Interstitial Irradiation Research Articles

Phase I Trial of Replication-competent Adenovirus-mediated Suicide Gene Therapy Combined with IMRT for Prostate Cancer

Replication-competent adenovirus-mediated suicide gene therapy is an investigational cancer treatment in which an oncolytic adenovirus armed with chemo-radiosensitizing genes is used to destroy tumor cells. Previously, we evaluated the toxicity and efficacy of this approach in two clinical trials of prostate cancer using a first-generation adenovirus. Here, we report the toxicity and preliminary efficacy of this approach in combination with intensity-modulated radiotherapy (IMRT) in patients with newly diagnosed prostate cancer using an improved, second-generation adenovirus. The investigational therapy was associated with low toxicity, and there were no dose-limiting toxicities or treatment-related serious adverse events. Relative to a previous trial using a first-generation adenovirus, there was no increase in hematologic, hepatic, gastrointestinal (GI), or genitourinary (GU) toxicities. Post-treatment prostate biopsies yielded provocative preliminary results. When the results of two similar trials were combined, 22% of evaluable patients were positive for adenocarcinoma at their last biopsy, which is better than expected (>or=40%) for this cohort of patients (P=0.038). When the results were categorized by prognostic risk, most of the treatment effect was observed in the intermediate-risk group, with 0 of 12 patients (0%) being positive for cancer at their last biopsy (P<0.01). These results further demonstrate the safety of this investigational approach and raise the possibility that it may have the potential to improve the outcome of conformal radiotherapy in select patient groups.

Image Fusion Analysis of Volumetric Changes after Interstitial Low-Dose-Rate Iodine-125 Irradiation of Supratentorial Low-Grade Gliomas

The aim of this study was to compare the volumes of tumor necrosis, reactive zone and edema with the three-dimensional dose distributions after brachytherapy treatments of gliomas. The investigation was performed an average of 14.2 months after low-dose-rate (125)I interstitial irradiation of 25 inoperable low-grade gliomas. The prescribed dose was 50-60 Gy to the tumor surface. Dose planning and image fusion were performed with the BrainLab-Target 1.19 software. In the CT/ MRI images, the "triple ring" (tumor necrosis, reactive ring and edema) developing after the interstitial irradiation of the brain tumors was examined. The images with the triple ring were fused with the planning images, and the isodose curves were superimposed on them. The volumes of the three regions were measured. The average dose at the necrosis border was determined from the isodose distribution. For quantitative assessment of the dose distributions, the dose nonuniformity ratio (DNR), homogeneity index (HI), coverage index (CI) and conformal index (COIN) were calculated. The relative volumes of the different parts of the triple ring after the interstitial irradiation compared to the reference dose volume were the following: necrosis, 40.9%, reactive zone, 47.1%, and edema, 367%. The tumor necrosis developed at 79.1 Gy on average. The average DNR, HI, CI and COIN were 0.45, 0.24, 0.94 and 0.57, respectively. The image fusion analysis of the volume of tumor necrosis, reactive ring and edema caused by interstitial irradiation and their correlation with the dose distribution provide valuable information for patient follow-up, treatment options, and effects and side effects of radio therapy.

The role of microglia/macrophage system in the tissue response to I-125 interstitial brachytherapy of cerebral gliomas

Objective: To study histopathologic changes and the role of the microglia/macrophage cell in the therapeutic effect of I-125 interstitial brachytherapy on the cerebral gliomas.Methods: Out of a series of 60 cases with cerebral astrocytomas and other brain tumors treated with I-125 interstitial brachytherapy, autopsy materials were available in ten cases 0.75 and 60 months after irradiation. The patients were treated with the maximum dosage (60 Gy) on the tumor periphery. Besides the routine hematoxylin-eosine and Mallory's PTAH trichrome staining, immunohistochemical reactions were carried out for CD15, CD31, CD34, CD45, CD68, CPM, HAM56 and HLR-DR antigens on paraffin sections to study immunologic phenotypic characteristics of the reaction cell population around gliomas after I-125 treatment.Result: One month after irradiation, a necrotic zone developed around the I-125 seeds within the 72 Gy isodose curve. Histologically, there was a fresh coagulation necrosis in the center of the lesion. Reactive zone has not yet developed but scattered interstitial and perivascular CD68 positive macrophages were present in the surrounding brain tissues. Six months after the I-125 isotope treatment, a reactive zone developed: a microglial rim around the necrosis tissue, and a broad area of proliferating vessels and glial fibrillary acidic protein (GFAP) positive astroglial cells which contained CD68 positive activated microglial and macrophage cells. Fifty-four months after I-125 interstitial irradiation, the necrotic center became colliquative and cystic. The microglial rim was replaced by round end stage (HLR-DR and CD31 positive) macrophages. The reactive zone was characterized by astrocytic gliosis but vascular proliferation and macrophages were lacking.Conclusion: Results of the present immunohistochemical study suggest that the early lesions are characterized by migrating macrophages apparently concerned with the removal of necrotic debris. The established phase of reactive zone around the necrotic center is characterized by a narrow inner rim of microglial accumulation and a broad outer area characterized by astrocytic gliosis, vascular proliferation, activated microglia and infiltration by macrophages. In the burned-out phases of I-125 interstitial brachytherapy of gliomas, the necrosis undergoes liquefaction and the microglial rim is replaced by astrocytic gliosis which can be considered as equivalent to the scar tissue formed around necrosis outside the central nervous system.

Predictors of Overall and Cancer-Free Survival of Patients With Localized Prostate Cancer Treated With Primary Androgen Suppression Therapy: Results From the Prostate Cancer Outcomes Study

Primary androgen suppression therapy for clinically localized prostate cancer is increasingly common in the United States despite a lack of supportive evidence for its use. We determined which demographic and clinical factors predict overall and cancer specific survival with this treatment strategy in patients enrolled in the Prostate Cancer Outcomes Study. In 1994 to 1995 the Prostate Cancer Outcomes Study recruited 3,533 men diagnosed with prostate cancer. Clinical and treatment information was abstracted from medical records and demographic characteristics were obtained from patient surveys 6, 12, 24 and 60 months after diagnosis. Overall and cancer specific mortality was analyzed through December 2002 using the Kaplan-Meier method and Cox regression. A total of 276 patients had organ confined (cT1-2) prostatic adenocarcinoma and received primary androgen suppression therapy within 1 year of diagnosis. Median followup for censored patients was 7.6 years (range 1.1 to 8.1). Five-year overall and cancer specific survival was 66% (95% CI 59-72) and 91% (95% CI 86-94), respectively. Independent predictors of shorter overall survival were patient age 75 years or older, prostate specific antigen 20 ng/ml or greater, Gleason score 7 or greater and abnormal digital rectal examination. Gleason score 7 or greater, prostate specific antigen 20 ng/ml or greater and a low comorbidity index were independent predictors of shorter cancer specific survival. The use of primary androgen suppression therapy in the Prostate Cancer Outcomes Study data set resulted in 91% 5-year cancer specific survival. Advanced age, and factors that reflect tumor burden and biology were predictive of overall survival, while cancer specific survival was predicted by tumor factors and the burden of comorbid conditions. A nomogram for predicting overall survival at 5 years was constructed.

Lumpectomy and Partial Breast Irradiation as an Alternative to Mastectomy After Prior Breast Irradiation

Mastectomy has long been regarded as the standard of care for local relapse after breast-conserving surgery and radiation therapy. Due to the perceived heightened risk of toxicity, a similar rationale and approach is often employed for patients that develop a new breast cancer after being treated with mantle field irradiation for Hodgkin’s disease or lymphoma. Patients are increasingly requesting additional breast conserving treatment following an initial excellent cosmetic outcome before recurrence. After receiving whole breast external beam radiation therapy, most recurrences occur within or close to the quadrant of the index lesion. Partial breast irradiation (PBI) can target the areas at greatest risk for residual microscopic disease while minimizing the volume of healthy breast tissue re-irradiated. Studies with short follow up suggest that catheter-based interstitial brachytherapy or limited-field external beam radiotherapy can be safely delivered to the breast following an initial course of external bream radiotherapy with acceptable outcomes. A prospective, randomized Phase II multicenter trial to evaluate repeat lumpectomy followed by PBI for in-breast tumor recurrence is warranted to explore the role of repeat breast-conservation.

Assessment of cognitive functions before and after stereotactic interstitial radiosurgery of hypothalamic hamartomas in patients with gelastic seizures

We assessed cognitive functions before and 3 months after interstitial radiotherapy in 14 patients with gelastic seizures caused by hypothalamic hamartoma. Cognitive functioning was assessed before temporary implantation of 125I-seed and 3 months after seed explantation. Performance was compared with that of a selected control group of conservatively treated patients with symptomatic focal epilepsy tested before add-on treatment with a new antiepileptic drug and after reaching steady state. No short-term negative side effects of the interstitial radiosurgery could be observed for the domains of attention and executive functions and verbal and figural memory performance. Cognitive development of the patients treated with seeds was comparable to that of the control group at both assessments. Thus, the stereotactic implantation of 125I-seeds in this patient group with gelastic seizures caused by hypothalamic hamartoma provides a well-tolerated minimally invasive method in the treatment of this severe epileptic syndrome without negative cognitive side effects.

Bladder Cancer Incidence and Risk Factors in Men With Prostate Cancer: Results From Cancer of the Prostate Strategic Urologic Research Endeavor

We evaluated a large disease registry to determine the incidence of bladder cancer in patients with prostate cancer and investigate whether the type of treatment for prostate cancer increased the risk of bladder cancer. We analyzed the CaPSURE disease registry for men diagnosed with prostate cancer plus bladder cancer between 1989 and 2003. Demographics, comorbidities and prostate cancer treatment modalities were compared in patients with and without bladder cancer. A backward stepwise Cox proportional hazards regression model was used to predict bladder cancer onset after treatment for prostate cancer in patients who had bladder cancer 30 days or greater after prostate cancer treatment. Of 9,780 patients from CaPSURE 143 (1.46%) also had bladder cancer. Patients with bladder cancer and prostate cancer were older (p<0.01) and more likely to be white (p=0.03), and they had lower levels of income (p<0.01) and education (p=0.04) than patients with prostate cancer only. Comorbidities did not differ between patients with and without bladder cancer. Patients treated with radical prostatectomy were approximately half as likely to have posttreatment bladder cancer as patients who underwent radiation therapy (HR 0.51, 95% CI 0.29-0.89). Patients who smoked had an independent increase in the risk of bladder cancer (HR 2.08, 95% CI 1.09-3.97), while smokers treated with radiation therapy were at almost 4-fold risk for bladder cancer (HR 3.65, 95% CI 1.45-9.16). The incidence of bladder cancer in patients with prostate cancer was 1.5%. Radiation therapy and smoking increased the risk of bladder cancer.

Lokoregionäre Hyperthermieverfahren in der Gynäkologie - Standortbestimmung und Perspektiven

Unter dem Begriff lokoregionäre Hyperthermieverfahren fasst man die lokale Hyperthermie (Erwärmung von oberflächlichen Tumoren, z. B. Brustwandrezidiv eines Mammakarzinoms), die regionale Hyperthermie (Behandlung größerer Körperregionen, z. B. pelvine Tumoren) und die interstitielle Hyperthermie (Einbringen von Sonden in den Tumor mit anschließender Erwärmung) zusammen. Gegenwärtige Einsatzmöglichkeiten der wissenschaftlich begründeten Hyperthermie bestehen in Deutschland lediglich im Rahmen kontrollierter Studien bzw. in Kooperation mit den Niederlanden. Durch prospektiv randomisierte Studien untermauerte Anwendungsbereiche betreffen vorbestrahlte Patientinnen mit Lokalrezidiven von Mammakarzinomen (in Kombination mit einer erneuten Radiatio) und Patientinnen mit Zervixkarzinomen (ebenfalls in Kombination mit einer Strahlentherapie und bei Rezidiven in Kombination mit einer Chemotherapie). Auch Patientinnen mit ausgedehnten Vaginalkarzinomen (Stadium II > 4 cm und Stadium III) profitieren möglicherweise ersten Ergebnissen zufolge von einer Kombination der Strahlentherapie mit einer Hyperthermie. Für eine abschließende Bewertung dieser Therapiemethode ist einerseits das Abwarten von Studienergebnissen erforderlich, insbesondere hinsichtlich des Vergleichs der hyperthermen Radiotherapie mit einer Radiochemotherapie bei Patientinnen mit Zervixkarzinom FIGO-Stadium I B - IV A und der magnetischen Flüssigkeitshyperthermie in Kombination mit einer interstitiellen Strahlentherapie bei Patientinnen mit inoperablen lokal begrenzten Residualtumoren. Andererseits bleibt abzuwarten, welche Fortschritte experimentelle Targeting-Verfahren im Hinblick auf ihre klinischen Einsatzmöglichkeiten erzielen.

Impact of a multi-disciplinary patient education session on accrual to a difficult clinical trial: the Toronto experience with the surgical prostatectomy versus interstitial radiation intervention trial: Wallace K, Fleshner N, Jewett M, Basiuk J, Crook J, Department of Radiation Medicine and the Division of Urology, Princess Margaret Hospital, University Health Network, Toronto, Canada

Random assignment to clinical trials involving different treatment modalities can be difficult. We describe our experience with the Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial (SPIRIT; ACOSOG Z0070 NCIC PR10), a randomized trial for early-stage prostate cancer comparing radical prostatectomy (RP), and brachytherapy (BT). A multidisciplinary educational session was developed to improve patient understanding of treatment options and to facilitate accrual. Prostate cancer referrals were screened and men who met favorable risk criteria (T1c/T2a, prostate-specific antigen [PSA] < 10 ng/mL, Gleason < or = 6) were invited to a structured education session before a specialty consultation. Men and their partners viewed the SPIRIT informed-consent video and heard from a cancer patient who described his participation in a randomized trial. Then, a urologist and radiation oncologist together compared and contrasted RP and BT to establish the rationale for the trial. In May 2002, SPIRIT opened for accrual and was endorsed by the University Health Network urologists and radiation oncologists. The first 27 eligible patients were approached about SPIRIT, consulted both specialties, and viewed an educational video. No patients consented. The multidisciplinary education session was then introduced. Forty-seven education sessions with 263 patients resulted in 34 consents. Of 203 patients who were suitable for the study but declined random assignment, 62 chose surgery, 94 chose brachytherapy, three patients chose external radiotherapy, and 11 chose no treatment. Consent rates for eligible and suitable patients were one in six. Men who understand their treatment options and trial rationale as presented jointly by representative specialists from competing treatment modalities may be better equipped to make an informed decision and are more likely to consent to random assignment.

Defining High Risk Prostate Cancer—Where do we Set the Bar? A Translational Science Approach to Risk Stratification

Risk stratification is commonly used in patients with prostate cancer but this effort has had no demonstrable effect on patient decision making for initial therapy. We propose new risk strata for clinically localized prostate cancer. We examined current stratification methods for prostate cancer and their impact on prostate cancer therapy. Three risk strata for patients with clinically localized prostate cancer are proposed. Stratum 1 includes patients in whom active surveillance is associated with a low risk of disease progression. Stratum 2 includes patients in whom monotherapy, including external beam, interstitial radiotherapy or radical prostatectomy, is generally successful. Stratum 3 includes patients at high risk for recurrence with monotherapy in whom multimodal therapy may be superior. Risk stratification systems for prostate cancer should harmonize the needs of researchers to develop comparable groupings of patients, of patients who seek guidance on optimal therapy and of clinical trialists who seek to advance therapy for this disease. Our new stratification system provides such a structure.

Recurrent pleomorphic adenoma of the parotid gland: Long-term outcome of patients treated with radiation therapy

To evaluate the role of radiation therapy in the management of recurrent pleomorphic adenoma of the parotid gland. Between 1960 and 2004, 34 patients were treated with postoperative radiation therapy for recurrent pleomorphic adenoma of the parotid gland to a median dose of 5000 cGy (range, 4,500-6,000 cGy). Median age was 48 years (range, 24-72 years). Gross total resection at the time of surgery before radiation was achieved in 30 patients (88%), and histologic analysis demonstrated multifocal disease in 16 patients (47%). Radiation was delivered for a first, second, third, fourth, fifth, and sixth local recurrence in 24%, 21%, 24%, 24%, 6%, and 3% of patients, respectively. With a median follow-up of 17.4 years (range, 2.3-28.9 years), 2 patients had local recurrences at a median of 3.4 years after completion of radiation. The 20-year actuarial local control rate was 94%. One patient developed a second malignancy at approximately 14 years after completion of therapy. The use of postoperative radiation therapy leads to excellent long-term local control for the treatment of recurrent pleomorphic adenoma with acceptable late toxicity. Although the incidence of second malignancy was low in this population, continued follow-up is warranted.

A Novel Approach to Advanced Carcinoma of the Tongue: Cases Successfully Treated with Combination of Superselective Intra-Arterial Chemotherapy and External/High-Dose-Rate Interstitial Radiotherapy

This study sought to evaluate the efficacy and safety of a novel treatment regimen, intra-arterial cisplatin infusion plus external/high-dose-rate radiotherapy. Superselective intra-arterial infusion of cisplatin (100-120 mg) was performed concomitantly with external radiotherapy in four patients with locally advanced carcinoma of the tongue. A high-dose-rate brachytherapy boost was performed after combination therapy in all patients. Brachytherapy was performed after external radiotherapy, and the treatment schedule was twice daily, with a fraction of 600 cGy up to a total of 30-48 Gy. All patients completed the therapy as scheduled. There were no vascular or neurological complications. Grade III acute radiation mucositis developed in all patients but this did not necessitate a treatment break. With a mean follow-up period of 35 months, loco-regional control was obtained for all patients. The combination of weekly administration of intra-arterial cisplatin plus external/high-dose-rate radiotherapy seems effective for advanced carcinoma of the tongue.

Long-term Functional Outcome of Brachytherapy for Carcinoma of the Mobile Tongue: Focus on the Atrophic Change of Irradiated Tongue

To assess tongue atrophy and long-term functional outcome of mobile tongue cancer patients after interstitial radiotherapy. Of 493 patients whose squamous cell carcinoma of the mobile tongue had been treated with low dose rate brachytherapy, there were 57 patients evaluated between July 2002 and April 2004 whose tongue had not been modified by surgical procedures and who had no primary recurrence. The median time from treatment to evaluation was 96 months (range: 9-214 months). Almost all of the patients belonged to the early stage tongue cancer (T1/T2/T3/T4=30:24:3:0), and all had received interstitial radiotherapy with a single-plane implant. To evaluate the deformity of the tongue, we used a grading system that classified the atrophic changes of the tongue into four categories (G0-G3). Thirty-nine patients (70%) showed mild tongue hemiatrophy (G1 or G2) in the irradiated side. However, no patients showed severe atrophy where the tongue cannot be made to protrude beyond the incisors (G3). The length of time after brachytherapy was >72 months and the age of the patients at brachytherapy had the same statistical significance (P=0.0366). As for functional outcome, understandability of speech and a normal diet were preserved for almost all patients. The progression of atrophic change in the irradiated tongue occurred over a long term after brachytherapy. However, most patients could maintain their activities of daily life without severe restriction.

Review of Radiosurgery of Pineal Parenchymal Tumors. Long Survival Following 125-Iodine Brachytherapy of Pineoblastomas in 2 Cases

The aim of the present work is to report the volumetric changes of tumor in two pineoblastoma patients treated with stereotactic interstitial irradiation and to present a review on radiosurgery of pineal parenchymal tumors. Two of our patients with pineoblastoma were treated with CT and image-fusion guided 125-iodine brachytherapy. The tumor volumes were determined with outlined contours on planning and control CT/MRI images and were compared. Until January 2006, there were 61- and 58-month follow-up periods in the two cases. 56 and 53 months after irradiation the MRI images showed significant tumor shrinkage. In case 1 tumor volume was 0.76 cm (3) on the last control MRI image, compared to the 2.87 cm (3) at the time of interstitial irradiation, which means 73% shrinkage. In case 2, tumor volume measured with the last control MRI examination was 0.29 cm (3), which represents 77% shrinkage of the original tumor volume. In both Cases 1 and 2, PET examinations using (11)C-methionine showed no active tumor mass 56 and 53 months following brachytherapy. Two successful treatments of pineoblastoma are reported. The interstitial irradiation of the tumors decreased their volumes significantly. The CT and image fusion-guided 125-iodine stereotactic brachytherapy can be planned well dosimetrically and is surgically precise.

Salvage-radikale Prostatektomie

Following external beam radiation and interstitial radiation for prostate cancer, between 30% and 50% of the patients experience locoregional recurrence of their cancer. Although radical salvage prostatectomy is a secondary treatment option with curative intent, so far only a few hundred patients (<2%) worldwide have undergone this operation. The subject of this paper is a review of the world literature with reference to the frequency with this operation is performed and the technique, and also the prospects of success and possible complications. After radiotherapy, approximately 30% of biopsies are positive. Nonetheless, only 536 cases of salvage radical prostatectomy had been reported in the world literature up to 2005. The diagnosis of a local recurrence was always confirmed by rectal punch biopsy, pelvic CT and bone scintigraphy. Salvage radical prostatectomy with or without nerve sparing, with pelvic lymphadenectomy and, in some patients with cystectomy plus urinary diversion was the operative treatment applied. Following secondary treatment after radiotherapy (RT), three parameters have been consistently identified as predictors of local failure: PSA nadir, time to nadir and PSA doubling time; clinical stage and type of first-line treatment are not helpful in predicting failure. The 5-year biochemical relapse-free survival rates are 77%, 71% and 28% for stages pT2, pT3a and pT3b/pN1, respectively. The success rate for salvage radical prostatectomy is thus similar to that for de novo radical prostatectomy for the same stages. In the past salvage radical prostatectomy following radiotherapy had a high complication rate. A salvage radical prostatectomy with curative intent is a radical prostatectomy following radiotherapy also performed with curative intent. The reasons for the few literature reports of salvage RPX are: (1) oncological misgivings (too long a period of observation of PSA by the radiation oncologist/urologist; (2) misgivings to do with surgical technique, as the operation is technically challenging and involves a high risk of complications, especially incontinence. In recent times the comorbidity rate has become acceptable in cases in which the indications have been correctly observed. We believe that salvage prostatectomy should be considered only for patients in good general health whose life expectancy is over 10 years and who have recurrent cancer confirmed by punch biopsy 1 year or longer after the completion of radiotherapy and whose cancer was initially in an early (T1-2) clinical stage before their radiotherapy. Ideally, serum PSA should be less than 10 ng/ml both initially (before radiotherapy) and before salvage surgery. In addition, patients should be highly motivated and able to accept the surgical morbidity (50% incontinence rate).

Impact of a Multi-Disciplinary Patient Education Session on Accrual to a Difficult Clinical Trial: The Toronto Experience With the Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial

Random assignment to clinical trials involving different treatment modalities can be difficult. We describe our experience with the Surgical Prostatectomy Versus Interstitial Radiation Intervention Trial (SPIRIT; ACOSOG Z0070 NCIC PR10), a randomized trial for early-stage prostate cancer comparing radical prostatectomy (RP), and brachytherapy (BT). A multidisciplinary educational session was developed to improve patient understanding of treatment options and to facilitate accrual. Prostate cancer referrals were screened and men who met favorable risk criteria (T1c/T2a, prostate-specific antigen [PSA] < 10 ng/mL, Gleason < or = 6) were invited to a structured education session before a specialty consultation. Men and their partners viewed the SPIRIT informed-consent video and heard from a cancer patient who described his participation in a randomized trial. Then, a urologist and radiation oncologist together compared and contrasted RP and BT to establish the rationale for the trial. In May 2002, SPIRIT opened for accrual and was endorsed by the University Health Network urologists and radiation oncologists. The first 27 eligible patients were approached about SPIRIT, consulted both specialties, and viewed an educational video. No patients consented. The multidisciplinary education session was then introduced. Forty-seven education sessions with 263 patients resulted in 34 consents. Of 203 patients who were suitable for the study but declined random assignment, 62 chose surgery, 94 chose brachytherapy, three patients chose external radiotherapy, and 11 chose no treatment. Consent rates for eligible and suitable patients were one in six. Men who understand their treatment options and trial rationale as presented jointly by representative specialists from competing treatment modalities may be better equipped to make an informed decision and are more likely to consent to random assignment.

Prostate Cancers Scored as Gleason 6 on Prostate Biopsy are Frequently Gleason 7 Tumors at Radical Prostatectomy: Implication on Outcome

Differentiation between Gleason score 6 and 7 in prostate biopsy is important for treatment decision making. Nevertheless, under grading errors compared with the actual pathological grade at radical prostatectomy are common. We compared the characteristics and outcomes of tumors that were scored 6 on prostate biopsy but were 7 on subsequent radical prostatectomy pathological evaluation to those in tumors with a consistent rating of Gleason score 6 or 7 at biopsy and surgery. We performed a retrospective database analysis from our referral center (1989 to 2004). We compared pre-prostatectomy characteristics, radical prostatectomy pathological features and the post-radical prostatectomy prostate specific antigen failure rate, defined as any 2 consecutive detectable prostate specific antigen measurements, in 3 subgroups of patients, including 156 with matched Gleason score 6 in the prostate biopsy and radical prostatectomy, 205 with upgraded Gleason score 6/7, that is prostate biopsy Gleason score 6 and radical prostatectomy Gleason score 7, and 412 with matched Gleason score 7 in the prostate biopsy and radical prostatectomy. Radical prostatectomy Gleason score matched the prostate biopsy score in 38.2% of biopsy Gleason score 6 and 81.4% of biopsy Gleason score 7 cases. Higher prostate specific antigen was associated and an increased percent of cancer in the prostate biopsy was predictive of discordance between the prostate biopsy and radical prostatectomy Gleason scores (p <0.001). Margin (p = 0.0075) or seminal vesicle involvement (p = 0.0002), cancer volume (p <0.001) and the prostate specific antigen failures rate (p = 0.014) were significantly higher in under graded Gleason score 7 cancer compared to those in matched Gleason score 6 cases. However, they were comparable to those with a matched Gleason score 7 tumor grade (p = 0.66). Almost half of tumors graded Gleason score 6 at biopsy are Gleason score 7 at surgery. Upgraded Gleason score 6 to 7 tumors have outcomes similar to those of genuine Gleason score 7 cancer. For prostate biopsy Gleason score 6 tumors clinicians should consider the overall likelihood of tumor upgrading as well as specific patient characteristics, such as prostate specific antigen and the percent of tumor in the prostate biopsy, when contemplating treatments that are optimized for low grade tumors, including watchful waiting or brachytherapy.

Interstitial radiation therapy for early-stage nasal vestibule cancer: A continuing quest for optimal tumor control and cosmesis

This article reports on the effectiveness, cosmetic outcome, and costs of interstitial high-dose-rate (HDR) brachytherapy for early-stage cancer of the nasal vestibule (NV) proper and/or columella high-dose-rate (HDR). Tumor control, survival, cosmetic outcome, functional results, and costs were established in 64 T1/T2N0 nasal vestibule cancers treated from 1991-2005 by fractionated interstitial radiation therapy (IRT) only. Total dose is 44 Gy: 2 fractions of 3 Gy per day, 6-hour interval, first and last fraction 4 Gy. Cosmesis is noted in the chart by the medical doctor during follow-up, by the patient (visual analog scale), and by a panel. Finally, full hospital costs are computed. A local relapse-free survival rate of 92% at 5 years was obtained. Four local failures were observed; all four patients were salvaged. The neck was not treated electively; no neck recurrence in follow-up was seen. Excellent cosmetic and functional results were observed. With 10 days admission for full treatment, hospital costs amounted to euro5772 (7044 US dollars). Excellent tumor control, cosmesis, and function of nasal airway passage can be achieved when HDR-IRT for T1/T2N0 NV cancers is used. For the more advanced cancers (Wang classification: T3 tumor stage), we elect to treat by local excision followed by a reconstructive procedure. The costs, admission to hospital inclusive, for treatment by HDR-IRT amounts to euro5772 (7044 US dollars). This contrasts substantially with the full hospital costs when NV cancers are treated by plastic reconstructive surgery, being on average threefold as expensive.

Endoscopic Ultrasonography-Guided Implantation of Iodine 125 Seeds in the Treatment of Unresectable Carcinoma of Pancreas

Objective: To introduce the procedures and evaluate the clinic value of endoscopic ultrasonography-guided interstitial implantation of iodine 125 seeds in pancreatic cancer. Methods: Ten cases patients with pancreatic cancer underwent endoscopic ultrasonography-guided interstitial I seeds implantation. All patients were scanned on EUS, needle, and iodion seeds were used. The 125I seed was implanted with 19G needle and mick-gun during procedure. First of all, according to the size of tumor, the optimal quantity of seeds were calculated. Then, under the guidance of endoscopic ultrasonography, iodion seeds were implanted into the tumors for interstitial radiotherapy. CT follow-up examinations were performed one month after the therapy. The mean number of 125I seed ranged from 4 to 12 and the activity per seed ranged from 0.4 to 0.6mCi. Results: After procedure, relief of pain was obtained in 9 cases from 1 to 3 days. Patients were followed-up for 1 month, partial relief was obtained in 4 cases. In one case the pancreatic cancer decreased in size obviously (PR), in 6 cases the cancer size did not changed, 2 cases were progressive. Such complications as gastrointestinal tract bleeding, pancreatic fistula and pancreatitis were not found. Conclusion: Endoscopic ultrasonography-guided implantation of iodine 125 seeds in pancreatic cancer was a safe, reliable, and effective curative method for pancreatic cancer.

Image-guided interstitial brachytherapy of lung tumors

Purpose: Interstitial radiation has been reported by a German group in the treatment of lung cancers in patients deemed inoperable or having contraindications to external beam radiotherapy (EBRT). We report on the feasibility, response and followup of patients treated using image-guided interstitial brachytherapy (IGIB).