Objective Radiological Response Research Articles

Molecular and Clinical Analysis of Locally Advanced Dermatofibrosarcoma Protuberans Treated With Imatinib: Imatinib Target Exploration Consortium Study B2225

The cutaneous malignant tumor dermatofibrosarcoma protuberans (DFSP) is typically associated with a translocation between chromosomes 17 and 22 that places the platelet-derived growth factor-B (PDGFB) under the control of the collagen 1A1 promoter. The purpose of this study was to evaluate molecular, cytogenetic, and kinase activation profiles in a series of DFSPs and to determine whether these biologic parameters are correlated with the clinical responses of DFSP to imatinib. We analyzed the objective radiologic and clinical response to imatinib at 400 mg twice daily in eight patients with locally advanced DFSP and two patients with metastatic disease. Each of eight patients with locally advanced DFSP had evidence of t(17;22) and showed a clinical response to imatinib. Four of these patients had complete clinical responses. The two patients with metastatic disease had fibrosarcomatous histology and karyotypes that were substantially more complex than those typically associated with localized DFSP. One patient with metastatic DFSP and an associated t(17;22) had a partial response to imatinib but experienced disease progression after 7 months of therapy. In contrast, the other patient with metastatic disease had a tumor lacking t(17;22), and there was no clinical response to imatinib. Unexpectedly, there was minimal platelet-derived growth factor receptor-beta phosphorylation in the untreated DFSP, despite the documented presence of a PDGFB autocrine mechanism. Imatinib has clinical activity against both localized and metastatic DFSP with t(17;22). However, fibrosarcomatous variants of DFSP lacking t(17;22) may not respond to imatinib.

Temozolomide as initial treatment for adults with low-grade oligodendrogliomas or oligoastrocytomas and correlation with chromosome 1p deletions.

To determine the response rate of low-grade oligodendroglial tumors (LGOT) to temozolomide (TMZ) as initial treatment and to evaluate the predictive value of chromosome 1p deletion on the radiologic response. Adult patients with pathologically proven LGOT with progressive disease on magnetic resonance imaging (MRI) were eligible for the study. TMZ was administered at the starting dose of 200 mg/m2/d for 5 days, repeated every 28 days. Response was evaluated clinically and by central review of MRIs. Chromosome 1p and 19q deletions were detected by the loss of heterozygosity technique. Sixty consecutive patients were included in the study. At the time of analysis, the median number of TMZ cycles delivered was 11. Clinically, 51% of patients improved, particularly those with uncontrolled epilepsy. The objective radiologic response rate was 31% (17% partial response and 14% minor response), whereas 61% of patients had stable disease and 8% experienced disease progression. The median time to maximum tumor response was 12 months (range, 5 to 20 months). Myelosuppression was the most frequent side effect, with grade 3 to 4 toxicity in 8% of patients. Loss of chromosome 1p was associated with objective tumor response (P < .004). TMZ is well tolerated and provides a substantial rate of response in LGOT. Chromosome 1p loss is correlated with radiographic response and could be a helpful marker for guiding therapeutic decision making in LGOT.

Chronomodulated delivery schedule of oxaliplatin, 5 fluorouracil and folinic acid (FFL4/10) as first line treatment in metastatic colorectal cancer: Preliminary data of a phase II study

3738 Background: Oxaliplatin(OHP) and 5Fluorouracil(5FU) efficacy and toxicity strictly depend on circadian rhythms in cell cycle regulation, reduced glutathione content, dehydropyrimidine and thymidilate synthase activities, topoisomerase I activity, membrane permeability as well as liver and renal blood flow. Methods: From August 2002 to December 2003 (Tab.1) 27 untreated colorectal cancer patients(pt) were treated with OHP based chronomodulated delivery schedule using Melodie infusion system: OHP 25 mg / m2 /d1–4q14 (sinusoidal 12 hour infusion with flow rate peak at 4:00pm); 5FU 900 mg/m2 and L-Folinic Acid (LFA) 150 mg/m2 d1–4,q14 (sinusoidal 12 hour infusion with flow rate peak at 4:00am. Results: 147 cycles (6.11 average per pt.) were performed: average dose intensity was 48,21 mg/sqm/w, 319,28 mg/sqm/w 1630,41mg/sqm/w for OHP, LFA and 5FU respectively. Average dose according to body surface was 501mg/sqm, 3184,17mg/sqm, 16705,74mg/sqm respectively. No cycle was delayed due to toxicity. Haematological and hepatic toxicity weren't observed, neither was any gr. 4(WHO) toxicity. Radiological Objective Response evaluation has been performed in 23 pt (Tab.2). ORR was 65,22%. Median survival reached 13 months (only 3 pt died). Conclusions: These data seem confirm that FFL4/10 schedule has very interesting activity in metastatic colorectal cancer. Moreover, chronomodulated infusion is considerably less toxic than conventional flat or bolo infusion. No significant financial relationships to disclose.

Chronomodulated delivery schedule of oxaliplatin, 5 fluorouracil and folinic acid (FFL4/10) as first line treatment in metastatic colorectal cancer: Preliminary data of a phase II study

3738 Background: Oxaliplatin(OHP) and 5Fluorouracil(5FU) efficacy and toxicity strictly depend on circadian rhythms in cell cycle regulation, reduced glutathione content, dehydropyrimidine and thymidilate synthase activities, topoisomerase I activity, membrane permeability as well as liver and renal blood flow. Methods: From August 2002 to December 2003 (Tab.1) 27 untreated colorectal cancer patients(pt) were treated with OHP based chronomodulated delivery schedule using Melodie infusion system: OHP 25 mg / m2 /d1–4q14 (sinusoidal 12 hour infusion with flow rate peak at 4:00pm); 5FU 900 mg/m2 and L-Folinic Acid (LFA) 150 mg/m2 d1–4,q14 (sinusoidal 12 hour infusion with flow rate peak at 4:00am. Results: 147 cycles (6.11 average per pt.) were performed: average dose intensity was 48,21 mg/sqm/w, 319,28 mg/sqm/w 1630,41mg/sqm/w for OHP, LFA and 5FU respectively. Average dose according to body surface was 501mg/sqm, 3184,17mg/sqm, 16705,74mg/sqm respectively. No cycle was delayed due to toxicity. Haematological and hepatic toxicity weren't observed, neither was any gr. 4(WHO) toxicity. Radiological Objective Response evaluation has been performed in 23 pt (Tab.2). ORR was 65,22%. Median survival reached 13 months (only 3 pt died). Conclusions: These data seem confirm that FFL4/10 schedule has very interesting activity in metastatic colorectal cancer. Moreover, chronomodulated infusion is considerably less toxic than conventional flat or bolo infusion. No significant financial relationships to disclose.

A novel intraarterial chemotherapy using paclitaxel in albumin nanoparticles to treat advanced squamous cell carcinoma of the tongue: preliminary findings.

The purpose of our study was to evaluate the effectiveness of intraarterial infusion of paclitaxel incorporated into human albumin nanoparticles for use as induction chemotherapy before definitive treatment of advanced squamous cell carcinoma of the tongue. Twenty-three previously untreated patients (age range, 27-75 years) who had carcinoma of the tongue (stage T3-T4, any N) received intraarterial therapy with paclitaxel incorporated into albumin nanoparticles delivered by transfemoral catheterization into the external carotid artery (10 patients), selectively into the lingual artery (12 patients), or into a faciolingual trunk (1 patient). Each patient received two to four infusions, with a 3-week interval between infusions. The dose administered was 230 mg/m(2) in eight patients, 180 mg/m(2) in six patients, and 150 mg/m(2) in nine patients. Sixteen patients underwent surgery. Of these 16 patients, eight subsequently received radiotherapy, and three received a combination of chemotherapy and radiotherapy. Of the remaining seven patients, one received chemotherapy alone, four received radiotherapy alone, one received chemotherapy plus radiotherapy, and one refused any further treatment. Sixty-seven infusions were performed successfully. Eighteen patients (78%) had a clinical and radiologic objective response (complete, 26%; partial, 52%). Three patients (13%) showed stable disease, and two (9%) showed disease progression. The four patients with complete clinical response who underwent surgery showed microscopic residual carcinoma measuring less than 1 mm in two patients, less than 5 mm in one patient, and less than 1 cm in one patient. The toxicities encountered were hematologic (grade 3) in two patients (8.6%) and neurologic (grade 4) in two patients (reversible paralysis of the facial nerve, 8.6%). Two catheter-related complications occurred: one reversible brachiofacial paralysis and one asymptomatic occlusion of the external carotid artery. Intraarterial infusion of paclitaxel in albumin nanoparticles proved reproducible and effective and deserves further investigation as induction chemotherapy before definitive treatment of advanced tumors of the tongue, with a view to organ preservation.

Treatment of relapsed malignant glioma with an adenoviral vector containing the herpes simplex thymidine kinase gene followed by ganciclovir

Between November 1998 and December 2001, we treated 14 patients with advanced recurrent high-grade gliomas with a total dose of 4.6 × 108, 4.6 × 109, 4.6 × 1010, or 4.6 × 1011 viral particles (VP) of a replication-incompetent adenoviral vector harboring the herpes simplex virus thymidine kinase gene driven by the adenoviral major late promoter (IG.Ad.MLPI.TK), followed by ganciclovir (GCV) treatment. The VP-to-infectious-unit ratio was 40. The vector was administered by 50 intraoperative wound-bed injections of 0.2 ml each (total volume 10 ml). The study's primary objective was to determine the safety of this treatment and establish the maximum tolerated dose (MTD). Injection of all doses of IG.Ad.MLPI.TK followed by GCV was safely tolerated and MTD was not reached. All patients had recurrence or progression of the tumor 1–24 months (median 3.5 months) after gene therapy. The overall median survival was 4 months. Four patients survived longer than 1 year following gene therapy. One patient is still alive, with histologically confirmed progression of the tumor, 29 months after treatment. Ten patients died within 8 months of treatment, all from progression of the tumor. In 5 patients residual and measurable tumor was visible on the direct (<48 h) postoperative MRI. No objective radiological response was documented on subsequent MRI. None of the patients came to autopsy. In conclusion, the administration of 4.6 × 1011 VP of IG.Ad.MLPI.TK by 50 injections into the wound bed following resection of recurrent malignant glioma, followed by GCV treatment, was well tolerated.

Résections hépatiques pour métastases de cancer du sein : résultats et facteurs pronostiques (65 cas)

Study aim: To report results of liver resections for breast cancer liver metastasis (BCLM) and to evaluate the rate of survival and the prognostic factors. Patients and method: Between 1988 and 1999, 69 patients were operated on for BCLM and 65 who had liver resection were analyzed. The selection criteria for surgery were: normal performance status and liver function test; radiological objective response to chemotherapy (and/or hormonotherapy); in cases of non-isolated BCLM, complete response of associated metastatic site (usually bone) and no brain metastases. The mean age of the 65 patients was 47 (30–70) years. BCLM was diagnosed an average of 60 (0–205) months after the initial cancer. The BCLM was more frequently solitary ( n = 44). The mean diameter was 3.8 (0–12) cm. The mean number of cycles of chemotherapy before surgery was 7.5 (3–24). Liver resections included major hepatectomy ( n = 31) : right n = 19, extended left n = 4, left n = 8, minor hepatectomy ( n = 25) and limited resection ( n = 9). Results: There was no postoperative mortality. The 18% morbidity rate included a majority of pleural effusions with two reoperations. The median follow-up was 41 months (6–100 months). The survival rate after surgery was 90% at 1 year, 71% at 3 and 46% at 4 years. Thirteen patients are alive at 4 years. The 36-month survival rate differed according to the time to onset of BCLM: 55% before versus 86% after 48 months ( p = 0.01). The other studied factors were not statistically associated with survival. The recurrence rate in the remaining liver at 36 months differed according to the lymph node status of the initial breast cancer: 40% for N0-N1 versus 81% for N1b-N2 ( p = 0.01) and according to the type of liver resection: 45% for minor liver resection versus 73% for major ( p = 0.02). Conclusion: Adjuvant liver surgery should be included in multicenter treatment protocols for medically-controlled breast cancer liver metastasis.