Complete remission of refractory dyshidrotic eczema with the use of radiation therapy.

Dyshidrotic eczema is a chronic, enigmatic condition that usually affects the hands and feet. Modern-technique radiation therapy using megavoltage equipment for the treatment of dyshidrotic eczema has not been described in the literature before. A dramatic clinical response to low-dose external beam radiation therapy was observed in a patient refractory to multiple forms of topical and systemic agents. Complete resolution of this severe presentation of dyshidrosis occurred within 1 month following therapy, with a durable response at 6 months. Withdrawal of oral steroids, without flare of disease, was possible after 6 weeks, with the patient remaining free of medication at the 6-month interval. Complete remission of severe dyshidrotic eczema is achievable using low-dose external beam megavoltage therapy in situations where other forms of conventional therapies have failed. Lasting remission may allow for the complete withdrawal of oral or topical agents, which may become harmful with chronic use.

Complete remission of nonresectable pancreatic cancer after infusional colloidal phosphorus-32 brachytherapy, external beam radiation therapy, and 5-fluorouracil: a preliminary report.

This is a preliminary report of five patients diagnosed with locally advanced nonresectable pancreatic cancer who achieved improved quality of life, delay of local progression, and reduction of biomarker CA 19-9 after infusion of colloidal phosphorus 32 (32P) and administration of combined chemoradiotherapy. A phase II trial using intratumoral colloidal 32P delivery for nonresectable pancreatic cancer without metastases is in progress. Patients initially were given infusions of decadron followed by macroaggregated albumin and 30 mCi colloidal 32P to the interstitial space of the tumor by two infusions 1 week apart. Through this method, doses ranging from 750,000 to 1,800,000 cGy were delivered. After administration of colloidal 32P, external radiation to a dose of 6000 cGy minimum tumor dose, including regional lymph nodes, was given concomitantly with four intravenous infusions of 500 mg bolus 5-fluorouracil on alternating days within the first 2 weeks after initiation of external radiation. All five of these patients demonstrated cessation of local tumor growth or regression of disease on serial computed tomography scans for a minimum of 10 months from completion of therapy. Three of these patients have survived without local disease progression over 24 months from initiation of therapy, with one patient approaching 36 months. CA 19-9 values for all patients declined within weeks after completion of therapy. This new method of isotope delivery has resulted in reduction of tumor volume, normalization of the biomarker CA 19-9, and improved performance status in those patients who have localized nonresectable disease without dissemination.

Changes in high-dose-rate tandem and ovoid applicator positions during treatment in an unfixed brachytherapy system.

PURPOSE: To measure the change in applicator position during treatment in an unfixed high-dose-rate (HDR) brachytherapy system and to evaluate the effect of the shifts on dose calculations. MATERIALS AND METHODS: Posttreatment localization radiographs were obtained for 47 HDR treatments (26 tandem and ovoid applicators, 21 ovoids-only applicators). The authors measured the change in applicator position relative to the patient's bone anatomy. Doses to the target and critical structures were calculated for posttreatment applicator positions for comparison. RESULTS: Average displacements of the tandem and ovoid applicators in anteroposterior dimension were 5 and 4 mm for the tandem and ovoids, respectively. Anterior displacement occurred twice as often as posterior displacement. The average lateral and longitudinal shifts were less. Less displacement was observed with ovoids-only insertions. The largest displacement for ovoids-only applicators was 3 mm in the anteroposterior dimension. A high bladder dose difference (17.4%) for tandem and ovoid applications correlated with anterior shifts of the applicators. CONCLUSION: Patient movement in an unfixed HDR brachytherapy system can displace the applicators, especially the tandem. Anterior shifts correlate with high bladder dose differences. Immobilization of the patient's hips and legs, as well as stabilization of applicators, would reduce these shifts.

Evaluation of cellular uptake, tumor retention, radiation response, and tumor pathophysiology in experimental solid tumors after an intratumoral infusion of colloidal 32P.

BACKGROUND: Order et al. successfully deposited > 85% of radionuclides in pancreatic carcinoma patients using an intratumoral (i. t.) infusion of macroaggregated albumin (MAA) prior to the i. t. infusion of colloidal 32P (32P-CP), apparently due to MAA-induced transient blockade. However, no studies regarding physiologic response and the inhibitory tumor growth of solid tumors after treatment with 32P-CP with or without MAA have been performed. METHODS: First, the authors determined the cellular uptake of 32P-CP in 10 cell lines. They then evaluated the relationship between tumor retention and radiation response in vivo. Third, they evaluated the changes in physiologic parameters such as tumor interstitial fluid pressure (TIFP) and tumor blood flow (TBF) after an i. t. infusion of MAA. RESULTS: In the plateau growth phase of both H4IIE and LS174T tumors, maximal uptake occurred at approximately 100 minutes after treatment with 10 microCi of 32P-CP, but uptake in LS174T was approximately 2 times higher than that in H4IIE. In animal experiments, 32P-CP alone significantly inhibited the tumor growth of H4IIE. However, additional i. t. infusion of MAA did not improve the growth delay induced by 32P-CP, mainly due to insignificant differences in retention of radioactivity when using 32P-CP with or without MAA. It was speculated that when the outflow of the tumor vasculature was obstructed by clamping (or an i. t. infusion of MAA), it would reduce TBF and increase TIFP. However, neither increased TIFP nor decreased TBF was observed when MAA was given i. t. to tumors. CONCLUSIONS: The authors concluded that an MAA-induced transient blockade of tumor vasculature after an i. t. infusion of MAA did not occur in experimental solid tumors.

Selective tumor irradiation by infusional brachytherapy in nonresectable pancreatic cancer: a phase I study.

PURPOSE: Selective high-dose radiation of solid tumors has been a goal of radiation oncology. The physiological barriers of solid tumors (high interstitial tumor pressure, reduced tumor vascularity, and poor perfusion) have been major barriers in achieving significant tumor dose of systemically infused radioconjugates. Direct tumor infusional brachytherapy overcomes these barriers and leads to selective high tumor doses. METHODS AND MATERIALS: The development of interstitial tumor infusion of macroaggregated albumin (MAA) followed by colloidal chromic phosphate 32P has overcome solid tumor obstacles in 47 patients with nonresectable pancreatic cancer in a Phase I dose escalation study. The colloidal 32P infusion was followed by external radiation and five fluorouracil. RESULTS: Of the 28 patients with cancer limited to the pancreas, 15 of 16 patients retained 86-100% (mean 96%) of the infused colloidal 32P isotope. While the other 12 patients had partial shunting to the liver, shunting to the liver was due to high interstitial resistance with tumor dose deposition of 17-88% (mean 52 %). Of the 19 patients with metastatic pancreas cancer, colloidal 32P tumor deposition ranged from 22 to 100% of the infused dose (mean 79%). The less than optimal tumor deposition led to our increasing the MAA from 600,000 to 1.5-2.5 million particles. Interstitial dexamethasone 2 mg and later 4 mg was infused first and prevented liver shunting by somehow reducing tumor resistance. The median survival in 28 Phase I patients with nonresectable pancreas cancer without metastasis, was 12 months. No significant toxicity occurred when treatment was limited to two infusions with as much as 30 mCi each. The maximum tumor dose was 17,000 Gy (1.700,000 cGy). In 19 nonresectable pancreatic cancer patients with metastasis, a 6.9 months median survival was observed. CONCLUSIONS: Infusional brachytherapy is an outpatient procedure that delivers high-dose radiation selectively to pancreatic cancer. Results of the Phase I study in nonresectable pancreas cancer has led to a national multiinstitutional Phase II trial.

Preliminary experience of infusional brachytherapy using colloidal 32P.

In the past, we have clinically evaluated radiolabelled antibodies in Hodgkin's disease and hepatocellular cancer. Increased tumour pressure, reduced vascularity and poor diffusion has limited significant radiolabelled antibody tumour dose deposition. Using intratumoural infusion of macroaggregated albumin to blockade exiting vasculature followed by colloidal chromic 32Phosphorous, we have been able to achieve 75% to 100% tumour dose deposition by interstitial tumour infusion under computerised tomographic guidance. Phase I studies in a variety of solid tumours indicate extremely high doses may be achieved without toxicity (i.e. non-resectable pancreas 900,000 cGy to 1.7 million cGy) with tumour control and remission. This is a review of those studies and how the technique was applied.

Quantitative bremsstrahlung single photon emission computed tomographic imaging: use for volume, activity, and absorbed dose calculations.

PURPOSE: To perform bremsstrahlung single photon emission computed tomographic (SPECT) imaging using 32P chronic phosphate for volume and activity quantitation to calculate absorbed dose estimates. METHODS AND MATERIALS: Seven cancer patients enrolled in clinical Phase I therapeutic protocols were injected with 2.5 million particles of macroaggregated albumin, followed by colloidal 32P chromic phosphate by direct interstitial injection into the tumor-bearing region under computed tomographic (CT) guidance. SPECT images were obtained in these patients. The patient body contour was defined through the use of two externally placed Compton backscatter 99mTc sources. A computer algorithm was written to facilitate region-of-interest volume and activity determination on the reconstructed SPECT slices based on a fixed threshold method. Three sequential SPECT studies were acquired in two of these patients, to determine the accuracy of activity quantitation for bremsstrahlung SPECT studies using Chang's postprocessing method of attenuation compensation with a computer-generated body contour based on the Compton backscatter sources, and an experimentally measured effective linear attenuation coefficient for 32P. The serial data in these two patients were used to calculate absorbed dose estimates. RESULTS: The 99mTc backscatter sources enabled the patient body outline to be clearly visualized in all the transaxial reconstructed slices and did not contribute significant counts to the patient 32P counts. The calculated activities from the SPECT studies were within 7.8% of the administered 32P activity. The two calculated patient absorbed doses were 4.2 x 10(3) Gy and 5.9 x 10(3) Gy for injected activities of 736 MBq and 920 MBq, respectively. CONCLUSION: We conclude that accurate quantitative bremsstrahlung SPECT imaging, for the case of high contrast well-localized activity distributions, with a commercially available postprocessing attenuation correction algorithm, can be performed in a clinical setting. Entirely SPECT-based measurements can be used to generate absorbed dose estimates.

Microprocessor-controlled Nd:YAG laser for hyperthermia induction in the RIF-1 tumor.

Near-infrared radiation from a Nd:YAG laser at 1,064 nm was used interstitially or superficially to induce hyperthermia in RIF-1 tumors in C3H male mice. A single 600-microns quartz fiber with a 0.5-cm cylindrical diffusor or a weakly diverging microlens at its distal end was used to deliver laser energy to tumors in the hind leg (mean volume = 100 mm3). Two thermocouples were inserted into each tumor. One thermocouple controlled a microprocessor-driven hyperthermia program (maximum output of 3.5 Watts) to maintain the desired temperature. Tumors were exposed to various temperature-time combinations (42-45 degrees C/30 min). Our initial results indicated that excellent temperature control to within 0.2 degrees C of the desired temperature at the feedback thermocouple was achievable during both superficial and interstitial heat treatments. Temperatures at the second thermocouple, however, were found to be lower by as much as 2.3 degrees C (using the cylindrical diffusor) or higher by up to 4.6 degrees C (using the microlens) when compared to the feedback thermocouple temperature. Several correlations were seen between total dose, tumor growth delay, percent skin necrosis, and temperature at the second thermocouple after several superficial and interstitial treatments. Statistically significant improvements in tumor growth delay (at 42 and 45 degrees C) and increased percent skin necrosis at all temperatures were observed after superficial versus interstitial treatment.

Effect of Fluosol-DA 20% and oxygen on response of C57BL/6 mice to whole-body irradiation.

Normal tissue effects in mice due to combinations of a perfluorochemical emulsion, Fluosol-DA 20%, 100% oxygen, and whole-body irradiation were investigated. Eight-to-10-week-old C57BL/6 male mice were injected via the tail vein with 10 ml/kg of Fluosol-DA with and without subsequent exposure to oxygen for 60 minutes. Animals then received graded doses of whole-body radiation (4 MV photons) at a dose rate of 2.85 +/- .015 Gy/minute. Using linear regression analysis, the lethal doses of radiation to 50% and 10% of the animals within 30 days in the absence of Fluosol-DA and oxygen were 8.35 Gy (95% c.l.:7.77-8.93 Gy) and 6.73 Gy (95% cl.:6.21-7.25 Gy), respectively, and were unaffected by Fluosol-DA and/or oxygen pre-treatment. However, Fluosol-DA given alone or in combination with oxygen produced increased balding and decreased graying incidence in mice within 60 days, and resulted in depressed weight gain 15 to 60 days post-treatment. Normal tissue effects due to administration of Fluosol-DA and oxygen in combination with whole-body irradiation have been demonstrated but appear minimal compared to other anti-tumor modalities currently under investigation.

Impact of initial quality control review on study outcome in lung and head/neck cancer studies--review of the Radiation Therapy Oncology Group experience.

The Radiation Therapy Oncology Group (RTOG) initiated cooperative clinical trials in 1971. In 1978, RTOG developed a formalized program of Quality Control (QC) divided into initial and final phases. The initial review process consisted of two steps. The first phase of review is an evaluation performed by a radiation oncologist to verify treatment plan and field borders. The second portion of the initial review process originally consisted of dosimetry calculation verification based on machine data provided by the regional Radiological Physics Center and treatment planning data provided by the accessioning institution. Between 1978 and December 31, 1987, a total of 11,343 cases in 96 RTOG protocols, excluding particle studies, underwent initial review. Of this number, 2227 patients were entered in lung cancer studies and 1341 patients were entered in head/neck cancer studies. Initial review was carried out in 2089 (93.8%) of the lung cancer cases. Missing or delayed data accounted for 138 (6.2%) cases not reviewed initially. In head/neck cancer trials, 1251 (93.2%) received initial review and 90 (6.8%) did not. Our findings suggest that there are sharply defined but long lasting learning experiences involved in clinical trial participation. Consideration may be given to modifying the initial review process to use random sampling of cases accessioned by experienced investigators in ongoing clinical trials and to continuing the total case evaluation on all new studies and cases entered by inexperienced investigators or investigators/institutions with unsatisfactory performance. Recommendations regarding initial review of other sites will await evaluation of the impact of initial review on those sites.

The effect of fraction size on control of early glottic cancer.

A retrospective analysis of 600 patients treated for head and neck malignancy at the Cooper Hospital/University Medical Center was undertaken. Patients who had surgical intervention (excluding biopsy) were withdrawn from this review. Fifty-eight patients with Stage I Glottic Laryngeal Carcinoma were identified and constitute the basis of this report. Various parameters were analyzed to assess their impact on local control. These include age, sex, serum hemoglobin, tumor bulk, differentiation, field size, total dose, total treatment time, and fraction size. Overall local control was 87% with a median follow-up of 63 months. The only factor that influenced local control was fraction size. Of 28 patients treated with 180 cGy fractions, seven (25%) had a local recurrence within 3 years. Twenty-eight patients treated with 200 cGy or greater fractions have had no failures to date. The difference in control rate when comparing the two treatment schema was significant (p less than 0.01). The median dose in the controlled 180 cGy group was 6660 cGy (range, 6300-7020 cGy). In the patients who failed in the 180 cGy group the median dose was 6660 cGy (range, 6480-6840 cGy). The patients receiving 200 cGy fractions or greater had a median dose of 6600 cGy (range, 6000-6950 cGy) and an average dose of 6507 cGy. The mean NSD in the 180 cGy group failing was 1787 RET (range, 1735-1843 RET). Patients who were controlled and received 180 cGy fractions had a median NSD of 1796 RET (range, 1743-1868). The mean NSD in the 200 cGy group was 1847 RET. The median TDF in the 180 cGy group of patients controlled was 102. Those failing also had a TDF of 102 (range, 101-105). Patients receiving 200 cGy fractions or greater had a median TDF of 109. It appears from this data that fraction size is a highly significant factor in our ability to control glottic laryngeal cancer.

Patterns of Care Study. Analysis of outcome survey data-anterior two-thirds of tongue and floor of mouth.

The Patterns of Care Study, begun in 1973, carried out its second outcome survey from December 1978 through April 1979. The review of patients with epidermoid carcinomas of the anterior two-thirds of tongue and floor of mouth included patients treated between January 1973 and June 1975 so that a minimum follow-up period of 2 years was evaluable. Records of 434 patients from 96 facilities were available for analysis, although not every patient could be evaluated for every variable. Almost three-fourths (320) were treated with radiation alone. In these data, four patient and disease characteristics were strongly related to recurrence rates including stage at presentation, deep ulceration, deep infiltration, and age. Treatment variables significantly affecting recurrence included use of interstitial therapy in Stages I and II, use of surgery in Stages III and IV, and a facility's best equipment.

Prognostic significance of cytomorphology in the cutaneous T-cell lymphomas.

In this retrospective study, the degree of differentiation of atypical lymphoid cells was assessed in pretreatment cutaneous biopsy specimens from 248 patients with cutaneous T-cell lymphomas (mycosis fungoides and Sézary syndrome) and the findings were correlated with the subsequent therapeutic results. Overall, patients with a predominance of cells with hyperchromatic nuclei (well-differentiated lymphoid cells) in cutaneous infiltrates responded better to treatment with improved survival rates than patients with infiltrates composed predominantly of cells with pale vascular nuclei (poorly differentiated lymphoid cells). Infiltrates with a predominance of poorly differentiated lymphoid cells were observed primarily in patients with advanced (tumor) stages of disease. However, comparison of the therapeutic results achieved for the two cytomorphologic patterns in patients at comparable stages of advanced disease did not reveal significant differences, indicating that the presence of poorly differentiated cells in large proportions does not have additional prognostic implications beyond those obtained from usual staging procedures. We speculate that the atypical cells with large, pale vesicular nuclei found in lesions of cutaneous T-cell lymphoma are not a more malignant cell population but rather evolve from more hyperchromatic cellular forms, perhaps a byproduct of malignant dedifferentiation.

A 10-year experience with topical mechlorethamine for mycosis fungoides: comparison with patients treated by total-skin electron-beam radiation therapy.

A group of 243 patients with mycosis fungoides (MF) received treatment with topical applications of dilute aqueous solutions of mechlorethamine and/or systemic chemotherapy over the past 10 years. The likelihood of a complete and relapse-free remission and survival was found to correlate inversely to the magnitude of disease as denoted by a simple staging system. Although disease-free intervals of greater than 3 years have occurred thus far in 32 (13%) patients, the permanency of these remissions and the curability of disease remain uncertain because of the variability of disease progression characteristic of MF. Comparison of treatment results with those published on a large group of patients treated with total-skin electron-beam radiation therapy indicates that the chemotherapeutic approach to the treatment of MF is equally effective in promoting survival.

Radiation therapy as initial treatment for early stage cancer of the breast without mastectomy.

This report describes 150 patients with clinical stage I and II carcinoma of the breast treated at four institutions--Yale University School of Medicine, Harvard Medical School-Joint Center for Radiation Therapy, Hahnemann Medical College, Jefferson Medical College--with radiotherapy only following excisional biopsy. Closely similar treatment policies were followed at all four centers, 4500-5000 rads minimum tumor dose being delivered to the entire breast and axillary, supraclavicular and internal mammary nodes. Forty-six of 49 stage I patients treated are alive without disease, the actuarial relapse-free survival being 91% at 5 years. Of the 101 stage II patients, 75 are alive without disease with a relapse-free actuarial survival of 60% at 5 years. Local failure has occurred in 10 patients (9 stage II and 1 stage I, 6.6%) 5 of whom are disease-free following mastectomy. The results obtained in this study are comparable to those of conventional surgery. It is our conclusion that mastectomy is not a necessary part of the treatment of small breast cancers, that radiation without mastectomy is an acceptable alternative with far superior cosmetic and functional results. Adjuvant chemotherapy should be considered particularly in stage II patients in view of their 40% relapse rate.