Average Tumor Volume Reduction Research Articles

Evaluation of two different transarterial chemoembolization protocols using Lipiodol and degradable starch microspheres in therapy of hepatocellular carcinoma: a prospective trial

BackgroundThis prospective randomized trial is designed to compare the performance of conventional transarterial chemoembolization (cTACE) using Lipiodol-only with additional use of degradable starch microspheres (DSM) for hepatocellular carcinoma (HCC) in BCLC-stage-B based on metric tumor response.MethodsSixty-one patients (44 men; 17 women; range 44–85) with HCC were evaluated in this IRB-approved HIPPA compliant study. The treatment protocol included three TACE-sessions in 4-week intervals, in all cases with Mitomycin C as a chemotherapeutic agent. Multiparametric magnetic resonance imaging (MRI) was performed prior to the first and 4 weeks after the last TACE. Two treatment groups were determined using a randomization sheet: In 30 patients, TACE was performed using Lipiodol only (group 1). In 31 cases Lipiodol was combined with DSMs (group 2). Response according to tumor volume, diameter, mRECIST criteria, and the development of necrotic areas were analyzed and compared using the Mann–Whitney-U, Kruskal–Wallis-H-test, and Spearman-Rho. Survival data were analyzed using the Kaplan–Meier estimator.ResultsA mean overall tumor volume reduction of 21.45% (± 62.34%) was observed with an average tumor volume reduction of 19.95% in group 1 vs. 22.95% in group 2 (p = 0.653). Mean diameter reduction was measured with 6.26% (± 34.75%), for group 1 with 11.86% vs. 4.06% in group 2 (p = 0.678). Regarding mRECIST criteria, group 1 versus group 2 showed complete response in 0 versus 3 cases, partial response in 2 versus 7 cases, stable disease in 21 versus 17 cases, and progressive disease in 3 versus 1 cases (p = 0.010). Estimated overall survival was in mean 33.4 months (95% CI 25.5–41.4) for cTACE with Lipiosol plus DSM, and 32.5 months (95% CI 26.6–38.4), for cTACE with Lipiodol-only (p = 0.844), respectively.ConclusionsThe additional application of DSM during cTACE showed a significant benefit in tumor response according to mRECIST compared to cTACE with Lipiodol-only. No benefit in survival time was observed.

Percutaneous Microwave Ablation of Desmoid Fibromatosis.

ObjectiveTo demonstrate the feasibility of percutaneous microwave ablation in desmoid fibromatosis with respect to tumor volume control and improvement in the quality of life.Materials and MethodsTwelve microwave ablations were performed in 9 patients with a histological diagnosis of desmoid fibromatosis between January 2010 and January 2019. The study population included 6 female and 3 male, with an age range of 21–76 years (mean = 46.6 years; standard deviation [SD] = 19.3 years). The mean major axis of the tumors was 10.9 cm (SD = 5.2 cm) and mean lesion volume was 212.7 cm3 (SD = 213 cm3). Their anatomical distribution was as follows: 3 lesions in the thigh, 2 in the gluteus, 2 in the leg and 2 in the periscapular region. We evaluated the reduction in tumor volume and improvement in the quality of life based on the Eastern Cooperative Oncology Group (ECOG) scale.ResultsAn average tumor volume reduction of 70.4% (SD = 24.9) was achieved, while the quality of life (ECOG scale) improved in 88.9% of patients.ConclusionPercutaneous microwave ablation may potentially be a safe, effective, and promising technique for controlling tumor volume and improving the quality of life in patients with desmoid fibromatosis.

The Role of 3D Tractography in Skull Base Surgery: Technological Advances, Feasibility, and Early Clinical Assessment with Anterior Skull Base Meningiomas.

Objective The aim of this study is to determine feasibility of incorporating three-dimensional (3D) tractography into routine skull base surgery planning and analyze our early clinical experience in a subset of anterior cranial base meningiomas (ACM). Methods Ninety-nine skull base endonasal and transcranial procedures were planned in 94 patients and retrospectively reviewed with a further analysis of the ACM subset. Main Outcome Measures (1) Automated generation of 3D tractography; (2) co-registration 3D tractography with computed tomography (CT), CT angiography (CTA), and magnetic resonance imaging (MRI); and (3) demonstration of real-time manipulation of 3D tractography intraoperatively. ACM subset: (1) pre- and postoperative cranial nerve function, (2) qualitative assessment of white matter tract preservation, and (3) frontal lobe fluid-attenuated inversion recovery (FLAIR) signal abnormality. Results Automated 3D tractography, with MRI, CT, and CTA overlay, was produced in all cases and was available intraoperatively. ACM subset : 8 (44%) procedures were performed via a ventral endoscopic endonasal approach (EEA) corridor and 12 (56%) via a dorsal anteromedial (DAM) transcranial corridor. Four cases (olfactory groove meningiomas) were managed with a combined, staged approach using ventral EEA and dorsal transcranial corridors. Average tumor volume reduction was 90.3 ± 15.0. Average FLAIR signal change was -30.9% ± 58.6. 11/12 (92%) patients (DAM subgroup) demonstrated preservation of, or improvement in, inferior fronto-occipital fasciculus volume. Functional cranial nerve recovery was 89% (all cases). Conclusion It is feasible to incorporate 3D tractography into the skull base surgical armamentarium. The utility of this tool in improving outcomes will require further study.

Fractionated Stereotactic Radiotherapy for Cavernous Venous Malformations of the Orbital Apex.

The objective of this study was to investigate the efficacy and safety of fractionated stereotactic radiotherapy in the treatment of cavernous venous malformation of the orbital apex. The authors reviewed a prospective database from a single center of patients with cavernous venous malformation of the orbital apex who had treatment with fractionated stereotactic radiotherapy. The authors compared the symptoms, visual function and the size of the tumor pre- and posttreatment as well as reviewed the treatment details and the incidence of complications. Six patients received treatment with fractionated stereotactic radiotherapy for cavernous venous malformation involving the orbital apex. The median age was 48 (range, 32-63), and 50% were female. Patients received a dose of 45 to 50.4 Gy in 1.8 to 2 Gy fractions. Median follow up was 33 months (range, 18-66 months). The average tumor volume reduction at posttreatment imaging after 12 months was 63%. All lesions reduced in size postradiotherapy and remained controlled for the duration of follow up. All patients who had proptosis or a visual field defect had an improvement in the symptoms posttreatment. There were no complications of the treatment. Fractionated stereotactic radiotherapy appears to be a safe and effective management option for cavernous venous malformation of the orbital apex and leads to a sustained reduction of the volume of the lesion with associated improvement in symptoms and visual function.

Treatment of Cavernous Sinus Hemangiomas with Gamma Knife Radiosurgery as a Primary and Sole Therapy.

To evaluate the effectiveness of Gamma Knife radiosurgery (GKRS) as the primary and only therapy for the treatment of cavernous sinus hemangiomas (CSH) and to report the tumor volume dynamics, course of symptoms, and complications after stereotactic radiosurgery. A total of 10 CSH patients were treated with GKRS using a median margin dose of 14.2Gy (range 13-16Gy). The median follow-up period was 42 months (range 12-85 months). Tumor volumes were calculated from magnetic resonance images before treatment and compared with those after treatment. Prior to the treatment, all patients complained of headache and retro-orbital pain, and six patients complained of diplopia due to abducens nerve paralysis. Within six months of treatment, all patients declared some improvement in headache and retro-orbital pain, and abducens nerve paralysis recovered fully in all six patients. At the first-year follow-up, at least 74% decrease in tumor volume was noted with average tumor volume reduction of 90.2% in all treated patients. Tumors less than 6 cm3 in volume nearly disappeared at 24 months. No tumor progression, re-growth, or radiation-induced adverse effects were noted in our patients. Characteristic radiological features that enable identification of CSH avert the need for an open biopsy for diagnosis. Under suitable circumstances, GKRS may be considered as the primary and only therapy for CSH. GKRS has favorable outcomes in the treatment of CSH, demonstrating good tumor shrinkage, symptom recovery, and low incidence of side effects.

Role of fractionated radiotherapy in patients with hemangioma of the cavernous sinus.

PurposeWe performed this retrospective study to investigate the outcomes of patients with hemangioma of the cavernous sinus after fractionated radiotherapy.Materials and MethodsWe analyzed 10 patients with hemangioma of the cavernous sinus who were treated with conventional radiotherapy between January 2000 and December 2016. The median patient age was 54 years (range, 31–65 years), and 8 patients (80.0%) were female. The mean hemangioma volume was 34.1 cm3 (range, 6.8–83.2 cm3), and fractionated radiation was administered to a total dose of 50–54 Gy with a daily dose of 2 Gy.ResultsThe median follow-up period was 6.8 years (range, 2.2–8.8 years). At last follow-up, the volume of the tumor had decreased in all patients. The average tumor volume reduction rate from the initial volume was 72.9% (range, 18.9–95.3%). All 10 of the cranial neuropathies observed before radiation therapy had improved, with complete symptomatic remission in 9 cases (90%) and partial remission in 1 case (10%). No new acute neurologic impairments were reported after radiotherapy. One probable compressive optic neuropathy was observed at 1 year after radiotherapy.ConclusionFractionated radiotherapy achieves both symptomatic and radiologic improvements. It is a well-tolerated treatment modality for hemangiomas of the cavernous sinus.

TU‐G‐BRA‐04: Changes in Regional Lung Function Measured by 4D‐CT Ventilation Imaging for Thoracic Radiotherapy

Purpose:To test the hypothesis: 4D‐CT ventilation imaging can show the known effects of radiotherapy on lung function: (1) radiation‐induced ventilation reductions, and (2) ventilation increases caused by tumor regression.Methods:Repeat 4D‐CT scans (pre‐, mid‐ and/or post‐treatment) were acquired prospectively for 11 thoracic cancer patients in an IRB‐approved clinical trial. A ventilation image for each time point was created using deformable image registration and the Hounsfield unit (HU)‐based or Jacobian‐based metric. The 11 patients were divided into two subgroups based on tumor volume reduction using a threshold of 5 cm3. To quantify radiation‐induced ventilation reduction, six patients who showed a small tumor volume reduction (<5 cm3) were analyzed for dose‐response relationships. To investigate ventilation increase caused by tumor regression, two of the other five patients were analyzed to compare ventilation changes in the lung lobes affected and unaffected by the tumor. The remaining three patients were excluded because there were no unaffected lobes.Results:Dose‐dependent reductions of HU‐based ventilation were observed in a majority of the patient‐specific dose‐response curves and in the population‐based dose‐response curve, whereas no clear relationship was seen for Jacobian‐based ventilation. The post‐treatment population‐based dose‐response curve of HU‐based ventilation demonstrated the average ventilation reductions of 20.9±7.0% at 35–40 Gy (equivalent dose in 2‐Gy fractions, EQD2), and 40.6±22.9% at 75–80 Gy EQD2. Remarkable ventilation increases in the affected lobes were observed for the two patients who showed an average tumor volume reduction of 37.1 cm3 and re‐opening airways. The mid‐treatment increase in HU‐based ventilation of patient 3 was 100.4% in the affected lobes, which was considerably greater than 7.8% in the unaffected lobes.Conclusion:This study has demonstrated that 4D‐CT ventilation imaging shows the known effects of radiotherapy on lung function: radiation‐induced ventilation reduction and ventilation increase caused by tumor regression, providing validation for 4D‐CT ventilation imaging.This study was supported in part by a National Lung Cancer Partnership Young Investigator Research grant.

AT-05 * TARGETING mTOR DOWNSTREAM OF LIN28 IN ATYPICAL TERATOID RHABDOID TUMORS PROMOTES APOPTOSIS AND SUPPRESSES TUMORIGENICITY

LIN28A and LIN28B are stem cell factors that regulate thousands of RNAs and are expressed in aggressive cancers. One of the canonical downstream targets of LIN28 is the mTOR pathway. We have previously shown that overexpression of LIN28 in Atypical Teratoid Rhabdoid Tumors (AT/RT) contributes to the aggressive nature of the tumor. We hypothesized that AT/RT would have increased expression of mTOR signaling due to high-level expression of LIN28. We found that primary human AT/RT samples do have high levels of P-S6 and P-AKT expression by immunohistochemistry staining (mean H-score for P-S6 36.3; p-AKT 150.4). The dual TORC1/2 inhibitor MLN0128 has good brain penetration and is currently being tested in phase I clinical trials in children. Treatment of AT/RT cell lines with MLN0128 inhibits TORC1/2 targets in vitro and suppresses cell proliferation at 10nM concentration (MTS assay for BT12 p = 0.0034 vs DMSO control; BT37 p = 0.0064 vs DMSO control; and CHLA-06 p = 0.002 vs DMSO control by t-test). MLN0128 also slows cell proliferation via BrdU assay (BT-37 p = 0.0241 10nM vs DMSO control; CHLA-06 p = 0.045 10nM vs DMSO control by t-test) and induces apoptosis measured by Western blot for PARP and cleaved caspase 3 assay (BT-37 p = 0.001 100nM vs DMSO; CHLA-06 p = 0.007 10nM vs DMSO by t-test). MLN0128 treatment of AT/RT xenograft mouse models leads to rapid reduction in tumor volume compared to controls treated with vector alone (61.9% average reduction in tumor volume with MLN0128 treatment vs 272.1% average increase in tumor volume in vector control; p = 0.006 by t-test). Targeting the overexpressed mTOR pathway with the TORC1/TORC2 inhibitor MLN0128 leads to potent in vitro and in vivo activity against AT/RT. MLN0128 may be a candidate for future clinical trials to treat this aggressive tumor.

Synergistic enhancement of anticancer effects on numerous human cancer cell lines treated with the combination of EGCG, other green tea catechins, and anticancer compounds.

In 2008, we reported that 10 Japanese-size cups of green tea daily, supplemented with tablets of green tea extract (GTE), reduced the recurrence of colorectal adenoma by 51.6% in patients after polypectomy. Based on these results, we paid special attention to Japanese cancer patients, who consume green tea every day and are administered anticancer drugs. This encouraged us to study whether the combination of green tea catechins and anticancer drugs has the potential to enhance the efficacy of the drugs. The combination of GTE and NSAIDs synergistically inhibited tumor development in rodents through the activation of the GADD153-DR5-TRAIL apoptotic pathway. Since then, this study was further extended by various investigators to the combinations of EGCG and other green tea catechins with anticancer compounds, the latter of which include NSAIDs, phytochemicals, and anticancer drugs. In order to demonstrate whether diversity of the combinations would generally induce synergistic anticancer effects on numerous human cancer cell lines, we studied the results of 42 in vitro combination experiments and the synergistic inhibition of tumor volume of 13 combination experiments using xenograft mouse models, which were previously reported by other investigators. The various combinations of EGCG and anticancer compounds induced similar synergistic anticancer effects for both in vitro and in vivo experiments, and showed an average reduction in tumor volume by 70.3%. Considering the evidence showing that treatment with EGCG inhibited self-renewal of cancer stem cells, the combination shows a great advantage. Green tea is a cancer preventive for humans, showing a new trend of green tea catechins as synergists with anticancer compounds.

Dedicated Breast CT: Feasibility for Monitoring Neoadjuvant Chemotherapy Treatment.

Objectives:In this prospective pilot study, the feasibility of non-contrast dedicated breast computed tomography (bCT) to determine primary tumor volume and monitor its changes during neoadjuvant chemotherapy (NAC) treatment was investigated.Materials and Methods:Eleven women who underwent NAC were imaged with a clinical prototype dedicated bCT system at three time points – pre-, mid-, and post-treatment. The study radiologist marked the boundary of the primary tumor from which the tumor volume was quantified. An automated algorithm was developed to quantify the primary tumor volume for comparison with radiologist's segmentation. The correlation between pre-treatment tumor volumes from bCT and MRI, and the correlation and concordance in tumor size between post-treatment bCT and pathology were determined.Results:Tumor volumes from automated and radiologist's segmentations were correlated (Pearson's r = 0.935, P < 0.001) and were not different over all time points [P = 0.808, repeated measures analysis of variance (ANOVA)]. Pre-treatment tumor volumes from MRI and bCT were correlated (r = 0.905, P < 0.001). Tumor size from post-treatment bCT was correlated with pathology (r = 0.987, P = 0.002) for invasive ductal carcinoma larger than 5 mm and the maximum difference in tumor size was 0.57 cm. The presence of biopsy clip (3 mm) limited the ability to accurately measure tumors smaller than 5 mm. All study participants were pathologically assessed to be responders, with three subjects experiencing complete pathologic response for invasive cancer and the reminder experiencing partial response. Compared to pre-treatment tumor volume, there was a statistically significant (P = 0.0003, paired t-test) reduction in tumor volume at mid-treatment observed with bCT, with an average tumor volume reduction of 47%.Conclusions:This pilot study suggests that dedicated non-contrast bCT has the potential to serve as an expedient imaging tool for monitoring tumor volume changes during NAC. Larger studies are needed in future.

Prolactinoma-associated headache and dopamine agonist treatment

The aim of this article is to investigate the phenotype and etiology of prolactinoma-associated headache as well as present and discuss the plausible pain-relieving effect of dopamine agonist treatment. In this case-based audit we included 11 patients with prolactinomas and one patient with idiopathic hyperprolactinemia presenting with headache that subsequently improved or resolved after dopamine agonist treatment. A significant ipsilateral location of tumor mass and reported headache symptoms was observed (p = 0.018). After dopamine agonist treatment seven out of 12 patients became pain free within 2.5 months; after one year of treatment 11 out of 12 reported headache improvement or resolution. Average tumor volume reduction after treatment was 47 ± 22% during 9.5 ± 8.4 months of follow-up. There was no significant association between headache relief and tumor shrinkage (p = 0.43) or normalization of serum prolactin (p = 1.00), respectively. 1) The significant association between lateralization of tumor and headache suggests a mechanical origin of the headache, 2) headache responded to dopamine agonist treatment in most patients, and 3) our observations encourage future prospective controlled trials to investigate the role of hyperprolactinemia in the pathogenesis of headache as well as the therapeutic effects of dopamine agonists.

Single-institution experience with neoadjuvant chemotherapy for metaplastic breast cancer (MBC).

140 Background: Metaplastic breast carcinoma (MBC) is a rare subtype that accounts for &lt;1% of all breast carcinomas. MBC is frequently triple-negative and neoadjuvant chemotherapy (NAC) is often used in triple-negative breast cancer (TNBC). The objective of this analysis is to ascertain response rates of MBC to NAC as compared to non-metaplastic TNBC. Methods: We searched the Magee Women’s Cancer Center of UPMC IRB-approved neo-adjuvant treatment database which contains outcome data on 594 patients treated from 2004-2010. 116 patients with triple negative breast cancer (ER /PR negative or ER /PR weakly positive [H score of 10 or less] and HER2 negative or indeterminate [HER2 1+ or 2+ without amplification by FISH]), were identified. Nine of these TNBCs had metaplastic subtype and two groups were analyzed: metaplastic breast carcinoma (MBC) (N= 9) and non-metaplastic breast carcinoma (NMBC) (N = 107). Tumor volume reduction (TVR), pathologic complete response (pCR), recurrence and mortality were compared in both groups. Results: Average follow-up in MBC group was 43 months and no patients were lost to follow-up. Average tumor size on presentation in MBC group was 4.47 cm while in NMBC group it was 3.33 cm. pCR was noted in 0/9 MBC and 43/107 NMBC cases (p = 0.0253). 6/9 patients had mastectomy, 2/9 had breast conserving surgery (BCS) and 1/9 patients did not have a surgery yet. Average TVR was 28% in MBC cases compared to 74% in NMBCs when cases with pCR were included (p = 0.0001) and 56% when cases with pCR were excluded (p = 0.0202). Follow up on 9 MBC cases revealed 1 recurrence and subsequent death (11%). Follow-up on 64 NMBC patients who failed to achieve pCR revealed 22 recurrences (34%) and 18 of them subsequently died (28%). Follow-up on 43 NMBC cases that achieved pCR revealed 3 recurrences (7%) and 1 death (2%). Conclusions: MBC was characterized by larger size at baseline as compared to NMBC. There were no pCR’s seen in MBC, but some MBC did achieve response that allowed for breast conservation. Although the average tumor volume reduction was significantly less in MBC compared to NMBC, the NMBC that failed to achieve pCR fared much worse than MBC who did not achieve pCR. Therefore, the triple-negative paradox is likely not applicable to MBC.

Single institution experience with neoadjuvant chemotherapy for metaplastic breast cancer (MBC).

1038 Background: Metaplastic breast carcinoma (MBC) is a rare subtype that accounts for &lt;1% of all breast carcinomas. MBC is frequently triple negative and neoadjuvant chemotherapy (NAC) is often used in triple negative breast cancer (TNBC). The objective of this analysis is to ascertain response rates of MBC to NAC as compared to non-metaplastic TNBC. Methods: We searched the Magee Women’s Cancer Center of UPMC IRB-approved neo-adjuvant treatment database which contains outcome data on 594 patients treated from 2004-2010. 116 patients with triple negative breast cancer (ER /PR negative or ER /PR weakly positive (H score of 10 or less) and HER2 negative or indeterminate (HER2 1+ or 2+ without amplification by FISH)), were identified. Nine of these TNBCs had metaplastic subtype and 2 groups were analyzed: metaplastic breast carcinoma (MBC) (N= 9) and non-metaplastic breast carcinoma (NMBC) (N = 107). Tumor volume reduction (TVR), pathologic complete response (pCR), recurrence and mortality were compared in both groups. Results: Mean follow up in MBC group was 43 months and no patients were lost to follow up. Mean tumor size on presentation in MBC group was 4.47 cm while in NMBC group it was 3.33 cm. pCR was noted in 0/9 MBC and 43/107 NMBC cases (p = 0.0253). 6/9 patients had mastectomy, 2/9 had breast conserving surgery (BCS) and 1/9 patients did not have a surgery yet. Average TVR was 28% in MBC cases compared to 74% in NMBCs when cases with pCR were included (p = 0.0001) and 56% when cases with pCR were excluded (p = 0.0202). Follow up on 9 MBC cases revealed 1 recurrence and subsequent death (11%). Follow up on 64 NMBC patients who failed to achieve pCR revealed 22 recurrences (34%) and 18 of them subsequently died (28%).Follow up on 43 NMBC cases that achieved pCR revealed 3 recurrences (7%) and 1 death (2%). Conclusions: MBC was characterized by larger size at baseline as compared to NMBC. There were no pCR’s seen in MBC, but some MBC did achieve response that allowed for breast conservation. Although the average tumor volume reduction was significantly less in MBC compared to NMBC, the NMBC that failed to achieve pCR fared much worse than MBC who did not achieve pCR. Therefore, the triple negative paradox is likely not applicable to MBC.

Gamma Knife Surgery for Cavernous Hemangiomas in the Cavernous Sinus

Cavernous hemangioma in the cavernous sinus (CS) is a rare vascular tumor. Direct microsurgical approach usually results in massive hemorrhage. Radiosurgery has emerged as a treatment alternative to microsurgery. To further investigate the role of Gamma Knife surgery (GKS) in treating CS hemangiomas. This was a retrospective analysis of 7 patients with CS hemangiomas treated by GKS between 1993 and 2008. Data from 84 CS meningiomas treated during the same period were also analyzed for comparison. The patients underwent follow-up magnetic resonance imaging at 6-month intervals. Data on clinical and imaging changes after radiosurgery were analyzed. Six months after GKS, magnetic resonance imaging revealed an average of 72% tumor volume reduction (range, 56%-83%). After 1 year, tumor volume decreased 80% (range, 69%-90%) compared with the pre-GKS volume. Three patients had > 5 years of follow-up, which showed the tumor volume further decreased by 90% of the original size. The average tumor volume reduction was 82%. In contrast, tumor volume reduction of the 84 cavernous sinus meningiomas after GKS was only 29% (P < .001 by Mann-Whitney U test). Before treatment, 6 patients had various degrees of ophthalmoplegia. After GKS, 5 improved markedly within 6 months. Two patients who suffered from poor vision improved after radiosurgery. GKS is an effective and safe treatment modality for CS hemangiomas with long-term treatment effect. Considering the high risks involved in microsurgery, GKS may serve as the primary treatment choice for CS hemangiomas.

CYBERKNIFE RADIOSURGERY FOR TRIGEMINAL SCHWANNOMAS

Trigeminal schwannomas (TS) are benign tumors that are managed by surgical resection and/or stereotactic radiosurgery. Most radiosurgical series report results using the gamma knife. The CyberKnife (Accuray, Inc., Sunnyvale, CA) is a frameless, robotic stereotactic radiosurgical system. In this series, we report our experience using the CyberKnife in the treatment of TS. We retrospectively reviewed the medical records and diagnostic imaging in 13 consecutive patients with TS who were treated with the CyberKnife from 2003 to 2007. Seven patients had a previous surgical resection. The mean tumor volume was 6.3 mL (range, 0.39-19.98 mL), and the mean marginal dose was 18.5 Gy. Six of the tumors were treated in a single session. The mean clinical follow-up period was 21.8 months (range, 7-53 months). In this series, the tumor control rate was 100%. The average reduction in tumor volume was 45% (range, 14-98%). A modest improvement in facial pain was noted in 4 of the 6 patients who presented with this symptom. One patient had improvement in facial numbness, and another had improvement in pretreatment headaches. One patient developed jaw weakness and facial dysesthesia, and another patient developed asymptomatic radiation necrosis. Although the length of follow-up is limited, we report our initial experience with CyberKnife treatment of TS. Our results demonstrate tumor control rates and clinical outcomes that parallel those of previous reports using gamma knife radiosurgery; however, long-term follow-up studies are needed.

Tumor Response Kinetics after Schedule-Dependent Paclitaxel Chemoradiation Treatment for Inoperable Non-small Cell Lung Cancer: A Model for Low-Dose Chemotherapy Radiosensitization

Poor local disease control remains a major obstacle for inoperable non-small cell lung cancer (NSCLC) after radiotherapy. We previously reported results of a phase I/II clinical study based on preclinical investigations of paclitaxel radiation interactions for inoperable locally advanced NSCLC, which yielded remarkable local tumor responses and durable in-field tumor control using schedule-dependent low-dose paclitaxel for radiosensitization. Given our unique results, we analyzed the tumor response kinetics and conducted a statistical modeling of tumor response to characterize this regimen. A total of 104 chest CT scans from 27 patients treated in the clinical trial were evaluated. Tumor volumes were calculated by three-dimensional measurements of pretreatment and serial post-therapy CT scans. A nonlinear mixed effects model was used to model response kinetics. The average tumor volume reduction at 1 month post-therapy was 69.9 +/- 22.6% (standard deviation), and was 80.6 +/- 17.9% at the last follow-up. The nonlinear mixed effects model predicts that tumor volume will ultimately shrink by at least 75% for more than 75% of patients treated by this regimen. The model also suggests that maximum shrinkage is reached within 2 months after treatment. Tumor volume response kinetics revealed a rapid shrinkage of gross tumors using schedule-dependent pulsed low-dose paclitaxel radiosensitization. This is contrary to the protracted tumor regression process observed in radiation alone or other chemoradiation combinations. Statistical modeling may prove useful in characterizing and comparing different therapeutic regimens.

In vivo sodium iodide symporter gene therapy of prostate cancer.

Radioiodine therapy, the most effective form of systemic radiotherapy available, is currently useful only for thyroid cancer because of thyroid-specific expression of the sodium iodide symporter (NIS). Here we explore the efficacy of a novel form of gene therapy using adenovirus-mediated in vivo NIS gene transfer followed by (131)I administration for treatment of prostate cancer. Prostate cancer xenografts in nude mice injected with an adenovirus carrying the NIS gene linked to the cytomegalovirus (CMV) promoter revealed highly active uptake of radioiodine. Following administration of 3 mCi of (131)I, we observed an average tumor volume reduction of 84 +/- 12%. These results show for the first time that in vivo NIS gene delivery into non-thyroidal tumors is capable of inducing accumulation of therapeutically effective radioiodine doses and might therefore represent an effective and potentially curative therapy for prostate cancer.

Chemotherapeutic evaluation of Celecoxib, a cyclooxygenase-2 inhibitor, in a rat mammary tumor model.

Epidemiological and experimental studies have shown that non-steroidal anti-inflammatory drugs (NSAIDs) reduce the relative risk of human cancer, including breast cancer. Recently, research studies in our laboratories have shown that the selective cyclooxygenase-2 (COX-2) blocker, Celecoxib, given daily in the diet, significantly inhibited the induction of rat mammary tumors by 7, 12-dimethylbenz(a)anthracene (DMBA). These studies were extended to evaluate Celecoxib for its effectiveness as an antineoplastic agent in this rat mammary tumor model. We examined the growth inhibitory effects of Celecoxib, given daily in the diet, on the volume and the number of established mammary tumors, vis-a-vis the cancer load (CL). Tumors continued to grow actively in control rats fed chow diet only. In contrast, the Celecoxib-supplemented diet (1500 mg/kg diet) significantly decreased the size of the mammary tumors in rats over the 6 week treatment period, resulting in an average reduction in tumor volume of approximately 32%, relative to the baseline volume (p<0.04). At the end of the 6 week treatment period, average tumor volume was 1.45 cm3 and 0.13 cm3 in the control and Celecoxib treated rats respectively. Tumor regression occurred in 90% of the rats. In addition, new tumors continued to emerge in the control group, in contrast to their significantly decreasing numbers in the Celecoxib treated group over the same time period (p<0.05). These results indicate that Celecoxib has significant antineoplastic activity, in addition to its anticarcinogenic effects.

Treatment of uterine fibroid tumors in a nude mouse model using high-intensity focused ultrasound

Objective: The purpose of this study was to investigate the potential efficacy of high-intensity focused ultrasound for the treatment of uterine fibroid tumors in a nude mouse model. Study Design: A total of 60 female athymic nude mice were inoculated subcutaneously with 3 to 5 × 106 ELT-3 cells, a uterine fibroid tumor cell line. Tumor size was monitored with transcutaneous caliper measurements. The high-intensity focused ultrasound probe was a concave, single-element, high-power transducer that operated at a frequency of 3.5 MHz. The tumors were treated for 30 to 60 seconds using a high-intensity focused ultrasonic intensity of 2000 W/cm2, depending on the tumor size. Results: A single high-intensity focused ultrasonic treatment resulted in an average reduction in tumor volume of 91% within 1 month of the treatment. Histologic analysis of tumors treated with high-intensity focused ultrasound showed coagulation necrosis and nuclear fragmentation of tumor cells. Conclusion: High-intensity focused ultrasound effectively reduced uterine fibroid tumor size in a nude mouse model. Further studies are needed to assess the in situ response of uterine fibroids to high-intensity focused ultrasonic treatment. (Am J Obstet Gynecol 2000;183:6-11.)

Treatment of uterine fibroid tumors in a nude mouse model using high-intensity focused ultrasound*1

Objective: The purpose of this study was to investigate the potential efficacy of high-intensity focused ultrasound for the treatment of uterine fibroid tumors in a nude mouse model. Study Design: A total of 60 female athymic nude mice were inoculated subcutaneously with 3 to 5 × 106 ELT-3 cells, a uterine fibroid tumor cell line. Tumor size was monitored with transcutaneous caliper measurements. The high-intensity focused ultrasound probe was a concave, single-element, high-power transducer that operated at a frequency of 3.5 MHz. The tumors were treated for 30 to 60 seconds using a high-intensity focused ultrasonic intensity of 2000 W/cm2, depending on the tumor size. Results: A single high-intensity focused ultrasonic treatment resulted in an average reduction in tumor volume of 91% within 1 month of the treatment. Histologic analysis of tumors treated with high-intensity focused ultrasound showed coagulation necrosis and nuclear fragmentation of tumor cells. Conclusion: High-intensity focused ultrasound effectively reduced uterine fibroid tumor size in a nude mouse model. Further studies are needed to assess the in situ response of uterine fibroids to high-intensity focused ultrasonic treatment. (Am J Obstet Gynecol 2000;183:6-11.)