Kyu H. Shin

Radiosurgery for the treatment of previously irradiated recurrent primary brain tumors and brain metastases: initial report of radiation therapy oncology group protocol (90-05).

PURPOSEnTo determine the maximum acutely tolerable dose of single fraction radiosurgery in patients with recurrent previously irradiated primary brain tumors or brain metastases.nnnMETHODS AND MATERIALSnBetween August 1990 and September 1993, 102 analyzable patients were entered on Radiation Therapy Oncology Group (RTOG) protocol 90-05, 38 of whom had recurrent primary brain tumors (median prior dose 60 Gy), and 64 of whom had recurrent brain metastases (median prior dose 30 Gy) < or = 40 mm in maximum diameter. Unacceptable toxicity was defined as irreversible Grade 3, any Grade 4, or Grade 5 central nervous system (CNS) toxicity according to the RTOG CNS criteria, occurring in > 20% of patients per treatment arm within 3 months of radiosurgery.nnnRESULTSnPatients were initially entered onto one of three treatment arms according to the maximum diameter of the recurrent lesion. Twelve to 22 patients were entered on each arm. The dose levels were: arm 1, < or = 20 mm, 18 Gy; arm 2, 21-30 mm, 15 Gy; and arm 3, 31-40 mm, 12 Gy. Subsequently, doses were escalated as follows: arm 4, < or = 20mm, 21 Gy; arm 5, 21-30 mm 18 Gy; and arm 6, 31-40 mm, 15 Gy. Unacceptable acute toxicity secondary to cerebral edema occurred in 0, 7 and 5% of patients on Arms 1, 2 and 3, respectively, and in no patients on arms 4, 5, or 6. Multivariate analysis revealed that tumor volume > or = 8200 mm(3) and a ratio of maximum dose to prescription dose (MD/PD) > or = 2 were significantly associated unacceptable toxicity. Of 15 patients with both tumor volume > or = 8200 mm(3) and MD/PD > or = 2, unacceptable toxicity occurred in 2 of 4 treated with a single isocenter and 1 of 11 treated with multiple isocenters. Subsequently, operation for symptomatic radionecrosis was required in 6% of patients.nnnCONCLUSIONnWe found that the incidence of acute toxicity was acceptable at 0-7% in patients with recurrent, previously irradiated primary brain tumors or brain metastases < or = 40 mm in maximum diameter treated according to the protocol described.

Excellent long-term survival and absence of vaginal recurrences in 332 patients with low-risk stage I endometrial adenocarcinoma treated with hysterectomy and vaginal brachytherapy without formal staging lymph node sampling : Report of a prospective trial

PURPOSEnThe value of adjuvant radiation therapy and staging pelvic lymphadenectomy in patients with low-risk, early-stage endometrial cancer is controversial. The aim of this study was to report the long-term survival, rate of recurrences, and complications in patients with Stage I endometrial cancer, Grade 1-2, with <50% myometrial invasion treated with hysterectomy (without formal staging pelvic and periaortic lymph node sampling or lymphadenectomy) and postoperative vaginal brachytherapy.nnnMETHODS AND MATERIALSnA total of 303 patients with pathologic Stage I endometrial cancer, Grade 1-2, with <50% myometrial invasion and nonmalignant peritoneal cytology, were treated with total abdominal hysterectomy, bilateral salpingo-oophorectomy, and postoperative vaginal brachytherapy (30 Gy to point 0.5 cm depth) in a prospective study extending from 1958 to 1994. In addition, 29 additional Stage I, Grade 1-2 patients with <50% myometrial invasion and malignant peritoneal cytology were treated with 1 year of progesterone therapy. Patients were followed for 1.2-32 years (median 8.1 y).nnnRESULTSnSix patients had recurrences and died secondary to disease. There were no vaginal recurrences. The 5-, 10-, 20-, and 30-year disease-free survivals of the 303 patients with nonmalignant peritoneal cytology were 98.9%, 97.8%, 96.7%, and 96.7%, respectively. Patients with malignant peritoneal cytology had a 5- and 10-year disease-free survival of 100%. Significant radiation complications occurred in 2.1% of the patients.nnnCONCLUSIONnIn patients with low-risk, Stage I endometrial cancer, hysterectomy and adjuvant postoperative vaginal brachytherapy provide excellent long-term survival, eliminate vaginal recurrences, and are not associated with significant complications. The addition of 1 year of progesterone therapy to patients with malignant cytology provides 100% long-term survival. Based on these results, patients with low-risk, Stage I endometrial adenocarcinoma do not need formal staging pelvic and periaortic lymphadenectomy.

A patient-specific in vivo tumor model

A significant body of research, spanning approximately the last 25 years, has focused upon the task of developing a better understanding of tumor growth through the use of in vitro mathematical models. Although such models are useful for simulation, in vivo growth differs in significant ways due to the variety of competing biological, biochemical, and mechanical factors present in a living biological system. An in vivo, macroscopic, primary brain tumor growth model is developed, incorporating previous in vitro growth pattern research as well as scientific investigations into the biological and biochemical factors that affect in vivo neoplastic growth. The tumor growth potential model presents an integrated, universal framework that can be employed to predict the direction and extent of spread of a primary brain tumor with respect to time for a specific patient. This framework may be extended as necessary to include the results of current and future research into parameters affecting neoplastic proliferation. The patient-specific primary brain tumor growth model is expected to have multiple clinical uses, including: predictive modeling, tumor boundary delineation, growth pattern research, improved radiation surgery planning, and expert diagnostic assistance.

Radiation and chemotherapy improve outcome in oligodendroglioma

PURPOSEnOligodendroglioma is a rare central nervous system tumor which may occur in pure or mixed histology. This scarcity results in difficulty in defining optimal management, mainly due to a lack of outcome analysis. Results are further complicated because the reported series include patients treated before megavoltage radiation or computed tomographic (CT) scan development. This makes extrapolation of outcome difficult to apply to modern-era patients. We report results obtained by current treatment and evaluation.nnnMETHODS AND MATERIALSnOutcome of all 38 patients (age 5-70 years) pathologically diagnosed between 1975 and 1993 were reviewed. Pure lesions were seen in 14 cases, of which three were anaplastic. The remainder had mixed tumors, of which six contained anaplastic astrocytic elements. Each patient had undergone maximal debulking surgery, but all remained with residual disease on postoperative CT.nnnRESULTSnFor nonanaplastic lesions, no local failure was seen in any patient receiving postoperative radiation (60 Gy) and chemotherapy (vincristine, procarbazine, and carmustine). Follow-up ranged from 28 to 240 months (median 125; N = 6). No postoperative therapy or chemotherapy alone resulted in local failure in all nine patients at risk [time to failure (TTF): 2-40 months; median 25]. Radiation alone in doses of 50 Gy at 2 Gy per day resulted in all six patients failing (TTF: 12-52 months; median 36). Achieving 60 Gy at 2 Gy a day allowed five of eight patients to remain disease free (disease-free survival: 24-160 months; median 66), with three failing at 26, 40, and 60 months. All lesions containing anaplastic elements underwent postoperative radiation therapy (60 Gy) and chemotherapy, with five of nine patients alive and well (median disease-free survival: 48 months; range 28-120).nnnCONCLUSIONnThe combination of radiation and chemotherapy increases local control of oligodendroglioma whether they contain pure, mixed, or anaplastic histology. Radiation alone may offer good local control as long as 60 Gy is delivered. Chemotherapy alone appears to delay TTF and may be useful for pediatric patients.

Symptomatic acute mucositis can be minimized or prophylaxed by the combination of sucralfate and fluconazole

Mucositis is a common and often serious acute morbidity when radiation is delivered to portals encompassing the oral cavity, pharynx, or esophagus. In an effort to minimize this side effect, the combination of sucralfate and fluconazole was prescribed to 40 patients. Half were given sucralfate, 1 g in suspension q.i.d. from the first week to the completion of radiation with fluconazole 100 mg., q.d. for 14 days initiated during the fourth week. The remaining individuals were placed on the same dosages of the two drugs dispensed simultaneously after symptoms appeared. For both cohorts the combination of sucralfate and fluconazole was effective in diminishing oral discomfort and pain associated with radiation and chemotherapy. When medication was delivered from the first week of therapy, all patients could achieve the prescribed radiation dose without treatment interruption and be maintained on a regular diet. The combination of drugs was also effective in minimizing symptoms once they appeared.

Surface matching of multimodality image volumes by a fuzzy elastic registration technique

Multimodality image registration is useful in diagnostic imaging and treatment planning for radiation therapy. In this paper, we present a technique which registers the surfaces of two volumes acquired by different medical imaging modalities. We represent the image volumes in terms of their surface elements known as tiles. We identify the fuzzy variables, assign fuzzy membership functions to them and generate a fuzzy rule database. The fuzzy algorithm reduces the discrepancy between the two set of tiles until the surfaces are matched. In order to study the efficacy of our approach, we severely warp a simulated image and register it with its original. We register CT and MR volumes of humanoid phantom images. Finally, we present the results at the end of the article.

If you ‘watch and wait,’ prostate cancer may progress dramatically

PURPOSEnObservation has been proposed as an option for localized prostate cancer. However, most series reporting on watch and wait include patients treated by TUR or hormones that may affect results. We retrospectively reviewed the natural history of truly untreated prostate cancer and report the outcome for these patients.nnnMETHODS AND MATERIALSnFrom 1976 to 1992, 34 patients of median age 70 years (range 56-88) with biopsy proven localized adenocarcinoma of the prostate refused therapy. All had negative bone scan and none underwent TUR or hormone treatment. No patient was lost to follow-up (median 76 months). Failure patterns and survival were analyzed.nnnRESULTSnAt diagnosis 27 patients had palpable nodules (T2), of which 13 were well differentiated and 14 moderately differentiated. Seven had moderately differentiated T3 lesions. Mild prostatitis including nocturia, hesistancy, and urgency were reported in 16 T2 and 6 T3 patients. Within 36 months, local progression requiring therapy occurred in all T3, all T2 moderate and 5 of 13 T2 well-differentiated patients. Systemic progression occurred in 6 of 7 T3, 9 of 14 T2 (mod), and 2 of 13 T2 (well) patients. Overall 59% are alive, 26% succumbed to prostate carcinoma and 15% to other causes.nnnCONCLUSIONnObservation results in a high rate of local progression requiring intervention (77%) and excessive systemic disease development (50%) for patients with clinically palpable disease. Perhaps this strategy is viable for earlier stage lesions detected by PSA but it must be tested in a rigorous fashion before accepted.

Two new parallel-plate ionization chambers for electron beam dosimetry

Abstract Two parallel-plate ionization chambers were projected, constructed and evauated for use in high energy electron beams. They were constructed using the two plastic materials recommended for clinical dosimetry protocols, i.e. acrylic and polystyrene. Both chambers have cylindrical shape with entrance windows in aluminized Mylar and they are open to the air. The acrylic chamber has a 2 mm air gap and the polystyrene chamber has a 1 mm air gap. Pre- and post-irradiation leakage, repeatability and long term stability were determined for these two ionization chambers. The ionic recombination and polarity effects, besides angular and energy dependencies, were also verified. The results obtained are within values recommended by IEC (1982) [Medical electrical equipment: dosimeters with ioniz chamber as used in radiotherapy. IEC, Geneva (IEC-731-82)] for this kind of ionization chamber. The ionization chambers were calibrated in a 20 MeV electron beam and gamma radiation of cobalt-60. The wall correction factors for the gamma radiation for cobalt-60 were 1.014 and 1.000 for the acrylic and polystyrene chambers, respectively. The ionization chambers do not present the energy dependence for the 6–20 MeV electron beam range. These results are comparable to commercially available ionization chambers.

Patient-specific tumor prognosis prediction via multimodality imaging

This paper proposes an approach to advance the utility of physical modeling techniques for medical applications by correlating finite element based models with the mechanical anatomy characteristic of a clinical patient. A methodology is presented to model the patient-specific mechanical response of brain tissue in vivo. The resultant model is parameterized in terms of clinical CT and MRI imaging sequences acquired for each patient. Applications of the proposed technique to the areas of brain tumor growth modeling and predicting tissue shifts during stereotactic neurosurgery, are described. Results are presented for an implementation of our approach to the problem of predictive brain tumor modeling.

Fractal-based characterization of structural changes in biomedical images

In the present work, distinct structures appearing in biomedical images are modeled as fractals. Within an image, the relevant structures are associated to a fractal dimension. Changes in the dimension values, as a function of time, reflect alterations of structural properties. Accurate and robust estimation of this dimension, leads to a precise characterization of changes undergone by the structure. The Continuous Pyramidal Alternating Sequential Filter method is proposed as a robust and accurate fractal dimension estimator. A study on bedrest data of human subjects was conducted. Bedrest is an accepted model for the study of osteoporosis. Here the spine is modeled as a fractal structure. Fractal model were also applied towards analysis of breast cancer and brain tumors. Results from these different studies confirm that fractals can suitably model a variety of biological structures. These studies also suggest that fractal models can be effectively utilized to detect temporal changes undergone by the structures.