Chemosensitivity Testing Research Articles

In vitro analysis of BCNU-sensitivity in human malignant gliomas

Like all chloroethyl-nitrosoureas of major clinical use, 1,3 bis-(2-chloroethyl)-1-nitrosourea (BCNU) - which is one of the most effective chemotherapeutic agents for CNS malignancies - biologically degrades into active alkylating and carbamoylating moieties. Using a human brain tumor stem cell assay, we analyzed a series of anaplastic astrocytomas of pediatric age, characterized by different degrees of BCNU-resistance. Early (2-4) passage cultures from these tumors were treated in vitro with model drugs for alkylation (BCNU, CHLZ (2-[3-(2-chloroethyl)-3-nitrosoureido]-2-deoxy-D-glucopyranose), ENU (N-ethyl-N-nitrosourea), cross-linking (BCNU, CHLZ) and carbamoylation BHCNU (1,3 bis (trans-4-hydrocyclohexyl)-1-nitrosourea): dose-schedules were compatible with clinically achievable levels. Results of chemosensitivity tests confirmed that - as previously reported in malignant gliomas of the adult - cellular resistance to BCNU was closely related to the cross-linking activity of alkylating species. However, in pediatric gliomas the levels of cell kill after treatment with the purely carbamoylating agent BHCNU, even at the highest doses tested, were lower than expected.

A case of advanced intrahepatic cholangiocarcinomasuccessfully treated with chemosensitivity test-guidedsystemic chemotherapy

Intrahepatic cholangiocarcinoma (ICC) is a relatively rare and highly fatal neoplasm that arises from the biliary epithelium. Prognosis is generally poor and survival is limited to a few months. Here we present a case of advanced ICC successfully treated by chemosensitivity test-guided systemic chemotherapy combining S-1 and cisplatin (CDDP). A 65-year-old woman with a liver tumor was referred to our hospital on November 21, 2007. Abdominal ultrasonography and computed tomography (CT) showed low-density masses of 50 and 15 mm in diameter, respectively in segment VIII of the liver and in the enlarged lymph node in the para-aorta. Ultrasonography-guided fine needle biopsy diagnosed the tumors as ICC. Since the patient was inoperable for lymph node metastasis, she underwent systemic chemotherapy with gemcitabine. Six months after initiation of chemotherapy, CT revealed ICC progression in the liver and pleural dissemination with pleural effusion. The patient was admitted to our hospital for anticancer drug sensitivity testing on June 9, 2008. Based on the sensitivity test results, we elected to administer systemic chemotherapy combining S-1 and CDDP. Two months into the second chemotherapy treatment, CT revealed a reduction of the tumors in the liver and lymph node and a decrease in pleural effusion. After eight cycles of the second chemotherapy, 17 mo after ICC diagnosis, she is alive and well with no sign of recurrence. We conclude that chemosensitivity testing may effectively determine the appropriate chemotherapy regimen for advanced ICC.

Comparison of Forcep-biopsy and Cryo-biopsy by a Flexible Bronchoscopy

,Background: A forceps-biopsy is performed to acquire tissue from patients with an endobronchial carcinoma using a flexible bronchoscope. Recently, a cryo-biopsy has also been used to acquire tissue samples. Cryo-biopsy is the diagnostic application of extreme cold for the local destruction of abnormal living tissue. This technique is safe, with no radiation danger, no risk of electrical accidents, and a little risk of bleeding. This study compared a forceps-biopsy with a cryo-biopsy using a flexible bronchoscope, and examined the chemosensitivity and level of VEGF (vascular endothelial growth factor) in the specimens obtained from the cryo-biopsy. Methods: We present a prospective study of 30 consecutive patients who underwent a forceps-biopsy between January 2007 and October 2007 with a mean age of 62.1 years and a male:female ratio of 5 : 1. A flexible bronchoscope was inserted to the area of the abnormal lesions, and a cryo-probe was then applied through the working channel of the flexible bronchoscope. A temperature of approximately −80 was delivered to the tumor site for 8 seconds. The cryo-biopsy was performed after destroying the tumor mass. Results: The mean size of the tissue from the forceps-biopsy and cryo-biopsy were 2.0±1.2 mm and 6.0±3.0 mm. A chemosensitivity test was performed on 5 specimens obtained using cryo-biopsy and the level of VEGF was examined in 2 specimens obtained from a cryo-biopsy. There were no side effects in either group. Conclusion: Cryo-biopsy using a flexible bronchoscope is a safe and effective technique for acquiring tissue samples.

Chemosensitivity of Uterine Cervical Cancer Demonstrated by the Histoculture Drug Response Assay

Uterine cervical cancer is a leading cause of cancer-related death in the female population worldwide. In vitro chemosensitivity test is important to find effective drugs in uterine cervical cancer that requires the established chemotherapeutic strategies. The purpose of this study is to investigate the chemosensitivity of uterine cervical cancer using the histoculture drug response assay (HDRA). Sixty-five fresh tumor tissues were obtained from patients with cervical cancer: 47 squamous cell carcinomas, 11 adenocarcinomas, and 7 adenosquamous cell carcinomas. The median age was 44 years (range, 25-74 years), and the median follow-up duration was 26.3 months (range, 1.6-52.7 months). The clinical stage by the International Federation of Gynecologists and Obstetricians (FIGO) was stage I of 80.0% (52/65) and stage IIA of 13.8% (9/65). The inhibition rates of ten chemotherapeutic agents against these cancer tissues were tested using the HDRA method according to established methods. Five agents were evaluated as sensitive drugs in cervical cancer with inhibition rates of greater than 30%: 41.0% for carboplatin, 35.0% for cisplatin, 33.8% for paclitaxel, 41.4% for belotecan, and 49.2% for topotecan. Especially, carboplatin combined with paclitaxel showed an inhibition rate of 54.0%, which was higher than any other single agent. However, there were no noticeable differences in chemosensitivity according to histopathologic types and FIGO stage. Despite such limitation, the HDRA may be a promising chemosensitivity test to predict an effective drug for each patient. The HDRA could provide useful information that is invaluable for the design of individualized treatments in patients with cervical cancer.

Heterogeneity of Adenosine Triphosphate-Based Chemotherapy Response Assay in Colorectal Cancer - Secondary Publication

PurposeAdenosine triphosphate-based chemotherapy response assay (ATP-CRA) is a well-documented and validated technology that can individualize chemotherapy for patients with lung, stomach, or breast cancer. This study explored the feasibility of ATP-CRA as a chemosensitivity test in patients with colorectal cancer.Materials and MethodsA total of 118 patients who underwent surgical resection for colorectal adenocarcinoma were analyzed for chemosensitivity to 6 anticancer drugs using ATP-CRA. We calculated the cell death rate (CDR) by measuring intracellular ATP levels of drug-exposed cells and untreated controls.ResultsInterpretable results were available for 85.5% (118/138) of patients. The mean coefficient of variation for triplicate ATP measurements was 9.2%. The highest CDR was observed in irinotecan (34.0%) and the lowest CDR in etoposide (21.0%). Paclitaxel had the broadest range of CDR (0-86.7%) and 5-FU had the narrowest range of CDR (0-56.8%). The overall highest responsiveness was seen most prevalently in irinotecan (24.7%, 23/93 patients). Irinotecan had the greatest responsiveness in patients with well differentiated and moderately differentiated carcinoma.ConclusionOur study suggests that ATP-CRA could be used to identify patients with colorectal cancer who might benefit from treatment with a specific chemotherapeutic agent.

Cytotoxicity of unsaturated fatty acids in fresh human tumor explants: concentration thresholds and implications for clinical efficacy

BackgroundUnsaturated fatty acids (UFAs) exhibit in vitro cytotoxicity against many malignant cell lines and yield decreased cancer incidence and reduced tumor growth in animal models. But clinical and animal studies to date have achieved response using only localized delivery methods such as intratumoral infusion. To explore possibilities for enhanced clinical efficacy, fresh surgical explants of tumors from 22 patients with five malignancies were exposed to γ-linolenic acid (GLA) and α-linolenic acid (ALA) and analyzed with an in vitro chemosensitivity testing system, the Fluorescent Cytoprint Assay (FCA). A total of 282 micro-organ cultures derived from these malignant tumors were exposed to GLA and ALA at different concentrations.ResultsGLA and ALA exhibited greater than 90% cytotoxicity at a sharp concentration threshold between 500 μM and 1 mM against all but two malignant micro-organ cultures tested in 5-10% serum. In tests using 30-40% serum, GLA and ALA killed tumor at concentrations of 2 mM and above.ConclusionsThe concentration threshold of 500 μM to 2 mM exhibited for antitumor activity by GLA and ALA is much higher than that observed in most previously reported cell culture studies but consistent with physiological concentrations found to kill tumor clinically and in animals. A mechanism of antitumor activity by unsaturated fatty acids through selective destabilization of the malignant plasma membrane is considered. An oral regimen is proposed for phase I clinical testing that could push the area under the curve for serum concentration of unbound unsaturated fatty acids over time to much higher levels than previously achieved for systemic administration and into the range that could yield antitumor response.

A Case of Genital Paget Carcinoma Treated with a Chemosensitivity Test Positive Agent

A Case of Genital Paget Carcinoma Treated with a Chemosensitivity Test Positive Agent

In vitro chemosensitivity testing of primary and recurrent breast carcinomas and its clinical significance

In this study, in vitro chemosensitivity testing was conducted on primary cultured breast cancer cells from 96 patients with breast cancer, and the results showed that the cells from a few patients with primary breast cancer developed multidrug resistance (MDR) prior to the first chemotherapy exposure. All the cells from the recurrent cancer patients had MDR. The findings suggested that patients having MDR would benefit from high-dose chemotherapy (HDC) regimens. In vitro chemosensitivity screening, which was aimed at improving the therapeutic efficacy and minimizing side effects, helps in choosing individualized treatment for breast cancer.

Efficacy of Weekly Docetaxel and Bevacizumab in Mesenchymal Chondrosarcoma: A New Theranostic Method Combining Xenografted Biopsies with a Mathematical Model

The paucity of clinical treatment data on rare tumors, such as mesenchymal chondrosarcoma (MCS), emphasizes the need in theranostic tools for these diseases. We put forward and validated a new theranostic method, combining tumor xenografts and mathematical models, and used it to suggest an improved treatment schedule for a particular MCS patient. Growth curves and gene expression analysis of xenografts, derived from a patient's lung metastasis, served for creating a mathematical model of MCS progression and adapting it to the xenograft setting. The pharmacokinetics and pharmacodynamics of six drugs were modeled, with model variables being adjusted by patient-specific chemosensitivity tests. The xenografted animals were treated by various monotherapy and combination schedules, and the MCS xenograft model was computer simulated under the same treatment scenario. The mathematical model for xenograft growth was then up-scaled to retrieve the MCS patient's tumor progression under different treatment schedules. An average accuracy of 87.1% was obtained when comparing model predictions with the observed tumor growth inhibition in the xenografted animals. Simulation results suggested that a regimen containing bevacizumab applied i.v. in combination with once-weekly docetaxel would be more efficacious in the MCS patient than all other simulated schedules. Weekly docetaxel in the patient resulted in stable metastatic disease and relief of pancytopenia due to tumor infiltration. We suggest that the advantage of weekly docetaxel on the triweekly regimen is directly related to the angiogenesis rate of the tumor. Further validation of this conclusion, and the theranostic method we provide, may facilitate personalization of solid cancer pharmacotherapy.

A New Chemosensitivity Test Using a Thermo-Reversible Gelation Polymer for Recurrent Gynecologic Cancer Patients and a Preliminary Study of Mechanisms of Anticancer Drug Resistance

TGP (thermo-reversible gelation polymer) is a high molecular compound that has so-gel transmitting temperature of 221C Since solid cancer tissue grows in this polymer three-dimensionally, and fibroblasts scarcely grow in it, TGP is suitable for chemosensitivity assays for solid tumors. In this study, a chemosensitivity test using TGP was applied to recurrent gynecologic cancer patients in order to evaluate its utility and efficacy. In some ovarian cancer cases, expression of anticancer drug resistance-related proteins was also analyzed. Recurrent tumor tissues were surgically obtained with informed consent. After these tissues were minced and incubated for 4 days with CDDP, mitomycin C, 5-fluorouracil, paclitaxel, and CPT-11, the sensitivity against these drugs was estimated. Western blotting was performed in 8 recurrent ovarian cancer tissues in order to analyze the expression of Bcl-2, MRP2, BCRP, and GST-pi. The total evaluability rate of this assay was 90.6% (29/32). Sensitive drugs could be determined in 5 of 7 ascites samples (71.4%) and in 2 of 3 intra-tumoral fluid samples (66.7%). The overall clinical response rate of chemotherapy determined by these results was 50.0%. There were significant correlations between the IC50 of CDDP and Bcl-2, BCRP, GST-pi, and between that of 5-FU and MRP 2. Although this was a preliminary study, the chemosensitivity test using this new material appears to be useful for designing 'made-to order' salvage chemotherapy for pretreated recurrent gynecologic patients. In order to overcome multidrug resistance, the mechanisms of multidrug resistance should be further investigated.

Ex vivo chemosensitivity testing and gene expression profiling predict response towards adjuvant gemcitabine treatment in pancreatic cancer

Efficacy of chemotherapy for pancreatic cancer may be improved by tailoring it to individual chemosensitivity profiles. Identification of nonresponders before initiation of treatment may help to avoid side effects. In this study, primary pancreatic cancer cells were isolated from 18 patients undergoing pancreaticoduodenectomy for pancreatic cancer. Eight commonly used pancreatic cancer cell lines were used as controls. Ex vivo chemosensitivity for gemcitabine, 5-fluorouracil, mitomycin-C, cisplatinum, oxaliplatinum, paclitaxel and a combination of gemcitabine with oxaliplatinum or mitomycin-C was determined using a cellular ATP-based tumour chemosensitivity assay (ATP-TCA). Quantitative real-time–polymerase chain reaction was performed to determine RNA expression levels of genes implicated in chemoresistance. Chemosensitivity towards cytotoxic agents was highly variable in primary pancreatic cancer cells and pancreatic cancer cell lines. ATP-TCA results for gemcitabine correlated to the tissue expression of human equilibrative nucleoside transporter-1 (hENT1). Time to relapse in patients with gemcitabine-sensitive tumours was significantly higher than in patients with chemoresistant pancreatic cancers (P=0.01; 71 vs 269 days). Furthermore, time to relapse in gemcitabine-treated patients was related to hENT1 expression (P=0.0067). Thus, chemosensitivity testing using ATP-TCA in pancreatic cancer is feasible and correlated with time to relapse in gemcitabine-treated patients. This suggests that ATP-TCA testing could be used as a decision-making tool in the adjuvant treatment of pancreatic cancer.

Genomic and proteomic characterization of YDOV-157, a newly established human epithelial ovarian cancer cell line

The existence of several model systems with which to investigate a particular disease is advantageous for researchers. This is especially true for ovarian cancer, which, due to its complex and heterogeneous nature, inherently requires a large number of model systems. Here, we report a new ovarian serous adenocarcinoma cell line, designated YDOV-157, and characterized via post genomics and post proteomics. In this study, primary culture of tumor cells from ascites was performed and the cells were immortalized up to at least 60 passages in vitro. We studied the morphologies, cell proliferation, BRCA1/2 mutations, tumorigenesis capacity, and chemosensitivity of YDOV-157. Using a cDNA microarray, differentially expressed genes were identified and some of them were validated. Using proteomic analysis, we identified proteins that were differentially expressed in YDOV-157. The newly derived cell line, designated YDOV-157, grew as a monolayer and the doubling time was 102 h. When transplanted into nude mice, it initiated the formation of tumor masses with microscopic findings identical to those of the primary tumor. Chemosensitivity test showed that paclitaxel induced the highest chemosensitivity index. In microarray analysis, 2,520 probes were differently expressed, compared to human ovarian surface epithelial cells (HOSEs). In SYBR Green real-time PCR, the expression of E2F2 (P = 0.040) and CRABP2 genes (P = 0.030) was significantly higher in the ovarian cancer cell lines than in HOSEs. Furthermore, proteomic analysis showed that expression of 28 spots was significantly altered between YDOV-157 and HOSE. In conclusion, the newly derived YDOV-157 cell line may be an important research resource for studying cancer cell biology and should also be very useful for developing new strategies that inhibit cancer cell growth and progression.

Expression of melatonin receptor (MT1) and interaction between melatonin and estrogen in endometrial cancer cell line

To determine the receptor subtypes of melatonin in estrogen receptor-positive endometrial cancer cell line, Ishikawa, and the influence of melatonin on chemosensitivity. To confirm the subtype of melatonin on Ishikawa cells, cells were treated with melatonin alone and with antagonists against melatonin receptor luzindole and 4-phenyl-2-propionamidotetralin (4-P-PDOT). Expression of MT1/MT2 mRNA was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). Immunocytochemistry of MT1/MT2 was also performed. The effect of melatonin against expression of MT1, MT2, and ERalpha-receptors mRNA was compared with RT-PCR. To determine whether melatonin enhances the effect of anticancer agents, chemosensitivity test was performed with or without melatonin. Our study revealed that Ishikawa cells express MT1 by both RT-PCR and immunocytochemistry. In contrast, expression of MT2 mRNA was not found. Furthermore, ERalpha mRNA expression was attenuated at melatonin level of 1 x 10(-9) M. Chemosensitivity test revealed that melatonin enhanced anti-tumor effects of paclitaxel among anticancer drugs tested. Based on the above results, MT1 receptor, but not MT2, is expressed in Ishikawa cells. It was also revealed that the cytostatic effect of melatonin is partly an action mediated by MT1 receptor, and attenuation of ERalpha expression was predicted as the mechanism of action. Clinical application of melatonin to biochemotherapy might be also expected.

Correlation between chemosensitivity testing and expression of P-gp,LRP in esophageal carcinoma cell cultured in vitro

Objective To study the correlation between chemotherapy drug sensitivity and the expression of P-glycoprotein protein(P-gp),lung resistant-related protein(LRP)in different esophageal carcinoma patients,which will offer experimental evidence for clinical individualized chemotherapy of esophageal carcinoma patients.Methods Selected fresh esophageal carcinoma's tissue,Common used drugs and chemoscheme for esophageal carcinoma were used for chemosensitivity testing of the primary cultured tumor cells.At the same time,immunohistochemistry method was used to detect the expression of P-gp and LRP of esophageal carcinoma cells.Results The chemotherapy drug sensitivity of single drug was different(P＜0.05).The combination of Tax and DDP had the best effect.DDP and NVB combination had a better effect than DDP and 5-FU combination.The sensitivity of DDP had no significant correlations with expression intensity of P-gp(P＞0.05),and it had significant correlation with expression intensity of LRP(P＜0.05).There were significant correlations between sensitivity of both NVB group and Tax group and expression intensity of P-gp and LRP(P＜0.05).There was no significant correlations between sensitivity of 5-FU and expression intensity of P-gp and LRP(P＞0.05).Conclusion The esophageal carcinoma chemosensitivity in vitro can indicate the sensitive drug of different patients,and guide individualized chemotherapy.The expression of P-gp and LRP has relationship with several chemotherapy drugs,which can provide base for individualized chemotherapy in clinic. Key words: Esophageal neoplasms; Tumor cells,cultured; Antineoplastic agent; P-glyeoprotein; Lung resistant-related protein

Establishing the method of collagen-gel droplet embedded culture drug sensitivity test with rat tail collagen

To explore the clinical application of collagen-gel droplet embedded-culture drug sensitivity test (CD-DST) in the malignant tumors. CD-DST was established with rat tail collagen. Three pancreatic cancer cell lines, surgical resection specimens including 15 cases of pancreatic cancer and 10 cases of gastrointestinal cancer were examined using CD-DST. The overall achievement ratio of CD-DST for clinical tumor specimens was 80% (20/25). In vitro chemosensitivities of pancreatic carcinoma cells to 5-FU, gemcitabine and oxaliplatin were lower than those of gastrointestinal carcinoma. CD-DST with rat tail collagen is a valuable chemosensitivity testing method for malignant tumors. It can be used to realize individualized anticancer chemotherapy.

Primary cell cultures from anaplastic thyroid cancer obtained by fine‐needle aspiration used for chemosensitivity tests

Anaplastic thyroid cancer (ATC) is often inoperable and chemotherapy and radiotherapy are the main treatments. Until now, 'primary ATC cell cultures' (ANA) have been developed from surgical biopsies. We investigated the possibility of obtaining ANA from fine-needle aspiration (FNA-ANA) and testing their sensitivity to chemotherapeutic agents, which could enable treatments to be more effective and avoid unnecessary surgical procedures. The aim of this study was to obtain FNA-ANA from three ATC patients and to evaluate the chemosensitivity of FNA-ANA to chemotherapeutic agents. FNA-ANA from ATC patients were cultured in RPMI 1640 and propagated in Dulbecco's modified Eagle's medium (DMEM). Chemosensitivity was evaluated by inhibiting the proliferation (analysing the number of viable cells by the cleavage of tetrazolium salts), by increasing the concentration of four different chemotherapeutic agents: bleomycin, cisplatin, gemcitabine and etoposide. The chemotherapeutic agents significantly inhibited (> 50%) FNA-ANA proliferation. Another ANA for each patient was obtained from a surgical biopsy specimen; the results for the chemosensitivity tests were similar to those obtained using FNA-ANA. Our study demonstrates the possibility of obtaining FNA-ANA, and opens the way to the use of FNA-ANA as a means of testing the chemosensitivity to different chemotherapeutic agents (and possibly the radiosensitivity) in each patient, avoiding unnecessary surgical procedures and the administration of inactive chemotherapeutics.

Evaluation of the sensitivity to chemotherapeutics or thiazolidinediones of primary anaplastic thyroid cancer cells obtained by fine-needle aspiration

Anaplastic thyroid cancer (ATC) is often unoperable and chemotherapy and radiotherapy are the main treatments. Until now 'primary ATC cell cultures' (ANA) have been developed from surgical biopsies. The possibility to obtain ANA from fine-needle aspiration (FNA-ANA) and to test their sensitivity to different drugs could increase the effectiveness of treatments and avoid unnecessary surgical procedures. To obtain FNA-ANA from six ATC patients before undergoing surgery and to evaluate the chemosensitivity of FNA-ANA to chemotherapeutic agents and thiazolidinediones (TZD). FNA-ANA from the six ATC patients were cultured in RPMI 1640 and propagated in DMEM. Chemosensitivity was evaluated by inhibiting the proliferation with increasing concentrations of five different chemotherapeutic agents (bleomycin, cisplatin, gemcitabine, etoposide, and carboplatin) or TZD (rosiglitazone). Chemotherapeutic agents significantly inhibited (P<0.0001) FNA-ANA proliferation, such as TZD (P<0.001); etoposide was the most effective in reducing cell growth. Another ANA culture for each patient was obtained from a biopsy specimen; the results for the chemosensitivity tests were similar to those obtained with FNA-ANA. The (V600E)BRAF mutation was observed in two ATC patients; the inhibition of proliferation by drugs was similar in tumors with or without (V600E)BRAF mutation. Our study demonstrates 1) the possibility to obtain FNA-ANA, and opens the way to the use of FNA-ANA to test the chemosensitivity to different drugs (chemotherapeutic agents or TZD; and possibly the radiosensitivity) in each patient, avoiding unnecessary surgical procedures and the administration of inactive chemotherapeutics; and 2) that etoposide is highly effective in reducing ATC cell growth in vitro.

Collagen gel droplet embedded culture-drug sensitivity test of primary tumor cells and its application

With the posing of individualized chemotherapy, chemosensitivity test has attracted more and more attention. As a new developing in-vitro chemosensitivity test system in the past ten years, collagen gel droplet embedded culture-drug sensitivity test can simulate the in-vivo microenvironment of cell growth and anti-tumor drug's effect. Moreover, its results have significant correlation with clinical response. It has already shown applicable value in clinical and preclinical study of lung cancer, breast cancer, gastrointestinal cancer and other cancers. Key words: Neoplasms; Drug screening assays, antitumor; Cell culture techniques; Collagen

Early Metabolic Response Evaluation by Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography Allows In vivo Testing of Chemosensitivity in Gastric Cancer: Long-term Results of a Prospective Study

We prospectively evaluated the predictive value of positron emission tomography using fluorine-18 fluorodeoxyglucose (FDG-PET) for in vivo testing of chemosensitivity in locally advanced gastric cancer using an a priori definition of metabolic response (a decrease of >35% of the standard uptake value). The goal of the study was the definition of biologically different groups of patients prior to or early during induction therapy, with special emphasis on FDG non-avid tumors. Based on our data, which was published in 2003, at least 36 patients with metabolic response or FDG non-avid tumors had to be recruited for an analysis of the group of FDG non-avid tumors with sufficient statistical power. Seventy-one patients (32 metabolic nonresponders, 17 metabolic responders, and 22 patients with FDG non-avid tumors) underwent FDG-PET at baseline. In FDG-avid tumors, FDG-PET was repeated 14 days after the initiation of chemotherapy. Metabolic responders (17 of 49) showed a high histopathologic response rate (69%) and a favorable prognosis (median survival not reached), whereas metabolic nonresponders (32 of 49) had a poor prognosis (median survival, 24.1 months) and showed a histopathologic response in 17%. The histopathologic response rate (24%) for FDG-PET non-avid patients showed no significant difference compared with FDG-avid nonresponders (P=0.72). Survival of FDG non-avid patients was 36.7 months (not significantly different from FDG-avid nonresponders, 24.1 months, P=0.46). In locally advanced gastric cancer, three different metabolic groups exist. Response and survival was predicted by PET in FDG-avid tumors. Metabolic response assessment was not possible in FDG non-avid tumors; however, due to unfavorable outcome, therapy modification might also be considered in FDG non-avid tumors.

Small cell carcinoma of the ovary: clinical and biological study

Ovarian small cell carcinoma of hypercalcemic type is a rare neoplasm that typically occurs in young females. We describe three cases of ovarian small cell carcinoma of hypercalcemic type occurring in patients aged 24, 37, and 25 years. The first patient had stage IIc disease and had primary surgery with a left salpingo-oophorectomy and omentectomy, followed by chemotherapy with cisplatin and etoposide. Upon a second relapse, pelvic lymphadenectomy was performed, followed by chemotherapy with docetaxel. She is alive for 4 years without any recurrence after the initial treatment. In vitro drug-sensitivity assay revealed the tumor cells were sensitive to taxane and resistant to irinotecan. The second patient had stage III disease and had primary debulking surgery with bilateral salpingo-oophorectomy, simple hysterectomy, omentectomy, low-anterior resection, and lymphadenectomy, followed by chemotherapy with paclitaxel and carboplatin. Four months after the initial treatment she relapsed and died. The tumor cells were sensitive to platinum, taxane, and doxorubicin, but resistant to irinotecan. The third patient had stage III disease and had right salpingo-oophorectomy, omentectomy, and lymphadenectomy, followed by chemotherapy with cisplatin, cyclophosphamide, and doxorubicin. She relapsed 4 months after completing the chemotherapy and died 5 months after secondary debulking surgery. The tumor cells were sensitive to platinum, taxane, and doxorubicin, but resistant to irinotecan. The drug-sensitivity assays suggested that a non-irinotecan, taxane-containing combination might have been suitable as first-line chemotherapy for these patients. However, an effect of such a regimen was seen in only one patient with early-stage disease, and this questions the validity of chemosensitivity testing.