The Molecular Tumor Board of the Regina Elena National Cancer Institute: from accrual to treatment in real-world.

BACKGROUND: Molecular Tumor Boards (MTB) operating in real-world have generated limited consensus on good practices for accrual, actionable alteration mapping, and outcome metrics. These topics are addressed herein in 124 MTB patients, all real-world accrued at progression, and lacking approved therapy options. METHODS: Actionable genomic alterations identified by tumor DNA (tDNA) and circulating tumor DNA (ctDNA) profiling were mapped by customized OncoKB criteria to reflect diagnostic/therapeutic indications as approved in Europe. Alterations were considered non-SoC when mapped at either OncoKB level 3, regardless of tDNA/ctDNA origin, or at OncoKB levels 1/2, provided they were undetectable in matched tDNA, and had not been exploited in previous therapy lines. RESULTS: Altogether, actionable alterations were detected in 54/124 (43.5%) MTB patients, but only in 39 cases (31%) were these alterations (25 from tDNA, 14 from ctDNA) actionable/unexploited, e.g. they had not resulted in the assignment of pre-MTB treatments. Interestingly, actionable and actionable/unexploited alterations both decreased (37.5% and 22.7% respectively) in a subset of 88 MTB patients profiled by tDNA-only, but increased considerably (77.7% and 66.7%) in 18 distinct patients undergoing combined tDNA/ctDNA testing, approaching the potential treatment opportunities (76.9%) in 147 treatment-naïve patients undergoing routine tDNA profiling for the first time. Non-SoC therapy was MTB-recommended to all 39 patients with actionable/unexploited alterations, but only 22 (56%) accessed the applicable drug, mainly due to clinical deterioration, lengthy drug-gathering procedures, and geographical distance from recruiting clinical trials. Partial response and stable disease were recorded in 8 and 7 of 19 evaluable patients, respectively. The time to progression (TTP) ratio (MTB-recommended treatment vs last pre-MTB treatment) exceeded the conventional Von Hoff 1.3 cut-off in 9/19 cases, high absolute TTP and Von Hoff values coinciding in 3 cases. Retrospectively, 8 patients receiving post-MTB treatment(s) as per physician's choice were noted to have a much longer overall survival from MTB accrual than 11 patients who had received no further treatment (35.09 vs 6.67 months, p = 0.006). CONCLUSIONS: MTB-recommended/non-SoC treatments are effective, including those assigned by ctDNA-only alterations. However, real-world MTBs may inadvertently recruit patients electively susceptible to diverse and/or multiple treatments.

A multicentre study with real-world data of the use of palbociclib in the treatment of breast cancer: Treatment duration correlates with dose reductions.

OBJECTIVE: Palbociclib, a highly selective reversible CDK4-6 kinase inhibitor, is indicated in combination with an aromatase inhibitor or in combination with fulvestrant in women who had received prior endocrine treatment. Studies have demonstrated the efficacy of palbociclib in combination with fulvestrant in increasing progression-free survival in patients who relapsed or progressed on previous endocrine therapy, or in combination with aromatase inhibitor in patients who had not received previous treatments. We analysed the prescribing patterns of palbociclib in real practice correlating it with the evidence of treatment-related toxicity management and to time-to-treatment discontinuation and treatment adherence. METHODS: For the observational, retrospective study, data were collected from five Italian hospital centres that prescribed palbociclib between April 2017 and April 2020. Each centre provided data derived from an administrative database of adult patients treated with palbociclib for the two therapeutic indications.Treatment adherence was calculated using the proportion of days covered method while time-to-treatment discontinuation was defined as the difference between the first and last date treatment was administered plus the days ideally covered by the last date treatment was given. RESULTS: There were 375 patients enrolled during the study period, of whom 159 were treated with palbociclib and aromatase inhibitor and 216 were treated with palbociclib and fulvestrant. The time-to-treatment discontinuation was 8.9 months in the case of P + f (95% CI: 7.1-12.7) and 13.7 months in the case of P + ia (95% CI: 8.9-17.5). In both cohorts, treatments that received at least one dose reduction had a statistically higher time-to-treatment discontinuation than those without dose reduction (17.7 months vs. 9.2 and 16.6 vs. 7.4).The mean adherence in our study was 0.9 and remained high in treatments with one dose reduction (0.83) and this with two dose reductions (0.87). CONCLUSION: Based on these findings, it appears that the management of toxicities through reducing doses, as required by the Summary of Product Characteristics, results in a better outcome in terms of therapy duration, and therefore time to failure due to progression or toxicity.

Interleukin-8 in Colorectal Cancer: A Systematic Review and Meta-Analysis of Its Potential Role as a Prognostic Biomarker.

Among soluble actors that have emerged as druggable factors, the chemokine interleukin-8 (IL-8) has emerged as a possible determinant of response to immunotherapy and targeted treatment in several cancer types; however, its prognostic/predictive role in colorectal cancer (CRC) remains to be established. We: (i) conducted a systematic review of published literature on IL-8 expression in CRC; (ii) searched public transcriptomics databases; (iii) investigated IL-8 expression, by tumor and infiltrating cells, in a series of CRC samples; and (iv) carried out a meta-analysis of published literature correlating IL-8 expression and CRC prognosis. IL-8 possesses an important role as a mediator of the bidirectional crosstalk between tumor/stromal cells. Transcriptomic analysis indicated that specific IL-8 transcripts were significantly overexpressed in CRC compared to normal colon mucosa. Moreover, in our series we observed a statistically significant correlation between PTEN-loss and IL-8 expression by infiltrating mononuclear and tumor cells. In total, 12 papers met our meta-analysis inclusion criteria, demonstrating that high IL-8 levels significantly correlated with shorter overall survival and progression-free survival. Sensitivity analysis demonstrated a highly significant correlation with outcome for circulating, but not for tissue-detected, IL-8. IL-8 is overexpressed in CRC tissues and differentially produced by tumor or stromal components depending on CRC genetic background. Moreover, circulating IL-8 represents a strong prognostic factor in CRC, suggesting its use in the refining of prognostic CRC assessment and potentially the tailoring of therapeutic strategies in individual CRC patients.

Fibroblast-Induced Paradoxical PI3K Pathway Activation in PTEN-Competent Colorectal Cancer: Implications for Therapeutic PI3K/mTOR Inhibition.

Purpose: Tumor-microenvironment interactions are important determinants of drug resistance in colorectal cancer (CRC). We, therefore, set out to understand how interactions between genetically characterized CRC cells and stromal fibroblasts might influence response to molecularly targeted inhibitors. Techniques: Sensitivity to PI3K/AKT/mTOR pathway inhibitors of CRC cell lines, with known genetic background, was investigated under different culture conditions [serum-free medium, fibroblasts' conditioned medium (CM), direct co-culture]. Molecular pathway activation was monitored using Western Blot analysis. Immunoprecipitation was used to detect specific mTOR complex activation. Immunofluorescence was used to analyze cellular PTEN distribution, while different mutant PTEN plasmids were used to map the observed function to specific PTEN protein domains. Results: Exposure to fibroblast-CM resulted in increased growth-inhibitory response to double PI3K/mTOR inhibitors in PTEN-competent CRC cell lines harboring KRAS and PI3K mutations. Such functional effect was attributable to fibroblast-CM induced paradoxical PI3K/mTORC1 pathway activation, occurring in the presence of a functional PTEN protein. At a molecular level, fibroblast-CM induced C-tail phosphorylation and cytoplasmic redistribution of the PTEN protein, thereby impairing its lipid phosphatase function and favored the formation of active, RAPTOR-containing, mTORC1 complexes. However, PTEN's lipid phosphatase function appeared to be dispensable, while complex protein-protein interactions, also involving PTEN/mTOR co-localization and subcellular distribution, were crucial for both mTORC1 activation and sensitivity to double PI3K/mTOR inhibitors. Data Interpretation: Microenvironmental cues, in particular soluble factors produced by stromal fibroblasts, profoundly influence PI3K pathway signaling and functional response to specific inhibitors in CRC cells, depending on their mutational background and PTEN status.

Radiotherapy and Immunotherapy: The Power of the Teamwork for the Treatment of NSCLC.

Immune checkpoint inhibitors (ICPi) targeting programmed cell death 1(PD-1)/programmed cell death ligand-1 (PD-L1) have revolutionized the treatment of patients with advanced non-small cell lung cancer (NSCLC). Despite impressive success, only a small proportion of patients benefit from PD1/PDL1 inhibitors. Radiotherapy (RT) can induce a systemic anti-tumor immune response on local and distant tumors. Some preclinical and clinical evidence showed a critical role of RT to overcome acquired resistance to immunotherapy. Currently, durvalumab consolidation represents the new standard treatment for unresectable stage III NSCLC patients whose tumors express PDL1 on ≥1% of tumor cells (TC), and whose disease has not progressed following platinum-based chemoradiotherapy (CRT). In this review, we focus on the synergic effect of RT with ICPi and the new role that different RT schedules can play in combination with immunotherapy for early-stage NSCLC.

Cross-sectional analysis of circulating tumor DNA in primary colorectal cancer at surgery and during post-surgery follow-up by liquid biopsy.

BACKGROUND: Liquid biopsy (LB) in early-stage, non-metastatic colorectal cancer (CRC) must be sensitive enough to detect extremely low circulating tumor DNA (ctDNA) levels. This challenge has been seldom and non-systematically investigated. METHODS: Next generation sequencing (NGS) and digital PCR (dPCR) were combined to test tumor DNAs (tDNAs) and paired ctDNAs collected at surgery from 39 patients, 12 of whom were also monitored during the immediate post-surgery follow up. Patients treated for metastatic disease (n = 14) were included as controls. RESULTS: NGS and dPCR concordantly (100% agreement) called at least one single nucleotide variant (SNV) in 34 tDNAs, estimated differences in allelic frequencies being negligible (±1.4%). However, despite dPCR testing, SNVs were only detectable in 15/34 (44.1%) ctDNAs from patients at surgery, as opposed to 14/14 (100%) metastatic patients. This was likely due to striking differences (average 10 times, up to 500) in ctDNA levels between groups. NGS revealed blood-only SNVs, suggesting spatial heterogeneity since pre-surgery disease stages, and raising the combined NGS/dPCR sensitivity to 58.8%. ctDNA levels at surgery correlated with neither tumor size, stage, grade, or nodal status, nor with variant abundance in paired tDNA. LB sensitivity reached 63.6% when ctDNA was combined with CEA. Finally, persistence and absence of ctDNA on the first conventional (month 3) post-surgery follow-up were associated with fast relapse and a disease-free status in 3 and 7 patients, respectively. CONCLUSIONS: A simple clinical NGS/dPCR/CEA combination effectively addresses the LB challenge in a fraction of non-metastatic CRC patients.

Gender effects of single nucleotide polymorphisms and miRNAs targeting clock-genes in metastatic colorectal cancer patients (mCRC).

The circadian system is composed of a set of clock-genes including PERIOD, CLOCK, BMAL1 and CRY. Disrupting this system promotes cancer development and progression. The expression levels of miR-206, miR-219, miR-192, miR-194 and miR-132 regulating clock-genes and three functional polymorphisms rs11133373 C/G, rs1801260 T/C, rs11133391 T/C in CLOCK sequence were associated with the survival of 83 mCRC patients (50 males and 33 females). Longer overall survival (OS) was observed in women compared to men, 50 versus 31 months. This difference was associated with rs11133373 C/C genotype (p = 0.01), rs1801260 T/C+C/C genotype (p = 0.06) and rs11133391 T/T genotype (p = 0.06). Moreover women expressing high levels (H) of miR-192 (p = 0.03), miR-206 (p = 0.003), miR-194 (p = 0.02) and miR-219 (p = 0.002) had a longer OS compared to men. In women longer OS was reinforced by the simultaneous presence of two or more H-miR, 58 months versus 15 months (p = 0.0008); in this group of women an OS of 87 months was reached with the additional presence of rs11133391T/T genotype (p = 0.02). In this study we identified a subgroup of female patients who seems to have a better prognosis. Personalized medicine should prospectively take into account both genetic and gender differences.

Epidermal growth factor receptor gene copy number in 101 advanced colorectal cancer patients treated with chemotherapy plus cetuximab.

BACKGROUND: Responsiveness to Cetuximab alone can be mediated by an increase of Epidermal Growth factor Receptor (EGFR) Gene Copy Number (GCN). Aim of this study was to assess the role of EGFR-GCN in advanced colorectal cancer (CRC) patients receiving chemotherapy plus Cetuximab. METHODS: One hundred and one advanced CRC patients (43 untreated- and 58 pre-treated) were retrospectively studied by fluorescence in situ hybridization (FISH) to assess EGFR-GCN and by immunohistochemistry (IHC) to determine EGFR expression. Sixty-one out of 101 patients were evaluated also for k-ras status by direct sequencing. Clinical end-points were response rate (RR), progression-free survival (PFS) and overall survival (OS). RESULTS: Increased EGFR-GCN was found in 60/101 (59%) tumor samples. There was no correlation between intensity of EGFR-IHC and EGFR-GCN (p = 0.43). Patients receiving chemotherapy plus Cetuximab as first line treatment had a RR of 70% (30/43) while it was 18% (10/56) in the group with previous lines of therapy (p < 0.0001). RR was observed in 29/60 (48%) of patients with increased EGFR-GCN and in 6/28 (21%) in those without (p = 0.02). At multivariate analyses, number of chemotherapy lines and increased EGFR-GCN were predictive of response; EGFR-IHC score, increased EGFR-GCN and number of chemotherapy lines were significantly associated with a significant better PFS. Response to therapy was the only prognostic predictive factor for OS. In the 60 patients analyzed for k-ras mutations, number of chemotherapy lines, increased EGFR-GCN and k-ras wild type status predicted a better PFS. CONCLUSION: In metastatic CRC patients treated with chemotherapy plus Cetuximab number of chemotherapy lines and increased EGFR-GCN were significantly associated with a better clinical outcome, independent of k-ras status.

Chordoma: clinical characteristics, management and prognosis of a case series of 25 patients.

BACKGROUND: Adequate surgery still remains the only curative treatment of chordoma. Interesting clinical data on advanced disease with molecularly targeted therapies were reported. METHODS: We described the clinical outcome of a series of chordoma patients followed at Regina Elena National Cancer Centre of Rome from 2004 to 2008. RESULTS: Twenty-five consecutive patients with sacral (11 patients), spine (13 patients), and skull base (1 patient) chordoma went to our observation. Six patients (24%) had primary disease, 14(56%) a recurrent disease, and 5(20%) a metastatic spreading. Surgery was the primary option for treatment in 22 out of 25 patients. Surgical margins were wide in 5 (23%) and intralesional in 17(77%) patients; 3 out of 4 in-house treated patients obtained wide margins. After first surgery, radiotherapy (protons or high-energy photons) were delivered to 3 patients. One out of the 5 patients with wide margins is still without evidence of disease at 20 months from surgery; 2 patients died without evidence of disease after 3 and 36 months from surgery. Sixteen out of 17 (94%) patients with intralesional margins underwent local progression at a median time of 18 months with a 2-year local progression-free survival of 47%. The 5-year metastasis-free survival rate was 78.3%. Seventeen patients with locally advanced and/or metastatic disease expressing platelet-derived growth factor receptor (PDGFR) beta were treated with imatinib mesylate. A RECIST stabilization of the disease was the best response observed in all treated cases. Pain relief with reduction in analgesics use was obtained in 6 out of 11 (54%) symptomatic patients. The 5- and 10-year survival rates of the entire series of patients were 76.7 and 59.7%, respectively. CONCLUSIONS: Despite progress of surgical techniques and the results obtained with targeted therapy, more effort is needed for better disease control. Specific experience of the multi-disciplinary therapeutic team is, however, essential to succeed in improving patients' outcome.

A phase II study of cetuximab/irinotecan in patients with heavily pretreated metastatic colorectal cancer: predictive value of early specific toxicities.

BACKGROUND: This study was designed to evaluate the predictive value of early specific toxicities on efficacy of weekly irinotecan/cetuximab administered as salvage therapy in patients with metastatic colorectal cancer (CRC) refractory to oxaliplatin and irinotecan. PATIENTS AND METHODS: Seventy patients received a regimen composed of weekly irinotecan 125 mg/m2 as a 1-hour intravenous infusion and cetuximab 400 mg/m2 infused over 2 hours as the initial dose and 250 mg/m2 infused over 1 hour for subsequent administrations. A single treatment cycle was composed of 4 weekly irinotecan infusions followed by 2 weeks of rest. The predictive value of adverse events (AEs) attributable to cetuximab (rash) and major toxicities attributable to irinotecan (gastrointestinal [GI] and hematologic) were observed after the first cycle of treatment and, therefore, correlated to activity and efficacy of cetuximab and weekly irinotecan. RESULTS: Sixty-six of 70 patients received >or= 1 cycle of chemotherapy and were therefore evaluable for response. Overall, toxicity observed was generally mild and manageable. According to an intent-to-treat analysis, a partial response was exhibited in 15.7% of patients, with a median progression-free survival (PFS) and median overall survival time of 4 months and 9 months, respectively. As expected, PFS (P = .01) and median survival (P = .04) correlated strongly with the presence and severity of the rash. Surprisingly, the presence of at least moderate hematologic and GI toxicity was associated with improved PFS (P = .03). CONCLUSION: Our data suggest that irinotecan-induced AEs might predict a better outcome in advanced CRC. This finding would identify a different subset of patients-those likely to benefit from a renewed sensitivity to irinotecan induced by cetuximab.

Unexpected clinical outcome in a patient with liver and brain metastasis from melanoma.

The treatment of disseminated melanoma is inadequate. The most active single agents provide brief objective response in 20% of patients, while the combination chemotherapy improves response rates without any apparent survival benefit. Median overall survival is, in fact, 7-9 months and 5 year survival is approximately 6%. Metastatic melanoma with a localization of the disease in the liver and brain are categorized as M1c and have the worst prognosis. Here we describe the history, treatment and favourable clinical outcome in a young man with liver and resected brain metastases who obtained complete remission for 6 years since chemotherapy with dacarbazine, cisplatin and vinblastine.

Gemcitabine at fixed dose-rate in patients with advanced soft-tissue sarcomas: a mono-institutional phase II study.

PURPOSE: To explore the clinical activity and toxicity of gemcitabine infused at the fixed dose of 10 mg/m(2)/min over 100 min in patients with soft tissue sarcomas (STSs). PATIENTS AND METHODS: Fourteen patients with advanced locally unresectable and/or metastatic, pretreated STSs (seven leiomyosarcoma, three malignant schwannoma, one synovialsarcoma, one malignant fibrous histiocytoma, one endometrial stromal cell sarcoma, one undifferentiated) were treated with gemcitabine 10 mg/m(2)/min/week over 100 min given for 3 weeks out of 4. The median age was 52 years (range 27-77), male/female ratio was 3/11, and the median WHO performance status was 0 (range 0-1). The median number of previous medical treatments for advanced disease was 1 (range 1-2). RESULTS: A median number of three cycles (range 1-10 cycles) and a total of 151 weekly administrations (median 9, range 3-27) of gemcitabine were administered. Treatment was well tolerated and the main causes of dose-reduction or omission/delay were hematological and liver toxicities. One patient (7%; 95% confidence interval: 0.2-33.9%) with a metastatic uterine leiomyosarcoma obtained a partial response that lasted for 6.5 months. Three patients (two leiomyosarcoma and one schwannoma) (21%) obtained a stabilization of disease. The median time to progression was 3.1 months (range 1.0-9.5). The median overall survival was 11.8 months (range 1.0-54.5+). CONCLUSIONS: Gemcitabine infused at the fixed dose of 10 mg/m(2)/min over 100 min shows a good tolerability but an overall modest activity in unselected STSs histotypes. Nevertheless, an interesting tumor growth control rate was observed in specific histological variants (i.e., leiomyosarcoma), thus confirming data from recent controlled clinical trials.

A phase II trial of gefitinib in combination with capecitabine and oxaliplatin as first-line chemotherapy in patients with advanced colorectal cancer.

OBJECTIVE: This study was designed as a multicentre phase II trial to assess the efficacy and safety of gefitinib in association with capecitabine and oxaliplatin in patients with untreated metastatic colorectal cancer. RESEARCH DESIGN AND METHODS: Patients with metastatic colorectal cancer that had received no prior chemotherapy for advanced disease were treated with oral gefitinib (250 mg daily) plus oral capecitabine (1000 mg/m2 twice a day on Days 1-14) and intravenous oxaliplatin (120 mg/m2 on Day 1 of each 3-week cycle). RESULTS: Thirty-five patients were enrolled. In the intention-to-treat analysis, 3 (8.6%) patients experienced a complete response (CR), 14 (40%) a partial response (PR) and 11 (31.4%) had stable disease (SD). The disease control rate (CR + PR + SD) was 80%, the median time to progression was 7.3 months (95%CI: 4.76-9.2) and the estimated median overall survival was 21.9 months (95% CI: 15.1--not reached). The most common grade 3 to 4 toxicities included diarrhoea (31%) and vomiting (5.7%). CONCLUSIONS: The combination of capecitabine, oxaliplatin and gefitinib appears to have promising activity in chemotherapy-naïve metastatic colorectal cancer. A higher disease control rate and an increase in median overall survival were seen compared with previous reports with capecitabine and oxaliplatin in similar patient populations. The tolerability profile appears to be predictable and similar to capecitabine/oxaliplatin regimens.

Severe skin reaction in a patient with gastrointestinal stromal tumor treated with imatinib mesylate.

Imatinib mesylate is a selective protein kinase inhibitor, highly active in patients with chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GISTs). Cutaneous toxicity, a well-recognized, dose-related side-effect of imatinib mesylate, has been reported in 18 to 69% of patients with GIST treated with doses ranging from 400 to 800 mg once a day. In this case-report a severe skin reaction observed in a patient with GIST treated with imatinib mesylate, in an adjuvant setting and whose severity led to definitive drug discontinuation, is described. Therapeutic management and clinical course are illustrated.

Nonmyeloablative allogeneic blood stem cell transplantation in patients with metastatic solid tumors.

BACKGROUND: The aim of the study was to evaluate the feasibility and efficacy of a non-myeloablative regimen to achieve complete donor chimerism after stem cell transplantation (SCT) in patients with metastatic solid tumors. PATIENTS AND METHODS: Seven patients with renal cell carcinoma (RCC), 3 with colorectal carcinoma and 1 with soft tissue sarcoma received an allogeneic SCT after fludarabine (90 mg/m2) and TBI 200 cGy. RESULTS: At day 30, median donor chimerism was 94%. Regression of tumor metastases has been observed in 1 patient with RCC. Overall, 8 patients (73%) died from progressive disease (median progression-free survival 3.7 months) and 1 (9%) from treatment-related complications; 2 patients were alive 152 and 862 days after transplantation. CONCLUSIONS: Our preliminary results suggest that non-myeloablative SCT for metastatic solid tumors is feasible, although may lead to durable responses in a minority of patients. Careful patient selection seems to be mandatory in this transplant setting.

Central nervous system as exclusive site of disease in patients with melanoma: treatment and clinical outcome of two cases.

The central nervous system (CNS) is a favourite site of metastasis in advanced melanoma and, despite the improvement obtained in the control of brain metastasis, most patients die as a result of extracranial progression of the disease. CNS primary malignant melanoma is a rare entity and the diagnosis is generally made after the exclusion of a primary cutaneous or mucosal/retinal malignant melanoma, as differential histological diagnosis between primary and metastatic origins is often difficult. From a review of the literature, patients with primary brain melanoma or exclusive (and limited) brain metastasis in the absence of extracranial melanoma present a relatively good prognosis if adequately treated with aggressive locoregional treatments (neurosurgery and/or radiotherapy) and, later, with drugs able to cross the blood-brain barrier (i.e. fotemustine). In this letter, we describe the history, treatment and favourable clinical outcome of two patients with melanoma and CNS as the exclusive site of disease.

PET scanning evaluation of response to imatinib mesylate therapy in gastrointestinal stromal tumor (GIST) patients.

BACKGROUND: Unresectable or metastatic gastrointestinal stromal tumors (GISTs) exhibit a dynamic clinical course, with no evidence of benefit from any standard cytotoxic chemotherapy and an inevitably fatal outcome. With the introduction of Imatinib, an oral drug able to inhibit the KIT receptor tyrosine kinase, new questions arise regarding our ability to monitor treatment response with conventional methods and optimally manage such patients on treatment with new agents. MATERIALS AND METHODS: Herein we report two cases of patients with a history of GIST in treatment with Imatinib. RESULTS: After 4 weeks from treatment start, CT scan evaluation demonstrated a massive increase in the size of metastatic lesions, but a confirmatory PET excluded, in both patients, the presence of any metabolic activity in the previously known metastatic sites. Imatinib therapy was continued with subjective clinical benefit for 12 further months before a PET scan-confirmed disease progression had occurred in one patient and is still ongoing after 15 months in the other. CONCLUSION: These cases open the obvious question of whether conventional imaging techniques are adequate to assess the response to Imatinib treatment in GIST patients.