Tumor Shrinkage Rate Research Articles

Correlation between response to chemotherapy with concomitant bevacizumab for hepatic metastasis of colorectal cancer and degree of enhancement using contrast-enhanced computed tomography

The imaging factor predicting the response to bevacizumab (BV) as concomitant chemotherapy has yet to be determined. This study examined correlation between response to chemotherapy with concomitant BV for hepatic metastasis of colorectal cancer and degree of contrast enhancement (CE) using contrast-enhanced computed tomography (CT). Data were analyzed retrospectively for 35 patients treated with oxaliplatin-based chemotherapy as the first-line chemotherapy. Patient data were divided according to treatment with concomitant BV (BV group: n = 20, non-BV group: n = 15). Using an image control system, the degree of CE was evaluated by the ratio of the contrast-enhanced CT value of hepatic metastatic lesions to plain CT value, whereby patients were classified into the high-CE and low-CE group. After completion of chemotherapy treatment, the degree of enhancement of hepatic metastasis in the BV group was significantly lower than that in the non-BV group (p = 0.03). In the BV group, a significant correlation between higher contrast enhancement and higher tumor shrinkage rate was observed (R² = 0.25, p = 0.03), whereas no such correlation was noted in the non-BV group. In the high-CE group (n = 18), the tumor shrinkage rate increased to 29.6 % in the BV group compared with -1.46 % in the non-BV group (p = 0.03), whereas in the low-CE group, no significant difference was noted between patients in the two groups. Pretreatment evaluation of the degree of CE correlated with the response to concomitant chemotherapy with BV.

1439 A PROSPECTIVE STUDY TO EXAMINE THE AVAILABILITY OF THE PREDICTION SYSTEM OF NEOADJUVANT CHEMOTHERAPY FOR MUSCLE INVASIVE BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Invasive (I)1 Apr 20131439 A PROSPECTIVE STUDY TO EXAMINE THE AVAILABILITY OF THE PREDICTION SYSTEM OF NEOADJUVANT CHEMOTHERAPY FOR MUSCLE INVASIVE BLADDER CANCER Yoichiro Kato, Hitoshi Zembutsu, Ryo Takata, Kazuhiro Iwasaki, Wataru Obara, Yusuke Nakamura, and Tomoaki Fujioka Yoichiro KatoYoichiro Kato Morioka, Japan More articles by this author , Hitoshi ZembutsuHitoshi Zembutsu Sapporo, Japan More articles by this author , Ryo TakataRyo Takata Morioka, Japan More articles by this author , Kazuhiro IwasakiKazuhiro Iwasaki Morioka, Japan More articles by this author , Wataru ObaraWataru Obara Morioka, Japan More articles by this author , Yusuke NakamuraYusuke Nakamura Chicago, IL More articles by this author , and Tomoaki FujiokaTomoaki Fujioka Morioka, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2793AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We had previously established prediction system using microarray analyses for methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC), and carboplatin and gemcitabine (CaG) neoadjuvant chemotherapy for invasive bladder cancer. The accuracies of the M-VAC/CaG prediction systems were 90.5% (19/21) /94.7% (18/19), respectively. The efficacies of the M-VAC/CaG therapy also were 59.0% (23/39) /54.1% (20/37). Moreover, when we applied one prediction system as well as the other system for each other, we expected that 82.9% (63/76) would achieve tumor shrinking (>60%) by selection of either the M-VAC or CaG regimens. (Takata et al, Clin Cancer Res, 2005, Kato et al, Exp and Ther Med, 2011). Based on these results, we conducted the prospective study to confirm the accuracies of the two prediction systems. We also investigated whether use of prediction systems which were combined with M-VAC and CaG would increase the efficacy compare to each previous result. METHODS Twenty two patients were enrolled in this prospective study from Feb, 2011 to October, 2012. When we used the prediction systems which were consisted of M-VAC 14 and CaG 12 ‘predictive' gene sets, the prediction scores of M-VAC and CaG were calculated using real time PCR analysis within two weeks from tumor biopsy. Based on the results of the prediction scores, each patient was allocated to receiving M-VAC, CaG, Surgery or Radiation therapy. According to their responses to the neoadjuvant chemotherapy, we categorized the patients into two groups: ‘responders' who achieved significant tumor shrinking (>60%), and ‘non-responders' (≤60%) after two cycles. Patients were evaluated either ‘accurate' or ‘inaccurate' according to a tumor shrinkage rate cut off line of a 60% decrease after chemotherapies. RESULTS 6 patients were allocated to M-VAC, 13 to CaG, 2 to surgery and one to radiation based on the results of the prediction scores. The accuracies of M-VAC was 100% (6/6) and CaG was 76.9% (10/13). There was no significant difference between the total accuracy of prospective and previous results (84.2% vs. 92.5%, p = 0.325). The predicted responder were 72.7% (16/22) in this prospective study, it was larger than that of previous responded patients 59.0% in M-VAC and 54.1% in CaG. There was no significant differences compare to our previous expectation (82.9%; p=0.288). CONCLUSIONS The results of this prospective study were not inferior to the previous one. These prediction systems could be available to clinical use. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e589-e590 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yoichiro Kato Morioka, Japan More articles by this author Hitoshi Zembutsu Sapporo, Japan More articles by this author Ryo Takata Morioka, Japan More articles by this author Kazuhiro Iwasaki Morioka, Japan More articles by this author Wataru Obara Morioka, Japan More articles by this author Yusuke Nakamura Chicago, IL More articles by this author Tomoaki Fujioka Morioka, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Determining timing of hepatectomy for colorectal cancer with distant metastasis according to imaging-based tumor shrinkage ratio.

Background: The optimal timing of surgical resection of liver metastasis remains controversial, and guidelines regarding the upper limits of operative indications have not yet been defined. Surgical indication for metastasis from colorectal cancer (CLM) based on results of preoperative chemotherapy and RNF8 was investigated. Methods: Differences in CLM size on CT were evaluated as shrinkage rate/day by dividing tumor shrinkage rates by the interval in days between CT. Levels of RNF8 of resected colorectal cancer and CLM frozen specimen were detected. Results: When the cut line for shrinkage rate at 12 weeks was set at 0.35%, disease-free survival was significantly better in patients with a shrinkage rate >0.35% vs. ≤0.35% (p=0.003). RNF8 expression was significantly higher in Tis (p=0.001). In liver metastasis, RNF8 expression level was significantly lower in patients with partial response to FOLFOX than with stable disease, (p=0.017). Conclusions: A strategy of FOLFOX administration for 12 weeks to patients with low RNF8 expression and hepatectomy planned after 4 weeks rest may be accepted as the best therapeutic option for treating CLM.

Distinct spontaneous shrinkage of a sporadic vestibular schwannoma

We present a case with outspoken spontaneous vestibular schwannoma shrinkage and review the related literature. The patient was initially diagnosed with a left-sided, intrameatal vestibular schwannoma, which subsequently grew into the cerebello-pontine angle (CPA), followed by total shrinkage of the CPA component without any intervention over a 12-year observation period. The literature on spontaneous tumor shrinkage was retrieved by searching the subject terms "vestibular schwannoma, conservative management" in PubMed/MEDLINE database, without a time limit. Of the published data, the articles on "shrinkage" or "negative growth" or "regression" or "involution" of the tumor were selected, and the contents on the rate, extent and mechanism of spontaneous tumor shrinkage were extracted and reviewed. The reported rate of spontaneous shrinkage of vestibular schwannoma is 5-10% of patients managed conservatively. Extreme shrinkage of the tumor may occur spontaneously.

EGFR status and daily dose: Effect on tumor growth inhibition in cancer patients treated with dacomitinib (PF-00299804).

e18093 Background: Dacomitinib (D) is a highly selective, irreversible small molecule pan-human epidermal growth factor (EGFR/HER) inhibitor. The effect of mean D daily dose (exposure) on tumor growth dynamics was analyzed using a longitudinal exposure-response tumor growth inhibition model. Methods: Estimated parameters included tumor shrinkage rate (KD), which changes over time as resistance to therapy develops according to an exponential decay function where λ = slope of the dynamic shrinkage rate change; and tumor growth rate constant (KL). eDose, the effect of mean D daily dose changes on tumor shrinkage rate, was tested in the base model to establish the best relationship between tumor shrinkage and drug exposure. Model parameters were estimated using a population (pop) approach. Pop pharmacodynamic analyses included data from 4 clinical trials (3 phase I and 1 phase II) of D (15–45 mg QD) in patients (pts) with advanced solid tumors. Multiple tumor size (SLD) measurements were collected from each pt. Data analysis used nonlinear mixed effects modeling (NONMEM, v 7.1.2). After visual inspection of relationships between covariates (weight, age, creatinine clearance, bilirubin, ALT, baseline ECOG PS, race, sex, EGFR status) and individual parameter estimates of KD; subpopulation analysis was carried out in pts with confirmed EGFR status (mutation [mu] or wild type [WT]) to quantify the potential effect of EGFR status on KD. Results: SLD values over time were collected from 200 pts (47% male). For a typical pt, KL = 0.63 year-1; KD = 1.6 year-1; developed therapy resistance over time (λ) = 13.7 year-1; and eDose = 0.45. Drug-specific parameters affecting tumor shrinkage (KD, λ, eDose) and the disease-specific KL were well estimated with low relative standard errors. Visual inspection of relationships between covariates and individual parameter estimates showed a higher shrinkage rate (KD) for pts with EGFR mu vs those with WT EGFR. Conclusions: D mean daily dose affected tumor growth dynamics. Tumor shrinkage rate at an averaged daily dose below 45 mg QD was lower vs 45 mg QD. EGFR status was a significant covariate affecting tumor shrinkage rate (83% less shrinkage in pts with EGFR WT vs. pts with EGFR mut).

Homeobox B9: A potential surrogate marker for bevacizumab in combination with chemotherapy in colorectal cancer.

10531 Background: Homeobox B9 (HOXB9) is known to be overexpressed in human breast cancer and profoundly related to tumorigenicity, lung metastasis and radio-resistance. (Hayashida, PNAS 2010, and Chiba, PNAS 2011). However, little is known about the relation between the expression of HOXB9 and angiogenesis in colorectal cancer (CRC). We aimed to clarify the impact of HOXB9 in CRC and evaluate the importance for bevacizumab treatment. Methods: The expression of HOXB9 in human CRC specimens was analyzed. Then, we introduced HOXB9 construct into human CRC cell lines and examined TGFβ signaling and angiogenic factors. Xenograft model was established by these cell lines either with or without the administration of bevacizumab (5mg/kg, weekly) intraperitoneally. Finally, we examined the mRNA levels of consecutive patients who were treated by chemotherapy with bevacizumab in our institute and calculated the Kaplan- Meier curve with log-rank test. Results: 47 of 69 surgical specimens (67%) showed positive expression of HOXB9 mRNA. The high HOXB9 mRNA levels significantly correlated with poor differentiation and liver metastasis. The HOXB9-overexpressed cell lines showed significantly higher expression of TGFβ signaling target genes and angiogenic factors. HOXB9 overexpression significantly increased tumor volume and burden with higher microvessel density in vivo, even though the cell proliferation decreased in vitro. Notably, HOXB9-overexpressed tumor was dramatically shrunk by administration of bevacizumab (tumor shrinkage rate; 93% vs. 42% in HT29, 83% vs. 27% in HCT116). Patients with high expression of HOXB9 in tumor showed significantly longer progression free and overall survival periods (n=39). Conclusions: Our results demonstrated that patients with high expression of HOXB9 in tumor had better prognosis with bevacizumab treatment but worse without. In vivo and in vitro experiments revealed that HOXB9 might orchestrate angiogenesis and establish positive feedback between cancer cells and microenvironment. Bevacizumab might inhibit the feedback to reduce tumor growth dramatically. Therefore, HOXB9 may work as a potential surrogate marker of bevacizumab treatment in CRC.

Gamma Knife Radiosurgery for Benign Cavernous Sinus Tumors: Treatment Concept and Outcomes in 120 Cases

Availability of modern computer-aided robotized devices, such as the Automatic Positioning System (APSTM; Elekta Instruments AB, Stockholm, Sweden) and PerfexionTM (Elekta Instruments AB), allowed us to develop the original concept of robotic gamma knife microradiosurgery, which is based on the very precise irradiation of the lesion with regard to conformity and selectivity; intentional avoidance of the excessive irradiation of functionally-important anatomical structures, particularly cranial nerves, located both within and in the vicinity of the target; and delivery of sufficient irradiation energy to the tumor with the intention to attain lesion shrinkage, while keeping the marginal dose sufficiently low for prevention of possible complications. The results of such treatment strategy were evaluated retrospectively in 120 patients with benign cavernous sinus neoplasms (pituitary adenomas, meningiomas, schwannomas, and hemangiomas), who were followed up from 24 to 78 months (mean 47 months) after radiosurgery. Tumor growth control and shrinkage rates were 98% and 68%, respectively. More than 50% volume reduction was noted in 25% of lesions. The most prominent volumetric tumor response was observed in hemangiomas, followed by schwannomas, pituitary adenomas, and meningiomas. Treatment-related complications were marked in 7% of cases, and were mainly related to transient isolated cranial neuropathy appearing within several months after radiosurgery. Major morbidity was limited to one patient (0.8%). Application of microradiosurgical treatment principles provides effective and safe management of benign cavernous sinus tumors and is associated with high probability of lesion shrinkage and minimal risk of complications.

Predictive value of contrast enhancement on computed tomography for the responses to oxaliplatin-based chemotherapy with bevacizumab for hepatic metastases from colorectal cancer.

e14105 Background: The addition of bevacizumab (Bev) to chemotherapy is associated with improved survival by anti-angiogenic mechanism in colorectal cancer (CRC). Therefore, the antitumor effect of Bev may correlate with the degree of the contrast-enhancement (CE) of targets reflecting tumor microvessels on the computed tomography (CT). The purpose of this study was to determine whether responses to chemotherapy with bevacizumab correlated with the degree of CE of hepatic metastatic lesions of colorectal cancer (CRC). Methods: Thirty one patients with hepatic metastases from CRC who underwent at least three course of mFOLFOX6 or XELOX therapy as the first-line chemotherapy between September 2006 and April 2010 were analyzed retrospectively. The patients were divided into two groups with or without Bev (17 in the Bev group and 14 in the non-Bev group). CT scans were performed during the late arterial phase following intravenous injection with a nonionic contrast medium at a dose of 600 mgI/kg, using a multi detector CT. Using an imaging control system, the diameter and mean CT values of metastatic lesions before chemotherapy were determined in each patient. The degree of CE was evaluated by the ratio of the CT value of hepatic metastases in the late arterial phase by in the noncontrast phase (i.e., CE ratio), whereby the patients were divided into the high or low CE group by the median CE ratio. Results: There was significant correlation between the CE ratio and the tumor shrinkage rate in the Bev group (R2 =0.3817, p=0.0082), whereas no such relationship was noted in the non-Bev group. In the high CE group (n=16), the tumor shrinkage rate increased to 35.9% in the Bev group from 8.6% in the non-Bev group (p=0.0716). In the low CE group, however, no significant difference was noted. Conclusions: The present study demonstrated the correlation between the CE ration and the tumor shrinkage in patients treated with Bev. The results suggest that the CE ratio on CT scanning in hepatic metastatic lesion can be a predictive value for the response to chemotherapy with Bev, although generalization of the CE ratio and the prospective study should be need.

Clinical observation of (125)I-labeled anti-alpha fetoprotein antibody radioimmunotherapy in hepatocellular carcinoma.

To observe the therapeutic effects and toxic side effects of (125)I labeled horse anti-human alpha fetoprotein (AFP) polyclonal antibodies in immune targeted therapy against hepatocellular carcinoma (HCC). A modified chloramine-T method to produce nuclide (125)I labeled horse anti-human AFP polyclonal antibodies was used to treat 22 cases of HCC. Drugs were administered by intravenous drip. The median dose of (125)I in the whole group was 289.3 (100.3-708.9) MBq. In this series of 22 cases, 19 were evaluated. HCC cases of the same period treated by (131)I anti AFP (A group), anti-cancer drugs and anti AFP conjugates (B group) and chemotherapy alone (C group) were used as controls. The effective rate (CR + PR) was 31.6%, tumor shrinkage rate was 63.2% (12/19), AFP descending rate 64.7% (11/17) and 6 cases became AFP negative. The post treatment 1 year survival rate was 47.1% (8/17). Seven cases are still alive. Five cases survived 14.33 mo, showing good therapeutic tolerance and minimal toxic side effects. The therapeutic effect in the treatment group was significantly better than that of the control groups. This may be due to the effect of the continuous radiation of the long half life (125)I within the tumor cells.

Gamma Knife Robotic Microradiosurgery for Benign Skull Base Meningiomas: Tumor Shrinkage May Depend on the Amount of Radiation Energy Delivered per Lesion Volume (Unit Energy)

Background/Aims: The objective of the present study was the evaluation of the effectiveness of robotic microradiosurgery of skull base meningiomas using Leksell Gamma Knife model C with an automatic positioning system. Methods: The results of the management of 66 tumors were analyzed retrospectively. Their volume varied from 0.3 to 50.6 cm³ (mean = 6.6). The treatment plan was based on the use of multiple small isocenters compactly positioned within the border of the lesion with resultant improved homogeneity of high-dose distribution, increased average dose within the target and sharp dose fall outside the treated volume. The marginal dose varied from 10 to 14 Gy (mean = 12). The length of follow-up ranged from 26 to 80 months (mean = 46). Results: The overall tumor growth control was 99%. Reduction of the mass volume was marked in 54 patients (82%), and in 15 of them it constituted ≧50%. In other 11 cases (17%) stabilization of the lesion growth was noted. The shrinkage rate significantly correlated with amount of radiation energy delivered per tumor volume, designated as unit energy (p = 0.007). One meningioma (1%) regrew 3.5 years after radiosurgery. The treatment-related morbidity was limited to transient abducens nerve palsy in 1 patient (1%). Conclusion: Application of the concept of Gamma Knife robotic microradiosurgery for the management of skull base meningiomas may change the paradigm of their treatment from stabilization of growth to reduction of the volume of the neoplasm. The tumor shrinkage rate may depend on the amount of radiation energy delivered per lesion volume (unit energy).

Interactive Modeling and Evaluation of Tumor Growth

This paper addresses the need to quantify tumor growth and detect changes as this information is relevant to manage the patient treatment and to aid biotechnological efforts to cure cancer (Silva et al. 2008). An interactive tumor segmentation technique is used to recover the shape and size of tumors without imposing shape constraints. This segmentation algorithm provides good convergence, is robust to the initialization conditions, and requires simple and intuitive user interactions. A parametric approach to model tumor growth analytically is proposed in this paper. The preliminary experimental results are encouraging. The segmentation method is shown to be robust and simple to use, even in situations where the tumor boundary definition is challenging. Also, the experiments indicate that the proposed model potentially can be used to extrapolate the available data and help predict the tumor size (assuming unconstrained growth). Additionally, the proposed method potentially can provide a quantitative reference to compare the tumor shrinkage rate in cancer treatments.

Tumor Shrinkage and Objective Response Rates

Phase II clinical trials have long been used to screen new cancer therapeutics for antitumor activity ("efficacy") worthy of further evaluation. Traditionally, the primary end point used in these screening trials has been objective response rate (RR), with the desired rate being arbitrarily set by the researchers before initiation of the trial. For cytotoxic agents, especially in common tumor types, response has been a reasonably robust and validated surrogate of benefit. Phase II trials with response as an end point have a modest sample size (15-40 patients) and are completed rapidly allowing early decisions regarding future development of a given agent. More recently, a number of new agents have proven successful in pivotal phase III studies, despite a low or very modest RR demonstrated in early clinical trials. Researchers have postulated that these novel agents, as a class, may not induce significant regression of tumors, and that the use of RR as an end point for phase II studies will result in false negative results, and point out that not all available data is used in making the decision. Others have pointed out that even novel agents have proven unsuccessful in pivotal trials if objective responses are not demonstrated in early clinical trials. We review here the historical and current information regarding objective tumor response.

A Landmark Point Analysis with Cytotoxic Agents for Advanced NSCLC

As a result of recent publications, we hypothesized that period of 8 weeks after initiation of treatment is a useful landmark point for cytotoxic agents for advanced non-small cell lung cancer (NSCLC). To test this hypothesis, we conducted landmark analyses with clinical trials employing cytotoxic agents. Our goal was to assess the proper design of clinical trials with cytotoxic agents for NSCLC for maximizing patients' benefit. We conducted landmark analyses of a phase II study of pemetrexed in locally advanced or metastatic NSCLC and a phase III study of Four-Arm Cooperative Study for advanced NSCLC. A total of 806 patients who received chemotherapy (pemetrexed, cisplatin and irinotecan, paclitaxel and carboplatin, cisplatin and gemcitabine, cisplatin and vinorelbine) were included in this assessment. Tumor-shrinkage rate at 8 weeks was significantly associated with longer survival in the study with pemetrexed (p = 0.043), whereas tumor-shrinkage rate at 4 weeks did not correlated with survival (p = 0.139). Similarly, using the Four-Arm Cooperative Study data, the optimal landmark point was 8 weeks (p = 0.002), not 4 weeks (p = 0.190). The landmark point for NSCLC was 8 weeks with all cytotoxic agents in our analysis when the therapy was given as a frontline or subsequent therapy. Our result suggests the concept of a disease-specific landmark point, which may lead to a change of phase II/III clinical study design to evaluate cytotoxic agents and clinical investigators, and their sponsors may consider an early look to assess the efficacy of cytotoxic agents for NSCLC.

Sunitinib in patients (pts) with unresectable primary renal cell carcinoma (RCC)

5096 Background: Sunitinib inhibits VEGF and related receptors, with high tumor shrinkage rates in metastatic (met) RCC. Shrinkage of primary tumors has been observed, although prospective investigation is lacking. The ability of sunitinib to convert primary RCC tumors from unresectable to resectable is of high clinical interest. Methods: Pts with histologically-confirmed RCC with an unresectable primary tumor with or without met disease were enrolled on a single-arm phase II trial. Primary tumors were unresectable due to ≥ 1 of the following: large tumor size, bulky lymphadenopathy, encasement of renal vessels, IVC thrombosis or proximity to vital structures. Pts received 50 mg sunitinib continuous dosing in repeated 6-week cycles. Staging by CT scans or MRI was done at baseline and every 2 cycles. A Simon 2-stage design was employed to test the alternative hypothesis of a conversion to resectability rate of 20% versus the null hypothesis of 5%; β = 0.8, α = 0.05 (n = 31). Results: 18 pts have been enrolled; 1 excluded due to a non-RCC diagnosis. Pts were unresectable due to bulky lymphadenopathy (6), IVC thrombosis (4), proximity to vital structures (4) or tumor size (3), although most pts had multiple factors. Median age among 14 evaluable pts was 61 years (range, 37–80), 59% male, 76% ECOG PS 0; 79% had distant met disease. The 14 evaluable pts have received a median of 3 cycles of therapy (range, 1–10+). Three pts (21%) have undergone primary tumor resection; viable RCC was identified in all specimens with no unexpected surgical morbidity. Nine pts (53%) had primary tumor reduction (median 19%; range, -64% to -1%). Overall, median best % change in tumor burden was 4.9% reduction for primary tumors (range, -43.1% to +8.5%) and 10.7% reduction for met sites (range, -89.5% to +28.6%). Median PFS is 4.9 months. Eleven pts (79%) discontinued therapy; 8 for PD, 1 for adverse events and 2 following surgery which removed all visible disease. Eight pts (57%) experienced grade 3 toxicity including thrombocytopenia, fatigue, hypertension, anemia, hemoptysis, and hand-foot syndrome; 1 pt had grade 4 neutropenia. Conclusions: Sunitinib has activity in unresectable primary RCC tumors, permitting resection in some pts. Continued prospective investigation is required to optimize patient selection and timing of surgery. [Table: see text]

Changes of hypoxia in primary lesion of nasopharyngeal carcinoma during the treatment course and the clinical value thereof

To investigate the hypoxia status in the primary lesion of nasopharyngeal carcinoma (NPC) during the treatment and the clinical value thereof. Sixty-two patients with untreated NPC were examined by 99m Tc-4, 9-diaza-3, 3, 10, 10-tetramethy ldodecan-2, 11-dione dioxime (99 Tcm-HL91) SPECT imaging and CT-simulation (CT-Sim) scan before the treatment, in the mid-treatment (after receiving about 40 Gy) and at the end of treatment respectively. (1) All hypoxia images obtained at the 3 time pints were analyzed by visual analysis and semi-quantitative analysis, the radioactivity ratio of the high density region in the nasopharyngeal lesion to the normal nasopharyngeal tissue (T+/N) was calculated with the technique of region of interesting (ROI). Then the changes of hypoxia status during the treatment were evaluated according to the changes of the visual results and the ratios of T+/N. (2) The tumor volumes in different time points were measured by relevant CT-Sim images in the CT-Sim working station (Exomio 2.0, Medintec), and the percentage of tumor shrinkage in the mid-treatment and at the end of treatment were calculated to evaluate the tumor's response to treatment. The relationships between the hypoxia status before treatment, hypoxic changes during the treatment, and the tumor's response to treatment were analyzed finally. Fifty-six of the 62 NPC cases were hypoxia-positive before the treatment, the hypoxic location in the same patient remained in the same site in different time points, and no new hypoxic area was found during the treatment. Eight cases changed to negative in the mid- treatment and 19 changed to negative at the end of treatment. The ratio of T+/N decreased gradually in the same case (F = 109.073, P = 0.000). The tumor shrinkage rates in the mid-treatment and at the end of treatment of those with high-grade hypoxia (T+/N >or= 1.52) were all both significantly lower than those of the cases with low-grade hypoxia (T+/N < 1.52) (P = 0.019 and 0.000) and those of the hypoxia-negative group (P = 0.038 and 0.000). The ratios of T+/N variation in the mid-treatment and at the end of treatment were both positively correlated with the percentages of tumor shrinkage in the mid-treatment and at the end of treatment (r = 0.587, P = 0.003 and r = 0.655, P = 0.001). The hypoxia of the primary lesion of NPC alleviates gradually or disappears along with the treatment course. Hypoxia has some negative effects on the tumor response to treatment.

Current treatment strategy for vestibular schwannoma: image-guided robotic microradiosurgery

Gamma Knife surgery (GKS) is becoming a standard treatment for vestibular schwannoma (VS); it is ranked with microsurgery from the perspective of tumor control and audiofacial nerve function preservation. A new treatment technique that will improve the tumor shrinkage ratio, shorten the patient's recovery time, and even recover some cranial nerve function is described. Along with advances in the GKS system, the authors have developed magnetic resonance imaging sequences specific to particular treatments. These newly developed sequences provide much clearer visualization of the distribution of the cranial nerves, especially in the area from the cisterns to the internal acoustic meatus. Magnetic resonance images have been fused with computed tomography scans to facilitate better delineation of the anatomical relationships. These dose-planning images allow for a higher isodose line (80%) inside the tumor. The aim is to shrink the tumor and not just to control it. To date 130 patients have been treated with GKS in conjunction with this new technique. Of the 130, 91 patients were observed for more than 12 months. The tumor shrinkage rate was 65.9% (76% for patients with > 24 months of follow up), the facial nerve preservation rate was 98.9%, the hearing preservation rate was 92.3%, and four (4%) of 91 patients recovered hearing function. Transient tumor enlargement was observed in most cases, but no severe complications were found. Although these results are preliminary, they would appear to represent a potential breakthrough in the treatment of VS. Longer follow-up periods and additional cases will firmly establish this method as an absolute treatment option for patients with a VS.

Maintenance Therapy to Suppress Micrometastasis: The New Challenge for Adjuvant Cancer Treatment

The palliative efficacy of cytotoxic drugs is routinely assessed using tumor shrinkage (response) rates shown in clinical trials. Although adjuvant drug therapy has a goal distinct from that of palliative therapy (i.e., to prolong survival by inhibiting progression of micrometastatic disease), it is widely assumed that the adjuvant efficacy of a drug will parallel its response rate ("activity") in advanced stages of the disease. Reconsideration of this assumption seems timely in view of recent developments: the realization that many predictors of short-term tumor response correlate inversely with long-term survival outcomes; the characterization of tumor progression as a discontinuous process that may include dormant phases; the understanding that micrometastasis is therapeutically suppressible by a variety of mechanisms including direct tumor cell kill, cytotoxic disruption of paracrine growth signals from normal tissues, and targeted inhibition of prometastatic pathways; the recognition that tumor dormancy not only blocks the antimetastatic efficacy of cytotoxic drugs but also represents a therapeutic end point for metastasis-suppressive noncytotoxic drugs such as hormone inhibitors; and the insight that optimal adjuvant drug therapy is likely to include both induction and maintenance components. The traditional view of cytoreductive response as a prerequisite for adjuvant drug efficacy thus merits reappraisal, with a view to accelerating incorporation of novel noncytotoxic maintenance therapies into controlled studies.

Gamma knife surgery for brain metastases from lung cancer

Object. The authors conducted a study to evaluate the safety and efficacy of gamma knife surgery (GKS) for the treatment of brain metastases from lung cancer. Methods. Between February 1993 and May 2003 191 patients underwent treatment for 424 brain metastases from non—small (171 cases) and small cell lung carcinoma (20 cases). Imaging and clinical status were monitored every 3 months following the treatment. Kaplan-Meier survival curves, Cox proportional hazards regression for risk factor analysis, and nonparametric methods for evaluating tumor response were used. There was no difference in median survival following combined whole-brain radiation therapy (WBRT) and gamma knife surgery (14 months) and GKS alone (15 months). There was also no difference between the median survival rates for either tumor type. In the multivariate analysis, age less than 65 years, Karnofsky Performance Scale score greater than 70, normal neurological status, multiple GKS treatments, and pre-GKS craniotomy were related to longer survival. Tumor control rates varied according to the volume of the metastases and were as follows: 84.4% (&lt; 0.5 cm3), 94% (0.5–2 cm3), 89.1% (2–4 cm3), 93.4% (4–8 cm3), 85.7% (8–14 cm3), and 87.5% (&gt; 14 cm3). Four lesions required post-GKS craniotomy due to swelling or rapid tumor progression. The rate of tumor shrinkage was higher when a volume was 2 cm3, lower in cystic lesions, lower in tumors with previous WBRT, and lower for margin doses less than 14 Gy. Conclusions. The risk—benefit ratio of GKS in this series was satisfactory. There was no difference in response rates of the two tumor types, and WBRT did not improve the duration of survival.

Gamma knife surgery for brain metastases from lung cancer

The authors conducted a study to evaluate the safety and efficacy of gamma knife surgery (GKS) for the treatment of brain metastases from lung cancer. Between February 1993 and May 2003 191 patients underwent treatment for 424 brain metastases from non-small (171 cases) and small cell lung carcinoma (20 cases). Imaging and clinical status were monitored every 3 months following the treatment. Kaplan-Meier survival curves, Cox proportional hazards regression for risk factor analysis, and nonparametric methods for evaluating tumor response were used. There was no difference in median survival following combined whole-brain radiation therapy (WBRT) and gamma knife surgery (14 months) and GKS alone (15 months). There was also no difference between the median survival rates for either tumor type. In the multivariate analysis, age less than 65 years, Karnofsky Performance Scale score greater than 70, normal neurological status, multiple GKS treatments, and pre-GKS craniotomy were related to longer survival. Tumor control rates varied according to the volume of the metastases and were as follows: 84.4% (< 0.5 cm3), 94% (0.5-2 cm3), 89.1% (2-4 cm3), 93.4% (4-8 cm3), 85.7% (8-14 cm3), and 87.5% (> 14 cm3). Four lesions required post-GKS craniotomy due to swelling or rapid tumor progression. The rate of tumor shrinkage was higher when a volume was 2 cm3, lower in cystic lesions, lower in tumors with previous WBRT, and lower for margin doses less than 14 Gy. The risk-benefit ratio of GKS in this series was satisfactory. There was no difference in response rates of the two tumor types, and WBRT did not improve the duration of survival.

Giant malignant gastrointestinal stromal tumors: Recurrence and effects of treatment with STI-571

Malignant gastrointestinal stromal tumors (GISTs) are rare. Tumors larger than 10 cm tend to recur earlier: the larger the volume of the tumor, the worse the prognosis. We hypothesized that treatment with imatinib mesylate (Gleevec; STI-571), a c-kit tyrosine kinase inhibitor, as palliative therapy would prolong the survival of patients with recurrent giant malignant GISTs after resection. We performed a retrospective analysis of the effects of resection on patients with giant GISTs (>10 cm in diameter) to determine the overall survival and recurrence rates. Twenty-three patients diagnosed with giant GISTs were included from June 1996 to December 2003. STI-571 was not available until January 2000. After that time, 9 patients received this drug. The factors of age, sex, tumor location, histological surgical margin, and STI-571, tumor size changes and drug side effects were reviewed. We compared the survival rate to determine the prognostic factors and the effects of STI-571 on patients with recurrent malignant gastrointestinal stromal tumor. The positive surgical margin group had a significantly higher recurrence rate than the negative margin group (P = 0.012). A negative surgical margin and palliative treatment with STI-571 were significant prognostic variables (Log-rank test, P<0.05). Age, sex and tumor location were not significant prognostic variables. The 5-year survival rate of the surgical margin free patients was 80% and the 2-year survival rate of the surgical margin positive patients was 28%. The 5-year survival rate was 80% for the patients given STI-571 and 30% for the patients not given STI-571. The use of STI-571 gave a significant tumor shrinkage (6/9) rate in patients with giant GIST recurrence after resection. A negative surgical margin and the use of STI-571 after surgical resection were good prognostic indicators. Achieving a tumor-free surgical margin is still the best primary treatment for patients with such tumors. If STI-571 is used immediately when the surgical margin is positive and the tumor recurs after resection, then the prognosis of patients with giant GISTs can be improved.