J. Robert Cassady

Chemotherapy alone compared with chemotherapy plus radiotherapy for localized intermediate- and high-grade non-Hodgkin's lymphoma

BACKGROUND Patients with clinically localized, intermediate- or high-grade non-Hodgkins lymphoma usually receive initial treatment with a doxorubicin-containing regimen such as cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Pilot studies suggest that eight cycles of CHOP alone or three cycles of CHOP followed by involved-field radiotherapy are effective in such patients. METHODS We compared these two approaches in a prospective, randomized, multi-institutional study. The end points were progression-free survival, overall survival, and life-threatening or fatal toxic effects. Two hundred eligible patients were randomly assigned to receive CHOP plus radiotherapy, and 201 received CHOP alone. RESULTS Patients treated with three cycles of CHOP plus radiotherapy had significantly better progression-free survival (P=0.03) and overall survival (P=0.02) than patients treated with CHOP alone. The five-year estimates of progression-free survival for patients receiving CHOP plus radiotherapy and for patients receiving CHOP alone were 77 percent and 64 percent, respectively. The five-year estimates of overall survival for patients receiving CHOP plus radiotherapy and for patients receiving CHOP alone were 82 percent and 72 percent, respectively. The adverse effects included one death in each treatment group. Life-threatening toxic effects of any type were seen in 61 of 200 patients treated with CHOP plus radiotherapy and in 80 of 201 patients treated with CHOP alone (P=0.06). The left ventricular function was decreased in seven patients who received CHOP alone, whereas no cardiac events were recorded in the group receiving CHOP plus radiotherapy (P=0.02). CONCLUSIONS Three cycles of CHOP followed by involved-field radiotherapy are superior to eight cycles of CHOP alone for the treatment of localized intermediate- and high-grade non-Hodgkins lymphoma.

Preliminary Clinical Experience with Linear Accelerator-based Spinal Stereotactic Radiosurgery

A prototype device called an extracranial stereotactic radiosurgery frame was used to deliver stereotactic radiosurgery, with a modified linear accelerator, to metastatic neoplasms in the cervical, thoracic, and lumbar regions in five patients. In all patients, the neoplasms had failed to respond to spinal cord tolerance doses delivered by standard external fractionated radiation therapy to a median dose of 45 Gy (range, 33-65 Gy/11-30 fractions). The tumors were treated with single-fraction stereotactic radiosurgery with the spinal stereotactic frame for immobilization, localization, and treatment. The median number of isocenters was one (range, one to five) with a median single fraction dose of 10 Gy (range, 8-10 Gy) with median normalization to 80% isodose contour (range, 80-160%). There has been a single complication of esophagitis to date from radiosurgery of a tumor involving the C6-T1 segments; the esophagitis resolved with medical therapy. Median follow-up in this group of patients has been 6 months (range, 1-12 mo). To date, there has been no radiographic or clinical progression of the treated tumor in any patient. Two patients have died from systemic metastatic disease. In the three surviving patients, there has been computed tomographic- or magnetic resonance-documented regression of the treated tumor with a decrease of thecal sac compression with a median follow-up of 6 months (range, 3-14 mo). These five patients represent the first clinical application of stereotactic radiosurgery in the spine. The results suggest that extracranial radiosurgery may be suitable for the treatment of paraspinal neoplasms after external fractionated radiation therapy, even in the face of spinal cord compression.

Definitive Radiation Therapy of Carcinoma of the Prostate

The charts of 310 consecutive patients with localized prostatic carcinoma treated definitively with small-field external-beam irradiation were reviewed. The 5- and 10-year uncorrected actuarial survival rates for patients with disease limited to the prostate were 72 and 48%, respectively, compared to 48 and 30% in patients with palpable extracapsular extension. Patients for whom the interval between histological diagnosis and initiation of radiotherapy was less than one year had a significantly higher survival rate than those for whom this interval was longer. Severe symptoms which persisted beyond one year after treatment developed in 5%. Sexual potency was maintained in 70% of patients not hormonally manipulated following radiotherapy.

Clinical radiation nephropathy

An analysis of the normal tissue effects of irradiation of the kidney is presented. Various clinical syndromes resulting from treatment are described as well as the potential cellular basis for these findings. Effects of concurrent and/or sequential treatment with irradiation and various chemotherapeutic agents are discussed and the impact of these agents on toxicity presented. Adverse consequences of renal treatment in the child is described and possible radiation effects on so-called compensatory hypertrophy following nephrectomy presented. Renal consequences described to date of bone marrow transplantation programs utilizing irradiation are also presented. The necessity of a dose-volume histogram analysis approach to analyzing renal toxic effects in patients followed for long (> 10 year) periods is essential in developing accurate guidelines of renal tolerance.

Medulloblastoma at the joint center for radiation therapy between 1968 and 1984. The influence of radiation dose on the patterns of failure and survival

In order to assess the efficacy of high‐dose irradiation to the posterior fossa and low‐dose irradiation to the spinal axis, we reviewed the results of 60 patients with biopsy‐proven medulloblastoma treated at the Joint Center for Radiation Therapy (JCRT) between 1968 and 1984. The 5‐ and 10‐year actuarial survival rates for all patients were 68% and 44%, respectively. The median time to recurrence was 19 months. Extent of surgery, age, and radiation dose to the posterior fossa all were of prognostic value. Complete or subtotal gross resection appeared to be a favorable prognostic indicator compared with biopsy only (P < 0.05), with a 69% versus 40% actuarial survival rate at 5 years, respectively. Infants 2 years of age or less had a diminished 5‐year actuarial survival rate of 48% (P < 0.05) compared with older age groups. The posterior fossa was the predominant site of recurrence and accounted for 78% of all failures. Local control in the posterior fossa was dose dependent. Seventy‐nine percent of the tumors that received 5000 cGy or greater were controlled versus only 33% of the tumors that received less than 5000 cGy (P < 0.02). There were no supratentorial failures, and there was only one isolated spinal cord failure. There were no solitary spinal failures in 24 patients who received a median dose of only 2400 cGy to the spinal axis. We concluded that low‐dose irradiation to the spine and whole brain may be indicated with maintenance of a posterior fossa dose of greater than 5000 cGy.

Risk factors for thyroid abnormalities after neck irradiation for childhood cancer

Thyroid evaluations were performed in 95 patients who received radiotherapy to the neck region for childhood cancer five to 34 years earlier. Fifty-six patients (61 percent) had at least one abnormality of serum free thyroxine index, serum thyroid-stimulating hormone (thyrotropin), or thyroid palpation. Seven had subnormal free thyroxine index and 40 had elevated thyrotropin concentrations. Thyroidal radiation doses of 3,000 or more rads and lymphangiography independently increased the risk (p less than or equal to 0.01) of an elevated serum thyrotropin concentration (present in 11 percent of patients with neither risk factor, 50 percent of those who underwent lymphangiography and received less than 3,000 rads, 46 percent of those who had 3,000 or more rads and no lymphangiography, and 76 percent of those with both), but duration of follow-up did not. Twenty-six patients had thyroid nodules and six others had diffuse thyroid enlargement. The frequency of palpable abnormalities increased with the follow-up time after radiation (30 percent of patients followed up less than 10 years had abnormalities versus 43 percent of those followed up 10 or more years, p = 0.03), but was not related to the serum thyrotropin level, radiation dose, or lymphangiography. Among 10 patients who had surgery for nodules, three had localized papillary thyroid carcinomas.

Treatment of Plasma Cell Granuloma of the Lung With Radiation Therapy A Report of Two Cases and a Review of the Literature

Plasma cell granuloma is a rare, benign tumor that affects people at all ages and most frequently involves the lung, gastrointestinal tract, and salivary gland. They are the most common, isolated, primary lesion of the lung in children less than 16 years of age, and usually present as circumscribed, peripheral, parenchymal tumors, which may be static or increase slowly in size without causing symptoms. Whereas surgical excision is the treatment of choice, there are situations in which the lesion cannot be resected without significant morbidity because of direct extension into the mediastinum or lymph nodes. In these circumstances, radiation therapy may be a better therapeutic option. Two cases of plasma cell granuloma that could not be completely resected are described. The patients were treated with radiation therapy consisting of 4320 rad in 4.5 weeks and 4500 rads in 4.5 weeks, respectively, and both have been cured. Although surgery as the primary treatment for most patients is still recommended, especially in the young so the potential side effects of radiation therapy can be avoided, the authors believe that in rare cases where the lesion is locally aggressive and surgically unresectable or resectable only with major morbidity, radiation therapy can be an effective alternative. Currently, the recommended treatment is 4000 to 4500 rad given in 180 to 200 rad fractions, with the fields being carefully tailored to the tumor volume in order to minimize the dose to the surrounding normal tissue.

Radiation therapy for pineal and suprasellar germ cell tumors

Radiation therapy (XRT) was used in the treatment of 25 patients with tumors of the pineal and suprasellar locations. A tissue diagnosis was obtained before XRT in 5 patients, and 20 were irradiated without histologic verification. The overall survival rate is 80% (76% with no evidence of disease (NED). Megavoltage XRT was delivered to the entire neuraxis in 22 patients, and 86% (19/22) are alive from 4 to 88 months (median, 30 months) after treatment. In two of three patients treated only to local fields, tumor recurred in the spine; both are dead of disease. Biopsy‐proven germinomas and multiple midline tumors responded favorably to XRT, whereas solitary pineal tumors and teratomas with marker positivity (human chorionic gonadotropin, alpha‐fetoprotein) did not respond as well. The endocrinologic presentation, tumor marker status, and early response to radiation measured on computed tomography are useful means for selecting patients for radiation therapy.

Improved outlook for Ewing's sarcoma with combination chemotherapy (vincristine, actinomycin D and cyclophosphamide) and radiation therapy.

Vincristine, actinomycin D, and cyclophosphamide (VAC) were administered to 14 patients with Ewings sarcoma. The primary tumors were treated with radiation therapy and concurrent chemotherapy. Nine patients had no visible metastases at diagnosis: two died following the development of pulmonary metastases and the rest have been free of disease for periods varying from 4 months to 4 1/2 years following completion of treatment. This contrasts with a 27% survival in patients previously treated at this center with single agent chemotherapy. Five other patients had demonstrable metastases at diagnosis: VAC chemotherapy achieved complete regression of pulmonary metastases in three for 9, 9+ and 24+ months, respectively. Following disappearance of tumor in the latter two, pulmonary irradiation was administered in an attempt to consolidate the response, but tumor recurred 6 months later. These patients eventually died of widespread disease although survival appeared prolonged in comparison to that seen in past experience. Chemotherapy was well tolerated, although three patients developed hemorrhagic cystitis, necessitating discontinuation of cyclophosphamide. The data suggest the potential for prolonged control and an increase in the cure rate with this therapeutic approach.

Renal Cell Carcinoma in Childhood and Adolescence: A Clinical and Pathological Study of 17 Cases

From 1955 through 1984, 17 patients aged 17 years or younger were treated or seen in consultation for renal cell carcinoma at the Childrens Hospital and Dana Farber Cancer Institute. There were 11 girls and 6 boys, with an average age at diagnosis of 11 years (range 4 to 17 years). Gross hematuria and abdominal or flank pain were the most common presenting complaints, and in 5 cases there was a history of antecedent trauma. The tumors ranged in size from 2 to 15 cm. (average diameter 7.5 cm.). There were 10 tumors in the left kidney and 7 in the right kidney. Childhood renal cell carcinoma displayed similar gross and microscopic features compared with counterparts in adults. The smallest renal cell carcinoma to metastasize measured 3 cm. in diameter and the pathological features suggested an origin from distal collecting tubules (ducts of Bellini). There were 6 tumor-related deaths (35 per cent over-all mortality) occurring 2 months to 2 years after diagnosis. Eleven children were well, with an average duration of followup of 12 years (range 4 to 27 years). The most important prognostic factor was clinical stage at the time of diagnosis. The presence of renal vascular invasion per se did not appear to be an adverse finding. The most optimal treatment for children with stage I renal cell carcinoma is radical nephrectomy with regional lymphadenectomy. While adjuvant radiation and/or chemotherapy may be used in patients with more advanced stage disease, their efficacy in achieving long-term survival free of relapse or cure is not well defined.