion (EMVI) is a poor prognostic factor in rectal cancer and identified on magnetic resonance imaging (MRI) (mrEMVI). The clinical relevance of improvement in mrEMVI following neoadjuvant therapy is unknown. This study aimed to demonstrate that regression of mrEMVI following neoadjuvant chemoradiotherapy (CRT) results in improved outcomes and mrEMVI can be used as an imaging biomarker

Methods:

Retrospective analysis of prospectively collected data was conducted examining the staging and post-treatment MRIs of patients who had presented with EMVI-positive rectal cancer. All patients had undergone neoadjuvant CRT and curative surgery. Changes in mrEMVI were graded with a new MRI-based TRG scale–mr-vTRG; and related to disease-free survival (DFS). The study fulfilled Reporting Recommendations for Tumour Marker Prognostic Studies criteria for biomarkers.

Results:

Sixty-two patients were included. Thirty-five patients showed more than 50% fibrosis of mrEMVI (mr-vTRG 1-3); 3-year DFS 87.8% and 9% recurrence. Twenty-seven patients showed less than 50% fibrosis (mr-vTRG 4-5); 3-year DFS 45.8% with 44% recurrence – P<0.0001. On multivariate Cox-regression, only mr-vTRG 4-5 increased risk of disease recurrence – HR=5.748.

Conclusion:

Patients in whom there has been a significant response of EMVI to CRT show improved DFS. Those patients with poor response should be considered for intensive treatment. As an imaging biomarker in rectal cancer, mrEMVI can be used.     

Trastuzumab or lapatinib with standard chemotherapy for HER2-positive breast cancer: results from the GEICAM/2006-14 trial

Background:

The addition of trastuzumab (T) and lapatinib (L) to neoadjuvant chemotherapy increases the pathological complete response (pCR) rate in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. We investigated the efficacy of T or L with neoadjuvant chemotherapy and specific efficacy biomarkers.

Methods:

Patients with stages I–III (including inflammatory) HER2-positive breast cancer were randomised to receive epirubicin (E) plus cyclophosphamide (C) × 4 cycles followed by docetaxel (D) plus either T (EC-DT) or L (EC-DL). End points included pCR (primary), clinical response, toxicity, and pCR-predictive biomarkers.

Results:

We randomised 102 patients to EC-DT (50) and EC-DL (52). Median age was 48, 56% were premenopausal and 58% had oestrogen receptor (ER)-positive tumours. Pathological complete response in breast was 52.1% (95% CI:38.0–66.2%) for EC-DT and 25.5% (95% CI:13.5–37.5%) for EC-DL (P=0.0065). Pathological complete response in breast and axilla was 47.9% for EC-DT and 23.5% for EC-DL (P=0.011). Grade 3–4 toxicity did not differ across treatments, except for diarrhoea (2% in EC-DT vs 13.5% in EC-DL, P=0.030). Multivariate analyses showed that treatment (P=0.036) and ER (P=0.014) were the only predictors of pCR in both groups.

Conclusion:

EC-DT exhibited higher efficacy and lower toxicity than EC-DL. Of the different biomarkers studied, only the absence of ER expression was associated with increased pCR.     

Familial diagnostic experiences in paediatric oncology

Background:

Diagnostic delays may not have significant prognostic implications in paediatric oncology, but psychological impacts remain understudied.

Methods:

Interviews exploring diagnostic experiences were conducted with childhood cancer survivors (n=19), parents (n=78) and siblings (n=15).

Results:

Median diagnostic time was 3 weeks. Participants described a mixture of rapid diagnoses (28.9%), plus delayed appraisal intervals (that is, parent- or patient-associated diagnostic delays; 40.0%) and diagnostic intervals (that is, healthcare-associated delays; 46.7%). Families experiencing delays described guilt and anger and deleterious impacts on the family–clinician relationship. Some believed delays impacted on treatment and prognosis.

Conclusions:

The effect of the diagnostic experience can be considerable.     

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.     

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.