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.     

Tumour regression grading after chemoradiotherapy for locally advanced rectal cancer: A near pathologic complete response does not translate into good clinical outcome

Background

After preoperative chemoradiotherapy (CRT) for rectal cancer, clinically undetectable residual tumour deposits or pathologic lymph nodes may remain in the mesorectum.

Aim

The aim of this study was to report histopathological effects of CRT and factors affecting outcome in a uniformly treated series of locally advanced rectal cancer (LARC) patients.

Methods

Between 2004 and 2008, 107 patients with cT3 (threatening the mesorectal fascia or <5 cm from the anal verge), cT4 or cN2 rectal cancer were treated with preoperative CRT (25 × 2 Gy with capecitabine) and TME 6–8 weeks later. Central histopathological review followed. Tumour regression grade (TRG) was scored in pCR, near-pCR, response and no response. Cox regression was performed to identify prognosticators.

Results

The 3-year distant metastasis-free interval, disease-free rate and overall survival rate were 82%, 73% and 87% (median 44 months follow-up). TRG consisted of 20% pCR, 11% near-pCR, 55% response and 14% no response. 6/21 pCR patients harboured nodal metastases. 5/12 near-pCR had ypT3 disease, while 6 harboured node metastases. 5/12 near-PCR patients developed distant metastases. ypN and TRG were powerful outcome discriminators.

Conclusion

The high number of near-pCR with ypT3 or ypN1/2 and their poor outcome demonstrates that “watch-and-wait” in LARC patients should be applied with care.     

Preoperative chemoradiotherapy in locally advanced gastric cancer,a phase I/II feasibility and efficacy study

Objectives

This study was initiated to investigate the feasibility and efficacy of preoperative radiotherapy with weekly paclitaxel and carboplatin in locally advanced gastric cancer.

Methods

In a prospective study, patients with locally advanced gastric cancer stage IB-IV(M0) were treated with chemoradiotherapy followed by surgery 4–6 weeks after the last irradiation. Chemoradiotherapy consisted of radiation to a total dose of 45 Gy given in 25 fractions of 1.8 Gy, combined with concurrent weekly carboplatin and paclitaxel.

Results

Between December 2007 and January 2012, 25 patients with cT3 (64%) or cT4 (36%) gastric cancer were included. One patient discontinued concurrent chemotherapy in the 4th week due to toxicity, but completed radiotherapy. Another patient discontinued chemoradiotherapy after the 3rd week due to progressive disease. Grade III adverse events of chemoradiotherapy were: gastrointestinal 12%, haematological 12% and other 8%. All patients, except one who developed progressive disease, were operated. Surgical complications were: general/infectious 48%, anastomotic leakage 12%, and bowel perforation 8%. Postoperative mortality was 4%. Microscopically radical resection rate was 72%. Pathological complete response rate was 16% and near complete response rate 24%.

Conclusions

In this study, preoperative chemoradiotherapy for patients with locally advanced gastric cancer was associated with manageable toxicity and encouraging pathological response rates.     

Oral contraceptives and the risk of myocardial infarction.

BACKGROUND: An association between the use of oral contraceptives and the risk of myocardial infarction has been found in some, but not all, studies. We investigated this association, according to the type of progestagen included in third-generation (i.e., desogestrel or gestodene) and second-generation (i.e., levonorgestrel) oral contraceptives, the dose of estrogen, and the presence or absence of prothrombotic mutations METHODS: In a nationwide, population-based, case-control study, we identified and enrolled 248 women 18 through 49 years of age who had had a first myocardial infarction between 1990 and 1995 and 925 control women who had not had a myocardial infarction and who were matched for age, calendar year of the index event, and area of residence. Subjects supplied information on oral-contraceptive use and major cardiovascular risk factors. An analysis for factor V Leiden and the G20210A mutation in the prothrombin gene was conducted in 217 patients and 763 controls RESULTS: The odds ratio for myocardial infarction among women who used any type of combined oral contraceptive, as compared with nonusers, was 2.0 (95 percent confidence interval, 1.5 to 2.8). The adjusted odds ratio was 2.5 (95 percent confidence interval, 1.5 to 4.1) among women who used second-generation oral contraceptives and 1.3 (95 percent confidence interval, 0.7 to 2.5) among those who used third-generation oral contraceptives. Among women who used oral contraceptives, the odds ratio was 2.1 (95 percent confidence interval, 1.5 to 3.0) for those without a prothrombotic mutation and 1.9 (95 percent confidence interval, 0.6 to 5.5) for those with a mutation CONCLUSIONS: The risk of myocardial infarction was increased among women who used second-generation oral contraceptives. The results with respect to the use of third-generation oral contraceptives were inconclusive but suggested that the risk was lower than the risk associated with second-generation oral contraceptives. The risk of myocardial infarction was similar among women who used oral contraceptives whether or not they had a prothrombotic mutation.     

Cognitive-behavioral mechanisms in a pain-avoidance and a pain-persistence treatment for high-risk fibromyalgia patients

Objective

The heterogeneity of cognitive–behavioral patterns in patients with fibromyalgia (FM) has been proposed to underlie the variability in treatment outcomes. It has previously been shown that pain‐avoidance and pain‐persistence treatments tailored to the patient's pattern are effective in improving physical and psychological functioning and overall impact in high‐risk patients with heigthened psychological distress. In the present study, the cognitive–behavioral effects of these treatments were evaluated to provide insight into the main proposed mechanisms, specifically pain‐avoidance behaviors and activity pacing in the pain‐avoidance and pain‐persistence treatments, respectively.

Methods

High‐risk FM patients were classified into 2 groups, pain avoidance and pain persistence, and randomized in groups to the relevant treatment or waiting‐list control condition. The pain‐avoidance and pain‐persistence treatments both comprised 16 twice‐weekly sessions of cognitive–behavioral therapy and exercise training. Cognitive–behavioral factors assessed at pre‐ and posttreatment and 6 months of followup were evaluated using linear mixed models.

Results

A significant treatment effect was found for pain‐avoidance behavior in the pain‐avoidance treatment and for activity pacing in the pain‐persistence treatment, showing improvements in the treatment condition relative to the controls. Furthermore, the effect on functioning was mediated by changes in pain‐avoidance behavior in the pain‐avoidance treatment and by changes in activity pacing in the pain‐persistence treatment. Both treatments also showed significant improvements in other relevant cognitive–behavioral factors.

Conclusion

Both the pain‐avoidance and pain‐persistence treatments are effective in improving cognitive–behavioral factors in high‐risk FM patients. Pain‐avoidance behavior and activity pacing might be important mediating mechanisms for beneficial outcomes in pain‐avoidance and pain‐persistence treatments, respectively.     

Intra-uterine tachycardia associated with multicystic encephalomalacia (MCE)

Multiple cystic brain lesions in neonates have been described as a result of a variety of causes. All events described thus far in association with multicystic encephalomalacia (MCE) seem to point to hypoxic-ischaemic injury as the common factor for this particular form of central nervous system damage. We describe a neonate in whom repeated, prolonged episodes of intrauterine tachycardia had been documented. Congestive heart failure and fetal hydrops were present at birth and MCE at the age of 13 wk. The obvious relationship between this child's intrauterine tachycardia and his MCE points to the fact that any fetus with prolonged tachycardia should be considered at risk of severe brain damage.