James S. Welsh

Clinical and Pathologic Predictors of Survival in Patients With Thymoma

OBJECTIVE To evaluate the Johns Hopkins Hospital experience with 136 thymomas over the past 40 years. This number of patients allowed quantitative estimation of the independent influence of common clinicopathologic risk factors using multivariate analysis. SUMMARY BACKGROUND DATA Thymomas vary widely in terms of recurrence and influence on overall survival. Several series have indicated the importance of initial tumor invasion, as well as the extent of surgical resection, as predictors of recurrence and survival after thymoma resection. However, findings have been equivocal when other predictors of prognosis were examined. METHODS The authors evaluated 136 patients seen at the Johns Hopkins Hospital between 1957 and 1997 with a pathologic diagnosis of thymoma. Demographic information, clinical staging data, surgical and adjuvant treatment details, and patient follow-up data were obtained from the patient record and from detailed patient or family interviews. Microscopic sections of all 136 patients were reviewed by two pathologists blinded to the clinical data. All data were analyzed by multivariate Cox regression analysis, which allowed the quantification of the independent predictive value of 12 putative clinicopathologic prognostic indicators. RESULTS Completeness of follow-up was 99%, 99%, and 98% of eligible patients at 5, 10, and 15 years, respectively. Forty percent of the patients had associated myasthenia gravis and 27% had a secondary primary malignancy. Overall patient survival rates were 71%, 56%, 44%, 38%, and 33% at 5, 10, 15, 20, and 25 years, respectively. Overall, the thymoma-related mortality rate was 14%; the nonthymoma-related mortality rate was 26%. Incomplete resection, preoperative absence of myasthenia gravis, and advanced Lattes/Bernatz pathologic class were found to be independent predictors of poorer overall survival. CONCLUSIONS These findings support a policy of aggressive, complete surgical resection of all thymomas when feasible. Thymoma behaves as a rather indolent tumor, with most deaths from causes unrelated to thymoma or its direct treatment. Clinicians should have an increased awareness of the possibility of second primary malignancies in patients with thymoma.

Phase I study of escalating doses of low-dose-rate, locoregional irradiation preceding Cytoxan-TBI for patients with chemotherapy-resistant non-Hodgkin’s or Hodgkin’s lymphoma

PURPOSE In patients in whom bone marrow transplantation (BMT) fails, recurrence often occurs at sites known to have contained disease before initiating BMT. The purpose of this study was to find the maximal tolerable dose of locoregional irradiation (LRT) between 1000 and 2000 cGy that could be integrated with our Cytoxan-total body irradiation (TBI) BMT conditioning regimen in the treatment of lymphoma. METHODS AND MATERIALS Patients had Hodgkins or non-Hodgkins lymphoma in chemotherapy-refractory relapse. All patients received LRT to a maximum of three sets of fields encompassing either all current or all previously known sites of disease. Cytoxan-TBI consisted of cyclophosphamide 50 mg/kg daily for 4 days followed by TBI of 1200 cGy given in four fractions. RESULTS Twenty-one patients were enrolled. Radiation Therapy Oncology Group Grade 3 in-field acute toxicity was observed in 1 patient at each dose level up to 1500 cGy and in 3 of 6 patients receiving 2000 cGy. Clinically evident late toxicities were limited to hypothyroidism and one second malignancy occurring outside the LRT fields. CONCLUSION Low-dose-rate, LRT with concurrent Cytoxan-TBI before BMT has acceptable rates of in-field toxicity for doses up to 1500 cGy in five fractions. This regimen safely permits the use of a total combined radiation dose of up to 2700 cGy during 2 weeks, with encouraging in-field response rates in treatment-refractory patients.

Solitary plasmacytoma of the epiglottis : a case report and review of the literature

A 59-year-old white male presented with a two-month history of dry cough and shortness of breath. At bronchoscopy, a 1 cm mass on the laryngeal surface of the epiglottis was found. Immunohistochemical stain of the biopsy specimen revealed a monoclonal proliferation of plasma cells. Serological tests revealed normal serum immunoglobulin levels, and a bone marrow aspirate and biopsy was also normal; no abnormalities were found on serum or urine electrophoresis. He received radiotherapy (50 Gy), and was doing well three years following therapy without evidence of disease.

Nonsegmental ventilation-perfusion scintigraphy mismatch after radiation therapy.

PURPOSE This report illustrates the utility of ventilation-perfusion scintigraphy in differentiating radiation pneumonitis from other causes of dyspnea, including pulmonary embolism, heart failure, obstructive tumor, and chronic obstructive pulmonary disease. METHODS AND RESULTS A nonsegmental mismatched perfusion abnormality, which exactly conformed to a radiation port, was diagnostic of radiation pneumonitis. CONCLUSION In patients with lung tumors presenting with dyspnea, ventilation-perfusion scintigraphy may be useful in diagnosing radiation pneumonitis and effectively excluding other causes of dyspnea.

Stereotactic radiotherapy for Cushing's disease and prolactinoma

Stereotactic radiotherapy (SRT) for secretory pituitary adenoma offers precise localization of dose with potential sparing of optic and hypothalamic functions. We collated the indications, treatment parameters, and both the clinical and biochemical results of Stereotactic radiotherapy for ACTH- 1 and prolactin-secreting pituitary adenoma. Between May 1990 and February 1996, nine patients (4 males and 5 females) with a mean age of 31.9 years had fractionated SRT for ACTH- or prolactin-secreting pituitary adenomas (Cushings disease: n = 5; prolactinoma: n = 3; Nelsons syndrome: n = 1). These 9 patients had subtotal transphenoidal resections before SRT. An additional patient with Cushings disease had aborted transphenoidal surgery and single-fraction Stereotactic radiosurgery (SRS). Prior to SRT, 4 patients received planned conventional fractionated external beam radiotherapy (XRT) (median dose 33.3 Gy). The median SRT dose was 34.5 Gy (range 14.4–50.4 Gy). The median total radiation dose (XRT plus SRT) for patients receiving fractionated treatment was 47.7 Gy. The median follow-up was 62 months (range 22–91 months). One patient with Nelsons syndrome was lost to follow-up. Of the 9 evaluable patients, none required reoperation for growth of pituitary tumor and all had radiographic control as shown by serial MRI scans. In 4 of the 6 patients with Cushings disease, treatment resulted in normalization of hormone levels and resolution of symptoms. All 4 patients were able to discontinue medications. In 2 patients, normalization occurred within 4 months of treatment. Two patients with Cushings disease failed, requiring adrenalectomy. For patients with prolactinoma, treatments resulted in a significant decrease of plasma prolactin levels. All patients treated for prolactinoma became asymptomatic; 2 were able to discontinue bromocriptine and 1 patient had a successful pregnancy. After radiation therapy, 1 patient developed new hypopituitarism. None of the patients developed worsened visual acuity, visual fields, or new neurological deficits. SRT with or without XRT may yield meaningful reductions in hormone levels with concomitant clinical improvement in selected patients with prolactinomas or Cushings disease. In certain situations, combining conventional XRT with SRT is appropriate. Modifications of the Stereotactic radiation delivery may maximally reduce the hypothalamic dose, thereby possibly reducing the risk of clinical hypopituitarism. This treatment is safe and is without visual or other neurological toxicity.

Focused neutron beam dose deposition profiles in tissue equivalent materials: a pilot study for BNCT

Boron Neutron Capture Therapy (BNCT) has been limited by the inability to direct neutrons toward the therapeutic target and away from sensitive normal tissues. The recently developed Kumakhov lens has focused a broad incident low energy neutron beam in air to a sub-mm spot. This study examines the radiation does distribution of a converging beam passing through tissue equivalent materials. A neutron beam exiting a focusing lens is directed toward a stack of thin radiochromic media sandwiched between plastic sheets. The depth dose and beam profile within the tissue equivalent materials are determined by optical scanning and image processing of the individual radiochromic media sheets, a polymer based dosimetry medium which darkens upon exposure to ionizing radiation. The alpha particle emission from boron is examined by substituting a plastic sheet with a 6Li enriched lithium carbonate sheet positioned at the focal plane. The information will help determine the feasibility of applying the focused neutron beam to BNCT for therapy.