Disease-related surgery in patients with distant metastatic breast cancer

Introduction

This study evaluates the frequency of and indications for disease-related surgical procedures in the palliative breast cancer (BC) situation.

Patients & methods

Based on a cohort of women who were treated for newly diagnosed BC during a 20-year period (1990–2009), we analyzed 340 patients who developed distant metastatic disease (DMD) until 2011 and died (i.e. still ongoing palliative disease courses were not included).

Results

One hundred and twenty-seven surgical procedures were performed in 100 patients (29.4% of all patients with metastatic disease). The most common site for surgery was breast (n = 60, 47.2%). The primary tumor was removed at first diagnosis of DMD in 43 patients (33.9%); sixteen operations (12.6%) were performed for local recurrence. In 37 patients, 50 surgical procedures (39.4%) were necessary to stabilize osseous structures due to metastases. Procedures were rarely performed on other common metastatic sites: lung: n = 1 (0.8%); liver: n = 1 (0.8%), brain: n = 4 (3.1%). When excluding surgery for primary breast tumors at initial diagnosis of DMD from analysis, 34 of 84 surgeries (40.4%) were performed in the first third of survival follow-up (i.e. period of metastatic disease survival); operations in the last two-thirds each totaled 29.8% (n = 25). The median survival after surgery was 16 months (range: 0.5–89 months).

Conclusions

In a cohort of BC patients who had primary or developed secondary DMD, nearly one third of the patients received disease-related surgical procedures during their palliative disease course. This high rate of operations shows that surgery has a clearly established role in the palliative therapy concept.     

A multicenter,observational study of metastatic breast cancer patients who were treated with eribulin mesylate or taxane‐based regimens

1 Aim

This multicenter, observational study aimed to investigate the survival benefit of eribulin as well as that of taxane‐based regimens in Japanese patients with metastatic breast cancer (MBC) in a real‐world setting.

2 Methods

This study enrolled women with MBC who received eribulin or taxane‐based regimens with or without bevacizumab in routine clinical practice from July 2011 to March 2014. Patients were followed until September 2015. The primary endpoint was overall survival (OS). Secondary endpoints included progression‐free survival (PFS), post‐progression survival (PPS) and adverse events. Efficacy findings were adjusted according to demographics.

3 Results

In total, 216 patients receiving eribulin monotherapy (n = 101), taxane monotherapy (n = 73) or taxane plus bevacizumab (n = 42) were followed for a median time of 15.4 months. Median OS, PFS and PPS were 22.3, 8.1 and 14 months in the eribulin monotherapy group; 13.2, 3.6 and 7.6 months in the taxane monotherapy group; and 12.9, 5.7 and 6.3 months, in the taxane plus bevacizumab group, respectively. The incidence of neutropenia was 67.3, 41.1 and 16.7%, and the incidence of grade 4 neutropenia was 1.0, 8.2 and 7.1% in the eribulin monotherapy, taxane monotherapy and taxane plus bevacizumab groups, respectively. One patient (1.0%) discontinued eribulin and 18 patients (15.7%) discontinued taxane‐based regimens because of adverse events.

4 Conclusion

In Japanese MBC patients in a real‐world setting, eribulin showed a survival benefit and tolerability similar to that in previous reports.     

Age-specific trends of survival in metastatic breast cancer: 26 years longitudinal data from a population-based cancer registry in Stockholm,Sweden

Treatment of metastatic breast cancer (MBC) has evolved during the last decades but it is largely unknown whether this has led to improved survival in the general MBC population. Based on the regional, population-based breast cancer registry, we identified 5,463 patients diagnosed with MBC in Stockholm County during 1979–2004. Patients were divided into five cohorts based on the year of first MBC diagnosis and observed and relative survival were compared across the cohorts after adjustment for potential confounders. A significant trend of better survival over time was demonstrated for patients 60 years or younger (P < 0.001, by log-rank test for trend), but not for older patients (P = 0.12) or for the whole MBC population (P = 0.13). The adjusted observed survival of patients ≤60 years was significantly improved in the 2000–2004 cohort (P < 0.001, hazard ratio = 0.7, 95% confidence interval = 0.58–0.84), corresponding to a clinically significant increase of median survival with more than 3 months and absolute increase of 5-year survival with 8% or more compared to previous periods. Similarly, relative survival analysis indicated a 31% decreased mortality for the younger subpopulation in the 2000–2004 cohort (P < 0.001). Systemic adjuvant treatment was a negative prognostic factor after distant recurrence. Treatment advancements in MBC are not reflected by better survival for the whole MBC population. An improvement is only observed after the year 2000 and is restricted to younger patients.     

Excision of the primary tumour in patients with metastatic breast cancer: a clinical dilemma

Background

Approximately 10% of new breast cancer patients will present with overt synchronous metastatic disease. The optimal local management of those patients is controversial. Several series suggest that removal of the primary tumour is associated with a survival benefit, but the retrospective nature of those studies raises considerable methodologic challenges. We evaluated our clinical experience with the management of such patients and, more specifically, the impact of surgery in patients with synchronous metastasis.

Methods

We reviewed patients with primary breast cancer and concurrent distant metastases seen at our centre between 2005 and 2007. Demographic and treatment data were collected. Study endpoints included overall survival and symptomatic local progression rates.

Results

The 111 patients identified had a median follow-up of 40 months (range: 0.6–71 months). We allocated the patients to one ot two groups: a nonsurgical group (those who did not have breast surgery, n = 63) and a surgical group (those who did have surgery, n = 48, 29 of whom had surgery before the metastatic diagnosis). When compared with patients in the nonsurgical group, patients in the surgical group were less likely to present with T4 tumours (23% vs. 35%), N3 nodal disease (8% vs. 19%), and visceral metastasis (67% vs. 73%). Patients in the surgical group experienced longer overall survival (49 months vs. 33 months, p = 0.01) and lower rates of symptomatic local progression (14% vs. 44%, p < 0.001).

Conclusions

In our study, improved overall survival and symptomatic local control were demonstrated in the surgically treated patients; however, this group had less aggressive disease at presentation. The optimal local management of patients with metastatic breast cancer remains unknown. An ongoing phase iii trial, E2108, has been designed to assess the effect of breast surgery in metastatic patients responding to first-line systemic therapy. If excision of the primary tumour is associated with a survival benefit, then the preselected subgroup of patients who have responded to initial systemic therapy is the desired population in which to put this hypothesis to the test.     

The BIG 2.04 MRC/EORTC SUPREMO Trial: pathology quality assurance of a large phase 3 randomised international clinical trial of postmastectomy radiotherapy in intermediate-risk breast cancer

Purpose

The PELICAN trial evaluates for the first time efficacy and safety of pegylated liposomal doxorubicin (PLD) versus capecitabine as first-line treatment of metastatic breast cancer (MBC).

Methods

This randomized, phase III, open-label, multicenter trial enrolled first-line MBC patients who were ineligible for endocrine or trastuzumab therapy. Cumulative adjuvant anthracyclines of 360 mg/m² doxorubicin or equivalent were allowed. Left ventricular ejection fraction of >50 % was required. Patients received PLD 50 mg/m² every 28 days or capecitabine 1250 mg/m² twice daily for 14 days every 21 days. The primary endpoint was time-to-disease progression (TTP).

Results

210 patients were randomized (n = 105, PLD and n = 105, capecitabine). Adjuvant anthracyclines were given to 37 % (PLD) and 36 % (capecitabine) of patients. No significant difference was observed in TTP [HR = 1.21 (95 % confidence interval, 0.838–1.750)]. Median TTP was 6.0 months for both PLD and capecitabine. Comparing patients with or without prior anthracyclines, no significant difference in TTP was observed in the PLD arm (log-rank P = 0.64). For PLD versus capecitabine, respectively, overall survival (median, 23.3 months vs. 26.8 months) and time-to-treatment failure (median, 4.6 months vs. 3.7 months) were not statistically significantly different. Compared to PLD, patients on capecitabine experienced more serious adverse events (P = 0.015) and more cardiac events among patients who had prior anthracycline exposure (18 vs. 8 %; P = 0.31).

Conclusion

Both PLD and capecitabine are effective first-line agents for MBC.

     

Early detection of nonperitoneal recurrence may contribute to survival benefit after curative gastrectomy for gastric cancer

Background

There is no evidence that strict follow-up using cross-sectional imaging after curative gastrectomy benefits survival; however, nonperitoneal recurrence detected early might be treated with additional surgery. The present study examined whether early detection of recurrence by imaging modalities could increase survival, particularly in patients with nonperitoneal recurrence.

Methods

We retrospectively analyzed 218 patients with recurrent gastric cancer after curative gastrectomy performed from 2002 to 2014. The patients were divided into an asymptomatic group (n = 117) and a symptomatic group (n = 101), according to the presence of symptoms at the time of recurrence, to compare clinicopathological characteristics and long-term survival.

Results

Peritoneal recurrence was less frequent in the asymptomatic group (22.2%) than in the symptomatic group (62.4%), the median time to recurrence was shorter (12.7 months vs 18.9 months; P < 0.001), and the median survival time after recurrence was longer (18.7 months vs 7.5 months; P < 0.001). In the asymptomatic group, 10 of 117 patients (8.5%) received additional curative surgery after recurrence. Median overall survival after gastrectomy was not significantly different between the groups (30.1 months for the asymptomatic group vs 30.0 months for the symptomatic group; P = 0.132); however, it was significantly longer among asymptomatic patients with nonperitoneal recurrence compared with symptomatic patients (35.9 months vs 24.0 months; P = 0.039).

Conclusions

The presence of symptoms at recurrence did not affect survival in patients with recurrent gastric cancer. However, detection of nonperitoneal recurrence before the appearance of symptoms may provide survival benefit. Therefore, regular follow-up, including use of imaging modalities, is recommended.

     

Prognostic factors for survival after surgery for adrenal metastasis

Aim

To better define the indications for adrenalectomy for adrenal metastasis we have analysed factors predicting survival in our institutional series.

Methods

A consecutive series of 30 patients undergoing adrenalectomy for metastasis (1996–2007), excluding patients with simultaneous ipsilateral renal cell carcinoma (RCC), was studied. Metastases were regarded as synchronous (<6 mo), or metachronous (>6 mo), depending on the interval after primary surgery. Survival was calculated from time of adrenalectomy and factors influencing survival were identified.

Results

The tumour diagnoses were RCC n = 9, malignant melanoma n = 5, non-small-cell lung cancer n = 5, colorectal carcinoma n = 4, foregut carcinoid n = 2, adrenocortical carcinoma, breast cancer, hepatocellular carcinoma, urothelial carcinoma, and liposarcoma (one each); nine adrenal metastases were synchronous and 21 metachronous. Ten patients had undergone previous surgery for extra-adrenal metastases. Out of 30 adrenalectomies 10 were laparoscopic (LAdx) and 20 open (OAdx) procedures without surgical complications. The local recurrence rate was low: LAdx 1/10, OAdx 1/20, and the median survival was 23 months. Independent prognosticators of favourable survival were adrenalectomy for potential cure (p = 0.01), no previous metastasis surgery (p = 0.02), and tumour type (p = 0.043), with better prognosis for patients with adrenal metastasis from colorectal carcinoma and RCC and worse prognosis in non-small-cell lung cancer and malignant melanoma.

Conclusions

Surgery for adrenal metastasis is safe and the indication for this procedure in an individual patient can be supported by several prognostic factors. The survival benefit in patients with adrenalectomy for potential cure indicates a therapeutic value of adrenalectomy in selected patients.     

Myotax: a phase II trial of docetaxel plus non-pegylated liposomal doxorubicin as first-line therapy of metastatic breast cancer previously treated with adjuvant anthracyclines

Aim

Non-pegylated liposomal doxorubicin (NPLD) has demonstrated equivalent antitumour activity to conventional doxorubicin and a significantly lower risk of cardiotoxicity when given as a single agent or in combination with cyclophosphamide. This phase II trial was performed to evaluate the efficacy and the safety of NPLD and docetaxel combination in patients with metastatic breast cancer previously exposed to adjuvant anthracyclines.

Patients and methods

Thirty-four patients received NPLD 60 mg/m² and docetaxel 75 mg/m² in a 21-day cycle as first-line therapy of metastatic breast cancer. Treatment was planned for six cycles and was continued until progression or toxicity.

Results

Objective response rate among response-assessable patients was 79% (95% CI (confidence interval), 64–94%) and 27% (95% CI, 11–43%) presented a complete response. Median progression free survival was 11.3 months (95% CI, 6.2–13.3 months) and median overall survival was 28.2 months (95% CI, 16–36.4 months). Symptomatic grade 3 cardiotoxicity occurred in 15% of cases and febrile neutropenia in 47% of the patients.

Conclusions

The combination of NPLD and docetaxel demonstrated high antitumour activity in a population of metastatic breast cancer patients exposed to adjuvant anthracyclines and showed an unexpected and unexplained 15% symptomatic left ventricular systolic dysfunction rate.     

Ixabepilone plus capecitabine in metastatic breast cancer patients with reduced performance status previously treated with anthracyclines and taxanes: a pooled analysis by performance status of efficacy and safety data from 2 phase III studies

Patients with metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes often have decreased performance status secondary to extensive tumor involvement. Here, we report the pooled analysis of efficacy and safety data from two similarly designed phase III studies to provide a more precise estimate of benefit of ixabepilone plus capecitabine in MBC patients with Karnofsky’s performance status (KPS) 70–80. Across the studies, anthracycline/taxane-pretreated MBC patients were randomized to receive ixabepilone plus capecitabine or capecitabine alone. Individual patient data for KPS 70–80 subset (n = 606) or KPS 90–100 subset (n = 1349) from the two studies were pooled by treatment. Analysis included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety. In patients with reduced performance status (KPS 70–80), ixabepilone plus capecitabine was associated with improvements in OS (median: 12.3 vs. 9.5 months; HR, 0.75; P = 0.0015), PFS (median: 4.6 vs. 3.1 months; HR, 0.76; P = 0.0021) and ORR (35 vs. 19%) over capecitabine alone. Corresponding results in patients with high performance status (KPS 90–100) were median OS of 16.7 versus 16.2 months (HR, 0.98; P = 0.8111), median PFS of 6.0 versus 4.4 months (HR, 0.58; P = 0.0009), and ORR of 45 versus 28%. The safety profile of combination therapy was similar between the subgroups. Ixabepilone plus capecitabine appeared to show superior efficacy compared to capecitabine alone in MBC patients previously treated with anthracyclines and taxanes, regardless of performance status, with a possible OS benefit favoring KPS 70–80 patients (ClinicalTrials.gov identifiers: NCT00080301 and NCT00082433).     

Brain-only metastatic breast cancer is a distinct clinical entity characterised by favourable median overall survival time and a high rate of long-term survivors

Background:

The clinical course of breast cancer patients with brain metastases (BM) as only metastatic site (brain-only metastatic breast cancer (BO-MBC)) has been insufficiently explored.

Methods:

All breast cancer patients with BM treated at our institution between 1990 and 2011 were identified. For each patient, full information on follow-up and administered therapies was mandatory for inclusion. Oestrogen receptor, progesterone receptor and Her2 status were determined according to standard protocols. Statistical analyses including computation of survival probabilities was performed.

Results:

In total, 222 female patients (26% luminal; 47% Her2; 27% triple negative) with BM of MBC were included in this study. In all, 38/222 (17%) BM patients did not develop extracranial metastases (ECM) during their disease course and were classified as BO-MBC. Brain-only-MBC was not associated with breast cancer subtype or number of BM. The median overall survival of BO-MBC patients was 11 months (range 0–69) and was significantly longer than in patients with BM and ECM (6 months, range 0–104; P=0.007). In all, 7/38 (18%) BO-MBC patients had long-term survival of >3 years after diagnosis of BM and long-term survival was significantly more common in BO-MBC patients as compared with BM patients with ECM (P<0.001).

Conclusions:

Brain-only metastatic behaviour occurs in around 17% of breast cancer with BM and is not associated with breast cancer subtype. Exploitation of all multimodal treatment options is warranted in BO-MBC patients, as these patients have favourable prognosis and long-term survival is not uncommon.     

Role of HER3 expression and PTEN loss in patients with HER2-overexpressing metastatic breast cancer (MBC) who received taxane plus trastuzumab treatment

Background:

The aim of this study was to investigate the role of human epidermal growth factor receptor (HER3) and PTEN expression in patients with HER2-overexpressing metastatic breast cancer (MBC).

Methods:

One hundred twenty-five MBC patients who were treated with taxane plus trastuzumab chemotherapy as first-line therapy were included in this analysis. Immunohistochemical (IHC) staining with HER3 and PTEN antibodies were conducted retrospectively.

Results:

Patients who had negative HER3 staining (62.4%) had a better progression-free survival (PFS) than did those who had positive HER3 staining (P=0.001; median PFS, 21 vs 11 months). Patients who had a PTEN score >20 (78.1%) showed longer PFS than did those with a PTEN score ⩽20 (P=0.006; median PFS, 13 vs 9 months). Patients who had a PTEN score >20 exhibited a longer overall survival (OS) than did those with a PTEN score ⩽20 (P=0.005; median OS, 48 vs 25 months). HER3 negativity and PTEN loss were identified as independent risk factors for PFS. PTEN loss was identified as an independent risk factor for OS.

Conclusion:

HER3 and PTEN expressions may be predictive markers, and PTEN expression may be a predictive and prognostic biomarker for trastuzumab treatment in HER2-positive MBCs.     

Vinorelbine and capecitabine in anthracycline- and/or taxane-pretreated metastatic breast cancer: sequential or combinational?

Purpose

The difference between combinational and pre-planned sequential therapies using regimens that include non-anthracycline and taxane in the first-line setting remains unclear. The purpose of this study is to explore the interaction between vinorelbine (N) and capecitabine (X) in breast cancer cells and to compare the simultaneous or sequential administration of the two drugs in patients with metastatic breast cancer (MBC) as first-line treatment.

Methods

First, we explored the effects of vinorelbine on thymidine phosphorylase (TP) and thymidylate synthase (TS) expression in breast cancer cells. Next, we designed a prospective randomized phase II trial of MBC patients comparing the combinational and pre-planned sequential administration of vinorelbine and capecitabine in the first-line metastatic setting. The primary end point was progression-free survival (PFS). The correlation between clinical characteristics and class III β-tubulin expression and patient survival was also explored.

Results

Vinorelbine upregulates TP and downregulates TS in breast cancer cells, thereby further sensitizing tumor cells to capecitabine, which indicated the proper order for sequential therapy should be N → X. Sixty patients were eligible for the phase II trial. No significant difference was observed between the combinational arm and the sequential arm in terms of progression-free survival (PFS), overall response rate (ORR), and overall survival (OS). Only in the subgroup of patients with liver metastases were median PFS and OS significantly prolonged in the combinational arm (8.5 vs. 6.4 months, P = 0.041 and 23.8 vs. 13.9 months, P = 0.028, respectively). No association between class III β-tubulin expression and patient outcome was identified. Grade 3/4 adverse events were more common in the combinational arm.

Conclusions

Both the NX regimen and pre-planned sequential N → X regimen are acceptable as first-line treatments with comparable efficacies for MBC patients previously treated with anthracyclines and/or taxanes. Sequential monotherapies are recommended as the preferred approach to first-line chemotherapy for most MBC patients in the absence of an imminent visceral crisis and the need for rapid symptom and/or disease control.     

Liver resection for metastatic soft tissue sarcoma: An analysis of prognostic factors

Aim

The aim of this retrospective study was to analyse the outcome following hepatic resection for metastatic STS and to identify factors predicting survival.

Methods

All patients who underwent hepatic resection for metastatic STS between August 1997 and April 2009 were included. The data was obtained from a prospectively maintained database. Patients’ demographics, clinico-pathological parameters, overall survival and the factors predicting survival were analysed.

Results

Thirty-six patients underwent hepatic resection for metastasis, with a median age of 58 years. The predominant site of primary tumour was the gastro-intestinal tract (50%). Leiomyosarcoma was the most common histological type (54%). The median interval between the primary and metastatic resections was 17 months. Thirteen patients had synchronous tumours. 24 patients had major liver resections and 10 patients had bi-lobar disease. The median number of liver lesions resected was 1(1-6) and the median maximum diameter was 11 cm (1-26 cm). R0 resection was performed in 31 patients. The 1-, 3- and 5-year overall survival from the time of metastasectomy was 90.3%, 48.0% and 31.8% respectively, with a median survival of 24 months. Factors associated with poor survival on univariate analysis were the presence of high grade tumours (p = 0.04), primary leiomyosarcoma (p = 0.01) and positive resection margin of liver metastasis (p = 0.04), whilst multivariate analysis predicted primary leiomyosarcoma as a risk factor for poor survival (p = 0.01).

Conclusion

Hepatic resection for metastatic STS appears to be valuable in carefully selected patients with acceptable long-term survival. The aim of surgery must be an R0 resection to offer a chance of cure.     

Early detection of metastatic disease in asymptomatic breast cancer patients with whole-body imaging and defined tumour marker increase

Background:

Follow-up care in breast cancer is still an issue of debate. Diagnostic methods are more sensitive, and more effective therapeutic options are now available. The risk of recurrence is not only influenced by tumour stage but also by the different molecular subtypes. This study was performed to evaluate the use of whole-body imaging combined with tumour marker monitoring for the early detection of asymptomatic metastatic breast cancer (MBC).

Methods:

This analysis was performed as part of a follow-up study evaluating 813 patients with a median follow-up of 63 months. After primary therapy, all patients underwent tumour marker monitoring for CEA, CA 15-3 and CA 125 at 6-week intervals within an intensified diagnostic aftercare algorithm. A reproducible previously defined increase was considered as a strong indicator of MBC. From 2007 to 2010, 44 patients with tumour marker increase underwent whole-body magnetic resonance imaging and/or an FDG-PET/CT scan. Histological clarification and/or imaging follow-up were done.

Results:

Metastases were detected in 65.9% (29/44) of patients, 13.6% (6/44) had secondary malignancies besides breast cancer and 20.5% (9/44) had no detectable malignancy. Limited disease was found in 24.1% (7/29) of patients. Median progression-free survival of MBC was 9.2 months and median overall survival was 41.1 months. The 3- and 5-year survival rates were 64.2% and 40.0%, respectively.

Conclusions:

A reproducible tumour marker increase followed by whole-body imaging is highly effective for early detection. By consequence, patients might benefit from earlier detection and improved therapeutic options with a prolonged survival.     

Results of a phase II open-label,nonrandomized trial of oral satraplatin in patients with metastatic breast cancer

Cisplatin and carboplatin have antitumor activity in breast cancer. Satraplatin, an orally bioavailable platinum analog, offers a potential alternative to intravenous chemotherapy. We conducted a multicenter phase II study of this agent as first- or second-line treatment of metastatic breast cancer. Satraplatin 80 mg/m² was taken PO Days 1–5 q 21 days in cycles 1 and 2, and if tolerated, increased to 100 mg/m² for subsequent cycles. Restaging studies to assess response were performed after every 2 cycles. Between November 2005 and March 2006, 40 patients were enrolled. Baseline characteristics: 48% prior adjuvant chemotherapy, 60% prior chemotherapy for MBC; median age, 62 years (ranges 43–83), 58% ER+/PR+, 23% ER+/PR−, 18% ER−/PR−/HER2−, and 5% HER2+. In 31 patients with measurable disease, there were two partial responses (PR; 6%; 95% CI 0, 15.2); and four patients (13%) had SD ≥6 months for a clinical benefit rate of 19%. Among the subanalysis of seven triple-negative patients with measurable disease, there were 2 SD and 2 PD. Median survival was 15 months and median progression-free survival was 2.7 months. The most common grade 3–4 toxicities were neutropenia (28%) and thrombocytopenia (25%). AEs leading to treatment discontinuation were nausea (n = 3), thrombocytopenia (n = 3), fever (n = 2), and vomiting (n = 2). This phase II study demonstrates oral satraplatin has limited activity as a single agent for MBC. Satraplatin, at a lower dose used in this study, could be combined with other chemotherapy agents in future trials in breast cancer.     

Prognosis of metastatic breast cancer: are there differences between patients with de novo and recurrent metastatic breast cancer?

Background:

We aimed to determine the prognostic impact of time between primary breast cancer and diagnosis of distant metastasis (metastatic-free interval, MFI) on the survival of metastatic breast cancer patients.

Methods:

Consecutive patients diagnosed with metastatic breast cancer in 2007–2009 in eight hospitals in the Southeast of the Netherlands were included and categorised based on MFI. Survival curves were estimated using the Kaplan–Meier method. Cox proportional hazards model was used to determine the prognostic impact of de novo metastatic breast cancer vs recurrent metastatic breast cancer (MFI ⩽24 months and >24 months), adjusted for age, hormone receptor and HER2 status, initial site of metastasis and use of prior (neo)adjuvant systemic therapy.

Results:

Eight hundred and fifteen patients were included and divided in three subgroups based on MFI; 154 patients with de novo metastatic breast cancer, 176 patients with MFI <24 months and 485 patients with MFI >24 months. Patients with de novo metastatic breast cancer had a prolonged survival compared with patients with recurrent metastatic breast cancer with MFI <24 months (median 29.4 vs 9.1 months, P<0.0001), but no difference in survival compared with patients with recurrent metastatic breast cancer with MFI >24 months (median, 29.4 vs 27.9 months, P=0.73). Adjusting for other prognostic factors, patients with MFI <24 months had increased mortality risk (hazard ratio 1.97, 95% CI 1.49–2.60, P<0.0001) compared with patients with de novo metastatic breast cancer. When comparing recurrent metastatic breast cancer with MFI >24 months with de novo metastatic breast cancer no significant difference in mortality risk was found. The association between MFI and survival was seen irrespective of use of (neo)adjuvant systemic therapy.

Conclusion:

Patients with de novo metastatic breast cancer had a significantly better outcome when compared with patients with MFI <24 months, irrespective of the use of prior adjuvant systemic therapy in the latter group. However, compared with patients with MFI >24 months, patients with de novo metastatic breast cancer had similar outcome.     

Long-term follow-up of patients with GIST undergoing metastasectomy in the era of imatinib – Analysis of prognostic factors (EORTC-STBSG collaborative study)

Background

Long-term complete remissions remain a rare exception in patients with metastatic gastrointestinal stromal tumors (GIST) treated with IM (imatinib). To date the therapeutic relevance of surgical resection of metastatic disease remains unknown except for the use in palliative intent.

Patients and methods

We analyzed overall survival (OS) and progression-free survival (PFS) in consecutive patients with metastatic GIST who underwent metastasectomy and received IM therapy (n = 239).

Results

Complete resection (R0+R1) was achieved in 177 patients. Median OS was 8.7 y for R0/R1 and 5.3 y in pts with R2 resection (p = 0.0001). In the group who were in remission at time of resection median OS was not reached in the R0/R1 surgery and 5.1 y in the R2-surgery (p = 0.0001). Median time to relapse/progression after resection of residual disease was not reached in the R0/R1 and 1.9 years in the R2 group of patients, who were resected in response. No difference in mPFS was seen in patients progressing at time of surgery. Conclusions: Our analysis implicates possible long-term survival in patients in whom surgical complete remission can be achieved. Incomplete resection, including debulking surgery does not seem to prolong survival. Despite the retrospective character and likely selection bias, this analysis may help in decision making for surgical approaches in metastatic GIST.     

Central retroperitoneal recurrences from colorectal cancer: Are lymph node and locoregional recurrences the same disease?

Background

Central retroperitoneal recurrences (CRRs) from colorectal carcinoma carry a poor prognosis. A CRR is sometimes defined as a locoregional recurrence (LR) and sometimes as a lymph node recurrence (NR). This study was conducted to determine the nature of CRR and evaluate prognostic factors after complete CRR resection.

Methods

Between January 1988 and December 2008, 31 patients underwent a complete resection of CRR. CRRs were divided into NR (n = 23) and LR (n = 8), whether pathological examination disclosed lymph node involvement or not.

Results

No differences were found between LR and NR regarding TNM stage, primary tumour location, time interval from primary tumour resection to CRR, number of metastatic sites, number of metastatic lesions and therapeutic management. The median preoperative CEA level was higher in the NR group (p = 0.003). After a median follow-up of 47 months NRs were associated with better overall survival (OS) (p = 0.03). Three-year OS and disease-free survival (DFS) in the LR and NR groups were 27% and 0% versus 81% and 26%, respectively. Twenty-seven (87%) patients developed a re-recurrence within a median interval of 15 months. The number of metastatic sites or lesions, the size of the CRR, the type of chemotherapy, radiotherapy, the interval between the primary resection and CRR and the TNM stage had no impact on OS.

Conclusion

LR in patients with CRR had a poorer prognosis than NR. A multimodality approach with complete resection may yield long-term survival for NR.     

A retrospective analysis of clinical outcome of patients with chemo-refractory metastatic breast cancer treated in a single institution phase I unit

Background and methods:

Novel approaches to treat chemo-refractory metastatic breast cancer (MBC) are currently under investigation. This retrospective series reviews the outcome of 70 MBC patients who have participated in 30 phase I trials at the Royal Marsden Hospital from 2002 to 2009.

Results:

The median treatment lines before phase I trial entry for MBC was 5 (range: 1–12 lines). The overall response rate was 11.4% (95% CI: 4.0–18.9%) and the clinical benefit rate at 4 months was 20% (95% CI: 10.6–29.3). The median time to progression was 7.0 weeks (95% CI: 6.4–7.5) and median overall survival was 8.7 months (95% CI: 7.6–9.8) from start of first phase I treatment. No patients discontinued trial because of treatment-related toxicities. Abnormal lactate dehydrogenase, serum albumin <35 mg  per 100 ml, ⩾5 previous treatment lines, liver metastases and Eastern Cooperative Group performance status ⩾2 at study entry were significantly associated with poor overall survival in multivariate analysis.

Conclusion:

This retrospective analysis provides evidence that patients with MBC tolerate phase I clinical trials and a significant proportion of patients with chemo-refractory disease, particularly those with triple-negative or Her2-positive breast cancer, may benefit from treatment.     

Radiosurgery versus surgery, both with adjuvant whole brain radiotherapy, for solitary brain metastases: a randomised controlled trial

Aims

This randomised non-inferiority trial was designed to assess whether radiosurgery plus adjuvant whole brain radiotherapy (RS + WBRT) is as effective as surgery plus whole brain radiotherapy (S + WBRT) for cancer patients with a solitary brain metastasis, with respect to overall survival and quality of life.

Materials and methods

Major inclusion criteria were a history of systemic cancer within 5 years and enhanced magnetic resonance imaging-confirmed solitary brain metastasis suitable for both radiosurgery and surgery. All patients were to receive WBRT (30 Gy in 10 fractions). Between February 2003 and April 2009, 40 patients were considered eligible, 22 consented to randomisation and 21 were analysed (11 RS + WBRT, 10 S + WBRT). The trial was closed early due to slow accrual.

Results

The estimated median overall survival times for RS + WBRT and S + WBRT patients were 6.2 and 2.8 months, respectively (hazard ratio 0.53, 95% confidence interval 0.20–1.43, P = 0.20). Corresponding median failure-free survival times were 3.1 and 1.7 months (P = 0.20). For 19 ‘per protocol’ patients, 2/10 in the RS + WBRT arm had distant intracranial failure (one also had local failure) and 3/9 S + WBRT patients had distant intracranial failure (no local failures). There were no grade 3–4 late radiation toxicities. Two months after starting treatment there were no significant differences in quality of life between the arms.

Conclusion

This randomised trial encountered the accrual difficulties and consequent low statistical power commonly associated with interdisciplinary studies drawing from a small eligible population, but can contribute to future overviews on the management of solitary brain metastases.